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tion) (modified from MacMunn, The Spectroscope in Medicine).

AN AMERICAN TEXTBOOK

OF

PHYSIOLOGY

BY

HENRY P. BOWDITCH, M. D., JOHN G. CUBTIS. M. D.,

HENRY PL DONALDSON, Ph.D., W. H. HOWELL, Ph.D., M.D.,

FREDERIC S. L^, Ph. D., WARREN P. LOMBARD, M.D.,

GRAHAM LUSK, Ph.D., W. T. PORTER, M.D., EDWARD T. REICHERT, M.D.,

AND HENRY SE^VALL, Ph. D., M. D.

EDITED BY

WILLIAM H. HOWELL, Ph.D., M: D.

Professor of Physiology in the Johns Hopkins University, Baltimore, Md.

FULLY ILLUSTRATED

PHILADELPHIA:

W. B. SAUNDERS,

925 Walnut Street.
189 7.

/e97

Copyright, 1896,
By VV. B. SAUNDERS.

ILEOTBOTYPED BY
WESTOOTT »i THOMSON, PHILADA.

PRESS OF
W. B. SAUNDERS. PHILADA.

CONTRIBUTORS.

HENRY P. BOWDITCH, M. D.,

Professor of Physiology in tlie Harvard Medical School.

JOHN G. CURTIS, M.D.,

Professor of Physiology in Columbia University (College of Physicians and Surgeons).

HENRY H. DONALDSON, Ph. D.,

Head-Professor of Xeurology in the University of Chicago.

W. H. HOWELL, Ph. D., M. D.,

Professor of Physiology in the Johns Hopkins University.

FREDERIC S. LEE, Ph. D.,

Adjunct Professor of Physiology in Columbia University (College of Physicians and
Surgeons).

WARREN P. LOMBARD, M. D.,

Professor of Physiology in the University of Michigan.

GRAHAM LUSK, Ph. D.,

Professor of Physiology in the Yale Medical School.

W. T. PORTER, M. D.,

Assistant Professor of Physiology in the Harvard Medical School.

EDWARD T. REICHERT, M. D.,

Professor of Physiology in the University of Pennsylvania.

HENRY SEWALL, Ph.D., M. D.,

Professor of Physiology in the Medical Department of the University of Denver

9

PREFACE.

The collaboration of several teachers in the preparation of an elementary
text-book of physiology is unusual, the almost invariable rule heretofore
having been for a single author to write the entire book. It does not seem
desirable to attempt a discussion of the relative merits and demerits of the two
plans, since the method of collaboration is untried in the teaching of physi-
ology, and there is therefore no basis for a satisfactory comparison. It is a fact,
however, that many teachers of physiology in this countiy have not been
altogether satisfied with the text-books at their disposal. Some of the more
successful older books have not kept pace with the rapid changes in modern
physiology, while few, if any, of the newer books have been uniformly satis-
factory in their treatment of all parts of this many-sided science. Indeed, the
literature of experimental physiology is so great that it would seem to be
almost impossible for any one teacher to keep thoroughly informed on all
topics. This fact undoubtedly accounts for some of the defects of our present
text-books, and it is hoped that one of the advantages derived from the col-
laboration method is that, owing to the less voluminous literature to be
consulted, each author has been enabled to base his elementary account upon
a comprehensive knowledge of the part of the subject assigned to him. Those
who are acquainted with the difficulty of making a satisfactory elementary
presentation of the complex and oftentimes unsettled questions of physiology
must agree that authoritative statements and generalizations, such as are fre-
quently necessary in text-books if they are to leave any impression at all upon
the student, are usually trustworthy in proportion to the fulness of informa-
tion possessed by the writer.

Perhaps the most important advantage which may be expected to follow

the use of the collaboration method is that the student gains thereby the point

of view of a number of teachers. In a measure he reaps the same benefit as

would be obtained by following courses of instruction under different teachers.

The different standpoints assumed, and the differences in emphasis laid upon

the various lines of procedure, chemical, physical, and anatomical, should

give the student a better insight into the methods of the science as it exists

11

12 PREFACE.

to-day. A similar advantage may be expected to follow the inevitable over-
lapping of the topics assigned to the various contributoi-s, since this has led
in many cases to a treatment of the same subject by several writers, who have
approached the matter under discussion from slightly varying standpoints, and
in a few instances have arrived at slightly different conclusions. In this
last respect the book reflects more faithfully perhaps than if written by a
single author the legitimate differences of opinion which are held by physi-
ologists at present with regard to certain questions, and in so far it fulfils
more perfectly its object of presenting in an unprejudiced way the existing
state of our knowledge. It is hoped, therefore, that the diversity in method
of treatment, which at first sight might seem to be disadvantageous, will prove
to be the most attractive feature of the book.

In the preparation of the book it has been assumed that the student has
previously obtained some knowledge of gross and microscopic anatomv, or is
taking courses in these subjects concurrently with his physiology. For this
reason no systematic attempt has been made to present details of histology or
anatomy, but each author has been left free to avail himself of material of
this kind according as he felt the necessity for it in developing the physiolog-
ical side.

In response to a general desire on the part of the contributors, references
to literature have been given in the book. Some of the authors have used
these freely, even to the point of giving a fairly complete bibliography of the
subject, while others have preferred to employ them only occasionally, where
the facts cited are recent or are noteworthy because of their importance or
historical interest. References of this character are not usually found in ele-
mentary text-books, so that a brief word of explanation seems desirable. It
has not been supposed that the student will necessarily look up the references
or commit to memory the names of the authorities quoted, although it is pos-
sible, of course, that individual students may be led to refer occasionally to
original sources, and thereby acquire a truer knowledge of the subject. The
main result hoped for, however, is a healthful pedagogical influence. It is too
often the case that the student of medicine, or indeed the graduate in medicine,
regards his text-book as a final authority, losing sight of the fact that such
books are mainly compilations from the works of various investigators, and
that in all matters in dispute in physiology the final decision must be made, so
far as possible, upon the evidence furnished by experimental work. To enforce
this latter idea and to indicate the character and source of the great literature
from which the material of the text-book is obtained have been the main
reasons for the adoption of the reference system. It is hoped also that the

PREFACE. 13

book will be found useful to many practitioners of medicine who may wisii to
keep themselves in touch with the development of modern physiology. For this
class of readers references to literature are not only valuable, but frequently
essential, since the limits of a text-book forbid an exhaustive discussion of
many points of interest concerning which fuller information may be desired.

The numerous additions which are constantly being made to the literature
of physiology and the closely related sciences make it a matter of difficulty to
escape errors of statement in any elementary treatment of the subject. It can-
not be hoped that this book will be found entirely free from defects of this
character, but an earnest effort has been made to render it a reliable repository
of the important facts and principles of physiology, and, moreover, to embody
in it, so far as possible, the recent discoveries and tendencies which have so
characterized the history of this science within the last few years.

CONTENTS.

PAOK

I. INTRODUCTION 17

By W. H. Howell.

II. GENERAL PHYSIOLOGY OF MUSCLE AND NERVE .... 32

By Warren P, Lombard.

III. SECRETION 152

By W. H. Howell.

IV. CHEMISTRY OP DIGESTION AND NUTRITION 213

By W. H. Howell.

V. MOVEMENTS OF THE ALIMENTARY CANAL, BLADDER,

AND URETER 307

By W. H. Howell.

VI. BLOOD AND LYMPH 331

By W. H. Howell.

VII. CIRCULATION 368

Part I. — The Mechanics of the Circulation of the
Blood and of the Movement of the Lymph 368

By John G. Curtis.

Part II. — The Innervation of the Heart 440

Part III. — The Nutrition of the Heart 471

Part IV.— The Innervation of the Blood-Vessels . . . 482
By W. T. Porter.

VIII. RESPIRATION 503

By Edward T. Reich ert.

IX. ANIMAL HEAT 575

By Edward T. Reichert.

X. CENTRAL NERVOUS SYSTEM 605

By Henry H. Donaldson.

15

16 CONTENTS.

PAGE

XI. THE SPECIAL SENSES 744

Vision 744

By Henry P. Bow ditch.

Hearing, Cutaneous and Muscular Sensibility, Equilib-
rium, Smell, and Taste 807

By Henry Sewall.

XII. PHYSIOLOGY OF SPECIAL MUSCULAR MECHANISMS . . 855

The Action of Locomotor Mechanisms 855

By Warren P. Lombard.

Voice and Speech 861

Bv Henry Sewall.

XIII. REPRODUCTION 878

By Frederic S. Lee.

XIV. THE CHEMISTRY OF THE ANIMAL BODY 943

By Graham Lusk.

AN AMERICAN

TEXT-BOOK OF PHYSIOLOGY.

I. INTRODUCTION.

The term " physiology " is, in an etymological sen.se, synonymous with
" natural philosophy," and occasionally the word is used with this significance
even at the present day,^ By common u.sage, however, the term is restricted
to the living side of nature, and is meant to include the sum of our know-
ledge concerning the properties of living matter. The active substance of
which living things are composed is supposed to be closely similar in all cases,
and is commonly designated as protoplasm (;r^a>roc, first, and Tz)Aafia^ any-
thing formed). It is usually .stated that this word was first introduced into
biological literature by the botani.-jt You Mohl to designate the granular semi-
liquid contents of the plant-cell. It seems, however, that priority in the use
of the word belongs to the physiologi.st Purkiuje (1840), who employetl it to
describe the material from which the young animal embryo is constructed.^
In recent years the term has been applied indiflPerently to the soft material
constituting the substance of either animal or plant-cells. The word must not
be misunderstood to mean a substance of a definite chemical nature or of an
invariable morphological structure ; it is applied to any part of a cell which
shows the properties of life, and is therefore only a convenient abbreviation
for the phrase " ma.ss of living matter."

Living things fall into two great groups, animals and plants, and corre-
sponding to this there is a natural separation of physiology into two sciences, one
dealing with the phenomena of animal life, the other with plant life. In what
follows in this introductory section the former of these two divisions is chiefly
considered, for although the most fundamental laws of physiology are, without
doubt, equally applicable to animal and vegetable protoplasm, nevertheless the
structure as well as the properties of the two forms of matter are in some
respects noticeably different, particularly in the higher types of organisms in
each group. The most striking contrast, perhaps, is found in the fact that
plants exhibit a le.s.ser degree of specialization in form and function and

^ See Mineral Physiology and Physiography, T. Sterry Huut, 1886.
• ' O. Hertwig : Die Zelle und die Gewebe, 1893.
2 17

18 AN AMERICAN TEXT-BOOK OF PIIYSIOI.OGY.

a much greater power of assimilalioii. Owing to tlii.s latter property tlie
plant-cell is able, 'vvitii the aid ol" solar energy, to construct its protoplasm
from very simple forms of inorganic matter, such as water, cari)on dioxide,
and inorganic salts. In this way energy is stored within the vegetable cell in
the form of complex organic compounds. Animal ])rotoplasm, on the con-
trary, has comparatively feeble synthetic properties ; it is characterized chiefly
by its destructive jiower. In the long run, animals obtain their food from the
plant kingdom, and the animal cell is able to dissociate or oxidize the com])lex
material of vegetable protoplasm and thus liberate the potential energy con-
tained therein, the energy taking the form mainly of heat and muscular work.
"We must suppose that there is a general resemblance in the ultimate structure
of animal and vegetable living matter to wdiich the fundamental similarity in
properties is due, but at the same time there must be also some common dif-
ference in internal structure between the two, and it is fair to assume that
the divergent properties exhibited by the two great groups of living things
are a direct outcome of this structural dissimilarity ; to make use of a figure
of speech employed by Bichat, plants and animals are cast in different moulds.

It is difficult if not impossible to settle upon any one property which
absolutely shall distinguish living from dead matter. Xutrition, that is, the
power of converting dead food material into living substance, and repro-
duction, that is, the power of each organism to perpetuate its kind by the
formation of new individuals, are probably the most fundamental charac-
teristics of living things; but in some of the specialized tissues of higher
• animals the power of reproduction, so far as this means mere multiplication
by cell-division, seems to be lost, as, for example, in the case of the nerve-cells
in the central nervous system or of the ovum itself before it is fertilized i)y
the spermatozoon. Nevertheless these cellular units are indisputably living
matter, and continue to exhibit the power of nutrition as well as other prop-
erties characteristic of the living state. It is possible also that the jxtwer
of nutrition may, under certain conditions, be held in abeyance temporarily at
least, although it is certain that a permanent loss of this property is incom-
patible with the retention of the living condition.

It is frequently said that the most general property of living matter is its
irritability. The precise meaning of the term vital irritability is hard to
define. The \yord implies the capability of reacting to a stimulus and usually
also the assumption that in the reaction some of the inner potential energy of
the living material is liberated, so that the energy of the res]M)nse is many
times greater, it may be, than the energy of the stimulus. This last idea is
illustrated by the case of a contracting muscle, in Ayhich the stimulus acts as a
liberating force causing chemical decompositions of the substance of the muscle
with the liberation of a comparatively large amount of energy, chiefly in the
form of heat or of heat and work. It may be remarked in ])assing, liowever,
that we are not justified at present in assuming that a similar liberation of
stored energy takes place in all irritable tissues. In the case of nerve-fibres,
for instance, we have a typically irritable tissue which responds readily to

iXTROhrc'i fON. 19

external stimuli, hut as yet it has not hcen possihle to show that the forma-
tion or conduction of a iiorvo inn)ulse is accompanied hy or dependent upon
the liheration of potential chemical energy. The nature of the reaction of
irritable living matter is found to vary with the character of the tissue or
organism on the one hand, and, so I'ar as intensity goes at least, with the
natui'c of the stimulus on the (»ther. Response of a definite character to
ajipropriate external stinuilation may be observed frequently enough in
dead matter, and in st)me cases the nature of the reaction sinmlates closely
some of those displayed by living thiugs. For instance, a dead catgut string
may be made to shorten after the manner of a nuiscular contraction by the
appropriate application of heat, or a mass of gunpowder may be exploded by
tlie action of a small spark and give rise to a great liberation of energy which
had previously existed in potential form within its molecules. As regards
any jiiece of matter we can only say that it exhibits vital irritability when the
I'eaction or response it gives upon stinuilation is one characteristic of living
matter in general or of the particular kind of living matter under observation ;
thus, a muscle-fibre contracts, a nerve-fibre conducts, a gland-cell secretes, an
entire organism moves or in some way adjusts itself more perfectly to its
environment. Considered from this standpoint, irritability means only the
exhibition of one or more of the peculiar properties of living matter and can-
not be used to designate a property in itself distinctive of living structure ;
the term, in fact, comprises nothing more specific or characteristic than is
implied in the more general phrase vitality. When an amoeba dies it is no
longer irritable, that is, its substance no longer assimilates when stimulated by
the presence of appropriate food, its conductivity and contractility disappear
so that mechanical irritation no longer causes the protrusion or retraction of
pseudopodia — no form of stimulation, in fact, is capable of calling forth any
of the recognized properties of living matter. To ascertain, therefore, whether
or not a given piece of matter possesses vital irritability we must first become
a('(]uainted with the fundamental properties of living matter in order to recog-
nize the response, if any, to the form of stimulation used.

Nutrition or assimilation, in a wide sense of the word, has already been
referred to as probably the most universal and characteristic of these proj)-
erties. By this term we designate that series of changes through which dead
matter is received into the structure of living substance. The term in its
broadest sense may be used to cover the subsidiary processes of digestion,
respiration, absorption, and excretion through which food material and
oxygen are prepared for the activity of the living molecules, and the waste
products of activity are removed from the organism, as well as the actual
conversion of dead material into living protoplasm. This last act, which is
presumably a synthetic process effected under the influence of living matter,
is especially designated as anabolism or as assimilation in a narrower sense
of the Avord as opposed to disassimilation. By disassimilation or katabolism
we mean those changes leading to the destruction of the complex substance of
the living molecules, or of the food material in contact with these molecules.

20 AN AMi:RirAX TEXT- HOOK OF PIIYSIOLOC Y.

As was said before, animal protoplasm is pre-eminently katabolic, ami the
evidence of its katal)()lisiii is t'oiind in the waste products, such as CO,, II,(),
and urea, which arc given off from animal organisms. Assiiiiilati(m and dis-
assimilation, or anabolism and katabolism, go hand in hand and together
constitute an cver-rccurring cycle of activity which })ersists as long as the
material retains its living structure and which as a whole is designated under
the nanu> metabolism. In most forms of living matter metabolism is in some
way self-limited, so that gradually it beco'mes less perfect, old age comes on,
and finally tleath ensues. It has been asserted that originally the metabolic
activity of protoplasm was self-perpetuating — that, barring accident, the cycle
of changes would go on forever. Resting upon this assumption it has been
suggested by Weissmann that tPTe protoplasm of the reproductive elements
still retains this primitive and perfect metabolism and thus provides for the
continuity of life. The speculations bearing upon this point will be discussed
in more detail in the section on Reproduction.

Reproduction in some form is also practically a universal property of
living matter. The unit of structure among living organisms is the cell.
Under proper conditions of nourishment the cell may undergo separation into
two daughter cells. In some cases the separation takes place by a simple act
of fission, in other cases the division is indirect and involves a number of
interesting changes in the structure of the nucleus and the protoplasm of the
body of the cell, or cytoplasm, as it is frequently called. In the latter case
the process is spoken of as karyokinesis or mitosis. This act of division was
supposed formerly to be under the control of the nucleus of the cell, but
modern histology has shown that in karyokinetic division the process, in
many cases at least, is initiated by a special structure to which the name cen-
trosome has been given. The many-celled animals arise by successive divi-
sions of a primitive cell, the ovum, and in the higher forms of life the ovum
requires to be fertilized by union with a spermatozoon before cell-division
becomes possible. The sperm-cell acts as a stimulus to the egg-cell (see section
on Reproduction) and rapid cell-division is the result of their union. It must
be noted also that the term reproduction includes the power of hereditary
transmission. The daughter-cells are similar in form to the parent-cell and
the organism produced from a fertilized ovum is sid)stantially a facsimile of
the parent forms. Living matter, therefore, not only exhibits the power of
separating off other units of living matter, but of transmitting to its progeny
its own peculiar internal structure and properties.

Contractility and conductivity are properties exhibited in one form or
another in all animal organisms and we must believe that they are to be
counted among the primitive properties of protoplasm. The power of con-
tracting or shortening is, in fact, one of the commonly recognized features of
a living thing. It is generally present in the simplest forms of animal as
well as vegetable life, although in the more specialized forms it is found for
the most part only in animal organisms. The opinion seems to be general
among physiologists that wherever this property is exhibited, whether in the

jyTR OD LCTION. 2 1

formation of tho pscudojMxlia of au amoeba or white blood-corpuscle, or in
the vibratilo movements of ciliary structures, or in the ])owerful contractions
of voluntary muscle, the underlying mechanism by whieh the shortening is
produced is essentially the same throughout. However general the property
mav be, it cannot be consiilered as distinctivelv characteristic of livin<r struc-
ture. As was mentioned befort', Kngelmann ' has been able to show that a dead
catgut string when surrounded by water of a certain temperature and exposed
to a sudden additional rise of temperature will contract or shorten in a man-
ner closely analogous to the contraction of ordinary muscular tissue, and it is
not at all impossible that the molecular processes involved in the shortening
of the catgut string and the muscle-iibre may be essentially the same.

That conductivity is also a fundamental property of primitive protoplasmic
structure seems to be assured by the reactions which the simple motile forms
of life exhibit when exposed to external stimulation. Au irritation applied
to one point of a protoplasmic mass may produce a reaction involving other
parts, or indeed the whole extent of the organism. The phenomenon is most
clearly exhibited in the more specialized animals which possess a distinct
nervous system. In these forms a stimulus applied to one organ, as for instance
light acting upon the eye, may be followed by a reaction involving quite
distant organs, such as the muscles of the extremities; we know that in these
cases the irritation has been conducted from one organ to the other by means
of the nervous tissues. But here also we have a property which is widely
exhibited in inanimate nature. The conduction of heat, electricity, and other
forms of energy is familiar to every one. While it is quite possible that con-
duction through the substance of living protoplasm is something sui generis,
and does not find a strict parallel in dead structures, yet it must be admitted
that it is conceivable that the molecular processes involved in nerve conduction
may be essentially the same as prevail in the conduction of heat through a
solid body, or in the conduction of a wave of pressure through a liquid mass.
At present we know nothing definite as to the exact nature of vital conduction,
and can therefore affirm nothing.

The four great properties enumerated, namely, nutrition or assimilation
(including digestion, secretion, absorption, excretion, anabolism,and katabolism),
reproduction, conduction, and contractility, form the important features which
we may recognize in all living things and which we make use of in distin-
guishing between dead and living matter. A fifth ])roperty perhaps should
be added, that of sensibility or sensation, but concerning this property as a
general accompaniment of living structure our knowledge is extremely im-
perfect; something more as to the difficulties connected with this subject will
be said presently. The four fundamental properties mentioned are all ex-
hibited in some degree in the simplest forms of life, such as the protozoa. In
the more highly organized animals, however, we find that specialization of
function prevails. Hand in hand with the diiferentiation in form which is
displayed in the structure of the constituent tissues there goes a specialization

' Ueber den Ursprung der Miiskelkraft, Leipzig, 1893.

22 .l^V AMERICAN TEXT-BOOK OF I'll YSK )L<)(; V.

in certain pi-ojxTtics with a com-oinitaDt sin)j)re.ssi()n of otlier properties, the
outcome of which is that iniiseular tissue exhibits pre-eniincutly the power of
contractility, the nerve tissues are characterized hy a liighly developed power
of conihictivity, and so on. While in the simple unicellular forms of animal
life the fundamental properties are all somewhat equally exhibited within the
compass of a sinj^le uuit or cell, in the higher animals we have to deal with
a vast community of cells segregated into tissues each of which possesses some
distinctive property. This specialization of function is known technicallv as
the physiological division of labor. The beginning of this ])rocess may be
recognized in the cell itself. The typical cell is already an oi-ganism of some
complexity as compared with a simple mass of undifferentiated protoj)lasm.
The protoplasm of the nucleus, particularly of that material in the nucleus
which is designated as chromatin, is differentiated, both histologicallv and
physiologically, from the protoplasm of the rest of the cell, the so-called cvto-
plasm. The chromatin material in the resting cell is arranged usually in a
network, but during the act of division (karyokinesis) it is segmented into a
number of rods or lilameuts known as chromosomes. In the ovum there are
good reasons for believing that the power of transmitting hereditary charac-
teristics has been especially acquired by these chromosomes. The nucleus,
moreover, controls in some way the metabolism of the entire cell, for it has
been shown, in some cells at least, that a non-nucleated piece of the cytoplasm
is not only deprived of the power of reproduction, but has also such limited
powers of nutrition that it quickly undergoes disintegration. On the other
hand contractility and conductivity, and some of the functions connected with
nutrition, such as digestion and excretion, seem often to be specialized in the
cytoplasm. As a further example of differentiation in the cell itself the ex-
istence of the centrosome may be referred to. The centrosome is a body of
very minute size which has been discovered in numerous kinds of cells. It
is considered by many observers to be a permanent structure of the cell, lying
either in the cytoplasm, or possibly in some cases within the substance of the
nucleus. When present it seems to have some special function in connection
with the movements of the chromosomes during the act of cell-division. In
the many-celled animals the primitive properties of protoplasm become highly
developed, in consequence of this subdivision of function among the various
tissues, and in many ways the most complex animals are, from a physiological
standpoint, the simplest for purposes of study, since the properties of living
matter become separated and emphasized in them to such an extent that they
are better fitted for accurate observation.

We are at liberty to suppose that the various properties so clearly recognizable
in the differentiated tissues of higher animals are all actually or potentially
contained in the comparatively undifferentiated protoplasm of the simplest uni-
cellular forms. That the lines of variation, or in other words the direction of
specialization in form and function, are not infinite, but on the contrary
comparatively limited, seems evident when we reflect that in spite of the
numerous branches of the phylogenetic stem the properties as well as the

INTR OD UCTION. 23

forms of the differentiated tissues througliuiit the animal kingdom are strikinj^dy
alike. Striated luusck', with tlie characteristic property of sharp and powcrl'nl
contraction, is cvcrywiiere fonnd ; the central nervons system in the inver-
tehrates is bnilt npon the same type as in the highest manunals, and the
variations met with in dilTcrcnt animals are probably bnt varying degrees of
])erte('tion in the dcvelo})ment of the innate possibility contained in primitive
protoplasm. It is not too much to say, perhaps, that were we acquainted with
the structure and chemistry of the ultimate units of living substance, the key
to the possibilities of the evolution of form and finiction would be in our
possession.

Most interesting suggestions have been made in recent years as to the
essential molecular structure of living matter. These views are necessarily
very incomplete and of a highly speculative character, and their correctness or
incorrectness is at })reseut beyond the range of experimental proof; never-
theless they are sufficiently interesting to warrant a brief statement of some
of them, as they seem to show at least the trend of physiological thought.

Pfliiger/ in a highly interesting paper upon the nature of the vital pro-
cesses, calls attention to the great instability of living matter. He supposes
that living substance consists of very complex and very unstable molecules of
a proteid nature which, because of the active iutra-molecnlar movement pre-
sent, are continually dissociating or falling to pieces with the formation of
simpler and more stable bodies such as water, carbon dioxide and urea, the act
of dissociation giving rise to a liberation of energy. " The intra-molecular
heat (movement) of the cell is its life." He suggests that in this living mole-
cule the nitrogen is contained in the form of a cyanogen compouad, and that
the instability of the molecule depends chiefly upon this particular grouping.
Moreover the power of the molecule to assimilate dead proteid and convert it to
living proteid like itself he attributes to the existence of the cyanogen group.
It is known that cyanogen compounds possess the property of polymerization,
that is, of combining with similar molecules to form more complex mole-
cules, and we may suppose that the molecules of dead proteid when brought
into contact with the living molecules are combined with the latter by a pro-
cess analogous to polymerization or condensation. By this means the stable
structure of dead proteid is converted to the labile structure of living proteid,
and the molecules of the latter increase in size and instability. When living
substance dies its molecules undergo alteration and become incapable of ex-
hibiting the usual properties of life. Pfliiger suggests that the change may
consist essentially in an absorption of water whereby the cyanogen grouping
passes over into an ammonia grouping. Loew^ assumes also that the dif-
ference between dead and living or active ])roteid lies chiefly in the fact that
in the latter we have a very unstable or labile molecule in which the atoms are
in active motion. The instability of the molecules he likewise attributes to

^ Archivfiir die f/esammie Physiologie, 1875, Bd. 10, p. 251.

* Ibid., 1880, Bd. 22 ; Loew and Bokorn y : Die chemische KrnftqueUe in lebenden Proioplasma,
Miinchen, 1882; Imperial Institute of Tokyo (College of Agriculture), 1894.

24 AN AMERTCAX TEXT-BOOK OF PIIYSIOIJXSY.

the exi.^^teiice of certain t:;njii|)inji;s of" the atoms. InllMciiccd in part l)V the
power of living jnaterial to rednce alkaline .silver solutions, lie supposes that
the specially important labile groiij) in the molecule is the aldehyde radiral

— C_iT. The nitrotrcn exists also in a lahile amido- combination, —NHj,

and the active or living foi-m of these two grouj)s may be exj»ressed by the

- Oil -Nil,
formula I _(j- If' this grouping by (ihemical change became con-

= C -C_H

verted to the grouping _ ^, — C'HOH ' ^* would form a comparatively iuert

compound such as we have in dead ])roteid. Starting with foiinic aldehyde
Loew and IJokorny give a schema according to wliicii there might be con-
structed a living molecule coutaiuiug the requisite aldehyde and araido-
groups ; thus :

4HCOH 4 H.N = CJT^NO^ + 2H2O.

Formic Ammonia. Aspartic
aldehyde. aldehyde.

Further possible conden.sation of the aspartic aldehyde would give

3(C,H,N02) = C12H17N3O, + 2H2O,

and by still fiu'ther condensation with the addition of sulj)hur and some re-
duction we would get

6(C.2H,,N30,) + 12H + H2S = CV^Hi^NigSO^^ + 2HA

which represents, from theii- standpoint, the simplest expression of the struc-
ture of a proteid molecule possessing great lability and the pow'er of further
polymerization. Latham ' proposes a theory which combines the ideas of
Pfliiger and of Loew. He suggests that the living molecule may be composed
of a chain of cyan-alcohols united to a benzene nucleus. The cyan-alcohols are
obtained by the union of an aldehyde with hydrocyanic acid ; they contain,
therefore, the labile-aldehyde grouping as well as the cyanogen nucleus to
which Pfliiger attributes such importance.

It has been assumed by many observers that the properties of living
matter, as we recognize them, are not solely an outcome of the inner .'structure
of the hypothetical living molecules. They believe that these latter units are
fashioned into larger secondary units each of which is a definite aggregate of
chemical molecules and po.ssesses certain properties or reactions that dejiend
upon the mode of arrangement. The idea is similar to that advanced by
mineralogists to ex])lain the .structure of crystals. They suppose that the
chemical molecules are arranged in larger or smaller groups to which the
name "physical molecules" has been given. So in living protoplasm it may
be that the smallest particles caj^able of exhibiting the es.sential jjrojierties
of life are grou]ys of ultimate molecules, in the chemical .sense, having a
definite arrangement and definite physical properties. These secondary units
1 Brili&h Medical Journal, 1886, p. 629.

INTRODUCTION. 25

of structure have been designated by various iiaiiu's such as "physiological
molecules/" " somacules," '^ micelUe,* etc. Many facts, especially from the
side of plant physiology, teach us that the ]>hysical constitution of protoplasm
is probably of great importance in understanding its reaction to its environ-
ment. Microscopic analysis is insufficient to reveal the existence or character
of these *' physiological molecules," but it has abundantly shown that proto-
]>lasni has always a certain j)hysi('al construction and is not merely a struc-
tureless fluid or semi-fluid mass. Most interesting in this connection are the
recent views of Bi'itschli/ who believes that proto})lasm is an aggregation of
fluid vesicles filled with fluid, resembling somewhat the structure of a foam
or the oily vesicles of an emulsion. He has in fact constructed an artificial
foam of oil and potassium carbonate which not only gives many of the micro-
scopic characters of protoplasm, but simulates the movements and currents
observed in lower forms of life.

What has been said above may serve at least to indicate the prevalent
physiological belief that the phenomena shown by living matter are in the
main the result of the action of the known forms of energy upon a substance
of a complex and unstable structure which possesses, moreover, a physical
organization responsible for some of the peculiarities exhibited. In other
words, the phenomena of life are referred to the physical and chemical struc-
ture of protoplasm and may be explained under the general physical and
chemical laws wdiich control the processes of inanimate nature. Just as in
the case of dead organic or inorganic substances we attempt to explain the
differences in properties between two substances by reference to the difference
in chemical and physical structure between the two, so with regard to living
matter the peculiar differences in properties which separate them from dead
matter, or for that matter the differences which distinguish one form of living
matter from another, must eventually depend upon the nature of the under-
lying physical and chemical structure.

In the early part of this century many prominent physiologists were still
so overwhelmed with the mysteriousness of life that they took refuge in the
hypothesis of a vital force or principle of life. By this term was meant a
something of an unknown nature Avhicli controlled all the phenomena ex-
hibited by living things. Even ordinary chemical compounds of a so-called
organic nature were supposed to be formed under the influence of this force,
and it was thought could not be produced otherwise. The error of this latter
view has been demonstrated conclusively within recent years : many of the
substances formed by the processes of plant and animal life are now easily
produced within the laboratory by comparatively simple synthetic methods.
By the distinguished labors of Emil Fischer^ even the structure of carbohy-

' Meltzer : " Ueber die fundamentale Bedeutung der Erschiitterung fiir die lebende Ma-
terie," Zeitschrift fiir Biohf/ie, Bd. xxx., 1894.

^ Foster : Physiology (Introduction). ^ Niigeli : Theorie der Gdhrung, Miinchen, 1879.

* Investigations on Microscopic Foams and on Protoplasm, London, 1894 ; abstracted in Science,
N. S., vol. ii. No. 52, 1895.

^ Die Chemie der Kohlenhydrate, Berlin, 1894.

26 AN AMERICAN TEXT-BOOK OF PIIYSIOLOOY.

drate bodies has boon (k'tcrmiiicd, and bodies beloiifjinj^ to this group have
been synthetically eonstrueted in the laborat(H-y. Moreover, the work of
Schiitzenberger and of (Jriniaux gives promise that before long, proteid bodies
may be produeed by similar methods. Physiologists have shown, furthermore,
that the digestion which takes place in the stomach or intestine may be effected
also in test-tubes, and at the present day probably no one doubts that in the
act of digestion we have to deal only with a series of chemical reactions which
iu time will be understood as clearly as it is possible to comprehend anv form
of chemical activity. Indeed, the whole history of food in the body follows
strictly the great mechanical laws of the conservation of matter and of energy
which prevail outside the body. No one disputes the pro])osition that the
material of growth and of excretion comes entirely from the food. It has
been demonstrated with scientific exactness that the measurable energy given
off from the body is all contained potentially within the food that is eaten,^
and may be liberated outside the bodv bv ordinarv combustion. Livintr
things, so far as can be determined, can only transform matter and energy ;
they cannot create or destroy them, and in this respect they are like inanimate
objects. But, in spite of the triumphs which have followed the use of the
experimental method in physiology, every one recognizes that our knowledge
is as yet very incomplete. Many important manifestations of life cannot be
explained by reference to any of the known facts or laws of physics and
chemistry, and in some cases these phenomena are seemingly removed from
the field of experimental investigations. As long as there is this residuum
of mystery connected with any of the processes of life, it is but natural that
there should be two points of view. Most physiologists believe that as
our knowledge and skill increase these mysteries will be explained, or rather
Avill be referred to the same great final mysteries of the action of matter and
energy under definite laws, under which we now classify the phenomena of
lifeless matter. Others, however, find the difficulties too great, — they perceive
that the laws of physics and chemistry are not completely adequate at present
to explain all the phenomena of life, and assume that they never will be.
They suppose that there is something iu activity in living matter which is
not present in dead matter, and which for want of a better term may be desig-
nated as vital force or vital energy. However this may be, it seems evident
that a doctrine of this kind stifles inquiry. Nothing is more certain than the
fact that the great advances made in physiology during the last four decades
are mainly owing to the abandonment of this idea of an unknown vital force
and the determination on the part of experimenters to push mechanical
explanations to their farthest limit. There is no reason to-day to suppose that
Ave have exhausted the results to be obtained by the application of the methods
of physics and chemistry to the study of living things, and as a matter of
fact the great bidk of physiological research is proceeding along these lines. It
is interesting, however, to stop for a moment to examine briefly some of the
problems which as yet have escaped satisfactory solution by these methods.
* Rubner: Ztitschrift fur Biologie, Bd. xxx. S. 73, 1894.

INTRODUGTIOX. 27

Tlie phenomena of sceri'tioii and aljsoiptiini (unii iinj)()rtaiit parts of" the
digestive process's in hinlii'i" animals, and wiihont donWt are exhibited in
a minor degree in the unic-elhdar types. In the higher animals the seeretions
may he eoUeeted and analyzed and their composition Ik; compared with that of
the Ivniph or blood from which they are d( rixcd. It has been i'ound that
secretions may contain entirely new snbstances not fonnd at all in tlie bh)od,
as for example the mucin of saliva or the ferments and liCl of gastric juice;
or, on the other hand, that they may e(»iitain substances which, although pres-
ent in the blood, are found in much greater })ercentage amounts in the secre-
tion— as, for instance, is the case with the urea eliminated in the urine. In the
latter case we have an instance of the peculiar, almost purposeful, elective
action of gland-cells of which many other examples might be given. With
regard to the new material present in the secretions, it finds a sufficient general
explanation in the theory that it arises from a metabolism of the protoplasmic
material of the gland-cell. It offers, therefore, a purely chemical problem,
which may and probably will be worlvcd out satisfactorily for each secretion.
The selective power of gland-cells for particular constituents of the blood is
a more difficult question. We find no exact parallel for this kind of action
in chemical literature, but there can be no reasonable doubt that the phe-
nomenon is essentially a chemical or physical reaction dependent upon an af-
finity of the secreted substance for some material within the gland-cell. We
may indulge the hope that the details of the reaction will be discovered by
more complete chemical and microscopical study of the structure of these cells.
If in the meantime the act of selection is spoken of as a vital phenomenon it
is not meant thereby that it is referred to the action of an unknown vital force,
but only that it is a kind of action dependent upon the living structure of the
cell-substance.

The act of absorption of digested products from the alimentary canal was
for a time supposed to be explained completely by the laws of imbibition and
diffusion. The epithelial lining and its basement membrane form a septum
dividing the blood and lymph on the one side from the contents of the ali-
mentary canal on the other. Inasmuch as the two liquids in question are of
unequal composition with regard to certain constituents, a diffusion stream
should be set up whereby the peptones, sugar, salts, etc. would pass from the
liquid in the alimentary canal, where they exist in greater concentration, into
the blood, where the concentration is less. Careful work of recent years has
shown that the laws of diffiision are not adequate to explain fully the ab-
sorption that actually occurs ; a more detailed account of the difficulties met
with may be found in the section on Digestion and Nutrition. It has become
customary to speak of absorption as caused in part by the physical laws of
diffusion, and in part by the vital activity of the epithelial cells. It will be
noticed that the vital property in this case is again a selective affinity for
certain constituents similar to that which has been referred to in the act of
secretion. The mere fiict that the old mechanical theory has proved to be in-
sufficient is in itself no reason for abandoning all hope of a satisfactory ex-

28 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

j)lanation. Most |)liy.si()l()i!;i.sts unquestionably believe that lurther experi-
nientiil work will bring this })henonienon out of its obscurity and show that it
is explicable in terms of known physical and chemical forces acting through
the peculiar substance of the absorptive cell.

The i'acts of heredity and consciousness offer difficulties of a much graver
character. The function of reproduction is two-sided. lu the first ])lace
there is an active multiplication of cells, beginning with (he segmentation of
the ovum into two blastomeres and continuing in the lai-gcr animals to the
formation of an iniuunerable multitude of cellular units. In the second jilace
there is ])resent in the ovum a form-building j)o\ver of such a character that
the great complex of cells arising from it form not a heterogeneous mass, but a
definite organism of the same structure, organ for organ and tissue for tissue,
as the parent form. The ovum of a starfish develops into a starfish, the
ovum of a dog into a dog, and the ovum of man into a human being.
Herein lies the great problem of heredity. The mere multiplication of cells
bv direct or indirect division is not beyond the range of a conceivable me-
chanical explanation. Given the properties of assimilation and contractility it
is possible that the act of cell-division may be traced to purely physical and
chemical causes, and already cytological work is opening the way to credible
hvpotheses of this character. But the phenomena of heredity, on the other
hand, are too complex and mysterious to justify any immediate expectation
that they can be explained in terms of the known properties of matter. The
crude theories of earlier times have not stood the test of investigation by
modern methods, the microscopic anatomy of both ovum and sperm showing
that they are to all api)earauces simple cells which exhibit no visible signs of
the wonderful potentialities contained within them. Histological and experi-
mental investigation has, however, cleared away some of the difficulties for-
merly surrounding the subject, for it has shown with a high degree of prob-
ability that the power of hereditary transmission resides in a ])articular sub-
stance in the nucleus, namely in the so-called chromatin material which forms
the chromosomes. The fascinating observations which have led to this con-
clusion promise to open up a new field of experimentation and speculation.
It seems to l)e possible to study heredity by accepted scientific methods, and
we may therefore hope that in time more light will be thrown upon the
conditions of its existence and possibly upon the nature of its activity.

In the facts of consciousness, lastly, we are confronted with a problem
seemingly more difficult than heredity. In ourselves we recogni/e difierent
states of consciousness following upon the physiological activity of certain
parts of the central nervous system. We know, or think we know, that these
so-called p.sychical states are correlated with changes in the ])rotoplasmic
material of the cortical cells of the cerebral hemispheres. When these cells
are stimulated, psychical states result; when they are injured or removed,
psychical activitv is depressed or destroyed altogether according to the extent
of the injury. From the physiological standpoint it would seem to be as
justifiable to assert that consciousness is a property of the cortical nerve-cells

INTR OD UCTION. 29

as it is to define contractility as a property of ninscle-tissue. But the short-
ening of a innscle is a })hysical phenomenon that can he observed with tlie
senses — be measured and theoretically explained in terms of the known pi-o|)-
erties of matter. Psychical states are, however, removed from such methods of
study ; they are subjective, and cannot be measured or weighed or otherwise esti-
mated with sufficient accuracy and completeness in terms of our units of energy
or matter. There nnist be a causative connection between the oiyective changes
in the brain-cells and the corresponding states of consciousness, but the nature
of this connection remains hidden from us ; and so hopeless does tlie problem
seem that some of our profonndcst thinkers have not hesitated to assert that it
can never be solved. Whether or not consciousness is possessed by all animals
it is impossible to say. In ourselves we know that it exists, and we have
convincing evidence, from their actions, that it is possessed by many of the
higher animals. But as we descend in the scale of animal forms the evidence
becomes less impressive. It is true that even the simplest forms of animal
life exhibit reactions of an apparently purposeful character which some have
explained upon the simple assumption that these animals are endowed with
consciousness or a psychical power of some sort. All such reactions, however,
may be explained, as in the case of reflex actions from the spinal cord, upon
purely mechanical principles, as the necessary response of a definite physical
or chemical mechanism to a definite stimulus. To assume that in all cases of
this kind conscious processes are involved amounts to making psychical activity
one of the universal and primitive properties of protoplasm whether animal
or vegetable, and indeed by the same kind of reasoning there would seem to
be no logical objection to extending the property to all matter whether living
or dead. All such views are of course purely speculative. As a matter of
fact we have no means of proving or disproving, in a scientific sense, the exist-
ence of consciousness in lower forms of life. To quote an appropriate remark
of Huxley's made in discussing this same point with reference to the crayfish,
" Nothing short of being a crayfish would give us positive assurance that such
an animal possesses consciousness." The study of psychical states in our-
selves, for reasons which have been suggested abov^e, does not usually form
a part of the science of physiology. The matter has been referred to here
simply because consciousness is a fact which our science cannot as yet explain.
So far, some of the broad principles of physiology have been considered —
principles which are applicable with more or less modification to all forms of
animal life and which make the basis of what is known as general physiology.
It must be borne in mind, however, that each particular organism possesses
a special physiology of its ow-n, which consists in part in a study of the
properties exhibited by the particular kinds or variations of protoplasm
in each individual, and in large part also in a study of the various mechan-
isms existing in each animal. In the higher animals, particularly, the com-
binations of various tissues and organs into complex mechanisms such as
those of respiration, circulation, digestion, or vision, differ more or less in
each group and to a minor extent in each individual of any one species. It

30 AX AMKliJCAy TKXT-HiJOK OF I'll YSKjlJjd \\

follows, therefore, that each animal has a special physiolotry of its own, and
in this sense we may sjx'ak of a special human physiolotry. It need
scarcely be said thai the ^|)eeial j)hysiol()gy of man is very imperfectly Unown.
Books like the present one, which profess to treat of human physioloi^v, eon-
tain in reality a large amount of general and special physiology which has
been derived from the study of lower animal forms upon which exact experi-
mentation is possible. Most of our fundamental knowledge of the physiology
of the heart and of muscles and nerves has been derived from experiments
upon frogs and similar animals, and much of our information concerning the
mechanisms of circulation, digestion, etc. has been obtained from a study of
other mammalian forms. We transfer this knowledge to the human being, and
in general without serious error, since the connection between man and related
mammalia is as close on the ]>hysiological as it is on the morphological side,
and the fundamental or general physiology of the tissues seems to be every-
where the same. Gradually, however, the material for a genuine special
human physiology is being acquired. In many directions special investigation
upon man is possible; for instance, in the study of the localization of function
in the cerebral cortex, or the details of body metabolism as obtained by exam-
ination of the excreta, or the peculiarities of vaso-motor regulation as revealed
by the use of plethysmographic methods, or the physiological optics of the
human eye. This special information, as rapidly as it is obtained, is incorpo-
rated into the text-books of human physiology, but the fact remains that the
greater part of our so-called human })hysiology is founded upon experiments
upon the lower aninals.

Physiology as a science is confessedly very imperfect ; it cannot compare in
exactness with the sciences of physics and chemistry. This condition of affairs
need excite no surprise Avhen we remember the very M'ide field ])hysiology
attempts to cover, a field co-ordinate in extent with the physics as well as the
chemistry of dead matter, and the enormous complexity and instability of the
form of matter which it seeks to investigate. The progress of physiology is
therefore comparatively slow. The present era seems to be one mainly of
accumulation of reliable data derived from laborious experiments and observa-
tions. The synthesis of these facts into great laws or generalizations is a task
for the future. Corresponding with the diversity of the problems to be
solved we find that the methods employed in physiological research are mani-
fold in character. Inasmuch as animal organisms are composed either of
single cells or aggregates of cells, it follows that every anatomical detail with
regard to the organization of the cell itself or the connection between dif-
ferent cells, and every advance in our knowledge of the arrangement of the
tissues and organs which form the more complicated mechanisms, is of imme-
diate value to physiology. The microseo})ic anatomy of the cell (a braucli of
histology which is frequently designated by the specific name of cytology),
general histology, and gross anatomical dissection are therefore frequently
employed in jihysiological investigations, and form what may be called the
observational side of the science. On the other hand we have the experimental

INTRODUCTION. 31

methods, wliicli seek to discover the |)i-(jpertios and functional relationships of
the tissues and organs by the use of direct experiments. These experiments
may be of a surgical character, involving the extirpation or destruction or
alteration of known parts by operations ni)on the living animal, or they
may consist in the application of the accepted methods of j)hvsies and
chemistry to the living organism. The physical methods include the study of
the physical properties of living matter and the interpretation of its activity
in terms of known physical laws, and also the use of various kinds of physical
ap]>aratus such as manometers, galvanometers, etc. for recording with accuracy
the j)henomena exhibited by living tissues. The chemical methods implv the
a})plication of the synthetic and analytic operations of chemistry to the study of
the composition and structure of living matter and the products of its activity.
The study of the subjective phenomena of conscious life — in fact, the whole
question of the psychic aspects or properties of living matter — for reasons
which have been mentioned is not usually included iu the science of physiol-
ogy, although strictly speaking it forms an integral part of the subject. This
province of physiology has, however, been organized into a separate science,
psychology, although the boundary line between psychology as it exists at
present and the scientific physiology of the nervous system cannot always be
sharply drawn.

It follows clearly enough from what has been said of the methods used in
animal physiology that even an elementary acquaintance with the subject as a
science requires some knowledge of general histology and anatomy, human as
well as comparative, of physics, and of chemistry. When this preliminary
training is lacking, physiology cannot be taught as a science ; it becomes
simply a heterogeneous mass of facts, and fails to accomplish its function as a
preparation for the scientific stndy of medicine. The mere facts of physiology
are valuable, indeed indispensable, as a basis for the study of the succeeding
branches of the medical curriculum, but in addition the subject, properly
taught, should impart a scientific discipline and an acquaintance with the
possible methods of experimental medicine; for among the so-called scientific
branches of medicine physiology is the most developed and the most exact,
and serves as a type, so far as methods are concerned, to which the others
must conform.

II. GENERAL PHYSIOLOGY OF MUSCLE AND

NERVE.

A. Introduction.

It is seldom that the physical and chemical structure of a tissue, as revealed
by the microscope aud the most careful analysis, gives even a suggestion as to
its function. No one would conclude from looking at a piece of beef, or even
micro.'?copically examining a muscle, that it had once been capable of motion,
nor would the most exact statement of its chemical constitution give indication
of such a form of activity. The most thorough histological and chemical
examination of the bundle of fibres which compose a nerve would fail to sug-
gest that a blow upon one end of it would cause to be transmitted to the other
end an invisible change capable of exciting to action the cell wnth which the
nerve communicated. To understand such a structure we must first learn the
forms of activity of which the tissue is capable, the influences which excite
it to action, and the conditions essential to its activity, and then seek an expla-
nation of these facts in its physical and chemical structure.

Contractility. — One of the most striking properties of living matter is
its power to move and to change its form. At times the movements oocur
apparently spontaneously, the exciting cau.se .seeming to originate within the
living substance, but more often the motions are developed in response to some
external influence. This power finds its best expression in muscle-sub.stance.
In its resting form a muscle, such as the biceps, is elongated, and when it is
excited to action it assumes a more spherical shape, i. e. shortens and thickens,
whence it is said to have the property of contractility. It is the shortening,
the contraction, of the muscle which enables it to perform its function of
moving the parts to which it is attached, as the bones of the arm or leg, and
of altering the size of the .structures of which it forms a part, as the walls
of the heart, intestine, or bladder. Ordinary nuiscle-substance is arranged
in fine threads, each one of wiiich is enveloped in a delicate membrane, the
sarcolemma ; these muscle-fibres can be compared to long sausages of micro-
scopic proportions. A muscle is composed of a vast number of fibres
arranged side bv side in bundles, the whole beino; firmlv bound tojjether bv
connective tissue. Since i.solated muscle-fibres have been seen under the
microso>ope to contract, each fibre can be looked upon as containing true muscle-
substance and being endowed with contractility. The movements of muscles
are the resultant of the combined activity of the many microscopic fibres of
which the muscles are composed.

The rate, extent, strength, and duration of muscular contractions are adapted

32

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE.

33

to the needs of the parts to be influenced, and it is found that the structure of
tlie muscles differs according to the work which they liave to perform. Thus
we find two hui^e classes of muscles : the one, like the muscles which move the
bones, remarkable for the raj)idity with which they chan<re their form, but
unsuited to long-continued action ; the other, occurring in the walls of the
intestine, blood-vessels, bladder, etc., sluggish of movem(;nt, but possessing great
endurance. The first of these, when examined with the microscope, is seen
to be composed of bundles of fibres, which are transversely marked by alter-
nating dark and light bands, and hence are cidled striated or striped muscles ;
the other, though com[)osed of fibres, shows no such cross markings, and
tlierefore is known as smooth or non-striated muscle. Striated muscles are

-m

Fig. 1.— Amoeba proteus, magnified 200 times: a, endosarc; 6, simple pseudopodium ; c, ectosarc; d,
first stage in the growth of a pseudopodium ; e, pseudopodium a little older than d ; /, branched pseudo-
podium; g, food-vacuole ; h, food-ball; i, endoplast; k, contractile vesicle (after Brooks: Handbook of
Invertebrate Zoology).

often called voluntary, because most of them can be excited to action by the
will, whereas non-striated muscles are termed involuntary, because in most
cases they cannot be so controlled. Within these two large classes of muscles
we find special forms presenting other, though lesser, differences in function
and structure. The muscle of the heart, though striated, differs so much from
other forms of striped muscle as almost to belong in a special class.
3

34

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Since contractility is possessed hyall forms of muscle-tissue, it is evident that
it is independent of superficial structural differences. Nor is muscle the only
substance possessing this property. Even isolated microscopic particles of liv-
ing matter are capable of making movements, both spontaneously and ^vhen
excite<l by external influences. As far back as 1755, Kosel von Rosenhof
described the apparently spontaneous changes in form of a living organism
composed of a single cell, a fresh-water ama'ba. Moreover, he noted that, if
quiet, it could be excited to action by mechanical shocks.

The amoeba (Fig. 1) is a little animal, of microscopic size, which is found
in the ooze at the bottom of pools, or in the slime 'which dings to some of our
fresh-water plants. Under the microscope it is seen to be composed of jelly-
like, almost transparent matter, in which are a vast number of fine granules, a
delicate tracery of finest fibrils, a small round body, called the nucleus or
endoplast, a round hollow space termed the contractile vesicle, which is seen to
change in size, appearing or disappearing from time to time, and small parti-
cles, which are bits of food or foreign bodies. In the resting state the body
has a somewhat flattened, irregular form, which, if the slide on which it rests l^e
kept warm, is found to alter from minute to minute. Little tongue-like projec-
tions, pseudopods (false feet), are protruded from the surface like feelers, and
are then withdrawn, while others appear in new places. Evidently the little
creature, though composed of a single cell, is endowed with life and has the
power of making movements. Moreover, it may be seen to change its place,

the method of locomotion being a j)eculiar
one. One of the processes, or pseudopods,
may be extended a considerable distance, and
then, instead of being withdrawn, grow in size,
while the body of the animal becomes corre-
spondingly smaller ; thus a transfer of material
takes place, and this continues until the whole
of the material of the cell has flowed over to
the new place. This power of movement }>er-
mits the animal to eat. If when moving over
the slide it encounters suitable food material, a
diatom for instance, it flows round it, engulf-
ing it in its semifluid mass ; and in a similar
manner the animal gets rid of the useless sub-
stances which it may have surrounded, by flow-
ing away from them. These movements may
result from changes which haveocrurred within
itsown substance,and apparently independently
of any external influence. On the other hand,
if its body be disturbed by being touched, by
an unusual temperature, by certain chemicals,
or by an electric shock, it replies by drawing in all of its pseudopods and
assuming a contracted, ball form.

Fig. 2.— Vorticella nebulifera, X 600:
a, cilia of ciliated disk; 6, ciliated disk;
c, peristome ; d, vestibule ; e, oesophagus ;
/, contractile vesicle ; g, food-vacuoles ;
h, endoplast ; r, endosarc ; Jfc, ectosarc : I,
cuticle: m, axis of stem (after Brooks:
Handbook of Invertebrate Zoology).

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 35

The movements of the leucocytes of the blood resemble in many respects
those of the amoeba.'

The property of contractility i.s possessed by a vast variety of unicellular
structures in lower forms of auin)al life. Another example is the Vorticella
(Fig. 2).

The vorticella, like the amoeba, is a little animal which, although consisting
of a single cell, possesses within its microscopic form all the phy.-iological prop-
erties essential to life and the perpetuation of its species. It consists of a bell,
with ciliated margin, borne upon a contractile stalk. If touched with a
hair, or jarred, the cell rapidly contracts ; the edge of the Ix'll is drawn in so
as to make the body nearly spherical, and the stalk is thrown into a spiral
and drags the body back toward the ])oint of attachment. The contraction is
rapid; the relaxation, which comes when the irritation ceases, is gradual. An
interesting account of the movements of Vorticella gracilis is given by Hodge
and Aikins^ under the title of '' The Daily Life of a Protozoan."

Other examples of contractile power possessed by apparently simple organ-
isms are to be found in the tentacles of Actiniae, the surface sarcode of sponges,
the chromatoblasts of Pleuronectidse,^ which are controlled by nerves and
under the influence of light and darkness change their size and so alter the
color of the skin, and the vast variety of ciliated forms, including spermatozoa,
and some of the cells of raucous membranes.*

Irritability. — We have thus far referred to but one of the vital properties
of protoplasm, viz. contractility. Another property intimately associated with
it is irritability. Irritability is the property of living protoplasm which causes
it to undergo characteristic chemical and physical changes when subjected to
certain external influences called irritants. Muscle protoplasm is very irri-
table, and is easily excited to contraction by such irritants as electric shocks,
mechanical blows, etc. The muscles which move the bones rarely, if ever, in
a normal condition, exhibit spontaneous alterations in form, and cannot be said
to possess automatic power. By automatism is meant that property of cell-
protoplasm which enables it to become active as a result of changes which
originate within itself, and independently of any external irritant. Examples
of this power may perhaps be found in the movements of ciliated organisms
and the infusoria. Possibly the rhythmic movements of heart muscle are of
this nature. Still another property of protoplasm, closely allied to contractility
and irritability, and possessed by muscle-substance, is conductivity.

Conductivity is the property which enables a substance, when excited in
one part, to transmit the condition of activity throughout the irritable mate-
rial. For example, an external influence capable of exciting an irritable
muscle-fibre to contraction, although it may directly affect only a small part of

1 An excellent description of these movements, accompanied by illustrations, is given in
Quain's Anatomy, vol. i., pt. 2, pp. 174-179.

^ Hodge and Aikins: American Journal of Psychology, 1895, vol. vi., No. 4, p. 524.

' Krukenberg : Vergleichend-physiologische Vortrdge, 1886, Bd. i. p. 274.

* A careful study of the different forms of movement exhibited by simple organisms has
been made by Engelmann: Hermann's Handbuch der Physiologie, 1879, Bd. i., Th. 1, p. 344.

36 ^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the fibre, may iiKlireotly influence tlie whole, because the condition of activity
which it excites at the point of" a})itlication is transmitted by the muscle-sub-
stijnce throiitjjhout the extent of the fibre.

Irritability and conductivity are not confined to contractile mechan-
ism. They are possessed to a still higher degree by nervous tissues, whidi are
not found to have the power of movement. The nervous system is composed
of nerve-cells and nerve-fibres. The nerve-cells are locatetl chiefly within tlie
brain and spinal cord, a smaller number being found in the spinal ganglia
and at special points along the course of certain nerve-fibres. The active part
of the nerve-fibre is the axis-cylinder, which is an outgntwth from a nerve-ct.ll,
and \\ hich outside of the central nervous system acquires a delicate membran-
ous sheath, the neurilemma, which invests it as the sareolemma does the muscle-
fibre. There are two classes of nerve-fil)res, medullated and non-meduUated,
which are distinguished by the fact that the former has between the axis-
cvlinder and the neurilemma another covering composed of fatty material,
called the medullary sheath, while iu the latter this is absent. Just as
it is the special function of the muscle-fibre to change its form when it
is excited, so it is the special function of the nerve-fibre to transmit the
condition of activity excitetl at one end throughout its length, and to
awaken to action the cell with which it conmiuuicate.*. Xerve-fibres are
the paths of communication between nerve-cells in the central nervous sys-
tem, between sense-organs at the surface of the body and the nerve-cells,
and between the nerve-cells and the muscle- and gland-cells. Nerve-
fibres are distinguished as afferent and efferent, or centripetal and centrifugal,
according as they carry impulses from the surface of the body inward or from
the central nervous system outward. Further, they receive names according
to the character of the activity which they excite : those which excite muscle-
fibres to contract are called motor nerves; those distributed to the muscles
in the walls of blood-vessels, vaso-motor ; those which stimulate gland-cells to
action, secretory ; those which influence certain nerve-cells in the brain and so
cause sensations, sensory. Still other names are given, as "trophic" to fibres
which are supposed to have a nutritive function, and "inhibitory" to those
which check the activities of various organs. The method of conduction is the
same in all these cases, the result depending wholly on the organ stimulated.

Nerve-fibres do not run for any distance separately, but always in company
with others. Thus large nerve-trunks may be fi»rme<l, as in the case of the
nerves to the limbs, in which afferent and efferent fibres run side by side, the
whole being bound together into a com]iact bundle by connective tissue. The
separate fibres, though thus grouped together, are anatomically and physiologi-
cally as distinct as the wires of an ocean cable ; that these many strands are
bound together is of anatomical interest, Init has little physiological significance.

The active substance of the nerve-fibre does not show contractility, but this
does not prevent it from being classed with other irritable forms of living cell-
substance as protoplasm. In spite of differences in structure and composition,
nerve protoplasm and muscle protoplasm are found to have many j)oiuts of

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 37

resemblance. An explanation of the physiological resemblances nuiy be found
in their common ancestry. All the cells of the many structures of the nniiiial
body are descended from the two parent cells from which (he animal is developed.
The fertilized ovum divides, and two eells are formed, tiiese new cells divide,
and so the process continues, the developing cells through unknown causes be-
coming ai'ranged to form more or less definite layers and groups, which bv means
of foldings and nnequal growths develop into the various structures and organs
of the fetus. At the same time that the division is going on, the total amount
of material is increasing. Each of the cells absorbs and assimilates dead food-
material, and this dead material is built into living substance. During this
process of development and growth the cells of special tissues and organs
acquire special anatomical and chemical characters. This development of
specialized cells is termed cell-differentiation. Hand in hand with the ana-
tomical and chemical differentiation goes a physiological differentiation. The
protoplasm of each type of cell, while retaining the general characteristics of
])rotoplasm, has certain physiological properties developed to a marked degree
and other properties but little developed, or altogether lacking. The fertilized
ovum does not have all the anatomical and chemical characteristics of all the
cells which are descended from it, not at least in just the form in which they
are possessed by these cells, and it cannot be assumed that its living sub-
stance possesses all the physiological properties which are owned by its
descendants. Many of these properties it must have, for many of them are
essential to the continuance of life of all active cells, — such as the power to take
in, alter, and utilize materials which are suitable for the building up and repair
of the cell-substance, the power of chemically changing materials possessing
potential energy so that the form of actual energy which is essential to the per-
formance of the work of the cell shall be liberated, and the power to give
oflT the waste materials which result from chemical changes. The proto])lasm
of the ovum, to have these powers, has properties closely allied to absorption,
digestion, assimilation, respiration, excretion ; and, in consideration of the special
function of the ovum, we may add that it possesses the property of reproduc-
tion. The question of its possessing the chai'acteristic properties of muscle and
nerve protoplasm cannot be answered off-hand. Careful study, however, has
shown the ovum of Hydra to possess irritability, conductivity, and contractility.
It undergoes amoeboid movements, as was first shown by Kleinenberg.
Balfour,^ in writing of the development of the ova of Tubularidae, which is
of a type similar to Hydra, says : " The mode of mitrition of the ovum may
be very instructively studied in this type. The process is one of actual feed-
ing, much as an amoeba might feed on other organisms." Something similar
seems to be true of the ova of echinodermata. During impregnation various
movements are described implying the properties of irritability, conductivity,
and contractility. Thus in the case o? Astenai^ glacialis, when the head of the
spermatozoon comes in contact with the mucilaginous covering of the ovum, "a
prominence pointing toward the nearest spermatozoon now rises from the super-
* Comparative Embryology, pp. 17, 29.

38 AN AMERICAN TEXT-BOOK OF PIIYSrOLOGY.

ficial layer of protoplasm of" the egg and grows until it conies in contact with
the nearest sperniatozuon." "At the moment of contact iH'twcen the sperma-
tozoon and the egg, the outermost layer of protoplasm of the latter raises itself
up as a distinct membrane, which separates from the egg and prevents the
entrance of other spermatozoa." Some of the eggs of arthroj)ods and other
forms have likewise been observed to undergo amoebcjid movements as a result
of the physiological stimulus given by the spermatozoon.*

Although irritability and contractility of the ovum have thus far been made
out in but few forms, it is probable that they play an important part in all
during fertilization and division. It would seem, then, that the ovum has all
the principal properties which we ascribe to cell-j)rotoplasm, and that these
properties are inherited more or less completely developed by the many forms
of cells descended from it. The protoplasm of specialized cells, in spite of
their differences in structure, still retains its protoplasmic nature. Undoubtedly
structural peculiarities are intimately related to specialized functions, — the
striped muscle, for example, is especially adapted for rapid movements, and
the nerve-fibre is remarkable for its power of conduction.

Physiological methods for the examination of individual cells are as yet in
their infancy, and we must, for the most part, be content to study the func-
tional activity of cells by observing the combined action of many cells of the
same kind.

B. Irritability of Muscle and Nerve.

Irritability is the property of living protoplasm which causes it to undergo
characteristic physical and chemical changes when it is subjected to certain
influences, called irritants, or stimuli. By an irritant is meant an external influ-
ence which, when applied to living protoplasm, as of a nerve or muscle, excites
it to action. Irritants may be roughly classed as mechanical, chemical, thermal,
and electrical. The normal physiological stimulus is developed within some
of the nervous mechanisms of the body as the result of the activity of the
nerve-protoplasm, this having been excited as a rule by some form of irritant.
The degree of irritiibility of a given form of protoplasm is measured by the
amount of activity which it displays in response to a definite irritant, or by the
minimal amount of irritation required to excite it to action. If the irritant be
applied directly to a muscle, the height to which the muscle contracts and raises
a given weight may be taken as an indication of its activity. As the nerve
gives no visible evidence of activity, the effect of the irritant upon it is usually
estimated by the extent to which the organ stimulate<l by the nerve reacts ; in
the case of motor nerves, the strength of the contraction of the corresponding
muscle is taken as an index.

To determine the exact relation of an ii-ritant to its irritating effect we should
be able to accurately measure them. This we cannot do. We are unable to
state in irritation-units the relative value of different kinds of irritanti>. Even

» Korschelt: Zoologischer Jahrhuch, 1891, Anat. Abtheil., Bd. iv., Heft 1, p. 1. Hertwig:
Morphologische Jahrhuch, 1876, Bd. 1. Herbst: Biologische Centralblatt, 1891, xiii. p. 22.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 39

if we could accurately estimate the aniouiit of energy wliicii eaeli form of irri-
tant can expend in iritation, we should have oidy one of the many factors
which determine its etiiciency. It is e(iually dillicudt to compare the irritating
eifect of irritants upon different forms of protoplasm ; e. g. we cannot state
what degree of activity of a nerve-fibre corresponds to a certain amount <jf
activity in a muscle-fibre. In spite of the lack of exact quantitative measure-
ments, we have gained a clear idea of the way different forms of irritants
act when applied to nerves and muscles in certain ways, and have learned to
control the methods of excitation sufficiently to permit the influences which
alter the irritability of nerves and muscles to show themselves. The effect of
irritants can best be studied upon the nerves and muscles of cold-blooded ani-
mals, because these retain their vitality and irritiibility for a considerable time
after they have been separated from the rest of the body. It is a common
observation of country folk that the body of a snake remains alive for a long
time after the head has been crushed, while the body of a chicken loses all signs
of life in a comparatively short time after it has been decapitated. More care-
ful examination would show that in neither case do all parts of the body die
simultaneously. Each of the myriad cells has a life of its own, which it
loses sooner or later according to its nature and to the alterations to which it
is subjected by the fatal change. The cells of cold-blooded animals, as the
snake and frog, are much more resistant than those of warm-blooded animals,
because the vital processes within the cells are less active, and the chemical
changes which precede and lead to the death of the part occur more slowly.
For instance, the nerves and muscles of a frog remain irritable for many hours,
or even days, after the animal has been killed and they have been removed
from the body. This fact is of the greatest use to the student. It enables him
to study the nerve or muscle by itself, and under such artificial conditions as
he cares to employ. Experience shows that the facts learned from the study of
the isolated nerve and muscle hold good, with but slight modification, for the
nerves and muscles when in the normal body. Moreover, it has been found
that the nerves and muscles of warm-blooded animals, and even man, resemble
physiologically as well as anatomically those of the frog. The correspondence
is by no means complete, but it is so great as to make the facts discovered by
a study of the nerves and muscles of the frog of the utmost importance to us.
We are driven to such sources of information because of the great difficulty of
keeping the muscles of warm-blooded animals alive and in a normal condition
after removal from the circulation.

Irritability of Nerves. — The following preparation suffices to illustrate
the more striking effects of irritants upon a nerve. A frog is rapidly killed,
and then the sciatic nerve is cut high up in the thigh and dissected out from
its groove, the branches going to the thigh-muscles being divided. The leg is
then cut through just above the knee. This gives a preparation consisting of
the uninjured lower leg and foot, and the carefully prepared nerve supplying
the muscles of these parts. The leg may be placed foot upward, and fastened
in this position by a clamp which grasps the bones at the knee, the clamp

40 AN AMERICAN TEXT-BOOK OF PHYSIOLOOY.

being supported by an upright (see Fig. 3). This preparation can i\\v\\ be

subjected to a variety of" tests,

Mechanioal Irritation. — If the nerve be cut, pinched, suddenly stretched, or

subjected to a blow, the muscles of the leg will
contract and the foot will be quickly moved.

Chemical IiTitation. — If acid, alkalies, vari-
ous salfc^, glycerin, or some other chenncal sub-
stances be placed upon the nerve, the muscles
of the leg begin to twitch irregularly, and as
the chemical enters more and more deeply into
the nerve the movements will become more
and more marked, until finally all the muscles
are actively contracted and the foot is held
straight up.

Fig. 3.-Experiment for determining Thermal Irritation.— l^ a hot iron, or the

the irritability of nerves.

flame of a match, be applied to the nerve, a
condition of activity will be developed in the rapidly heated nerve-fibres, and
be responded to by more or less vigorous muscular contractions.

Electrical Irritation. — If the wires connected with the two poles of a
galvanic cell, static machine, or induction apparatus be brought in contact
with the nerve, the muscles will twitch each time there is a sudden change in
potential.

]VIore exact statements with reference to these different forms of irritation
will be given later. By all these methods the nerve was excited by irritants
applied to it from without, and the muscle was excited to action by the physio-
logical stimulus coming to it from the excited nerve. The irritant produced
no visible change in the nerve, but the movement of the muscles was an evi-
dence that the nerve had undergone a change at the point of stimulation, and
that the active state thus induced had been transmitted through the length of
the nerve, and had been .suflficiently marked to stinuilate the muscle to contrac-
tion. This condition of activity which was transmitted along the nerve is called
the nerve-impulse.

Independent Irritability of Muscle. — In the above instances the irritants
were applied to the nerve, and the muscle was indirectly stimulated. Muscle
protoplasm, like nerve protoplasm, may be directly excited to action by various
forms of irritants. A' nerve after entering a muscle branches freely, and the
nerve-fibres are distributed quite generally through the muscle. An irritant,
if directly applied to muscle, would probably excite the nerve-fibres present as
well as the muscle-fibres, and to obtain proof of independent irritability of
muscle-substance it would be neces.sarv to prevent the nerves from stimulating
the muscle. This can be done by paralyzing the nerve-endings with curare.

Curare, the South American arrow-poison, is used by the Indians in hunt-
ing. The bird shot by these poisoned arrows gradually becomes paralyzed,
and, losing power to move its muscles, is easily captured. The following
experiment reveals the method of the action of this drug, and at the same

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 41

time shows, first, that the nuiscle prutophisin can be irritated directly, and
secondly, tiiat the nerves do not eonimuuicate directly with the muscles, but
stimulate them through the agency of terminal end-organs, called moUn- end-
plaics}

Curare Experiment. — Rapidly destroy the brain of a frog with a slightly
curved, blunt needle, and, to prevent hemorrhage, plug the wound by thrust-
ing a pointed match through the foramen magnum into the brain-cavitv.
Expose the sciatic nerve of the left thigh, carefully j)ass a ligature under it, and
tie the ligature tightly about all the tissues of the thigh excepting the nerve,
thus cutting off the circulation from all the leg below the ligature without in-
jury to the nerve. Inject into the dorsal lymph-sac or tlie abdominal cavity a
few drops of a 2 per cent, solution of curare. In from twenty to forty minutes
the drug will have reached the general circulation and produced its effect.

Although the brain has been destroyed and the frog is incapable of having
sensation, it will be found that muscular moveraeuts will be made if the skin
be pinched soon after the drug has been given. These are reflex movements,
and are due to excitation of the spinal cord by the nerves connected with the
skin. As the paralyzing action of the drug progresses, these reflex actions be-
come feebler and feebler until altogether lost in the parts exposed to the drug,
although they may still be shown by the parts from which the drug has been
excluded. The condition of the nerves and muscles can be examined as soon
as reflex movements of the poisoned parts cease.

To ascertain the action of the poison, expose the nerves of the two legs,
either high up in the thigh or inside the abdominal cavity, where they have
been subjected to the poison, and test their irritability by exciting them with
electric shocks. Stimulation of the motor nerve of the right leg (a, Fig. 4)
causes no contraction of the muscles of that leg, while stimulation of the motor
nerve of the left leg (6), results in active movements of the muscles of that
leg. The response of the left leg shows that nerve-trunks are not injured by
the poison, and that the paralysis of the right leg must find some other expla-
nation. On testing the muscles it is found that they are irritable and contract
when directly stimulated. Since neither nerve-trunks nor muscles are poisoned,
it is necessary to assume that the cause of the paralysis is something which pre-
vents the nerve-impulse from passing from the nerve to the muscle. Micro-
scopic examination shows that the nerve-fibre does not communicate directly
with the muscle-fibre, but ends inside the sarcolemma in an organ which is
called the motor end-plate. It appears that the nerve acts on the muscle
through this organ, and its failure to act on the side which was exposed to the
curare was because the end-plate had been paralyzed by the drug. By the
use of curare, therefore, we are enabled to prevent the nerve-impulse from
reaching the muscles, and, when we have done this, we find that the muscle
is still able to respond to direct excitation wnth all forms of irritants, viz.

^ Ch. Bernard : "Analyse physiologique des Propri^t^s des Systemes mnsculaires et nerveux
au moyen- du Curare," Comptes-rendus, 1856, p. 825. KoUiker: " Physiologische Untersuch-
ungen iiber den Wirkungen einiger Gifte," Arckiv fur pathologische Anatomie, 1856.

42

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

electrical, mechanical, thermal, and chemical. Evidently the muscle- proto-
plasm is irritable and is caj)able of developing a contraction independently of
the nerves.

Other Proofs that the Muscle-protoplasm can be Directly Irritated.
— Muscles with long [)arallel fibres, such as the sartorius of the fi'og, contain no
nerves at tiieir extremities, the nerve-fibres joining the
nuiscle-fibres at some little distance from their ends.
The tip of such a muscle, where no nerve-fibres can
be discovered by the most careful microscopical exam-
ination, is found to be irritable. The fact that in some
of the lower animals there are simple forms of contrac-
tile tissue in which nerves cannot be discovered, and
which are irritable, is interesting as corroborative evi-
dence, although it is not a proof, of the independent
irritability of a highly diffi?rentiated tissue such as
striated muscle. Another similar piece of evidence is
to be found in the fact that the heart of the embryo
beats rhythmically before nerve appears to have been
developed. A proof can be found in the observation
that if a nerve be cut it begins to undergo degenera-
tion and loses its irritability and conductivity in four
or five days, and the excitation of such a nerve has
no effect upon the muscle although direct stimulation
of the muscle itself is followed by contraction. As
degeneration involves not only the whole course of the
nerve, but also the nerve end-plates, the contraction
must be attributed to the irritability of the muscle-
substance. Another point of interest in this connection
is the behavior of a dying muscle. If it be struck,
instead of contracting as a whole it contracts at the
place where it was irritated, the drawing together of
the fibres at the part forming a local swelling, or welt.
If such a muscle be stroked, a wave of contraction spreads over it, following
the instrument, instead of extending, as under normal conditions, by means of
the excited nerve-fibres to other parts. Under these circumstances the circum-
scribed contraction would seem to show that the nerves had lost their irrita-
bility, or that the nerve-ends no longer transmitted the stimulus to the muscle,
and the response was due to the direct excitation of the dying muscle-fibres.
This phenomenon is known as an idiomuscular contraction.

Fig. 4.— Curare experiment :
the shaded parts show the re-
gion of the body to which the
drug had access; theunshaded
part, the portion which was
protected by the ligature
from the action of the drug.
The unbroken lines represent
the sensory nerves which
carry sensory impulses from
the skin to the central nerv-
ous system ; the broken lines
indicate the motor nerves,
which carry motor impulses
from the central nervous sys-
tem out to the muscles (after
Lauder Brunton: Pharmacol-
ogy, Therapeutics, and Materia
Medica).

Conditions which Determine the Effect of Excitation.

The result of the irritation of nerve and muscle is dependent on two sets
of conditions — namely, (1) Conditions which determine the irritability; (2)
Conditions which determine the efficiency of the irritant.

It will be necessary for us to study the second set of conditions first, — for.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 43

before we fan judge of the irritability and the efU'ct of various influences upon
it, we must consider how far the activity of the nerve and muscle is depend-
ent on the cliarai'ter, strength, and method of application of the irritant.

Conditions which Determine .the EflQciency of Irritants. — Some of
these conditions can be best studied on nerves, while others are more ap-
parent in their effects on muscles. The most useful irritant for ])urposes of
study is the electric current. INIechanical, thermal, and chemical irritants are
likely to injure the tissue, and are not manageable, whereas electricity, if not
too strong, can be applied again and again without producing any permanent
alteration, and can be accurately graded as to strength, place, time, and dura-
tion of application, etc. Of course the results obtained by the use of a given
irritant cannot be accepted for others until verified. The conditions which
determine the eifectiveness of the electric current as an irritant may be classed
as follows :

(a) The rate at which the intensity changes.

(6) The strength of current.

(c) The density of current.

{d) The duration of application.

(e) The angle of application.

(/) The direction of flow.

Irritating Effect of the Electric Current. — Galvani, in seeking to find the
effect of atmospheric electricity upon the animal body, suspended frogs by
copper wires from an iron balcony, and observed the remarkable fact, that
when the wind blew the legs against the balcony the muscles of the frogs
twitched. He repeated the experiment in his laboratory, and concluded that
the frogs had been excited to action by electric currents developed within them-
selves ; he looked upon the metals which he had used merely as conductors for
this current. Volta, Professor of Natural Philosophy at Pavia, repeated Gal-
vani's experiment, and concluded that there had been an electric current
developed from the contact of the dissimilar metals with the moist tissues of
the frog. In accordance with this idea he constructed the voltaic pile, and
this was the starting-point of the electric science of to-day.

Although it is true that, under certain conditions, differences in electric
potential sufficient to excite muscles to contraction can be developed in the
animal body, the contractions of the frog's leg which Galvani observed were
due to the metals which he employed. The experiment can be easily per-
formed by connecting a bit of zinc to a piece of curved copper wire, and bring-
ing the two ends of the arc against the moist nerve and muscle of a frog. A
stronger and more efficient shock can be obtained from a Daniell or some other
voltaic cell.

A Daniell cell (Fig. 5) is composed of a zinc and copper plate, the former dipping
into dilute sulphuric acid, the latter into a strong copper-sulphate solution. Although
gravity will keep these liquids separated, if the cell is to be moved about it is better
to enclose one of them in a porous cup. A common form of cell consists of a glass jar,
in the middle of which is a porous cup ; outside the cup is the sulphuric acid and the

44

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY

zinc plate, and inside the cup is the copper sulphate solution and the copper plate.

The zinc plate is acted upon by the sulphuric acid, and, as a result of the chenjical
change, a difference of electric potential is set up between the
metals, so that if the zinc and copper be connected by a piece of
metal, what we call an electric current flows from the zinc tv the
copper inside the cell, and from the copper to the zinc outside the
cell. The zinc plate, being the seat of the chemical change, is
called the positive plate, and the copper the negative plate.
Several such cells may be connected together to form a batterj',
each cell adding to the electro-motive force, and hence to the
strength of the current. As the current is always considered to
flow from -r to — , we call the end of the wire connected with the
copper (negative plate) the positive pole, or anode, and the end
of the wire connected with the zinc (positive plate) the negative
pole, or kathode. If one of these wires be touched to a nerve,
under ordinary circumstances no effect is produced ; but when the
other wire is likewise brought in contact with the nerve, the
moist tissues of the nerve form a conductor, complete the cir-
cuit, and an electric current at once flows through the nerve from
the anode to the kathode. The effect of the sudden flow of
electricity into the nerve is to give it a shock — as we say, it

irritates the nerve — and the muscle which the nerve controls is seen to contract.

In the place of using ordinary wires for applying the electricity, we vise electrodes.

These are practically the same thing, but have insulated handles, and have a form better

suited to stimulate nerves or other tissues. The two wires mav be held in two different

Fig. 5.— Darnell cell.

Fig. 6.— a, Ordinary tk-ttrmk- fur excitiiiir exposed nerves and muscles, consisting of two wires
enclosed, except at their extremities, in a handle of non-conducting material ; b, c, non-polarizable elec-
trodes. When metals come in contact with moist tissues a galvanic action is likely to occur and polariz-
ing currents to be formed. These extra currents would complicate or interfere with the results of many
forms of experiment, and they are avoided by the use of non-polarizable electrodes. A simple form con-
sists of a short glass tube, at one end of which is a plug of china clay mixed with a 0,6 per cent, solution
of sodium chloride, and at the other end a cork through which an amalgamated zinc rod is thrust. The
zinc rod dips into a saturated solution of zinc sulphate, which is in contact with the clay. The clay plugs
touch the tissue to be excited, and the current passes from the zinc rods through the zinc-sulphate and
sodium-chloride solutions in the clay to the tissues; d-f, electrodes for exciting htiman nerves and mus-
cles through the skin (after Erb) : these may be of various forms and sizes, and are arranged to screw
into handles (g), to which the wires are attached : they are usually made of brass and covered with
sponge or other absorbent material wet with salt-solution. The smaller electrodes are used when a dense,
well-localized stream is required, and the larger electrodes when little action is wished aud it is of
advantage to have the stream ditluse.

handles, in which case we speak of the positive and negative electrodes, or the anode
and the kathode, or they may be held in the same handle (Fig. 6).

Keys. — It is not as convenient to stimulate a nerve by touching it with the electrodes as

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 45

it is to place it upon tlic electrodes and close the connection between the zinc and copper at
some other part of the circuit ; this may be done by what is called a key. Any mechanism
which can be used to complete the circuit could
receive this name, and there are a number
ol" convenient forms. The one mo.^t used by
physiologists is that devised by J)u liois-Key-
mond, and whicli bears his name (.see Fig. 7).
This \\Ji» the advantage of being capable of
being used in two different ways — one simply
as a means to close tlie circuit, and the other
to short-circuit tlie current. These two meth-
ods are sliown in Figure 8.

By the former method the key supplies a
movable piece of metal by which contact be-
tween the two ends of the wires may be made
as in a (Fig. 8), or broken as in 6, and the
current be sent through the nerve, or prevented
from entering it. By the latter method the
battery is all the time connected with the
electrodes, and the key acts as a movable
bridge between the wires, and when closed gives a path of slight resistance by which
the current can return to the battery without passing through the nerve. The current
always takes the path of least resistance, and so, if the key be closed as in c, all the cur-
rent will pass through the key and none will go to the nerve, which has a high resistance,
whereas if the key be opened as in </, the bridge being removed, all the current will go
through the nerve. It is often better to let the cell or battery work a short time and to
get its full strength before letting the current enter the nerve, and the short-circuiting key
permits of this. Moreover, there are times when a nerve may be stimulated if connected

Fig. 7.— Electric key.

Fig. 8.— Electric circuiting.

with the source of electricity by only one wire, the circuit being completed through the
earth ; when the nerve is so excited, it is called unipolar stimulation ; this may be pre-
vented by the short-circuiting key.

As has been said, a nerve is irritated if it be counected with a battery and
an electric current suddenly passes through it. Unless the current be very
strong the irritation is transient, however; the muscle connected with the

46

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

nerve gives a single twitch at the moment that the current enters the
nerve, and then remains quiet; and thus we meet with the remari<al)le fact
that an electric current, though irritating a nerve at the moment that it
enters it, can flow through the nerve continuously without exciting it. Fur-
ther, although the current while flowing through the nerve does not excite
it, a sudden withdrawal of the current from the nerve irritates it, and causes
the muscle connected with it to contract. It is our custom to speak of
closing, or making, the circuit when we complete the circuit and let the
current flow through the nerve, and of opening, or breaking, the circuit
when we withdraw the current from the nerve. Since the closing of the
circuit acts as a sudden irritant to the nerve, we speak of this irritant as
a "making" or "closing" shock, and the corresponding contraction of the
muscles as a making or closing contraction ; similarly we s})eak of the effect
of opening the circuit as an "opening" or " breaking" shock, and the result-
ing contraction as an oi)ening or breaking contraction. As we shall see later,
the making contraction excited by the direct battery current is stronger than the
breaking contraction : the explanation of this must be deferred (see page 53). •
(a) Effect of the Rate at tohich an Irritant is Apjdied, llluatrated by the Elec-
tric Current. — As has been said, an electric current of constant medium strength

Fig. '.».— Rheonome.

does not irritate a nerve while flowing through it, but the nerve is irritated at
the instant that the current enters it, and at the instant that the current leaves
it. Is it the change of condition to which the nerve is subjected, or is it the
suddenness of the change, which produces the excitation? Would it be possi-
ble to turn an electric current into a nerve and remove it from a nerve so
slowly that it would not act as an irritant ?

The experiment has been tried, and it has been found that if the nerve be
subjected to an electric current the strength of which is increased or decreased
very gradually, no change occurs in the nerve sufficient to cause a contraction
of the muscle. In this experiment, instead of using the ordinary key, we close
and open the circuit by means of a rheonome (see Fig. 9).

This instrument contains a fluid resistance, which can be altered at will, thereby per-
mitting a greater or less strength of current to pass from the battery into the circuit

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 47

containing the nerve. The wires from the battery are connected with binding-posts, a, b
(Fig. 9), at opposite sides of a circuhir groove containing a saturated solution of zinc sul-
phate. Strips of amalgamated zinc connect the binding-posts with the fluid, and so com-
plete a circuit which ofl'ers much resistance to the passage of the current. From the centre
of the block containing the groove rises an upright bearing a movaljlc horizontal bar, from
each extremity of which an amalgamated zinc rod, e and/, descends and dips inf(j the zinc-
sulphate solution. The zinc n)ds are connected with binding-posts on the movable bar, and
from these wires pass to the electrodes on which the nerve rests. The bar revolves on a
pivot on the top of the upright, and thus the zinc rods can be readily approached to
or removed from the zinc strips, the poles of the battery. When the zinc rods hold a
position midway between these poles, the current all passes by the way of the fluid. As
the bar is turned, so as to bring the zinc rods nearer and nearer the two poles of the bat-
tery, the current divides, and more and mcjre of it passes through the path of le&sening
resistance of which the nerve is a part. When the zinc rods are brought directly opposite
the poles of the battery nearly all the current passes by the way of the nerve. If the bar be
turned more or less rapidly, the current is thrown into, or withdrawn from, the nerve more
or less quickly.

By this arraugement we can not only observe that the nerve fails to be irritated
when the current is made to enter or leave it gradually, and when it is flowing
continuously through it, but that sudden variations in the density of the cur-
rent flowing through the nerve, such as are caused by quick movements of the
bar, although they do not make or break the circuit, serve to excite. This
experiment shows that electricity, as such, does not irritate a nerve, but that a
sudden change in the density of the current, whether it be an increase or
decrease, produces an alteration in the nerve-protoplasm which excites it to
action and causes the development of what we call the nerve-impulse.

Du Bois-Reymond's Law. — Du Bois-Reymond formulated the following
rule for the irritation of nerves by the electrical current : " It is not the abso-
lute value of the. current at each instant to which the motor nerve replies by a
contraction of its muscle, but the alteration of this value from one moment to
another; and, indeed, the excitation to movement which results from this change
is greater the more rapidly it occurs by equal amounts, or the greater it is in
a given time."

We shall have occasion to see that this rule has exception.?, or rather that
there is an upper as well as lower limit to the rate of change of density of the
electric current which is favorable to irritation.

Similar observations may be made with other forms of irritants. Pres-
sure, if brought to bear on a nerve gradually enough, may be increased to the
point of crushing it Avithout causing sufficient irritation to excite the attached
muscle to contract, although, as has been said, a very slight tap is capable of
stimulating a nerve. Temperature, and various chemicals, likewi.se, must be so
applied as to produce rapid alterations in the nerve-protoplasm in order to act
as irritants. The same rule would seem to hold good for the nerve-cells of the
central nervous system. It is a matter of daily experience that the nervous
mechanisms through which sensory impressions are perceived are vigorously
excited by sudden alterations in the intensity of stimuli reaching them, and but
little affected by their continuous application ; the withdrawal of light, a sudden

48

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

alteration of temperature, an uuexpeeted noise, or the cessation of a monotonous
sound, as exempliiied by the common experience that a sleeper is awakened

Fig. 10.— Induction apparatus; a, primary coil; h, secondarj- coil ; c, the automatic interrupter.

when reading aloud abruptly ceases, attract the attention, although a continu-
ous sensory irritation may be unnoticed. This physiological law of the nervous
system would seem to have a psychological bearing as well.

Fig. 11.— Schema of induction apparatus.

Irritating Effect of Induced Electric Currents. — Within certain limits, the
more rapid the change in intensity of an electric current the greater its power to

irritate. This })robably accounts in part
for the fact that the induced current is a
more powerful irritant to nerves than the
direct galvanic current. Induced currents
are usually obtained by means of an induc-
tion apparatus (sec Fig. 10).

The ordinary induction apparatus employed
in the laboratory (see Fig. 1 1 ) consists of a coil of
wire, p, which may be connected with the ter-
minals of a battery, h, and a second coil, .s, wholly
independent of the first, which is connected with
electrodes, e. At the instant that the key, /r, in
the primary circuit is closed, and the battery cur-
rent enters tlie priniarj' coil, an induced cuiTcnt
isdevdoijcd in the secondary coil, and the nerve
resting on the electrodes is irritated. The in-
duced current is of exceedinjrly short duration,
suddenly rising to ftill intensity and falling to
zero. As long as the battery current continues to
flow constantly through the primarj- coil, there is
no change in the electrical condition of the sec-
ondary coil, but at the instant the primary current is broken another mduccd current of short
duration is set u]) in the secondary coil, and again the nerve receives a shock. The rise and

^

3

l^

-^..^-^

1

Fig. 12.— Schema of the relative intensity
of induction currents (after Hermann, Hand-
buch der Phyniologie, Bd. ii. S. 37) : /', abscissa
for the primary current; S, abscissa for the
secondary current; 1, curve of the rise of
intensity of the primary current when made ;
2, curve of the rise and fall of intensity of
tiie cnrre.sponding induced current; 3, curve
of fall of the intensity of the primary cur-
rent when it is broken ; 4, curve of the rise
and fall of intensity of the corresponding in-
duced current.

GENEBAL PHYSIOLOGY OF MUSCLE AXD NERVE. 49

fall of the density of the current in the secondary coil is very rapid, and this raj)id double change
in density of the current causes the induetion shock to he a very effective irritant. The break-
ing induction shock, as we call that which is pruiliiced by breaking the primary current, is
found to act more vigorously than the niaking shock, which is the reverse of what is found
with direct battery currents. The cause of this lies in the nature of the apparatus. At tlie
moment that the current begins to flow into the primary coil, it induces not only a current
in the secondary coil, but also currents in the coils of wire of the i)riniary coil. These
extra induced currents in the primary coil have the opposite direction to the battery cur-
rent and tend to oppose its entrance, and thereby to prevent it from immediately gain-
ing its full intensity. This delay affects the development of the induced current in the
secondary coil, causing it to be weaker and to have a slower rise and fall of intensity than
would otherwise be the case. When the primary current is broken, on the other hand,
there is no opposition to its cessation, and the current induced in the secondary coil is
intense and has a rapid rise and fall. These differences are illustrated in Figure 12.

To accurately test the effect of tlie making and breaking induction shocks,
it is necessary to record the reaction of the nerve ; this can be done by record-
ing the extent to which the corresponding muscle contracts in response to the
stimulus which it receives from the nerve. In such an experiment it is
customary to use what is known as a nerve-muscle preparation. The gas-
trocnemius muscle and sciatic nerve of a frog, for instance, are carefully
dissected out, the attachment of the muscle to the femur being preserved, and
the bone being cut through at such a point that a sufficiently long piece of
it shall be left to fasten in a clamp, and so support the muscle (see Fig. 13).

Fig. 13. — Method of recording muscular contraction.

The simplest method of recording the extent of the muscular contraction
is to connect the muscle by means of a fine thread with a light lever, and let
the point of the lever rest against a smooth surface covered with soot, so that
when the muscle contracts it shall draw up the lever and trace a line of cor-
responding length upon the blackened surface. The combination of instru-

4

50 .LV AMERICA. \ TEXT-IIOOK OF PHYSIOLOGY.

ments omplovtHl to iccord tlic contriK'tioii of :i nui.scle is called ;i intiocintjih, and
tlu' ivt'onl of the contraction is termed a vii/i)(/r(nii. If, wlien the ninsclc of a
ncrvc-niuscle preparation is tluis arranged to Mrite its
loutractions, the nerve be irritated with alternating mak-
ing and breaking indnction shocks of medium strength,
(he muscle will make a series of movements, which, if
the suifaoe be moved past the writing-point a short
distance after each contraction, will be pictured in the
record as a row of alternatino; long and short lines the

Fig. 14.— Effect of making ^ . • i • i i

and breaking induction rccords of the breaking contractions being higher than
^^°^^^- those of the making contractions (Fig. 14). Similar

results are obtained if, instead of irritating the nerve, we irritate the ciirarized
muscle directly.

Stimulating Effects of Making and Breaking the Direct Battery Current. —
On account of the construction of the induction apparatus, breaking induction
shocks are more effective stimuli than making induction shocks. The reverse
is true of the stimulating effects which come from making and breaking the
direct battery current. The excitation wdiich results from sending a galvanic
current into a nerve or muscle is stronger than that which is cau.sed by the
withdrawal of the current. This difference is due to the physiological altera-
tions produced by the current as it flows through the irritable substance, and
is M-itliout doubt closely associated with changes in the irritability which occur
at the moment of the entrance and exit of the current.

The making contraction starts from the kathode, and the breaking contraciion
from the anode. The irritation process which results from making the current
is developed at the kathode, and that which results from breaking the current
is developed at the anode. This was first demonstrated on normal muscles by
Von Bezold,^ and has since been substantiated for nerves as well as muscles

Fig. 15.— Schema of Ilering's double myojiraph : C, clamp holding middle of muscle; P,P, pulleys to
the axes of which the recording levers are attached; p, p. pulleys for the light weights which keep the
muscle under slight tension; ^, positive electrode; if, negative electrode ; r, commutator for reversing
the current ; k, key ; 6, battery.

by the experiments of a great many observers. Perhaps the most striking
demonstration is to be obtained by Engelmann's method. The positive and
negative electrodes are applied to the two extremities of a long curarized sai*to-

^ Untersnchunfjen iiber die elcktrische Eivegung von Muskeln und Nen-en, 1861.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 51

rius niusclo, which is ohunpcd in the middle firndy cnouj^h to prevent the con-
tnietions of one half from moving the otlier, Wnt not en(ni<rh to interfere with
the conduction-power of the tissue. The record of the contractions is best
ohtained by tlie douhle myogra})h of Ilering (Fig. 15), wliieh permits the
reeouling levers attached to the two ends of the muscle to write directly under
each other, so that any diiference in the beginning of the contraction of the
two halves of the muscle is immediately recognizable from the relative posi-
tions of the records of their contractions.

The current is applied to the two extremities of the muscle by non-polarizable electrodes.
In all experiments with the direct battery current it is essential to emi)loy non-polarizable
electrodes. The tbrm devised by Hering is very useful where the current has to be apjdied
d'u-ectly to the muscle, because the two electrodes are hung from j^ivots in such a way that
they move with the movements of the muscle, and hence do not shift their position when
the muscle contracts. Some kind of apparatus has to be employed for quickly reversing
the direction of the current. A convenient in-
strument for this purpose is Pohl's mercury com-
mutator (Fig. 16). This instrument consists of
a block of insulating material in which are six
little cups containing mercury, which is in con-
nection with binding-posts on the sides of the
block. Two of the mercury cups on the opposite

Figs. 16, 17.— Pohl's mercury commutator.

sides of the block a and h (Fig. 17, A), are connected by wires with the battery ; two others,
c and d, are connected with wires which pass to the electrodes ; the remaining two on the
opposite side of the block, e and /. are joined by movable good conducting wires with the
cups c and d in such a way that c connects with /, and d with e. Two anchor-like pieces of
metal are connected by an insulated handle, and are so placed that the stocks of the anchors
dip into the mercury cups a and h (Fig. 16). The anchors can be rocked to one side or the
other, so that the ends of the curved arms shall dip into the cups c and d (in which case
cup a will be connected with cup c, and cup h with cup r? ), or so that the other ends of the
arms shall dip into cups e and / (in which case cup a will be connected with cup e, and by
means of the cross wire with cup rf, and cup h will be connected with cup /, and by means
of the cross wire with cup c). By the arrangement shown in Fig. 17, ^ the current can
pass from the battery by way of a and c down the nerve, and by way of d and h back to
the battery ; or it can pass from the battery by way of a, e, d, and in the reverse direction,
up the nerve and back to the battery, by way of c, /, h.

This commutator can be used in another way (see Fig. 17, B). If the battery be con-
nected with it as before, and the cross wires be removed, the current can be sent at will
into either one of two separate circuits. For instance, if the cups c, d be connected with
the electrodes on one part of the nerve, and the cups e, / with the electrodes on another

52

AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

part, the ;uk1u)i> liavo only to be rocked to one side or the other to complete the commu-
nication between the battery and one or the other of these pairs of electrodes.

Ill experiiiicnts with the douhle nivogra])h, in which the makinf/ of the
current is used to irritate, records are oWtained such as an- shown in Fi<rure 18.

Fig. 18.— The making contraction starts at the kathode (after Biedermann).

In the.se records the beginning of the tuning-fork waves shows the moment
that the current wa.s made and the irritation given. In the experiment from
which record a was taken the anode was at the knee-end of a curarized sartorius
muscle and the kathode at the pelvic end — i. e. the current was ascending
through the muscle. The lower of the two curves was that got from the
kathode lialf, the arrangement being that shown in Figure 15, and the lower
curve began before that got from the anode half; /. e. the contraction originated
at the kathode and spread thence over the muscle. In b the current was
reversed, and the upper curve w^as obtained from the kathode half and the
lower from the anode half; in this also the kathode end contracted first.
In the above experiments the making of the current was u.sed to irritate,
and the muscular contraction began at the kathode; in experiments in which
the breaking of the current was employed the opposite was ob.<erved, the
anode end being .seen to contract first, regardless of the direction of tlie cur-
rent.

If strong currents be used, the fleeting contractions which result from
opening and closing the current are followed by continued contractions, the
closing, Wundt's, and the opening, Hitter's tetanus, a-s they are called. These
continued contractions, which last for a considerable time, remain strictly
located at the region where they originate, and Engclmann proved by his

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 53

experiiucnts tluit the tetanus which results irom eh)sii)<;- a stronj^ oiUTeut
reiiKiins located at the kathode, and the tetanus tbllowinj; the opening of
the current remains located at the anode.

The same is true of the nerve as of the muscle; the irrilatinj;' j)rocess which
is callwl out by the sudden entrance of a battery current into a nerve starts
from the negative pole, the kathode, and spreads thence throut^hout the nerve,
while the irritating process excited by the cessation of the flow of the current
starts from the region of the positive pole, the anode, and spreads from that
point throughout the nerve. A proof of this was obtained by Von Bezold,
who observed the difference in the time between the moment of excitation and
the beginning of the contraction of the muscle, when the nerve was excited
by opening and by closing the current, with the anode next to the muscle,
and with the kathode next to the muscle. He found the time to be longer
when the current was closed if the kathode was the more distant, and to be
longer when the current was opened if the anode was farther from the muscle.
Evidently in the case of the nerve as of the muscle, the irritable substance
subjected to the current is not all affected alike. The current does not
set free the irritating process at every part of the nerve, but produces
peculiar and different effects at the two poles, the change which occurs at the
kathode when the current is closed being of a nature to cause the development
of the excitatory process which awakens the closing contraction, and the
change which occurs at the anode when the current is opened being such a?
to cause the development of the excitatory process which calls out the opening
contraction.

Closing contractions are stronger than 02:)ening contractions. The irritation
developed at the kathode is stronger than that developed at the anode. It is
true of both striated and uustriated muscles that an efficient irritation can be
developed at the kathode with a weaker irritant than at the anode. Moreover,
a greater strength of current is required to produce opening than closing con-
tinued contractions.

The same may be said of nerves. If one applies a very weak battery cur-
rent to the nerve of a nerve-muscle preparation, he notices when he closes the
key a single slight contraction of the muscle, and when he opens the key, no
effect. If he then increases the strength of the current very gradually, and
tests the effects of the making and breaking of the current from time to time,
he observes that each time the strength of the current is increased the closing
contraction, which is due to irritation originating in the part of the nerve sub-
ject to the kathode, grows stronger, and finally contractions are also seen wdien
the circuit is broken, the irritation process developed at the anode having
become strong enough to excite the muscle. These opening contractions at
first are weak, but gradually increase in strength, until with a medium strength
of current vigorous contractions are seen to follow both opening and closing of
the current. If the strength of the current be still further increased, it is
found that either the closing or opening contraction begins to decrease in
size, and if a very strong current be employed, the closing or opening con-

54 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

traction will be absent. It has been ascertained that the direction in which
the current is flowing through the nerve determines which of these van-
tractions shall cease to appear. The cause of this will be explained a little
later.

ib) Effect of Strength of Irritant. — As a rule, the stronger an electric current
the greater its irritating effect. This can be readily tested upon a nerve with
the induction current, the strength of which can be varied at jjleasure. The
strength of the induced current obtained from a given apparatus depends
upon the strength of the current in the primary coil, and on the distance of
the secondary from the primary coil. In ordinary induction machines (see Fig.
10, p. 48) the secondary coil is arranged to slide in a groove, and can be easily
approached to or removed from the primary coil, thus placing the coils of wire
of the secondary coil more or less under the influence of the magnetic field
about the primary coil. This permits the strength of the current to be graded
at will. The strength of the induced current does not increase, however, in
direct proportion to the nearness of the coils. As the secondary approaches
the primary coil, the induced current increases in strength at first very slowly,
and later more and more rapidly, reaching its greatest intensity when the
secondary coil has been pushed over the primary.

The relation of the strength of a current to the irritating effect upon a nerve
can be readily tested with such an induction apparatus. The secondary coils
can be connected with a pair of electrodes on which the nerve of a nerve-
muscle preparation rests (as in Fig. 11, page 48), and the muscle can be
arranged to record the height of its contractions (as in Fig. 13, p. 49).
The experiment can be begun by })lacing the secondary coil at such a dis-
tance from the primary that the making and breaking shocks are too feeble to
have any effect upon the nerve. Then the secondary coil can be gradually
approached to the primary, the primary current being made and broken at
regular intervals. At a certain point the breaking shock will excite a very
feeble contraction, the making shock producing no effect. If this contraction
is barely sufficient to be recognized, we call it the minimal breaking contraction
(see Fig. 19, a). In seeking the minimal contraction care must be taken not
to excite the preparation at too short intervals of time, for, as we shall see,
an irritation too slight to excite even a minimal contraction may, if repeated
at short intervals, increase the irritability of the preparation and so become
effective. By using a short-circuiting key in the secondary circuit we can
cut out the making shocks, and test the effect of a liiitlur increase in the
strength of the current by the response of the muscle to the breaking shocks.
As the contractions become larger, care must be taken not to irritate the muscle
too frequently, lest it be fatigued and so fail to give the normal response. As
the current is strengthened the l^reaking contractions will become higher and
higher until a point is reached beyond which the strength of the current may
be increased to a considerable extent without any further heightening effect (Fig.
19, b). If the current be still further increased, this first maximum is suc-
ceeded by a still further growth in the height of the contractions, until finally

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 55

a secoutl maxiimuu (Fig. lU, (/) is reached, l)eyontl which no further increase
is to be obtained, liowever much the current may be strengthened.'

Fig. 19.— Effect of increase oi streiigtli oi current on ilie ellicioncy of breftkinj; induction shocks (after
Fick): a, minimal contraction ; 6-c, first maximum ; d-e, second maximum.

If both the making and breaking contractions be recorded, inasmuch as
the making shocks are weaker stimuli than the breaking (see p. 50), the mak-
ing contractions do not appear until after the breaking contractions have
acquired a considerable height. After the making minimal contraction lias
been obtained, the making contractions rapidly gain in height as the current
is strengthened, and finally acquire the same height as the maximal breaking
shocks.

The relation of the strength of the electric current to its irritating power
can be demonstrated equally well by using the direct galvanic current. The
strength of the galvanic current depends upon the character and number of the
cells employed, and the total resistance in the circuit. The strength of the
current can be easily varied by altering the resistance, and there are a number
of forms of apparatus for this purpose.

Fig. 20.— Rheostat.

A convenient instrument is the rheostat (Fig. 20). This is a box containing coils of
wire of known resistance. These coils are connected with a series of heavy brass blocks on top
of the box. The current enters the box by a binding-post attached to the first of the brass
blocks and passes thence from block to block, by going through the coils of wire connecting
them, until it reaches the binding-post at the other end of the series. The blocks can be
also connected by good conducting brass plugs, which can be pushed in between them, and
when this is done, as the current passes directly from block to block instead of going through
the resistance coils beneath, the resistance is reduced to a corresponding amount.

Another method of altering the strength of the current flowing through the
nerve is to employ some form of shunt to split the current so that only a part
of it shall pa.ss by way of the nerve. A current takes the path of least resist-
^ Fick: Unlersuchungen liber elektrische Nervenreizung, Braunschweig, 18,64.

5G AN AMEIilCAN TEXT- HOOK OF I'lfYSIOLOay.

ance, aud if two paths are ojK-iicd to it, more or less can he sent tliroii;^ii one
of them by decreasing or increasing tlie resistance in the other.

A usiliil iiistriiiiuMit lor ilividiiii? the current is the rlieouord. The schema given in

Figure 21 iUustrates the way in
which it is used The amount
of current i)assing to tlie nerve
will vary with the relative re-
sistance in II, h. r, if, e, /, and
in «, b, I/, h, t, /. The bridge
f, d can be slid along the fine
German-silver wires h, ! and
e, j, and thus the resistance
Fig. 21.— Rheocuid. a, 6, c, f/, e. /, and the amount

of current passing through tlie nerve, can be varied at pleasure.

With snch an arranoemeut we sliould find that the irritating effect of the
current is largely dependent upon its strength. In tlie case of strong currents,
however, the results may be complicated by alterations in the irritability and
conductivity, which we will consider later. It is true also of other forms of
irritants, and of muscles as of nei'ves, that the effect of stimulation, up to a
certain limit, increases with the strength of the irritant,

(e) Efect of Density of the Current. — Although the strength of the current
is an all-important fiictor in its excitatory action, the effectiveness of the cur-
rent as an irritant depends very largely on the density of the stream. When
the current enters into a conductor, it spreads widely through the conducting
substance, and though the larger part of it takes the path of least resistance,
which is usually the shortest path to the point of exit, many of the threads
of current make a comparatively wide circuit to reach the outlet. If the con-
ductor is equally good at all points, but is irreguhirly shaped, the density of
the stream will be greatest where the diameter of the conductor is least. Thus
it happens that if a current be made to flow from end to end of a mu.scle, like
the sartorius of the frog, which is smaller at the knee end than at the pdvic
end, the density of the current will be greater at the lower than at the ujiper
end, and the irritating power of the current will be greater at the lower end.'

This question of the effect of the density of the current is important, as it
helps to explain the peculiar reactions to the electric stream obtained when a
current is applied under normal conditions to the human nerve.

{d) Efect of the Duration of the Electric Current on its Power to Jmtate
Nerves and Jfiisries. — As we have seen, a constant battery current, when flow-
ing uninterruptedly through a motor nerve, does not ordinarily excite it; very
slow variations in the strength of the current also fail to irritate ; but rapid
alterations in the strength, whether in the direction of increase or decrease, act
as vigorous stimuli. For example, medullated nerves are irritated more vigor-
ously by the rapid changes of intensity of induced currents than by the some-
what slower changes occurring at the make and break of battery currents.
Within certain limits, at lea.st, the more rapidly the intensity of the current

' Biedormann : Eleklrophjisiiilnrfir, 1895, Bd. i. p. 185.

GENERAL PHYSIOLOaV OP' MUSCLE AND NERVE. 57

changes, the greater the irritating ellLet upon nerves. Not all nerves, however,
are equally susceptible to rapitl alterations of the intensity of the current.
Non-nu'du Hated nerves do not apjjcar to react as readily as medullated to
electric currents of short duration. For instance, the nerves of the claw mus-
cles of the crab are not readily excited by induced currents, and respond better
to the more prolonged influence of the closing and opening of battery currents.^

The question now arises. Is the reaction of muscles to electric currents the
same as that of nerves? Experiment shows that muscles wdiich have been
removed from the action of nerves, by means of curare, differ from iiicdiillated
nerves in that they are excited more vigorously by the opening and closing of
battery currents than by making and breaking induction currents. The max-
imal conti-action got on opening and closing a battery current is both higher
and more prolonged than that to be obtained with a single induction shock.
Unstriated muscles exhibit this difference to a still greater degree than
striated muscle; they react well to the closing of battery currents of medium
strength, provided these last some little time, but respond to induced currents
only when they are very strong. Thus the unstriated muscle which closes the
shell of some of the fresh-water mussels, as the Anodonta, gives larger and
larger contractions as the duration of the current is increased from one-quarter
of a second to three seconds.- Much the same is true of the unstriated muscles
of the ureters;^ the battery current must remain closed quite a while for the
closing contraction to be called out, the length of time depending upon the
strength of the current ; and induction shocks have little or no effect unless
very strong. Such a comparison makes it evident that the duration of the
current is an important element in the influence exerted by electric currents
on various forms of protoplasm. Unstriated muscles require that the current
shall last from one-quarter of a second to three seconds to produce maximum
contractions. Striated muscles require that a current shall last 0.001 second
(Fick), and even medullated nerves fail to react if the current lasts too short
a time. Various forms of irritable tissue can be arranged in series according
to their ability to respond to electric currents of short duration, viz. medul-
lated nerves, non-medullated nerves, striated muscles, non-striated muscles,
and the little-differentiated forms of protoplasm of many of the protozoa.
On the other hand these tissues are found to respond in the reverse order to
currents which are more prolonged and which change their intensity slowly.
It would seem as if the less perfectly differentiated the form of protoplasm,
the less its mobility and its susceptibity to passing influences.

The same form of tissue reacts differently in different animals. For instance,
the sluggish striated muscles of the turtle do not respond as well to induced
currents as the more ra])id striated muscles of the frog. Further, the condition
of the tissue at the time is found to have an influence on its irritability and its
power to respond to stimuli of short duration. Yon Kries reports that nerves,
if cooled, react better to slow variations in the intensity of the electric current,

^ Biedermann : Elektrophysiologie, 1895, Bd. ii. p. 546.
» Engelmann: Pfluger's Archiv, 1870, Bd. iii. p. 263,

58 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and, if wariiRd, to rapid variations. Under pathological conditions the reac-
tion of nerve and muscle to electric currents may become blunted, and, as the
tissue degenerates, its power to respond to rai)id changes of the electric current
is lessened. If a nerve be cut, the part which is separated from the influence
of the nerve-cells degenerates. The irritability at first increases and then
very rapidly decreases, in from three to four days being wholly lost. As the
nerve regenerates, the irritability is recovered very gradually, and the power
to respond to the relatively prolonged action of ine(-hanical stimuli is regained
sooner than the ability to reply to changes as rapid as those of induced cur-
rents. Howell and Huber observed that regenerating nerve-fibres when they
have reached the stage resembling embryonic fibres, i. e. are strands of proto-
plasm without axis-cylinders, fail to respond to induction currents, though they
can be excited by mechanical stimuli. It was found that it is not until the
axis-cylinder has grown down into the regenerating fibres that the nerve is
capable of responding to induction shocks.

When human striated muscle undergoes degeneration as a result of an in-
jury to its nerve, the degenerating muscle comes to resemble normal unstriated
muscle in its reactions to electricity, responding feebly to induced currents, at
a time when irritability to mechanical stimuli and to direct battery currents
is even increased. This is used by clinicians as a means of diagnosis of the
condition of the nerve and muscle.

From what has been said it is evident that the rule laid down by Du Bois-
Reymond (see p. 47) must be modified in so far that there is for each tissue
a limit to the rate at which a change of intensity of the electric current acts
as an irritant. An extreme illustration of this may be found in the astonish-
ing fact lately published by Tessla, that although in general alternating dynamo
currents are very deadly, a current of even high voltage may be passed through
the human body with impunity, provided that the rate of alternations be suf-
ficiently rapid.

(<?) Effect of the Angle at ivhich the Current Enters and Leaves the Muscle
and Nerve. — The angle at which the current acts on the muscle-fibre has
been found to have a bearing upon its jiower to stimulate. Leicher^ succeeded
in obtaining definite experimental (evidence that when the current is so sent
through a muscle as to cross it at right angles to its fibres it has no irritating
effect, and that its jwwer to stimulate increases as the angle at which the
threads of current strike the muscle-fibres decreases, being greatest when the
current passes longitudinally through the fibres.

Similarly, it was found by Albrecht and Meyer" that the irritating effect
of the electric current is most active when it flows longitudinally through the
nerve, and that it is altogether absent when it flows transversely through it.
'This view is doubted by some observers, who would attribute the difference
observed to differences in the electrical resistance. It is true that the resist-
ance to cross transmission is greater than to longitudinal transmission, but it

^ Untersuchungen aus dem physiologischen Institut der Universitdt Halle, Hefl i. p. 5.
* Ppger's Archiv, 1880, Bd. xxi. p. 462.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 59

is not likely that this (lititrenco suffices to explain the lack ol" response to cur-
rents applied at right angles to the nerve-axis.

Relative Ejfficacii of the above Conditions upon the Irritating Power of the
Electric Current. — When a current is applied to an irritable part of a nerve
or muscle at an angle suitable to excitation, the stimulating effect of the current
depends upon the rate at which its intensity is changed, the strength and
densitv of the current, /. c. its intensity, and the duration of tiie current.

Fick ' gives the following schema (Fig. 22) for the dilferent M'ays in which
the intensity of the electric current may be varied, and compares the eifects
of these diiferent methods of application of the current. It must be re-
membered that a decrease of inteusity acts no less than an increase to produce

-.'",

a

10-

_______

0

■

10

20

'/ 40

IDIi

110

.'0'

b

/

10.

/

0

/

10

20

20'

10

n

d

c

e ./■

/ \

Fig. 22.— Schema of relation of the method of application of the electric current to the

irritating efl'ect.

excitation. In the above schema the abscissa represents the time, and the
ordiuates the strength, of the current. Suppose the rise of intensity has a
form such as is represented in a, Figure 22 — that is, that the strength of the
current increases to a considerable height, but very slowly. Such a rate of
change, even though the rise of intensity were continued until the strength of
current was very great, would have no exciting eifect upon a nerve and might
fail to irritate a striated or non-striated muscle. A more rapid rise, such as
is shown in 6, might irritate a non-striated muscle, but fail to irritate a nerve
or a striated muscle. With currents which rapidly gain their full intensity
and then return again to zero, the following cases would be possible: A
rapid rise and fall of intensity (see c), such as occurs by an induction shock
or by the momentary closure of a battery current, might suffice to excite
a nerve but not be an effective irritant to a striated, much less a non-striated
muscle, unless the short duration of the current were compensated for by
a considerable increase in the intensity (see d). On the other hand a form
of variation such as is shown in e, where the rate of change is very rapid,
although the intensity is not great, might act to irritate nerves, and, because
of the longer duration of the current, striated muscles, though having no effect
on non-striated muscles; and the slower rate of change, and considerable dura-
^ Beitrdge zur vergleichende Physiologic der irrilablen Substanzen, Braunschweig, 1863.

60 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

tion, illustrated hy J\ though uot afroding nerves, might suffice for striated
muscles and be favorable to the excitation of non-striated nmscles.

In the case of nerves, duration of current is less injportant than a rapid
change of intensity. In the case of striated muscles the advantage to be
gained by rapid variations can be easily overstepped, and the importance of
the duration of the current is greater; while in the citse of non-striated muscles
duration of current is of the first importance and ra])id variation mav tail to
excite. In the case of all tissues, strength and density of current, what we
may call intensity of current, is favorable to excitation.

(/) Kfecf of fjir Direction in which the Current Jioirs along the Xerre. —
The result of the irritating change produced in a nerve l)y a battery current
has been found to dejiend upon whether the current flows toward or awav
from the organ stimulated by the nerve. This fact can be most readily ob-
served in the case of isolated motor nerves. In the case of these nerves, the
effects produced by opening and closing the current are different according as
the current is descending, /. e. flows through the nerve in the direction of the
muscle, or ascending, i. c. flows through the nerve in the opposite direction.
Moreover, by a given rate of change of intensity, the stimulating effect varies
with the strength of the current employed. Pfliiger in his celebrated mono-
graph, Untermchnngen liber die Physiologie des Elehtrotonvs, pui)lished in
Berlin, 1859, p. 454, formulated the following rule for the result of excitations
under varying conditions :

Pfliiger's Law of Contraction.

Ascending Current. Descending Current.

Closing. Opening. Closing. Opening.

'Weak current Contr. Rest. Contr. Rest.

Medium " Contr. Contr. Contr. Contr.

Strong " Rest. Contr. Contr. Rest.

To understand this so-called " law of contraction " we must bear in mind
certain fimdamental facts, namely :

a. When a nerve is subjected to a battery current, an excitatory process is
developed in the part of the nerve near the kathode when the current is
closed, and in the part of the nerve near the anode when the current is ojx'ued
(see p. 53).

b. The excitatory process developed at the kathode is stronger than that
developed at the anode (see p. 53).

c. A third fact which is of no less importance, and which will be considered
in detail when we study the effects of the constant current on the irritability
and conductivity of nerve and mu.scle (.see p. 95), is the following: During
the time that a strong constant current is flowing through a nerve, the conduct-
ing power is somewhat lessened in the part to which the kathode is applied, and
is greatly decreased, or altogether lost, in the region of the anode ; moreover,
at the in.stant that the current is withdrawn from the nerve the conducting
power is suddenly restored in the region of the anode, and greatly lessened, or
lost, in the region of the kathode.

QENERAL PHYSIOLOGY OF MUSCLE AND NERVE.

61

The twelve cases included in the above table can be represented in the fol-
lowing diagram (Fig. 23), in which a cross is marked at the part of the nerve

Ascending Current.
K A

Weak current.

Medium current.

Strong current

Descending Current.

A r

» >

Fig. 23.— Diagram illustrating Pfliiger's law.

from which the irritation which is effective in producing a contraction takes
its rise.

In the case of fresli motor nerves of the frog, when the current is weak,
oulv closing contractions, i. e. those originating at the kathode, are obtained bv
both directions of the current. As the strength of the current is increased, at
the same time that the closing kathodic contractions grow stronger, opening
anodic contractions begin to appear ; and with currents of medium strength
both closing and oj^ening contractions are obtained with both directions of the
current. If the .strenp'th of the current be .still further increased, a change is
observed ; with a strong current, the closing of the ascending and the opening
of the descending current fails to excite a
muscular contraction. This fact is demon-
strated most clearly if we employ two
nerve-muscle preparations, and lay the nerves
in opposite directions across the non-polar-
izable electrodes, so that the current from
the battery shall flow through one of the
nerves in an ascending direction and through
the other in the descending direction (.see
Fig. 24). If under these conditions a strong
battery current be employed, muscle a (through
the nerve of which the curi-ent is descending)
will contract only when the circuit is closed,
and muscle h (through the nerve of which the current is ascending) will con-
tract only when the circuit is opened.

Since in the case of currents of medium strength, both opening and clos-
ing the circuit, when the current is ascending and when it is descending,
develops a condition of excitation in the nerve sufficient to cause contractions,
the failure of the contraction bv the closing of the strong ascending current,

A 5-^ K

Fig. 24.— Effect of direction of current
as shown by simultaneous excitation of
two nerve-muscle preparations.

G2

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

aud by the openiDg of the strong descending current, can scarcely be supposed
to be due to a failure of the exciting process to be developed in the nerve ; and
it would seem more likely that the nerve-impulse is for some reason jirevented
from reac-hiiig the muscle — which, as has been said, is the flict, the region of the
anode being incapable of conducting during the flow of a strong current, and
the region of the kathode losing its power to conduct at the instant such
a current is ojiencd.

Effect of Battery Currents upon Normal Human Nerves. — In experi-
ments upon normal human nerves, the current cannot be applied directly to the
nerve, but has to be applied to the skin over the nerve. As it passes from the
anode, the positive electrode, through the skin, the threads of current spread
through the fluids and tissues beneath, somewhat as the bristles of a brush
spread out, and the current flows in a more or less difliisc stream toward the
point of exit, where the threads of current concentrate again to enter the
kathode, the negative electrode. This spread of the current is illustrated in
Figure 25.

The density of the current entering any structure beneath the skin will
depend in part upon the size of the electrode directly over it — that is, the

amount to which the current is
concentrated at its point of en-
trance or exit^ — in part on the
nearness of the structure to the
skin, and in part on the con-
ductivity of the tissues of the
organ in question as compared
with the tissues and fluids
about it. If the conditions be
such as are given in Figure 25,
the current will not, as in the
case of the isolated nerve, enter
the nerve at a given point, flow
longitudinally through it, and
then leave it at a given point ;
most of the threads of current
will pass at varying angles di-
agonally through the part of
the nerve beneath the positive
pole, then flow through the fluids and tissues about the nerve, until, at a point
beneath the negative pole, the concentrating threads of current again pass
through the nerve. A distinction is to be drawn between the physical and
physiological anode and kathode. The physical anode is the extremity of the
positive electrode, and the physical kathode is the extremity of the negative
electrode; the physiological anode is the point at which the current enters the
tissue under consideration, and the physiological kathode is the point where it
leaves it. There is a physiological anode at every point where the current

Fig. 25.— Rough schema of active threads of current by
the ordinary application of electrodes to the skin over a
nerve (ulnar nerve in the upper arm). The inactive threads
are given in dotted lines (after Erb : ZiemssetCs Pathologie und
Therapie, Bd. iii. S. 76).

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 63

enters the nerve, and a physiological kathode at every point where it leaves the
nerve; therefore there is a physiological anode and kathode, or groups of
anodes and kathodes, for the part of the nerve beneath the positive electrode,
and an()tli(>r physiological anode and kathode, or collection of anodes and
kathodes, for the part of the nerve beneath the negative electrode.

To understand the effect ui)on the normal human nerve of opening and
closing the battery current, it is necessary to bear in mind three facts, viz. :

1. At the moment that a battery current is closed, an irritating process is
developed at the physiological kathode, and when it is opened, at the physio-
logical anode.

2. The irritating process developed at the kathode on the closing of the
current is stronger than that developed at the anode on the opening of the
current.

3. The effect of the current is greatest where its density is greatest.

The amount of the irritation process developed in a motor nerve is esti-
mated from the amount of the contraction of the muscle. The contraction
which results from closing the current, the closing contraction as it is called,
represents the irritating change which occurs at the physiological kathode, while
the contraction which results from opening the current, the opening contrac-
tion, represents the irritating change developed at the physiological anode.
Since there are physiological anodes and kathodes under each of the two elec-
trodes— the physical anode and physical kathode (see Fig. 26) — four possible
cases may arise, namely:

1. Anodic closing contraction — i. e. the effect of the change developed at
the physiological kathode, beneath the physical anode (the positive pole).

2. Anodic ojjemng contraction — i e. the effect of the change developed at
the physiological anode, beneath the physical anode (the positive pole).

Fig. 26.— Diagram showing physical and physiological anodes and kathodes: ^, the physical anode,
or positive electrode ; A', the physical kathode, or negative electrode -,0,0,0, physiological anodes ; k, k, k,
physiological kathodes.

3. Kathodic dosing contraction — i. e. the effect of the change developed at
the physiological kathode, beneath the physical kathode (the negative pole).

4. Kathodic opening contraction — i. e. the effect of the change developed at
the physiological anode, beneath the physical kathode (the negative pole).

64 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

For convenience these four cases are represented by the abbreviations ACC,
AOC, KCC, and KOC.

These oases may be arnuigcd in order according to the strengtii of the
irritation whicli is developed.

Since the irritation process developed at a physiological kathode by
closing a current, is, other things being equal, stronger than that developed
at a physiological anode by opening the current, we should expect that tiie
two closing contractions, KCC and ACC, would be stronger than the two
opening contractions, KOC and AOC. This is the case, and as the current is
more dense in the region of the physiological kathode, beneath the physical
kathode, than at the physiological kathode, beneath the physical anode, KCC
is stronger than ACC.

Of the two opening contractions, AOC is stronger than KOC because
of the greater density of the current in the region of the physiological anode,
beneath the physical anode, than in the region of the physiological anode,
beneath the physical kathode.

These differences in the strength of the irritation process developed in these
different regions is well shown by examining the reaction of nerves to cur-
rents of gradually increasing strength. The effect of the opening and closing
irritation is seen to be as follows :

Weak currents. Medium currents. Strong currents.

KCC KCC KCC

ACC ACC

AOC AOC

KOC

The natural order, therefore, would be KCC, ACC, AOC, KOC. Some-
times, however, AOC is stronger than ACC; this hapj^ens when on account
of the relation of the surrounding tissues to the nerve the density of the cur-
rent at the physiological anode is great as compared with the density at the
physiological kathode.

When the currents employed are strong, it not infrequently hap]>ens in the
case of men that not only are the make and break followed by the usual rapid
contractions of short duration, but during the closure of the current there is
a continued contraction — galvanotonus, as it is sometimes called.

Conditions which Determine the Irritability of Nerves and Muscles.
— We have thus far considered the conditions which determine the efficiency
of such an irritant as the electric current. Other irritants are subject to like
conditions, their activity being controlled to a consiihM-able extent by the sud-
denness, strength, density, duration, and, possibly, direction of ajiplication. It
is not necessary for us to consider how each special form of irritant is affected
by these conditions ; it will be more instructive for us to study how different
irritants alter the irritability of nerve and muscle, and the relation of irri-
tability to the state of excitation.

The power to irritate is intimately connected with the power to heighten

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 65

ii'ritability — for ii coiulition of" hcij2;htened irritability is difficult to distin-
guisjj tVoiii a state of excitation. The irritability of cell-protoplasm is very
dependent upon its physical and chemical constitution, and even slight altera-
tions of this constitution, such as may be induced by various irritants,
will modify the finely adjusted molecular structure upon which the normal
response to irritants depends. If this change be in the direction of increased
irritability, the result may be irritation. But we must defer the discussion of
the relation of irritability to irritation until we have considered the conditions
upon which the irritability of nerve and muscle depends. These conditions
ciiu be best studied in connection with the influences which modify them —
namely :

(a) Irritants.

{h) Influences which favor the maintenance of the normal physiological
condition.

(c) The effects of functional activity.

(«) The Influence of Irritants upon the Irritability of Nerve and 3Iuscle. —
Effect of llechanical Agencies. — A sudden blow, pinch, twitch, or cut excites
a nerve or muscle. All have experienced the effect of a mechanical stimulation
of a sensory nerve, through accidental blow\s on the ulnar nerve where it passes
over the elbow, " the crazy bone." The amount of mechanical energy required
to cause a maximal excitation of an exposed motor nerve of a frog is estimated
by Tigerstedt^ to be 7000 to 8000 milligrammillimeters, which would corre-
spond roughly to a weight of 0.500 gram falling fifteen millimeters — at least
a hundred times less energy than that given out by the muscles in response to
the nerve-impulse developed. Such stimuli can be repeated a great many
times, if not given at too short intervals, without interfering with the activity
of the nerve. A nerve can be irritated thirty to forty times, at intervals of
three to four minutes, by blows from a weight of 0.485 gram, falling 1 to 20
millimeters, the contractions of the muscle, weighted with 30 to 50 grams,
varying from minimal to from 3 to 4 millimeters in height. Rapidly following
light blows or twitches applied to a motor nerve, by the tetanomotor of Heiden-
hain or Tigerstedt, excite a series of contractions in the corresponding muscles
which fuse more or less into a form of continuous contraction, known as
tetanus.

Mechanical applications to nerve and muscle first increase and later lessen
and destroy the irritability. Thus pressure gradually applied first increases
and later reduces the power to respond to irritants. Stretching a nerve acts in
a similar way, for this also is a form of pressure ; as Valentin said, the stretch-
ing causes the outer sheath of the nerve to compress the myelin, and this in
turn to compress the axis-cylinder. Tigerstedt states :^ " From a tension of
0 up to 20 grams the irritability of the nerve is continually increased, but
it lessens as soon as the weight is further increased."

Surgically the stretching of nerves is sometimes employed to destroy their

'"Studien iiber mechanische Nervenreizung," Acta Sodetati's Scientiarum Fennicce, 1880,
lorn. xi. p. 32. ^ Op. cit, p. 43.

66 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

excitability. Slight stretching heightens the excitability and even (juite vigor-
ous stretching has only a ternjxjrary depressing effect unless it be carried to
the point of doing positive injury to the axis-cylinder, and of causing degen-
eration. As nerves have the power to regenerate tiny may recover from even
such an iiijury.

The irritability of muscles is likewise increased by moderate stretching and
destroyed if it be excessive. Thus slight stretching produced by a weight
causes a muscle to respond more vigorously to irritants. Similarly tension of
the muscles of the leg, produced by slight over-flexion or extension, makes
them more irritable to reflex stimuli, as in the case of the knee-jerk and ankle-
clonus. Tension must be very marked to permanently alter the irritability of
the mascles.

Effect of Temperature. — Changes in temperature, if sudden and extreme,
irritate nerv^es and muscles. If the nerve or muscle be quickly frozen or
plunged into a hot fluid it will be excited and the muscle be seen to contract
The cause of the irritation has been attributed to mechanical or chemical
alterations produced by the change of temperature. The ulnar nerve at the
elbow is excited if the part be dipped into ice-water and allowed to remain
there until the cold has had time to penetrate ; as is proved by the fact that in
addition to the sensations from the skin, pain is felt which is attributed by the
subject of the experiment to the region supplied by the nerve. As the effect
of the cold becomes greater the pain is replaced by numbness, both the irrita-
bility and power of conduction of the nerve being reduced. Gradual cooling
of motor nerves or muscles, and gradual heating, even to the point of death
of the tissue, fails to excite contractions. It is stated that if a frog whose
brain has been destroyed is placed in a bath the temperature of which is very
gradually increased, the heating may be carried so far as to boil the frog without
active movements having been called out. If a muscle be heated to 45° C.
for frogs and 50° C. for mammals, it undergoes a chemical change, which is
accompanied by a form of shortening different from the contraction induced by
irritants. This form of contraction, though extensive, is feeble and is asso-
ciated with a stiffening of the muscle, known as ric/or oalork.

In general it may be said that raising the temperature above the usual tem-
perature of the animal increases, \vhile cooling decreases the irritability of the
nerves and muscles. Cold, unless excessive and long continued, though it
temporarily suspends does not destroy the irritability, while heat, if at all great,
so alters the chemical constitution of the cell-protoplasm as to destroy its life.

The higher the temperature, the more rapid the chemical changes of the
body and the less its power of resistance ; low tem])erature, on the other hand,
slows chemical processes and increases the endurance. It is noticeable that
nerves and muscles remain irritable much longer than ordinarily in case the
body l)e cooled before their removal. In the case of a mammal the irritability
may last from six to eight hours instead of two and a half, while in the case
of frogs it may be preserved at 0° for ten days, although at summer heat it lasts
onlv twenty-four hours. In the case of frogs which have been kept at a low

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 67

temperature the irritahility becomes abnormally high when they are warmed
to ordinary room-teniiKTatiirc

Effecl of Chemicak and iJrugs. — The activity of nerve and muscle proto-
plasm is markedly influenced by even slight changes in its constitution. If
a nerve or muscle be allowed to lie in a liquid of a different constitution from
its own fluid, and especially if such a liquid be injected into its blood-vessels,
an interchange of materials takes place which results in an alteration of the
constitution of the tissue, and a change in its irritability. Indeed, the only
solutions which fail to alter the irritability are those which closely resemble
serum and lymph. Fluids having other than the normal percentage of salts
have a marked effect, while the absence of proteids appears to have little
influence unless continued for a considerable time. These facts have been most
clearly demonstrated in experiments upon the nature of fluids essential to the
maintenance of the activity of isolated heart muscle. Most drugs and chemicals
capable of influencing the irritability of nerves first increase and later destroy
the irritability. It is said that sensory fibres are less susceptible to chemical
stimulation than motor, but this is not certain. If the change in the chemical
condition of the nerve or muscle be a rapid one, it is usually accompanied by
the phenomenon of excitation ; if more gradual, the irritability alone is altered.
The simple withdrawal of water from a motor nerve, by drying, or by strong
solutions of neutral alkaline salts, urea, glycerin, etc., causes first an increase
and later a decrease and loss of irritability. The increase of irritability is
frequently accompanied by active irritation, the muscle in connection with the
nerve showing rapid irregular contractions as different fibres of the nerve are
one after the other affected. If the drying has not been too long continued,
the irritability may be restored by supplying water. On the other hand,
imbibition of distilled water may, by altering the relative amount of salts, or
from mechanical causes, produce a lessening of irritability. If water be
applied to the tissues by being injected into the blood-vessels, it first excites
contractions and later causes a decline of irritability. Veratria, eserin
digitalis, alcohol, chloroform, ether, sublimate, mineral acids (except phosphoric),
many organic acids, free alkalies, most salts of the heavy metals, destroy the
irritability of nerves and muscles, as a rule after first producing increased
excitability. Carbon dioxide, either because it is an acid or because of some
specific effect, acid potassium phosphate, and lactic acid, lessen the irritability.
Neutral potash salts, if concentrated, rapidly kill but excite less than do soda
compounds. Many gases and fumes chemically irritate and kill nerve and
muscle protoplasm.

Ammonia, neutral salts, carbon bisulphide, and ethereal oils may destroy
the irritability of nerves without causing excitation, at least not sufficiently to
produce visible contractions of the muscle. If directly applied, however,
these substances excite muscles.

A sodium-chloride solution, of a strength of 6 parts per 1000 of distilled
water, has been called the physiological solution because it was supposed to
have no effect on the irritability of nerves and muscles ; but late experiments

68 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

have .shown that even tliis if hjnji; euutiiiued lirst iuoreases and hiter deereases
the irritability of tnusc'le.s. Tlie cause of this is, however, probably the removal
of other salts whiih are essential to the irritability, or the presence of carbonic
acid.

From all these results it becomes evident that the normal irritability of
nerves and muscles requires that a certain chemical constitution be maintained,
and that even slight variations from this suffice to alter, and if continued to
destroy, the irritability. Further, it is noticeable that in most cases the first
step toward deterioration is a rise of irritability, which, if marked, is accom-
panied by a condition of irritiition. If the cause of the increase in irritability
and excitation be continued, sooner or later exhaustion supervenes, the irrita-
bility lessens, and finally is lost.

Effect of the Electnc Current upon 3Iasdes. — If a constant-battery current
of medium strength be sent through a muscle for a short time, the muscle will
give a single short contraction at the moment that the current enters it, and
again when the current leaves it. If a strong current be used, the short
closing contraction may be followed by a prolonged contraction (Wundt's closing
tetanus), which, though gradually decreasing, may last as long as the current
is closed ; and when the current is broken, the usual opening contraction may
be likewise followed by a prolonged contraction (Rittcr's opening tetanus),
which only gradually passes off. The closing contraction originates at, and
the closing continued contraction may be limited to, the region of the kathode;
and the opening contraction originates at, and the opening continued contrac-
tion may be limited to, the region of the anode.

In case a very weak current is used, no contraction will be observed ;
nevertheless, while the current is flowing through the muscle it modifies its
condition ; a state of latent excitation is produced at the kathode, which shows
itself in an apparent increase of irritability of that part of the muscle. On
the other hand, the irritability of the muscle at the kathode will be found to
be lessened after the withdrawal of the polarizing current, because the condi-
tion of excitation which it causes fatigues that part of the muscle.

The effects of the battery current at the region of the anode are just oppo-
site to those produced at the kathode. While the current is flowing, the irri-
tability at the anode is lessened, and when the polarizing current is removed,
irritability at the anode is found to be greater than it was before the battery
current was applied.

The lessened irritability which is produced at the anode during the flow
of the battery current may be shown by an inhibition of a condition of exci-
tation which may be present at the time that the current is ap})lied to the
muscle. For example, in the case of unstriated muscles, not only does closing
the battery circuit never cause a contraction at the anode, but if the ]>art of
the muscle exposed to the influence of the anode happens to be at the time in
a condition of tonic contraction, the entrance of the current causes that part
of the muscle to relax. The inhibitory influence exerted by the anode, as a
result of the lowering of the irritability, is seen to a remarkable degree in its

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 69

eifect upon the heart.' If tlie anode rest on the ventricle of the frog's heart,
and the kathode at some indifferent point, relaxation is seen in the region of the
anode with each systole of the ventricle. Inasmuch as the rest of the ventricle
contracts, the pressure of the blood causes the wall of the ventricle to bulge
out, anil make a little vesicle at the region of the anode. A similar inhibitory
intlu(Mice may be observed upon an ordinary striated muscle at the point of
ap[)lication of the anode, if it be in a condition of tonic contraction when the
battery current is sent into it. During the flow of the constant current through
a muscle, the irritability is increased in the region of the kathode and decreased
in the region of the anode. When the current is withdrawn from the muscle,
on the other hand, the irritability of the kathode is found to be decreased, and
at the anode to be increased.

Effect of the Eleetiic Current upon Nerves. — The polarizing eifects of a con-
tinuous constant current are the same upon a nerve as upon a muscle, with the
exception that in the case of the nerve the condition of altered irritability is
not so strictly limited to the point of application of the anode and kathode, but
spreads thence throughout the part of the nerve between the two electrodes, the
intrapolar region, as it is called, and for a considerable distance into the parts
of the nerve through which the current does not flow, i. e. the extrapolar region.
The term electrotouus has been applied to the effects of battery currents on
nerves and muscles, and includes two sets of changes — (1) physiological, mani-
fested by the alterations of irritability which we are considering; (2) physical,
exhibited in changes of the electrical condition of the tissue. The most im-
portant work on the influence of the constant current on the irritability of nerves
was done by Pfliiger. He ascertained the electrotonic effects of the polarizing
current to be most vigorous in the immediate vicinity of the anode and kathode,
and to spread thence in both directions along the nerve. He called the change
produced in the nerve in the region of the anode " anelectrotonic," and the
condition itself " anelectrotonus," while the change at the kathode was termed
" katelectrotonic," and the condition " katelectrotonus." The same names are
given to the effects of battery currents upon muscles.

To test the effect of a constant battery current upon the irritability of a
nerve, put the nerve of a nerve-muscle preparation upon two non-polarizable
electrodes (A, K, Fig. 27) which are placed at some little distance apart and
at a considerable distance from the muscle. Connect these electrodes with a
battery, introducing into the circuit a key (k), which permits the current to
be quickly thrown into or removed from the nerve, and a commutator ((7),
which allows the current to be reversed and to be sent through the nerve in
either the ascending or descending direction. Connect the nniscle with a myo-
graph lever, arranged so as to record the height of tiie muscle contractions.
Then apply to the nerve at some point between the polarizing electrodes and
the muscle a pair of electrodes (I) connected with the secondary coil of an
induction apparatus, which is placed near enough to the primary coil to cause
excitations of medium strength, and introduce into the secondary circuit a
^ Biedermann : Elektrophysioiogie, 1895, p. 195.

70

A.y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

short-circuitiug key (N), by which the closing sliocks can be prevented from
reaching the nerve.

If, with this arrangenjt'ut, a breaking induction shock of medium strength
be given, the nerve will be excited, and the height of the muscular contraction
which results may be taken as a test of the irritability of the nerve at /.

Fig. 27.— Method of testing anelectrotonic and katelectrotonic alterations of irritability in nerves.

Now send the polarizing current through the nerve, in the ascending direction,
that is, with the anode nearer the muscle. At the moment the current is
closed, if it be of medium strength, a closing contraction will be observed ;
then comes a period during which the muscle is not contracting and the polar-
izing current is apparently producing no effect on the nerve; if, however, after
the current has acted a short time, the irritability of the nerve at the point
/ be again tested with a breaking induction shock, it will be found to be de-
creased, on account of the condition of anelectrotonus which has been induced.
If the key in the polarizing current be then opened, the usual opening con-
traction will be recorded. After the polarizing current has been removed, the
condition of the nerve at I can be again tested, and it will be seen that the
jrritabilitv has returned to the normal, or is even greater than it was at the
start.

The effect of the kathode on the irritability may be tested in a similar way,
by reversing the polarizing current and again sending it into the nerve. This
time the current will be descending, i. e. the kathode nearest the mu.'^cle. As
before, a closing contraction will be seen when the circuit is made, but on test-
ing the irritability at /with an induction shock of the same strength as before,

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 71

it will be luiuul to he iiicreuscd, the shock eaiirtiiig- u larger contraction. On
opening the polarizing current the usual opening contraction will be seen, and
if after the current has been removed the irritability be again t^'.sted, it will
be found to have returned to the normal, or to be decrea.sed. The changes
in irritability dcscribeil can be ascertained by using mechanical or chemical
stimuli as well as induction shocks. Alterations of the irritability induced by
anelectrotonic and katelectrotouic changes of the nerve-substance are to be
found not only in the part of the nerve between the point to which the polar-
izing current is applied and the muscle, but in the extrapolar region at the
ceutral end of the nerve, and in the intrapolar region. The experimental
evidence of this is not so readily obtained, but there is no doubt of the fact.
The effect of the polarizing current is the greater, the better the condition
of the nerve; moreover, the stronger the current employed, the more of the
nerve influenced by it. Of course, in the intrapolar region there is a point
where the effect of the anode to decrease the irritability comes into conflict with
the effect of the kathode to increase it, and where, in consequence, the irrita-
bility remains unchanged. This indifferent point may be observed to approach
the kathode as the strength of the current is increased. The following schema
is given by Pfliiger to illustrate the way in which the irritability is changed in
the anelectrotonic and katelectrotouic regions as the strength of the current is
increased :

Fig. 28.— Electrotonic alterations of irritability caused by weak, medium, and strong battery
currents : A and B indicate the points of application of the electrodes to the nerve, A being the anode,
B the kathode. The horizontal line represents the nerve at normal irritability ; the curved lines illus-
trate hovir the irritability is altered at different parts of the nerve with currents of different strengths.
Curve 2/1 shows the effect of a weak current, the part below the line indicating decreased, and that above
the line increased irritability, at x^ the curve crosses the line, this being the indifferent point at which
the katelectrotouic effects are compensated for by anelectrotonic effects : if gives the effect of a stronger
current, and y^, of a still stronger current. As the strength of the current is increased the effect becomes
greater and extends farther into the extrapolar regions. In the intrapolar region the indifferent point is
seen to advance with increasing strengths of current from the anode toward the kathode.

As in the case of the muscle, so of the nerve, the constant current leaves
behind it important after-effects. In general it may be stated that wherever
during the flow of the current the irritability is increased, there is a decrease
of irritability immediately after the removal of the current, and vice versa.
When the current is withdrawn from the nerve, the irritability in the region
of the kathode is lowered, and in the region of the anode raised. It must be
added, however, that the decrease of irritability seen at the kathode gradually
passes over into a second increase of irritability, while the increase seen at the

72 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

anode upon the reiiioval of the current continues a considerable time and is
not reconverted to a decrease; therefore the total after-effect is an increase of
irritability.

The lact that when the current is closed the irritation starts from the kathode,
and when the current is opened from the anode, may well be associated with the
chauires in irritability wiiich take place at the kathode and anode upon the closing
and the ojicning of the current. The setting free of an irritation appears to be
associated only with an increase of irritability. When the current is closed the
establishment of the condition of katelectrotonus is accompanied by a rise of
irritai)ilitv at the kathode, and when the current is opened the cessation of the
condition of anelectrotonus is likewise accompanied by a rise of irritability. In
the first case the irritability rises from the normal to something above the
normal, and in the second case the irritability rises from the condition of
decreased irritability up to something above the normal irritability. The change
from the normal to the anelectrotonic condition of decreased irritability, or
from the katelectrotonic condition of increased irritability down to normal
irritability, does not irritate. As has often been said, it is hard to distinguish
between increase of irritability and irritation.

The effects produced by battery currents upon irritability are found to be
associated with peculiar alterations in the electrical condition of nerves and
muscles. The relation is a suggestive one, but cannot be taken as a definite
explanation of the changes of irritability.

Efect of Frequency of Application of the Stimulus on Irritability. — We have
seen that influences which act as irritants may also have an effect upon the irri-
tabilitv of the nerve or muscle. In order to produce this change they must be
as a rule powerful, or act for a considerable time. Nevertheless, in the case
of muscles, at least, even a weak irritant of short duration, if repeated fre-
quently, tends to heighten irritability. For example, if a muscle be stimulated
bv separate weak induction shocks at long intervals, the effect of each shock is
slight, and the change produced by it is compensated for by restorative pro-
cesses which occur within the living protoplasm during the following interval
of rest, and each of the succeeding irritations finds the mechanism in much the
same condition ; if, however, the shocks follow each other rapidly, each stimu-
lation leaves an after-effect which may have an influence upon the effectiveness
of the stimulus following it. As a result of this, induction shocks too feeble to
excite contractions may, if frequently repeated, after a little time cause a visible
movement, and shocks of medium strength, if given at short intervals, may
each cause a larger contraction than its predecessor, until a certain height of
contraction has been reached, beyond which there is no further increase pos-
sible. It is not known whether the irritability of nerves is similarly increased,
nor is it known whether physiological stimuli exert such an influence. We
shall consider these so-called " staircase contractions " more carefully later (see
page 110). When irritations follow each other very rapidly, the whole cha-
racter of the contraction is changed, and the muscle, instead of making rapid
single contractions, enters into the condition of apparently continuous contrac-

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 73

tion Uiiowii ;i8 tetanus, diiriji};- which it shurtfiis (•(tn>i(lerably more thuii it cl(X'.s
when inakiiijr single contractions. Increase in irritability plays only a com-
paratively small ])art in the production of tiiis remarkable ])henomenon, which
we shall study more ciiref'ully when we come to the mechanical ])r()blems
involved in muscular contractions.

Rapidly repeated stimuli, though at first favorable to activity of a muscle,
soon exert an unfavorable influence by causing the h'ssenod irritability which
is associated with fati}j:ue.

{h) Influences which favor the Maintenance of the Normal FhymAofjical
Condition of Nerve and Muscle. — Effect of Blood-sujypl y on Nerve and Muscle.
— The vascular system is a i)ath of communication between the several organs
and tissues, and the circulating blood is a medium of exchange. Tlie blood
carries nutritive materials from the digestive organs and oxygen from the
lungs to all the tissues of the body, and it transports the waste materials which
the cells give off to the excretory organs. In addition to these functions it
has the power to neutralize the acids which are produced by the cells during
action, and so maintain the alkalinity essential to the life of the cell ; it su})-
plies all parts with moisture ; by virtue of the salts which it contains, it secures
the imbibition relations which are necessary to the preservation of the normal
chemical constitution of the cell-protoplasm ; it distributes the heat, and so
equalizes the temperature of the body ; finally, in addition to these and other
similar functions, it is itself the seat of important chemical changes, in which
the living cells which it contains play an active part. It is not strange that
such a fluid should exert a marked influence upon the irritability of the nerves
and muscles. Since the metabolism of muscles is best understood, we will
first consider the importance of the circulation to the muscle. Muscles, even
in the so-called state of rest, are the seat of chemical changes by which energy
is liberated, and when they are active these changes may be very extensive.
If the cell is to continue its work, it must be at all times in receipt of mate-
rials to replenish the continually lessening store of energy-holding compounds;
moreover, as the setting free of energy is largely a process of oxidation, a free
supply of oxygen ls likewise indispensable to action. These oxidation pro-
cesses result in the formation of waste products — such as carbon dioxide, water,
lactic acid — and these are injurious to the muscle protoplasm, and if allowed
to accumulate would finally kill it. Of the services Mhich the blood renders
to the muscle there are, therefore, two of paramount importance, viz. the
bringing of nutriment and oxygen and the removal of waste matter and sur-
plus energy.

A classical experiment illustrating the effect of depriving tissues of blood
is that of Stenson, which consists in the closure of the abdominal aorta of a
warm-blooded animal by a ligature, or by compression. In the case of a
rabbit, for example, the blood is shut off, not only from the limbs but from the
lower part of the spinal cord. The effect is soon manifested in a complete
paralysis of the lower extremities, sensation as well as power of voluntary and
reflex movements being lost. The paralysis is due, in the first instance, to the

74 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

I0&5 of fuuction of tlie uerve-celLs iu the cord by which the muscles are nor-
mally excited to action. Later, however, the nerves and muscles of the limbs
lose their irritability. Of the peripheral mechanisms the motor nerve-ends
are found to succumb before the nerves and muscles. This is shown by the
fact that although the muscles are still capable of responding to direct irrita-
tion, they are not aflPected by stimuli applied to the nerve, although the nerve
at the time, to judge from electrical changes which occur when it is excited,
is still irritable. Since the nerve and muscle are irritable, the lack of response
must be attributed to the nerve-ends. The response to indirect stimulation
(/. e. excitation of a muscle by irritating its nerve) is lost in about twenty
minutes, while the irritability of the muscle, as tested by direct excitation, is
not lost for four or five hours. Iu this as in so many instances the loss of
irritability of the muscle is due primarily to the disturbance of the respira-
tion of the muscle. Of the substances supplied to the muscle by the blood,
oxygen is one the want of which is soonest felt. The muscle contains within
itself a certain store of oxygen, but one which is by no means equal to the
amount of oxidizable substances. Of this oxygen, that which is in the least
stable combinations, and which is available for immediate needs, is soon
exhausted. A continual supply of oxygen is required even for the chem-
ical changes which occur iu the quiet muscle. Of the waste substances which
the blood removes from the cell, carbon dioxide is the one which accumu-
lates most rapidly and is the first to lessen the irritability. Lactic acid and
waste products from the breaking down of nitrogenous materials of the cell
are also injurious.

The dependence of nerve-fibres upon the blood-supply is by no means so
well understood. The nerve-fibre is a branch of a nerve-cell, and it seems as
if the nourishment of the fibre was largely dependent upon that of the cell
(see Fatigue of Xerve, p. 79). Nevertheless, the nerve-fibre requires a con-
stant supply of blood for the maintenance of its irritability. The irritability
of the nerve cannot long continue without oxygen, and a nerve which has
been removed from the i)o(ly is found to remain irritable longer in oxygen
than in air, and in air than in an atmosphere containing no oxygen. Waste
products liberated by active muscles have a deleterious effect on nerves ;
whether such substances are produced in the nerves themselves will be con-
sidered later.

The efficacy of the blood to preserve the irritability is to be seen in such
experiments as those of Ludwig and Schmidt;' they succeeded in maintaining
the artificial circulation of defibrinated, aerated blood through the muscles
of a dog, and kept them irritable for many hours after death of the animal.
If such an experiment is to be successful, the blood must be maintained at the
normal temperature, be plentifully supplied with oxygen, and be kept as free
from carbon dioxide as possible. Von Frey ^ made an elaborate experiment of

* Sitzungsberichte der math.-phys. CUutse der k. sacks. Gesellschaft der Wissenschfiffen, vol. xx., 1868.

* " Versiiche iiber den Stoffwechsel des Muskeb," Archiv fur Anatomie und Physiologic,
1885; physiologische Abtheilung, p. 533.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 75

this nature. A dog was killed, the body was cut in halves, ami the aorta aud
inferior vena cava were quickly connected with an apparatus for pumping the
blood at a regular rate through the hind part of the bcjdy. Before the blood
entered the arteries it passed through coils in which it was warmed to the nor-
mal temperature, and an artiticial lung, where it received a supply of oxygen
and was relieved of its carbon dioxide. Under these conditions the muscles
were kept alive for more than seven hours, and so far retained their normal
condition that throughout this period they were able to respond to stimuli
sent to them through their nerves aud contract with sufficient vigor to raise a
considerable weight. H. N. Martin ^ made a similar experiment on the heart
of a dog. The heart and lungs were isolated from the rest of the b<jdy, the
lieart was fed with defibrinated blood from a Mariotte's flask, and the lungs
were supplied with air by an artificial respiration apparatus. The heart, which
was kept moist and at the normal temperature, contirmed to beat for four hours
and more.

Normally the blood-supply to the muscle is varied according to its needs.
When the muscle is stimulated to action, its blood-vessels are at the same time
dilated so that it receives a free supply of blood.^ Moreover, if muscular work
is extensive, the heart beats faster and the respiratory movements are quicker,
so that a larger amount of oxygen is provided and the carbon dioxide is
removed more rapidly. The importance of the blood-supply to a muscle can
be best understood if we consider it in relation to the eflPects of fatiguing work
upon the muscles. The relation of other substances in the blood to the
needs of the muscle can be best considered together with the chemistry of

the muscle.

Effect of Separation from the Central Net'vous System.— If a motor nerve be
cut, or if some part of it be so injured that the fibres lose their power of conduc-
tion, the portion of the nerve thus separated from the central nervous system
sooner or later completely degenerates. Each of the motor nerve-fibres is a
branch of a motor cell in the anterior horns of the spinal cord. These nerve-
cells are supposed to govern the nutrition of their processes, though how a
microscopic cell can thus influence a nerve-fibre a meter or so long is by no
means clear. Soon after the nerve is separated from its cell it exhdnts an
increase of excitabilitv near the point of section, and this change progresses
down the fibre toward the periphery. The rule that the change in irritability
progresses centrifugallv along the motor nerves is known as the Ritter-Yalli
law. The increase is soon followed by a decrease of irritability. In the case
of mammalian nerves loss of irritability may be complete at the end of three
or four days, but the nerves of cold-blooded animals may retain their irri-
tabilitv for several weeks. The immediate cause of the loss of irritability is
the change in the chemical and physiological structure of the axis-cylinder.
The degenerative changes result finally in the complete destruction of the
nerve-fibres, and involve the motor end-organs as well, but do not imme-

1 Stmlip, from the Biological Laboratory of Johns Hopkins University, 1882, vol. ii. p. 188.
» Sczelkow: Sitzungsber. d. k. Akad. Wien, 1862, vol. xlv. Abth. 1.

76 ^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

diately iuvatlt- the luusele, which iimy be considered a proof" that nerve and
muscle j)rotopla.siu are not continuous.

Though wo ininietliate cliangc in the structure of the muscle is ohservahle,
the irritability ol" the muscle soon begins to alter. At the end of a fortnight
the irritability of the muscle for all forms of stimuli is lessened. From this
time on, the irritability gradually undergoes a remarkable change, the excita-
bility for mechanical irritants and for direct battery currents beginning to
increase, but the power to respond to electric currents of short duration,
as induction shocks, continuing to lessen ; indeed, the reactions of the
muscle appear to take on more of the character of those of smooth muscle-
fibres. The condition of increasing irritability to direct battery currents and
mechanical irritants reaches its maximum by the end of the seventh week,
and from that time on the power to respond to all forms of stimuli lessens,
the excitability being wiiolly lost by the end of the seventh or eighth month.
During the stage of increased excitability fibrillary contractions are often
observed.

As in the case of a nerve so in the muscle the loss of irritability is due to
degenerative changes which gradually lead to the destruction of the muscle
protoplasm. The cause of the change in the muscle is still a matter of doubt,
some regarding it as due to the absence of some nutritive, trophic influence
from the central nervous system, while others consider it to be the result of
circulatory disturbances, consequent upon the lack of a proper regulation of
the blood-supply, due to the division of the vaso-motor nerves. As regards
the latter view, it may be said that muscles whose vaso-motor nerves are intact,
the vessels being innervated through other nerves than those which supply the
muscle-tissue proper, as is the case with some of the facial muscles, undergo
similar changes in irritability when their motor nerves are cut. As regards
the former view, it may be said that if the muscles be artificially excited, as by
electric stimuli, and thus are exercised daily, the coming on of degeneration can
be at least greatly delayed. The question as to whether the anabolic processes
within the nmscle-cell are dependent on the central nervous system, in the sense
of there being specific trophic influences sent from the nerve-cells to the mus-
cles, is still under discussion and need not be considered further in this place.
Without doubt the reflex tonus impulses which during waking hours are all
the time coming to the muscles are productive of katabolic changes and,
indirectly at least, favor anabolism.

(c) Effect of Infiuences which remdt from the Functional Actimty of Nei^ea
and Muscles. — Fatigue of Muscles. — The condition of muscular fatigue is cha-
racterized by lessened irrital)ility, decrease in the rate and vigor with which
the muscle conti-acts and liberates energy, and a still greater decrease in the
rate with which it relaxes and recovers its normal form. In a sense, whatever
induces such a state can be said to cause fatigue, but it is ])erhaps best to
restrict the term to the form of fatigue which is produced by excessive
functional activity. The cause of exhaustion which results from over-
work is much the same as the cause of the loss of irritability and power

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 11

which follows the cutting ott' of the blood-siii)i)ly. The working cell liberates
energy at the expense of its store of nutriment and oxygen, and through oxi-
dation processes forms waste products which arc poisonous to its protoplasm.
The fatigue which results from functional activity has, therefore, a twofold
cause, the decreiise in energy-holding compounds and the accumulation of
poisonous waste matters.

It is evident that the leno;th of time that the cell can continue to work will
dej)end very much upou the rapidity with which the energy-holding exijlosive
compounds are formed by the cell-protoplasm and the waste products are
excreted. If a muscle is made to contract vigorously and continuously, as
when a heavy weight is held up, fatigue comes quickly ; on the other hand, a
muscle may be contracted a great many times if eacii contraction is of short
duration and considerable intervals of rest intervene between the succeeding
contractions. The best illustration of this is the heart, which, though making
contractions in the case of man at the rate of seventy or more times a minute,
is able to beat without fatigue throughout the life of the individual. Each
of the vigorous contractions, or systoles, is followed by an interval of rest,
diastole, during which the cells have time to recuperate. The same is true of
the skeletal muscles. It was found in an experiment that if a muscle of the
hand, the abductor incUcis, were contracted at regular intervals, a weight being
so arranged that it was lifted by the finger each time the muscle shortened, a
light weight could be raised at the rate of once a second for two hours and a
half, i. e. more than 9000 times, without any evidence of fatigue. If, however,
the weight was increased, which required a greater output of energy, or if the
rate of contractions was increased, which shortened the time of repose, the mus-
cle fatigued rapidly. In general, the greater the weight which the muscle has
to lift, the shorter must be the periods of contraction in proportion to the inter-
val of rest if the muscle is to maintain its power to work. Maggiora,^ in his
interesting experiments in Mosso's laboratory at Turin, made a very careful study
of this subject, and ascertained that for a special group of muscles there is for
each individual a definite weight and rate of contraction essential to the accom-
plishment of the greatest possible work in a given time. Either increasing
the weight or the rate of contraction hastens the coming on of fatigue and so
lessens the power and the total amount of work. In such an exercise as
walking the muscles are not continually acting, but intervals of rest alternate
with the periods of work, and the time for recu])eration is sufficiently long to
permit the protoplasm of the muscle-cells to prepare the cliemical compounds
from Avhich the energy is liberated, as fast as they are used, and get rid
of the waste products of contraction, so that vigorous muscles can be em-
ployed many hours before any marked fatigue is experienced. Sooner
or later, however, the vigor of the muscle begins to decrease. The reason
for this is not wholly clear. It is noticeable, however, that not only the
muscles employed in the work, but other muscles, such as those of the
arms for instance, even when purposely kept quiet, have their irritability
' Archiv fur Analmiie und Physiologie, 1890 ; physiologische Abtheilnng, p. 191.

78 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

reduced. This would .•^uj^gest that tlie fatigue wliich finally asserts itself is
due to some general rather than local influence. To understand this we must
recall the fact tluit all parts of" the body are in c()mnuiui(;ation by means of
the circulatory system. The ever-circulating blood as it is thrown out by the
heart is divided into minute streams, which, after passing through the many
organs of the body, unite again on their return to the heart. If materials l)e
taken from the blood by one l)art, they are lost to all the rest, and if materials
be added to the blood by any part, tliey are sooner or later carried to all the rest.
During the course of a long march, the muscles of the leg take up a great deal
of nutriment, and give off many waste products, and all the organs suffer in con-
sequence. Mosso,* in his experiments upon soldiers taking long forced marches,
found that lack of nutriment is not the only cause of the general fatigue
produced by long-continued muscular work. The soldiers, though somewhat
refreshed bv the taking of food, did not recover completely until after a pro-
longed interval of rest. He attributed this to the fatigue-products which he
supposed the muscles to have given off, and concluded .hat they were only
gradually eliminated from the blood. To see if there were fatigue-products
in the blood of a tired animal capable of lessening the irritability of organs
other than those which had been working, he made the following experiment :
He drew a certain weight of blood from the veins of a dog, and then put back
into the animal an equal amount of blood from another completely rested dog.
The dog which was the subject of the experiment appeared to be all right after
the operation. On another day he repeated the experiment, but this time the
blood which was put back was taken from a dog that was completely tired out
by running. The effect of the blood from the fatigued animal was very
marked ; the dog receiving it showed all the signs of fatigue, and crept off into
a corner to sleep. Mosso concluded from this experiment, that duriug muscular
work fatigue-products are generated in the muscles, pass from thence into the
blood, and are conveyed to other muscles, where they produce the lowered
irritability and loss of power characteristic of fatigue. Many years before.
Von Ranke extracted from the tired muscles of frogs substances which he
considered fatigue materials. We know many of the waste products formed
by muscles, and have learned that some of them lower the irritability, but
what the exact substances are which produce the effects observed in the above
experiments is not known.

Maggiora, in his experiments upon the fatigue of special groups of muscles,
likewise found that the taking of food causes only a partial recovery of the
tired muscles, and that an interval of rest is essential to complete recovery.
In these experiments the irritability of the muscles was tested not only by
volitional impulses, lint by the strength of the electric current required to
cause direct excitation. In the case of vigorous men, one and a half horn's
suffices to restore the muscles of the forearm which have been com]>letely tire^l
out by raising a heavy weight many times. He also observed that the time
required for recovery can be greatly shortened if the circulation of the blood
' Archiv fiir Anatmnie und Physiologic, 1890 ; phvsiologische Abtheilung.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 79

and Ivn,,,!, in the muscles be increasal l.y .nas^ige. Tl.is suggests ^.at the
power of the cell to give off its waste procluds to the blood >s sufficcntly
Lid to keep pace with the ordinary prcKlucti.m, but not with the n>„re rap.d
formation ulklng place during iatigniug work. This would s..,n to be th
case in spite of the fact that circulation of the blo,xl n, the n,ns<:lcs ,s increased
,l„,.ing action. When nm.scles arc stimulated to action l,y nnpnlscs conung
to the™ from the ..cntral nervous system, the muscles m the walls of the blood-
vessels of the umsclc are also irritated by their vaso-dilator nerves and, relax-
ing, permit a greater flow of blood through the muscle; when the muscles
ceSe to be exdtcd the muscles iu the vessel walls are gradually eontraet«^
again through the action of the vaso-coostrietor nerves, and the blood-snpp y
to the muscle tissue is correspondingly lessened. Tins arrangement would
seem to suffice for the bringing of nutriment and oxygen and the removal of
waste matters under ordinary conditions.

Normally the muscles are never con.pletcly fatigued. It won d seem
that as the muscles tire and their irritability is lessene<l, the central nei-ve-
eells which send the stimulating impulses to them have to work harder
and that the nerve-cells give out sooner than the muscles On the o he
hand certain exi«riments seem to show that the nervc-eells recover from
fat ™ more rapidly than the muscles do, so that it is an advantage to
; fo g n m that they should eease to excite the mt,seles before muscular
fetieue .s complete. With the decreasing irritability of the mu.scle, a feelmg
rf dslomfort in the muscle and an increasing sense of effort are expenenced
S he" *Wual, both of which tend to cause a cessation of coutract.o,, and
prevent a harmful amount of work. That such an arrangemen -0"U ' of
LrvL was apparent in the experiments of Maggiora, m winch he found that
^ mils a.' 'forced to work after fatigue ha. developed, the^me of recovery
is prolonged out of all proportion to the extra work accomplished.

Ta^W y.,«..-Mnscle-, gland- and nerve-cells-m fact, almost eyety
fori o ;;fto;iasm_if excited'to vigorotts long-continued -t.on, deter.
oZ and exhbit a decline of functional activity. As we have seen, n
leea" of muscle there is a using up of energy-holdmg compounds and
a productL of poisonous waste matters, and these two effects mdnce he con-
liS nCvn as Ligue. A priori, we should exj^ct sim.lar d-ges o -nr
in the active nerve-fibre; alnmst all the experimental evide, ee ,s however
om sir o this view. tLc form of activity which is most character.sfe of
n usee s CO Ltion ; that which is ntost characteristic of nerve tseonducttm.
In the in the m;sele it is exceedingly difficult to distingu.sh between the
in tiie case oi me chansre of form and those

effects produced by the processes associated -;'' * « f ^^ge. There is little
which result from *e .transm,ss.m of the ex« ^^^^,^^^

doubt but that fat,gue ts --»-*«^j" ^™ ;;,,here the transmi^ion
''^ Apparently the same may be said of the processes which result in the

80 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

development ot" what we call the nerve-impulse. We have already seen that
the nerve may undergo an alteration of irritability if subjected to artificial
irritants. Such a change at the point of application of the irritant is hardly
to be regarded as a latigue effect, however, for in many cases, at least, it is
due to the direct effect of the irritant on the physical or chemical structure of
the nerve-protoplasm rather than to molecular changes which are j^eculiar to
the development of the nerve-impulse. Thus the change of irritability which
results from a series of light blows, such as may be given to a nerve by
Tigerstedt's tetanomotor, cannot properly be said to be the result of fatigue. It
has been found that a medullary nerve may be excited many times a second
for houi*s, by an induced current, and still be capable of developing at the
stimulated point what we call the nerve-impulse. The change which is de-
veloped at the point of excitation and which passes thence the length of the
nerve, would seem to be the expression of a form of energy liberated within
the nerve, and since the liberation of energy implies the breaking down of
chemical combinations, the apparent lack of fatigue of the nerve is incompre-
hensible. It is the more remarkable since the nerve-fibre is to be considered a
branch of a nerve-cell, and nerve-cells appear to fatigue if frequently excited
to vigorous action. Inasmuch as we have as yet no definite knowledge of the
nature of what we c^ll the nerve-impulse, or of the character of the jwocesses
by which it is transmitted along the nerve, we can afford to leave this question
open, and simply state that the evidence thus far obtained is opposed to the
view that nerve-fibres fatigue.

Effect of Use and Disuse. — Different kinds of muscle- tissues possess very
different degrees of endurance. By endurance we mean the capacity to liber-
ate energy during long periods of time. This capacity is intimately associated
with irritability, for one of the first marks of failure of power is a decline of
irritability. In general, the more irritable a muscle the less its endurance,
because with an increase of irritability there is associated a more rapid and
extensive liberation of energy in response to irritants. For example, the rap-
idly responding and acting pale striated muscles of the rabbit have le&s resist-
ing power than the red striated muscles, while the sluggish unstriated muscle-
fibres can contract a long time without suffering from fatigue.

The endurance of muscles of even the same kind may differ very considera-
bly in the same individual, but the differences are more striking in the case of
different individuals. One of the causes of this is the extent to which the
muscles are employed. Use, exercise, is the most effective method of increasing
not only the strength, but the endurance of the muscle. Though this fact is
so well known as to scarcely need repeating, the explanation of it is by no
means so clear. Undoubtedly one of the causes is a more perfect circulation
in a muscle which is often used, but this is not all. It would seem as if the
protoplasm of the muscle-cell was educated, so to speak, to be more expert in
assimilating materials containing energy, in building up the explosive compounds
employed in its work, and in excreting deleterious waste matters.

The effect of exercise upon irritability has not been thoroughly worked out.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 81

It would seem as if there were a normal degree of irritability for each special
form of muscle-tissue, and as if either an increase or decrease of the irritability
above or below this level was a sif2;n of det<!rioration. J^xercise, if not excess-
ive, is favorable to the maintenance of this normal physiological condition.
Without doubt many of the differences which we attribute to the muscles of
different men arc really due to differences in the central nerve-cells, the action
of muscles, rightly inter[)reted, being rather an expression of central nervous
activity than the result of peculiarities of the muscles themselves. To exercise
the muscles is to exercise the nerve-cells, and the effects of exercise upon these
nervous mechanisms is of as much importance as the effect upon the muscles.
In admiring visible proportions we must always bear in mind "the power
behind the throne." "Beef" is of use to the athlete, but the muscles are
merely the servants, and can accomplish nothing if the master is sick. The
nerve-cells always give out before the muscles, and the man preparing for a
contest should watch his nervous system more than his muscles. He who
forgets this can easily over-train, and do himself a permanent injury, besides
failing in the race.

Effect of Enforced Rest. — Not only is the strength of the muscles greatly
increased by exercise, but a lack of exercise soon results in a loss of strength.
This is seen when an individual is confined to his bed for even a comparatively
short time, or when a limb is subjected to enforced rest by being placed in a
splint. The cause is to be sought in changes peculiar to the muscle proto-
plasm itself, although reduced circulation may also play a part. The effect of
prolonged rest on the irritability of muscles, is seen most markedly when they
are separated from the central nervous system by injuries of their nerves (see
13. 79). The lowered irritability which results from prolonged rest is not
peculiar to muscles, but is shared by all forms of protoplasm.

0. Conductivity.

Conductivity is that property of protoplasm by virtue of which a condition
of activity aroused in one portion of the substance by the action of a stimulus
of any kind may be transmitted to any other portion. For example, if the
edge of the bell of a vorticella (see Fig. 2, p. 34) be irritated by a hair, not
only do the movements of the cilia cease, but the contractile substance of the
bell draws it into a more compact shape, and the fibrillae of the stalk shorten
and pull the bell away from the offending irritant. In such a case an exciting
process must have been transmitted throughout the cell, and through several more
or less differentiated forms of protoplasm. This property of conductivity is not
known to be limited to any one peculiar structural arrangement of protoplasm
distinguishable with the microscope, but is exhibited by a vast variety of forms
of cell-protoplasm, and by plants as well as animals. The cytoplasm of cells,
the part of the protoplasm surrounding the nucleus, appears to be composed
of a semifluid granular material, traversed in all directions by finest fibrillse
which in some cases appear to form an irregular meshwork, the reticulum, and
in others to be arranged side by side as more or less complete fibrils. It is not

82 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

known whether the power of conduction is possessed by the whole of" the pro-
toplasmic substance or is confined to the reticular substance, but there are cer-
tain reasons why the former view may be considered the more probable. The
rate and the strcng:tli of the conduction process varies greatly in different forms
of prot()i)lasm, and there aj)pear to be dififcrences in the facility with which
the exciting process spreads through different jiarts of even the same cell.' Not
only are such differences to Ijc noticed in many of tiie ciliated infusoria, but
even the substance of striated muscles seems to conduct in two different ways,
the sarcoplasm appearing to conduct slowly, and the more highly differentiated
fibrilldry jiortion of the fibre rapidly. In general the })r()cess appears to be
more rapid and vigorous where a fibrillated structure is observable. Smooth
muscle-tissue, which has a somewhat simple structure, conducts comparatively
slowly; striated muscle, which is more highly differentiated, more rapidly, and
the fibrillated axis-cylinder of the nerve-fibre, most rapidly of all.

Protoplasmic Continuity is Essential to Conduction. — Effect of a
Break in Protoplasmic Continuity. — A break of protoplasmic continuity in any
part of a nerve- or muscle-fibre acts as a barrier to conduction. If a nerve be cut
through, the irritability and conductivity remain for a considerable time in the
severed extremities, but communication between them is lost, and remains absent
however well the cut extremities may be adjusted. The nerve-impuLse is not
transmitted through the nerve-substance as electricity is transmitted along a
wire : join the cut ends of a wire, and the contact suffices for the passage of
the current ; join the cut ends of a nerve, and the nerve-impulse cannot pass.
Any severe injury to a nerve alters the proto})lasmic structure and prevents
the chemical and physical processes through which conductivity is made
possible. It is probable that the same may be said of all forms of liv-
ing cells, and the absence of protoplasmic continuity would .seem to be an
explanation of the fact that nerve- and muscle-fibres which lie close together
may physiologically act as separate mechanisms.

Even in the case of apparently homogeneous protoplasm there is probably
a definite structural relation of the finest particles, and upon this the physi-
ological properties of the substance depends. Slight physical and chemical
alterations suffice to change the rate and stretigth of the conduction })roccss,
and the power to conduct is altogether lost if the protoplasm is so altered that
it dies.

The relation of conductivity to .structure of cell-protoplasm is illustrated in
the effects of degeneration and regeneration upon the physiological jiroperties of
the nerve-fibre. The life of the nerve-fibre is dependent on influences exerted
upon it by the nerve-cell of which it is a branch. When any part of the fibre is
injured it loses its power to conduct, and the portion of the fibre separated by
this block from its cell soon dies. The irritability and conductivity are wholly
lo.st at the end of three or four days, and the fibre begins to undergo degenera-
tion. The axis-cylinder and the myelin are seen to break up and are then
absorbed, apparently Mith the assistance of the nuclei which normally lie just
' Biedernianii : Elektrophysiologie, 1895, p. 137.

GENERAL PHYSIOLOGY OF MUSCLE AND NEJiVE. 83

inside the neurilcmina, and Avliifh at this time proliferate greatly and eonie to
occupy most of the lumen of the tube. The process of absorption is nearly com-
plete at the end of a fortnight after the injury. Under suitable conditions, how-
ever, regeneration may occur, and as this takes place there is a recovery of physi-
ological activities. The order in which conductivity and irritability return is
instructive, llowcll and Huber' made a careful study of this subject. They
found that the many nuclei which develop during degeneration are apparently
the source of new pr()t()])lasm, which is seen to accumulate in the old sheath until
a continuous band of protoplasm is ibrmed. About this thread of protoplasm
a new membranous sheath develops, and thus is built up what closely resembles
an embryonic nerve-fibre. The embryonic fibre formed in the peri])heral end
of the regenerating nerve joins that of the central end in the cicatricial tissue
Avhich has been deposited at the point of injury. Thus a temporary nerve-
fibre is formed and united to the undegenerated part of the old fibre, and this
new structure, though possessing neither myelin nor axis-cylinder, is found to
be capable of conduction and to have a low form of irritability, being ex-
citable to violent mechanical stimuli but not to induction currents. The power
of conduction appears to return before irritability, and may be observed first
at the end of the third week. Apparently sensation is recovered before the
power of making voluntary movements ; this difference may w^ell be due, not
to any essential difference between sensory and motor fibres, but to the fact
that extra time is required for the motor fibres to make connection with the
muscle. The embryonic fibre gradually gives place to the adult fibre, new
myelin being formed all along the fibre, and a new axis-cylinder growing down
from the old axis-cylinder. As the axis-cylinder grows down, the irritability
for induction shocks is recovered. Many months may be necessary for the
complete recovery of function.

The same is true of muscle as of nerve protoplasm, — the power of con-
duction ceases with the life of the cell-substance ; thus, if the middle part of
a muscle-fibre be killed, by pressure, heat, or some chemical, the dead proto-
plasm acts as a block to prevent the state of activity which may be excited at
one end from being transmitted to the other, and the conduction power is only
recovered on the regeneration of the injured tissue.

Isolated Conduction is the Rule. — (a) Conduction in Kerve-trunks. — The
axis-cylinders of the many fibres which run side by side in a nerve-trunk are
separated from each other by the neurilemma, and in the case of the medullary
nerves by the myelin substance as well, so that there is not even contiguity,
much less continuity of nerve-substance. Thus the many fibres of a nerve-
trunk, some afferent and others efferent, though running side by side, conduct
independently of one another. For example. If the skin of the foot be pricked,
the excitation of its sense-organs is communicated to sensory nerve-fibres, and
is transmitted along them to the spinal cord, where the stimulus awakens cer-
tain groups of cells to activity; these cells in turn, by means of their branches,
the motor nerve-fibres, transmit the condition of excitation down to the mus-
^ Journal of Physiology, 1892, vol. xiii. p. 361.

84 AN AMERICAN TEXT-BOOK OF PllWSlOLOGY.

cle-fibres of the legs, wliich, when stimulated, contract and withdraw the foot
from the offending irritant. The sensory and motor nerves concerned in this
reflex act run for a considerable part of their course in the same nerve-trunk,
but the sensory impulses have no direct effect on the motor nerve-fibres, and
the roundabout course which has been described is the only way by which
they can influence them.

It is probable that isolated conduction by separate fibres and their branches
holds gootl within the central nervous system, as elsewhere, otherwise we could
scarcely explain the localization of sensations, or co-ordinated movements. It
is possible that within the central nervous system the neuroglia may act to
secure isolated conduction. This question will be considered elsewhere.

(6) Distribidioii of Excitation by Branches of Nerves. — Nerve-fibres rarely
branch in their passage along the peripheral nerves. The branches which are
seen to be given off from the nerve-trunks are composed of bundles of nerve-
fibres which have separated off from the rest, but which remain intact. After
the nerves have entered a peripheral organ, or the central nervous system, the
axis-cylinders may give off branches. Thus in muscles, and to a still greater
degree in the electric organs of certain fish, the nerve-fibre and its axis-cylinder
may divide again and again, or after entering the spinal cord the fibre may be
seen to give off a great many lateral branches — collaterals, as they are called.
It is not known whether in such cases the fibrilhe of the axis-cylinder give
off branches, or whether they simply separate, a part of them entering the
branch while the rest of them continue on in the main fibre. Though the
exciting process does not pass from fibre to fibre, it probably involves in a
greater or less degree all the elements of the same fibre, and passes into all its
branches. It is evident that where it is necessary for the irritation to be
localized, branching could not occur ; but where a more general distribution
is permissible, especially where several parts of an organ ought to act at the
same instant, conduction through a single fibre wliich branches freely near its
termination would be useful.

(c) Conduction in 3lHscles. — Each fibre of the muscles which move the
bones — the skeletal muscles, as they are sometimes called — is physiologically
independent of the rest. The sarcolemma prevents not only continuity, but
contiguity of the muscle-substance of the separate fibres, and there is no cross
conduction from fibre to fibre. Each of the separate muscle-fibres is sup]>lied
by at least one nerve-fibre, and, under normal conditions, only acts when
stimulated by the nerve. In the case of ])lant-cells, and of certain forms of
muscle-cells, about which there is a more or less definite wall or sheath, there
are little bridges of protoplasm binding the cells together. For example,
Engelmann describes the muscle of the intestines of the fly as composed of
striated cells, sheathed by sarcolemma, except whore bound together by little
branches of sarcoplasma, which may act as conducting wires between the cells.

There are certi\in cells, however, which have been supposed to be exceptions
to the rule that protoplasmic continuity is essential to conduction. The stri-
ated muscle-fibres of the heart are quite different from those of ordinary

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 85

skeletal muscles, physiologically as well as anatomically. They are stumpy,
quadrantrular colls, wiiich are not known to have a sarculemma, and which are
united not only by their broad ends, but by lateral branches. Engelniann
and others have considered conduction to take place in the heart from cell to
cell, without the intervention of nerves, and in all directions with equal readi-
ness. This view was held because the irritation was found to spread in all
directions through the muscle-substance, and no nerves had been discovered
which could account for this free communication. Quite lately, however,
Hegmans and Demoor claim to have discovered in the heart of the frog, by
the Golgi staining method, an anastomosing network of nerve-fibres which
extends over the whole heart. This nervous network would appear to give
ample means of communication between the different parts of the heart,^ but
it is possible that it has only a regulatory function.

The cells of the contractile substance of some of the medusae (as Aurelia),
have been supposed to communicate by contiguity rather than by continuity.
The same has been thought to be the case with many forms of unstriated
muscle-tissue ;^ moreover, there are groups of ciliated cells, the members of
which act in unison although they have not been found to be connected either
directly or by nerves. These cells have apparently no membranous covering,
and though living as independent units, are so related that a condition of
activity excited in one seems to be transmitted to the rest by means of contact,
or through the mediation of cement-substance.

From what has been said it will be seen that protoplasmic continuity
ensures free communication between different cells ; that protoplasmic con-
tiguity, either directly or through the mediation of the cement-substance, may
possibly permit of conduction; but that the intervention of a different tissue,
even as delicate as the sarcolemma, suffices to cause complete isolation of the
cell from its neighbors.

Transmission of Excitation by means of End-organs. — The latest
researches on the anatomy of the spinal cord seem to show that the incoming fibres
do not communicate directly with nerve-cells, but terminate in brush-like end-
ings in the immediate vicinity of the cells. A similar arrangement is found
wherever nerve-cells are excited to action by nerve-fibres. It is doubtful
whether the brush-like endings should be regarded as special exciting mechan-
isms, or whether the brush endings should be considered to be in contact with the
nerve-cells or their protoplasmic processes, and this relation to be sufficiently
close to permit the cells to be stimulated. The former view is favored by the
fact that though the end-brush can excite the cell, the cell does not seem to be
able to excite the brush. Much the same can be said of the end-plates by
which the condition of excitation of nerve-fibres is conveyed to muscle-fibres,
for they seem to be in contact with, rather than continuous with the muscle-
substance. Though the nerve end-organ can excite the muscle, the muscle
does not appear to be able to excite the nerve.

' Archives de Biologie, 1895, vol. xiii., No. 4, p. 619.
^ Engelmann: Pfliiger^s Archiv, 1871, Bd. iv.

86 A.y AMERICAN TEXT-HOOK OF PHYSIOLOGY.

Wa liuve little knowledge of the j)liysi()l()o;i('al activities of the eiul-hiiishcs.
We know that much more time is lost in the central nervous processes than
would be required to transmit the excitation through nerve-fibres, and that the
time occu])ied is apparently the greater the longer the chain of nerve-cells en-
tering into the act. A i)art of this time is undoubtedly sjKMit in the processes
occurring within the nerve-cells, but it is not unlikely that a |)ortion of it may
be spent bv the nerve end-brushes in the excitation of the cells.

It is certain that the motor end-plates use up more time in the excitation of
the nuiscles than would be recpiired for the transmission of the irritation
through a corresponding amount of nerve-substance. It is found by experi-
ment that a nniscle does not contract so quickly if it be excited through its
nerve as when directly stimulated. Part of the lost time is spent in transmis-
sion of the excitation through the nerve, but after allowance has been made for
this loss there is a balance to be accounted for, and this is credited to the motor
end-plates. The average time used by the motor end-plate is found to be
0.0032 second.^ There are many facts which go to show that the motor end-
organ is different physiologically from the nerve ; viz. the latent period
of the motor end-plate, the effect of curare on the nerve end-plate as dis-
tinguished from nerve and muscle, the fact that the end-organ loses its vitality
quicker than do nerve and muscle when the blood-supply is cut off, and the
very existence of an end-organ distinguishable with the microscope.

Conduction in Both Directions. — [a) In Muscle. — Wherever proto-
plasmic continuity exists, conductivity would seem to be possible; moreover,
the active change excited by an irritant would seem to be able to pass in all
directions, though whether with the same facility is not known. Where the
spread of the excitatory process is accompanied by a change in form, as is the
case in many of the lower organisms and in muscle-tissue, it is not difficult to
trace the process. The rate at which the excitation spreads through the ifrita-
ble substance is very rapid, and special arrangements have to be employed to
follow it, but the change is not so swift that its course cannot be accurately
determined. It has been found that if a muscle-fibre be stimulated, as nor-
mally, by a nerve-fibre, the active condition produced at the })oint of stimula-
tion spreads along the muscle-fibre in both directions to its extremities ; if the
fibre be artificially irritated at either end, the exciting change runs the length
of the fibre, regardless of the direction, and stimulates every part of it to con-
traction.

(6) In Nei'ves. — In the cases of nerves where excitation is accompanied by
no visible manifestation of activity, a definite answer to the question is not so
readily obtained. As long as a nerve is within the normal body, the activity
of the nerve-fibre can only be estimated from the response of the cell which the
nerve-fibre excites, and there is such an organ only at one extremity of the fibre.
Efforts have been made to elucidate the pn^blem by attempting to unite the
central part of a cut sensory nerve with the perijiheral part of a divided motor
nerve, and observing, after the healing was complete, whether excitation of the

^ Bernstein : Archiv fur Anutomie unci Phijxiolocjir, 1882, p. 329.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 87

sensory nerve caused movements in the part ^uj)i)lietl by the niotcn- nerve,
Whh a simihir j)urpose Paul Bert made a well-known experiment, in which
he succeeded in bringing about union of the end of the tail of a rat witii
the tissues of the back, and found, when the union was complete, after the tail
was cut oif at its base, it was still capable of giving sensations of pain. Ail
such experiments fail to throw light on the problem, for we now know that the
]KM"ipheral part of the cut nerve dies, and the conduction power manifested
later is dependetit on new axis-cylinders which have grown down from the
central nerve-stump.

There is, however, an entirely different method of experimentation which
seems to prove that nerve-, like muscle-protoplasm, can conduct in both direc-
tions. This method is based on the fact that though nerve-fibres rarely branch
in the peripheral nerve-trunks on their way to an organ, they may divide very
freely after reaching it. Such branchings of fibres occur in muscle, and Kuehne^
found that if one of these branches was stimulated, the irritation passed up
the branch to the nerve-fibre and then down the other branches to tlic muscle.
For example, he split the end of the sartorius muscle of a
frog by a longitudinal cut, and then found on exciting one
of the slips that the other contracted (see Fig. 29). Since
cross conduction between striated muscle-fibres does not
occur, no other explanation presents itself. Perhaps a still
more striking example is to be found in an experiment of
Babuchin ^ on the nerve of the electric organ of an electric
fish, the Malopterurus. The organ, consisting of many
thousand plates, is supplied by a single enormous nerve-
fibre which after entering the organ divides very freely so ^^^ 29.-Kuehnes
as to supply every plate. In this case mechanical stirau- preparation of sarto-
lation of the central end of one of the cut branches of the conduct ion Ln?rye^
nerve sufficed to cause an electric discharge of the whole
organ. The irritation must have passed backward along the irritated branch
until the main trunk w^as reached and then in the usual direction down the
other branches to the electric plates.

Still another method is that which was employed by Du Bois-Reymond,^
on the fibres of the spinal nerve-roots. When a nerve is excited to action it
underiroes a change in electrical condition, and this change progresses along
the fibre at the same rate and in same direction as the nerve-impulse. This
electrical change, though entirely different from the nerve-impulse itself, can
be taken as an indication of the direction of movement of the process of
conduction. Du Bois-Reymond found that if he stimulated the afferent fibres
of the posterior spinal nerve-roots of the sciatic nerve of the frog, a " nega-
tive variation current," as the current resulting from the change in the elec-
trical condition of the nerve is called, passed down the nerve in a direction

1 Archivfilr Anatomie und Physiologie, 1859, p. 595.

2 Ibkl, 1877, p. 262.

» Thierische Electriciidt, 1849, Bd. ii. S. 587.

88 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

opposite to tliat whicli the noriual iiiij)ul.st' takes. Furtlier, it was louud
that if the sciatic nerve was excited, a negative variation current could be
detected in the anterior as well as the posterior roots. Normally the irritation
only passes up the posterior roots and down the anterior, for normally the
sensory fibres of the posterior roots are excited only at the })eripheral end and
the motor fibres of the anterior roots only at the central end. The ex|)eriment
showed both sensory and motor fibres to be capable of conducting in both
directions.

There is no doubt but that uerve-protoj)lasm can conduct in both directions,
although normally the nerve is stimulated only at one end and therefore con-
ducts in only one direction. This question is of considerable importance, not
only with reference to the possil)ility of the central nervous .system being
influenced by stimuli passing from the muscles, for instance, back along the
motor nerves, but more especially with reference to the spread of impulses
through the central nervous system, — a problem which will be considered later
with others of a similar character.

Rate of Conduction. — The activity of the conduction process varies
greatly in different tissues. The nerves of warm-blooded animals conduct more
rapidly than those of cold ; in a given animal the nerve-fibres conduct more
rapidly than muscle-fibres ; striated muscle conducts more rapidly than smooth
muscle; and even within a single cell different portions may transmit the ex-
citing process at different rates ; thus the jiiyoid substance of the contractile fibres
of one of the rhizopods conducts more rapidly than the less highly differen-
tiated protoplasm of the cell. In general, it may be said that, " the power to
conduct increases with increase of mobility and sensitiveness to external irri-
tants, a fact which reveals itself in the protozoa, by a comparison of the slowly
moving rhizopods with the lively flagellata and ciliata."* A study of different
classes of muscle-tissue supports this view.

(a) Rale of Conduction in Muscles. — The conduction process is invisible,
hence we estimate its strength and rate by its effects. It is most readily fol-
lowed in such mechanisms as muscle, where the conducting medium itself
undergoes a change of form as the exciting influence passes along it.

Rate of Transmission of Wave of Contraction. — If a muscle be excited to
action by an irritant applied to one end, it does not contract at once as a whole,
but the change of form starts at the point which is irritated and spreads thence
the length of the fibres. At the same time that the muscle shortens it
thickens, and under certain conditions the swelling of the muscle can be seen
to travel from the end which is excited to the further extremity. In the case
of normal, active, striated muscle, the rate at which the change of form spreads
over the muscle is far too rapid to be followed by the eye, and hence the
muscle ajipears to act as a whole. By suitable recording mechanisms, evidence
can be obtained of the rate at which the exciting influence and contraction ]iro-
cess pass along the fibre. Thus two levers can be so placed as to rest on the
two extremities of a muscle, at the same time that the free ends of the levers
^ Biedermann : FAektrophysiologie, 1895, Bd. i. S. 124.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 89

touch a revolving cylinder, the surface of wiiich is covered with paj)er black
eued with lampblack. If, when the cylinder is revolving, one end of the mus
cle be stimulated, the record will
show that the lever resting on that
part is the first to move, making
it evident that that part of the mus-
cle begins to thicken first, and that
the contraction does not begrin at
the further extremity of the mus-
cle until somewhat later. The re-
cord given in Figure 30 was ob-
tained in a similar experiment, but
one in which the contraction of
the muscle was registered by the
pince myographique and recording tambour of Marey (see Fig. 31).

Bernstein ^ measured the rate at which the irritating process is transmitted
along the muscle by recording the latent period, the time elapsing between the

Fk;. 30.— Rate of conduction of the fontraetion pro-
cess along a muscle, as shown by the difl'erence in the
time of thickening of the two extremities. The tuning-
fork waves record ^Jj second (after Marey).

Fig. 31.— Method of recording the rate of passage of the contraction process along a muscle (after
Marey). The movements of the muscle are recorded by means of air-transmission. The pince myo-
graphique consists of two light bars, the upper of which acts as a lever, moving freely on an axis sup-
ported by the lower. When the free end of the upper bar is raised, the other end presses down on a
delicate rubber membrane which covers a little metal capsule, which is carried on the corresponding
extremity of the lower bar. The capsule is in air-communic.ation, by a stiff-walled rubber tube, with
another capsule which is similarly covered with rubber membrane. A light lever is connected with the
membrane of the second tambour, and records its movements on the surface of a revolving cylinder.
The muscle is placed between the free ends of the bars of the pince myographique, and, when the muscle
thickens in contraction, it raises one end of the lever, depresses the membrane at the other end, and
drives air into the recording tambour, and thus, by automatically raising the writing-point, records its
change in form on the cylinder.

moment of irritation and the beginning of the contraction (see p. 101). A
lever was so connected with one end of the muscle as to record the instant that
it began to thicken. The muscle was stimulated in one experiment at the end
from which the record of its contraction was taken, and in another immediately
' Untersuchungen iiber die ekktrische Erregung von Muskeln und Nerven, 1871, p. 79.

90 AiX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

lolloping exjx'rinient it was stiiniilatcd near the uther en<l. 'Die distance
between the .stimulated points being- known, tlie rate of transmission was
reckoned from the difference in the hitent j)eriods. Jn his experiments he
found the rate of conduction in the semimembranosus of the frog to be from
3.2 to 4.4 meters per second. Hermann found the rate to be 2.7 meters for
the curarized sartorius of the frog. The results obtained l)y A bey and some
others are a little lower, but probably 3 meters per second can be accepted as
the average normal rate for frog's muscle.

Length of Wave. — By such experiments it becomes obvious that the con-
traction process passes over the muscle, in the form of a wave. In an experi-
ment, such as Bernstein's, in which the thickening of the muscle is recorded,
we can determine from the length of tlie curve written by the contracting
muscle how long the contraction remains at a given place. Knowing this,
and the rate at which the process passes along the fibre, we can estimate the
length of the contraction wave, just as we could reckon the length of a train
of cars if we knew how fast it was moving and how long it required to pass
a given station. Thus, if the contraction is found to last at a given point
on the muscle 0.1 second, and the rate at Avhich the contraction process is
travelling is 3000 millimeters per second, the length of the wave is 300 milli-
meters. According to Bernstein's determinations, the length of the wave of
contraction in a frog's striated muscle is from 198-380 millimeters. The
length of a striated muscle-fibre is, at the most, scarcely more than 40 milli-
meters, and normally the muscle-fibre is stimulated, not as in the above ex-
periment at one end, but near its centre, at the point wdiere the nerve joins
it ; the irritation process spreads along the fibre in both directions from this
point, and would pass over the distance 20 millimeters so quickly that practi-
cally the whole muscle-fibre would be in the same phase of contraction at the
same time.

Rate of Conduction in Different Kinds of Muscle. — The rate of conduction
varies veiy considerably in the muscles of different animals, and in different
kinds of muscle in the same animal, just as the contraction process itself dif-
fers in its rate and strength.

Meters per second.

Smooth muscle-fibres of the ureters of the rabbit . . . 0.02-0.03 (Engelmann).

Muscle of the heart-ventricle of the frog 0.1 (Waller).

Contractile substance of medusae 0.5 (Waller).

Neck-muscles of the turtle 0.1 -0.5 (Hermann and Abey).

Gracilis and semimembranosus of the frog .... 3.2 -4.4 (Bernstein).

Cruralis (red muscle) of the rabbit 3.4 ( Rollet).

Sterno-mastoid of the dog .3. -6 (Bernstein and Steiner).

Semimembranosus (white muscle) of the rabbit ... 5.4 -11.4 (Rollet).

Human muscle 10. -13 (Ilermannl.

(6) Rate of Conduction in Nerves. — Conduc-tivity is most highly developed
in the case of the nerve-fibre. The distances through which it acts and the
rapidity of the process excite our wonder. The process is accompanied by no
visible change in the nerve-fibre it.<elf, and the strength and rate have to be

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 91

estimated by tlie t'llect [)fi)ducc'd on llic organ wliidi tlie nerve excites to action,
or by the change which takes phice iu the electrical condition of" the nerve as
the wave of excitation sweeps over it.

Rate in Motor Nerves. — J lelniholtz was the first to measure the rate of con-
duction in nerves.* Originally he employed Pouillet's method for measuring
short intervals of time. The arrangement is illustrated in Figure 32. The
moment that the current in the primary coil of an induction apparatus was
broken and the nerve connected with the secondary coil received a shock,
a current was thrown into the coils of a galvanometer (see p. 136). An instant
after, the contraction of the muscle wiiich resulted from the stimulation of the
nerve broke the galvanometer circuit. The amount of deviation of the magnet
of the galvanometer varied with the time that the circuit remained closed, and
therefore could be taken as a measure of the interval elapsing between the
stinmlation of the nerve and the contraction of the muscle. The nerve was
excited in two succeeding experiments at two points, at a known distance apart,
and the difference in the time records obtained was the time required for the
transmission of the nerve-impulse through this distance.

Fig. 32.— Method of estimating rate of conduction in motor nerve of frog, as used by Helmholtz.
The horizontal bar a-b is supported on an axis in such a manner that when the contact is made at a it is
broken at b, therefore at the same instant a current is made in the galvanometer circuit and opened in
the primary circuit of the induction apparatus. When the muscle contracts, the galvanometer circuit
is broken at c. The nerve was stimulated in two successive experiments at d and e.

Later, Helmholtz devised a method of directly recording the contractions
of the muscle, and employed this to measure the rate of conduction in motor
nerves. He stimulated the nerve as near as possible to the muscle and re-
corded the contraction, then he stimulated the nerve as far as possible from the
muscle and again recorded the contraction. The difference in time between
the moment of excitation and the beginning of the contraction in the two
experiments was due to the difference in the distance that the nerve-impulse
had to pass in the two cases, and, this distance being known, the rate of con-
duction could be readily calculated. By this means he found the rate of trans-
mission in the motor nerves of the frog to be 27 meters per second. In
similar experiments upon men he recorded the contractions of the muscles of
the ball of the thumb, and noted the difference in the time of the beginning
of the contractions when the median nerve was excited through the skin at two
1 Helmholtz: Archiv fur Anatomic und Physiologie, 1850, p. 71-276; 1852, p. 199.

92 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

different places. Ho found the average normal rate lor man to he nhont .'i4
meters per second, a rate which is considerably (juicker than that of our
fastest express trains, but a million times less than the rate at which an electric
current is transmitted along a wire. These determinations are still accc|)tc(l
as approximately correct for human nerves, although they are found to varv
very considerably under different conditions, a high temperature and stront:;
irritation quickening the rate to 90 or more meters per second. Moreover,
considerable differences exist in nerves controlling different functions, even in
the same animal. Thus Chauveau gives the rate for the fibres of the vagus
nerve, which su})ply the rapidly contracting striated muscles of the larynx, as
66.7 meters ])cr second ; and the rate for vagus fibres, controlling the slower
smooth muscles of the €eso})hagus, ag 8.2 meters per second. The rate of
transmission in the non-medullated nerves of invertebrates appears to be still
slower ; the nerve for the claw-muscles of the lobster conducts at a rate of
from 6 to 12 meters per second, according as the temperature is high or low
(Fredericq and Vandervelde).

Rate in Sensory Nerves. — We have no definite knowledge of the rate of
conduction in sensory nerves. The attempt has been made to measure it, by
stimulating the sensory fibres of a nerve-trunk at two different points and
noting the difference in the time of the beginning of the resulting reflex acts;
or, in experiments on men, the difference in the length of the reaction time
has been taken as an indication. By reaction time is meant the interval which
elapses between the moment that the irritant is applied and the signal which is
made by the subject as soon as he feels the sensation. Oehl found the mean
normal rate of conduction in the sensory nerves of men to be 36.6 meters per
second.^ Dolley and Cattell,^ by employing the reaction-time method, found
the rate for the sensory fibres of the median nerve of one of them to be 21.1
meters per second, and for the other 49.5 meters per second, while the posterior
tibial nerve gave rates, for one of them 31.1 meters, and for the other 64.9
meters. They attribute these wide variations in part to differences in the
effectiveness of the irritant at different ])arts of the skin, but chiefly to difler-
ences in the activity of the central nervous processes involved in the act.

In spite of the great difficulty of getting definite measurements on men,
we may conclude from the work of these and other observers that the rate of
conduction in sensory fibres is about the same as in motor fibres ; in the case
of man about 35 meters ])er second.

Influences ■which Alter the Rate and Strength of the Conduction Pro-
cess.— (a) Effect of Death-processes. — Normally, the rate of conduction in mus-
cle-fibres is so rapid that the whole muscle appears to contract at the same time;
but there are certain conditions under which the transmission of the exciting
influence is very much slowed, or even altogether prevented, so that the stinui-
lation of a given part of the muscle results in a local swelling, or welt, limited
to the excited area. When a muscle is dying, the rate of conduction as well

' Oehl : Archives italiennes de Biologie, 1895, xxi., 3. p. 401.
* Psychological Review, New York and London, 1894, i. p. 159.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 93

as the rapidity of contraction is lessened. The muscles of warm-blooded ani-
mals exhiWit more strikiiit^ dilferemjes than tlu)se of cold-blooded, but both are
affe<!tcd by th( in. If a dying muscle be mechanically .stimulated, as by adirect
blow, a locali/t(l swcUino- develops at the place; and if the muscle be stroked
with a dull instrument, a wave of contraction maybe seen to follow the instru-
ment, the contraction beinji; quite strictly limited to the excited area, so that
one can write on the nuiscle. The strict localization of the contraction to the
irritated parts makes it evident that the nerves take no part in it, hence Schiff
called it an idio-muscular contraction, in distinction from the normal neuro-
muscular contraction. In the dying nerve as in the dying muscle the rate of
transmission is found to be slowed.

(6) Effeet of Mechanical Conditions. — The effect of pressure to lessen the
conduction-power of nerves is one which everyone has had occasion to demon-
strate on himself. For example, if pressure be brought to bear on the ulnar
nerve where it crosses the elbow, the region su})plied by the nerve becomes numb,
" goes to sleep," so to speak. It is noticeable that only a slightly greater
effort is required to move the muscles, at a time when no sensations are received
from the hand. For some unexplained reason the sensory nerve- fibres appear
to be less resistant than the motor. Gradually applied pressure may paralyze
the nerve without exciting it, but on the removal of the pressure the recovery
of function of the sensory fibres is accompanied by excitation processes, which
are felt as pricking sensations referred to the region supplied by the nerve. The
exact reason of the loss of functional power caused by pressure which is insuf-
ficient to produce permanent injury is not altogether clear. Stretching a nerve
may act to lessen, and if severe destroy, conductivity. It is in one sense another
way of applying pressure, since the calibre of the sheath is lessened and through
the fluids pressure is brought to bear on the axis-cylinder. Of course, if the
stretching were excessive, the nerve-fibres would be ruptured and degenerate.

(c) Effect of Tempei'oture on Conduction. — Helmholtz and Baxt found that
by cooling motor nerves they could lower the rate of conduction, and by heat-
ing them they could increase it even more markedly. By altering the tem-
perature of the motor nerves of man, they observed rates varying from 30 to
90 meters per second. The rate of the motor nerves of other animals is like-
wise greatly altered by heat and cold. This is true of the invertebrates as well
as the vertebrates ; the rate in the nerves of the claw-muscles of the lobster,
for example, changes from 6 to 12 meters per second as the temperature is
varied from 10° to 20° C. Sensory nerve-fibres are similarly influenced by
temperature. Oehl found by cooling and heating the nerves of men, variations
of from 34 to 96 meters per second, and in some cases even greater differences
were observed. Both the sympathetic and vagus nerve-fibres in the frog have
their influence on the heart-beat decreased by cold and increased by heat.^ The
favorable influence of heat on the conduction power seems common to all
nerves, but only within certain limits. The motor fibres of the sciatic of the
frog lose their power to conduct at 41° to 44° C, but may recover the power
^ Stewart: Journal of Physiology, 1891, vol. xii., No. 3, p. 22.

94 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

if quiokly cooled; if tlie temperature has reached 50° ('. oondin-tivilv is per-
manently lost.

Nerves of like function in diHerent animals may lose the power of cimkIuc-
tion at different temperatures. Thus the motor fibres of the sciatic nerve of
the dog cease to conduct at G° ('., those of the cat at o° to 3° C, of the frog at
about 0° C. The inhibitory fibres of the vagus nerve of the dog show dimin-
ished activity at 3° C, and bi'come Mliolly inactive at 0° C. ; the inhii)itorv
fibres of the vagus of the rabbit become inactive at 15° C.

Different kinds of fibres in the same nerve-trunk may be differentlv affected
by temperature, and this difference may be sufficiently marked in some cases to
be used as a means of distinguishing thcm.^ For example, the temperature
limits at which the vaso-coustrictor fibres of the sciatic of the cat can conduct
are 2°-3° C. to 47° C, while the limits for the dilator fibres are both lower
and higher than for the constrictors. If cold be a])plied to the sciatic nerve,
the fibres suj)plying the extensor muscles seem to fail before those M'hich in-
nervate the flexors.

Further, it has been observed that if cold be applied locally to a nerve, the
part affected loses its power to conduct, and acts as a block to the passage of
the nerve-impulse generated in another part of the nerve ; on the other hand,
the strength of an impulse is increased by passage through a region which has
been warmed. These facts remind us of the effect of heat and cold on the
activity of other forms of protoplasm and would find a comparatively easy
explanation were we content to look upon conduction as the result of chemical
change in the axis-cvlinder. The fact that conduction does not cause fatisrue
is opposed to such an explanation, and so we take refuge in the idea that heat
is favorable and cold unfavorable to molecular activity in general.

{d) Effect of Chemicals and Drugs. — The conductivity, like the irritabilitv,
of nerve and muscle is greatly influenced by anything which alters the chemical
constitution of active substance. In general it may be said that influences
w-hich increase or decrease the one have a similar effect upon the other, but
there are important exceptions to the rule. Thus the dii-ect application of
alcohol, ether, etc., may destroy the conductivity without greatly lessening the
irritabilitv, while carbon dioxide mav destrov the irritabilitv, thouirh leavinsr
the conductivity unimpaired.

(e) Effect of a Constant Battery Current. — A constant electric current, if al-
lowed to flow through a nerve or muscle, not only alters the irrital)ility but also
the conductivity. The change in the conductivity affects both the strength
and rate of the conduction process. Von BezokP found that weak and
medium currents have little effect on the conductivity, but that strong currents
completely destroy the power of the nerve to transmit the nerve-impulse. As
the strength of the current is increased the first effect is observed at the anode,
and shows itself in a slowing of the passage of the exciting imj)ulse. This
action is the greater the more of the nerve exposed to the current, the stronger

' Howell, Budgett, and Leonard : Journal of Physiology, vol. xvi., Nos. 3 and 4, 1894.
* Untersuchungeyi iiber die elektrische Erregung den Nerven und Muskeln, Leipzig, 1861.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 95

the curi'cnt, and the l(,)iiii('i' it is closed. The loss of conduction ])owcr is asso-
ciated with cliauges at the j)Iace wlicre the cun-cnt enters and where it leaves
the nerve ratlier than with alterations witiiin the intrapolar re<:;ion. Engclniann,
in his experiments on the smooth muscle-fibres ot" the ureter, saw a decline of
j)ower of conduction at tlie anode by weak currents, which when the strength
of the current was increased appeared also at the kathode ; the conductivity
was wholly lost at botii poles when the current was very strong. In the case
of a striated muscle, such as the sartorius of the frog, the kathode has been
found to become impassable after strong currents have flowed through a nuiscle
for a considerable time. The same is true of nerves.

It is not surprising that a current which can greatly decrease the ii-ritability
at the anode, and even inhibit a contraction which may be present wlien it is
applied, should be found to decrease the conductivity as well, but that the con-
ductivity should be decreased at the kathode, where the irritability is greatly
increased, was not to be expected. Rutherford ^ found that with M^eak currents
the rate of the conduction power at the kathode was increased rather than
diminished, and that it was only when strong currents acted a considerable
tin)e that the conduction power lessened at the kathode. Biedermann explains
this on the ground that the increased excitability at the kathode leads in the
muscle to a condition of latent contraction and therefore to fatigue, and that
it is this which lessens the conductivity. The lessened power to conduct con-
tinues at the kathode after the removal of the current. There is little doubt
that fatigue interferes with the conduction power of muscle, but this explana-
tion would hardly apply to nerves which are not known to fatigue at the point
of stimulation, i. e. if we limit the term fatigue to changes resulting from
physiological activity. Undoubtedly chemical and j)hysical alterations may
occur in nerves as a result of the passage of an electric current through them,
and it would seem as if the loss of conductivity which they show when sub-
jected to strong currents is to be accounted for by such changes.

The changes produced in the conductivity of nerves by strong currents
explain the failure of the closing of the ascending current and opening of the
descending current to irritate the muscle (see Pfliiger's law, p. 60). In the
former case the anode region of decreased conductivity intervenes between the
kathode, wdiere the closing stimulus is developed, and the muscle. In the
latter case the irritation developed at the anode, on the opening of the current,
is unable to pass the region of decreased conductivity which is formed at the
kathode, and which persists after the current is opened.

Practical A-pplkation of Alterations produced by Battery Currents, — The
alterations produced by strong battery currents in the irritability and conduc-
tivity of nerves and muscles may be made use of by the physician. If the
effect of only one pole is desired, it may be applied as a small electrode im-
mediately over the region to be influenced, while the other pole may be a large
electrode placed over some distant part of the body where there are no import-
ant organs. The size of the electrodes used determines the density of the
' Journal of Anatomy and Physiologic, 1867, vol. 2, p. 87.

96 AX AMEBICAX TEXT-BOOK OF PHYSIOLOGY.

current leaving or entering the Ixxly and consequently the intensity of its
action. The application of the anode to a region of increased excitai)ility, hy
decreasing the irritability, may for the tinie lessen irritation; on the other
hand the kathode may heighten the irritability of a region of decreased
excitability. The sending of a strong polarizing current through a motor
nerve, by lessening the conductivity, may prevent abnormal motor impulses
from reaching muscles, and so stop harmful '' cramps ; " or the sending of
such a current through a sensory nerve may, during the flow of the cur-
rent, keep painful impulses from reaching the central nervous system. In
applving a strong battery current to lessen irritability or conductivity it
must be remembered that the after-effect of such a current is increa.sed
irritability.

(/) Effect of Conduction. — Many experiments have been made in the hope
of detecting some form of chemical change as a result of conduction. The
nerve has been stimulated for many hours in succession with an electric cur-
rent, and then been examined with the utmost care to find whether there had
been an accumulation of some waste product, as carbon dioxide, or some other
acid body. The gray matter of the spinal cord, which is largely composed of
nerve-cells, is found to become acid as a result of activity,^ but this cannot be
found to be the case w^ith the white matter of the cord, which is chiefly made
up of nerve-fibres, nor has an acid reaction been obtained with certainty in
nerve-trunks.^

Not only has an attempt to discover this or other waste products which
might be supposed to result from chemical changes within the nerve-fibre
failed, but observers have been unable to obtain evidence of the liberation
of heat, which one would expect to find were the nerve-fibre the seat of chem-
ical changes during the process of conduction.^ Stewart writes : " Speaking
quite roughly, I think we may say that in the nerves of rabbits and dogs there
is not even a rise of temperature of the general nerve-sheath of -^ijy^ of a
degree during excitation."

Many experiments have been made to ascertain whether a nerve would
fatigue if made to conduct for a long time. Most of these have been made
upon motor nerves, the amount of contraction of the muscle, in response to a
definite stimulus applied to the nerve, being taken as an index of the activity
of the nerve. Since the muscle would fatigue if stimulated continuously for
a long time, various means have been employed to block the nerve-impulse
and prevent it from reaching the muscle, except at the beginning and end of
the experiment. This block has been established by passing a continuous
current through the nerve near the muscle, thus inducing an electrotonic

' Funke: Archivfiir Anatomie unci Physioloyie, 1859, p. 835. Ranke: Centralblatt fiir medicin-
ische Winsenschafl, 1868 and 1869.

^ Heidenhain: Studien aus dem physiologischen Institut zu Breslau, ix. p. 248; Centralblatt Jiir
Medicin, 1868, p. 833. Tigerstedt: "Studien iiber meclianische Nervenreizung," Acta Socielatis
Scienliarnm Fennmz, 1880, torn. xi.

^Helmholtz: ArcMv fiir Anatomie und Phymologie, 1848, p. 158. Heidenhain: op. cit.
RoUeston : Journal of Physiology, 1890, vol. xi. p. 208. Stewart : ihid., 1891, vol. xii. p. 424.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 9?

cluuit^o aud uun-conclucting aiva ; ' or the nerve-eiids were poisoned with
curare (see p. 41), and tiie nerve excited until the effect of the dru«r wore off",
and the nerve-impulse was able to reach the muscle;^ or the part of the nerve
near the muscle was temporarily deprived of its conducting power by an
anaesthetic, such as ether. Another method of experimentation consisted in
using the negative variation current of a nerve (see p. 140) as an indication
of its activity, the presence of the current being observed with the galvanom-
eter.^ Other experimenters have examined the vagus nerve, to see if after
long-continued stimulation it was still capable of inhibiting the heart, the
effect of the stimulation being prevented from acting on the heart muscle
during the experiment by atropin/ or by cold, applied locally to the nerve.*
Still another method was to study the effect of long-continued stimulation on
the secretory fibres of the chorda tympani, the exciting impulse being kept
from the gland-cells by atropin.*' Most of these experiments have yielded nega-
tive results, aud it is doubtful whether nerves are fatigued by the process of
conduction.

These results, of course, do not show that the nerve-fibres can live and
function independently of chemical changes. As has been said, nerves lose their
irritability in time if deprived of the normal blood-supply, and undoubtedly
they are, like all protoplasmic structures, continually the seat of metabolic
processes. The normal function of the nerve, however, the conduction of the
nerve-impulse, seems to take place without any marked chemical change.

Nature of the Conduction Process. — There have been a great many
views as to the nature of the conduction process, one after the other being
advanced and combated as physiological facts bearing on the question have
been accumulated. It has been suggested that the whole nerve moved like a
bell-rope ; that the nerve w'as a tube, and that a biting acid flowed along it ;
that the nerve contained an elastic fluid which was thrown into oscillations ;
that it conducted an electric current, like a wire; that it was composed of
definitely arranged electro-motor molecules which exerted an electro-dynamic
effect on each other ; that it was made up of chemical })articles, which like
the particles of powder in a fuse, underwent an explosive change, each in
turn exciting its neighbor ; that the irritant caused a chemical change, which
produced an alteration of the electrical condition of such a nature as to excite
neighboring parts to chemical change aud thereby to electrical change, and
so alternating chemical and electrical changes progressed along the fibre in the
form of a w^ave ; finally, tliat the molecules of the nerve-substance underwent
a form of physical vibration analogous to that assumed for light.

^ Bernstein: Pfliicjei-'s Archiv, \^11, xv. p. 289. Wedenski : CentralblaU fur die medicinischen
Wi'-semrhaften, 1884.

'^ Bowditch : Journal of Phi/siolof/y, 1885, vi. p. 133.

^ Wedenski : loc. cit. Maschek : Sitzungsberichte dcr Wiener Academie, 1887, Bd. xcv. Abthl. 3.

* Szana: Archiv fiir Anatnmie und Physiologie, 1891, p. 315.

* Howell, Budgett, and Leonard: Journal of Physiolo(/ij, 1894, xvi. p. 312.
^ Lambert : Comptes-rendus de la Societe de Biolofjie, 1894, p. 511.

7

98 ^l.V AMERICAN TEXT- BOOK OF PHYSIOLOGY.

A discussion of these different theories, none ot" whicii can be regarded
as entirely satisfactory, cannot be entered upon here.

D. Contractility.

Contractility is the property of protoplasm by virtue of which the cell is
able to change its form when subjected to certain external influences called
irritants, or when excited by certain changes occurring within itself. The
change of form does not involve a change of size. The contraction is the
result of a change in the position of the more fluid parts of the cell-protoplasm,
and the effect is to cause the cell to approach a sjihcrical sha|>e. In the case of
an amwba, for instance, excitation causes a drawing in of the pseudopods, and
as the material in them flows back into the cell the body of the cell expands
and acquires a globular form. In the simpler forms of contractile protoplasm
the movement does not appear to be limited to any special direction, but in the
case of the highly difJ'erentiated forms, such as muscle, both contraction and
relaxation occur on definite lines.

When a muscle is excited to action, energy is liberated through chemical
change of certain constituents of the muscle-substance, and this energy in some
unknown way causes a rearrangement of the finest particles of the muscle-sub-
stance, and the consequent change of form ])eculiar to the contracted stjite.
When the irritation ceases and relaxation takes place, there is a sudden return
of the muscle-substance to the position of rest, either because of elastic recoil or
of some other force at work within the muscle itself. That the recovery of
the elongated form peculiar to the resting muscle is not dependent on external
influences is evidenced by the fact that a muscle floating on mercury, and
subjected to no extending force, will on the cessation of irritation assume its
resting form. The relaxation no less than the contraction must be. regarded
as an active process, but on account of their flexibility muscle-fibres are incap-
able of exerting an expansion force, therefore cannot by relaxing do external
work.

Both the histological structure and physiological action of the striated mus-
cles which move the bones show them to be the most highly differentiated, the
most perfect form of contractile tissue. It is by means of these structures that
the higher animals perform all those voluntary movements by which they change
their position with reference to external objects, acquire nourishment, protect
themselves, and influence their surroundings. Aii exact knowledge of the
method of action of these mechanisms and the influences which affect them is
therefore of the greatest importance to us.

1. Simple Muscle -Contractions Studied by the Graphic Method. —
When a mu.-icle makes a single contraction, in respon.se to an electric shock or
other irritant, the change of form is too rapid to be followed by the eye. To
acquire an adequate idea of the character of the movement it is necessary that
we should obtain a continuous record of the alterations in shajie which it un-
dergoes. This can be done by connecting the muscle with a mechanism which
enables it automatically to record its movements.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 99

If one moves a pencil vertically up and down on a piece of paper, a straight
line is written ; if while the vertical movements are continued the paper be
drawn along at a regular rate in a direction at right angles to the move-
ment of the pencil, a curve will be traced. If the paper be moved at a regular
rate, the shape of the curve will depend on the rate at which the pencil is
moved, and, if the speed of the paper be known, the rate of movement of the
pencil can be readily determined. This princi})le is employed in recording the
movements of muscles. The muscle is connected with a mechanism which
rises and falls as the muscle contracts and relaxes, and records the movement
of the muscle on a surface which passes by the writing-point at a regular
speed (see Fig. 35) ; such a record is called a myogram.

The Myograph. — The writing mechanism, together with the apparatus
which moves the surface on which the record of the movement of a contracting
muscle is taken is called a myograph. The writing mechanism has usuallv the
form of a light, stitf lever, which moves very easily on a delicate axis ; the
lever is so connected w^ith the muscle as to magnify its movements. The point
of the lever rests very lightly against a glass plate, or surface covered with
glazed paper, which is coated with a thin layer of soot. The point of the lever
scratches oflP the soot, and the movements are recorded as
a very fine white line. At the close of the experiment
the record is made permanent by passing it through a
thin alcoholic solution of shellac. The recording surface
in some cases is in the form of a plate, in others of a cyl-
inder, and is moved at a regular rate by a spring, pendu-
lum, falling weight, clockwork, electric or other motor.^

The record which is traced with the myograph lever
by the muscle has the form- of a curve. From the height
of the curve we can readily estimate the amount that
the muscle changes its length, but in order to accu-
rately determine the duration of. the contraction process
and the time relations of different parts of the curve,
it is necessary to know the exact rate at which the
recording surface is moving. The shape of the curve
drawn by the muscle will depend very largely on the
rate of the movement of the surface on which the record
is taken. This is illustrated by the four records repro-
duced in Figure 33. These were all taken from the
same muscle within a few minutes of each other and
under exactly the same conditions, except that in the
successive experiments the speed of the drum on which
the record was traced was increased.

A glance at these records shows that a knowledge
of the rate of movement of the surface on which the record is taken is indis-
pensable to an understanding of the time relations of the different parts of the
^ See O. Langendorff; Physiologische Graphik, Franz Deuticke, Leipzig, 1891.

Fig. 33.— Records of four
contractions of a gas-
trocnemius muscle of a
frog: a, recording sur-
face at rest; b, surface
moving slowly ; c, sur-
face moving more rapidly ;
d, surface moving even
faster.

100

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

curve written by the muscle. The rate of movement of the reconlin*; surface
can be registered by an instrument called a chronograph.

The chronograph [g, Fig. 34), consists of one or two coils of wire wound
round cores of soft iron, and a little lever bearing a strip of iron, which is
attracted to the soft-iron cores whenever they are magnetized by an elec-
tric current flowing through the coils of wire about them. When the current
ceases to flow and the iron cejises to be magnetized, a spring draws the lever
away from the iron. Many of the instruments employed for this purpose are

rfr

Fig. 34.— Method of interrupting an electric circuit by a tuning-fork, and of recording the interrup-
tions by means of an electro-magnet: a, battery: b, tuning-fork, with platinum wire at the extremity
of one of its arms, which with each vibration of the fork makes and breaks contact with the mercury
in the cup below: c, mercury cup: c, electro-magnet which keeps the fork vibrating; ^, chronograph.
The current from the battery a, passes to the fork h, then, by way of the platinum wire, to the mercury
in cup c, then to the binding-post d, where it divides, a part going through the coils of wire of the
chronograph g, and thence to the binding-post /, the rest through the coil of wire of electro-magnet
e, and then to the post/, from which the united threads of current flow back to the battery. The
electro-magnet e keeps the fork in vibration, because when the platinum wire enters the mercury
at c, the circuit is completed and the electro-magnet magnetizes its soft-iron core, which attract.^ the
arms of the fork, and thus draws the wire out of the mercury and so breaks the circuit. When the
current is broken the fork, being released, springs back, dips the wire into the mercury, and by
closing the circuit causes the process to be repeated.

very delicate, and are capable of responding to ver^' rapid interruptions of the
current. The electric current is made and broken at regular intervals by a clock,
tuning-fork (6, Fig. 34), or other interrupting mechanism, and the lever of the
chronograph, which has a writing-point at its free end, moves correspondingly

a

Ir

C c

f.

rv,.-V.,VA.-A-..V..VtfJtfJ-/';'J-/AW«

wwwwwJ

hN\tj\t\t\rN\tjv\i

^^^w^^^^^w^^A^^^WA^^^^^^; y

Fig. 35. — Myogram from gastrocnemiii? muscle of frog ; beneath, ihe time is recorded in 0.005 second :
a, moment of excitation ; b, beginning of contraction ; c, height of contraction ; d, end of contraction.

and traces an interrupted line on the recording surface of the myograph (see
Fig. 35). The space between the succeeding jogs marked by the chronograph
lever is a measure of the amount of the surface which passed the point of the
chronograph in one second, ^^ second, or jl^ second, as the ca.se may be.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 101

Myogram of Simple Muscle-contraction. — 'J'lic rate of the movement of the
muscle during every part of its contraction can he loadily determined hv com-
paring the record it has (h'awii witli that of the chronograph.

Figure 35 is the repnuUK'tion of a single contraction of a gastrocnemius
muscle of a frog. The rise of the curve shows that the contraction began
comparatively slowly, soon became very rapid, but toward its close was again
gradual ; the relaxation began almost immediately, and took a similar course,
though occupying a somewhat longer time. The electric current which
actuated the chronograph was made and broken by a tuning-fork which
made 200 complete vibrations per second, therefore the s]>aces between the
succeeding peaks of the chronograph curve each represents 0.005 second. A
comparison of the movements of the muscle with the tuning-fork curve
reveals that about yfg- second elapsed between the point />, at which the muscle
curve began to rise, and c, the point at which the full height of the contraction
was reached, and that about ^^ second was occupied by the return of the
muscle curve from c to point d, at the level from which it started. The muscle
employed in this experiment was slightly fatigued, and the movements were
in consequence a little slower than normal.

Latent Period. — The time that elapses between the moment that a stim-
ulus reaches a muscle and the instant the muscle begins to change its form is
called the latent period. In the experiment recorded in Fig. 35 the muscle
received the shock at the point a on the curve, but the lever did not begin to
rise until the point h was reached. The latent jieriod as recorded in this ex-
periment was about 0.006 second. The latent period and the time relations of the
muscle-curve were first measured by Helmholtz, Avho introduced the use of the
myograpli.^ Helmholtz concluded from his experiments that the latent period
for a frog's muscle is about y^ second, that the rise of the curve occupies
about yI^, and the fall about -^^ second, the total time occupying about -^
second. These rates (^an be considered approximately correct, excepting for
the latent period, which has been found by more accurate methods to be con-
siderably shorter. Tigerstedt connected a curarized frog's muscle with a myo-
graph lever, which was so arranged as to break an electric contact at the
instant that the muscle made the slightest movement ; the break in the electric
circuit was recorded on a rapidly revolving drum, by an electro-magnet similar
to the chronograph. By this means he found the latent period of a frog's
muscle may be as short as 0.004 second. Tigerstedt^ did not regard this as
the true latent ])eriod, however ; he expressed the belief that the muscle proto-
plasm must have begun to respond to the excitation much sooner than this.
The contraction of the whole muscle is the result of a shortening of each of the
myriad of light and dark disks of which each of the muscle-fibres is composed
(see Fig. 36). The distance to be traversed by the finest particles of muscle-
substance is microscopic, hence the raj^idity of the change of form of the M^hole
muscle. Even such a change would require time, however, and it is probable

* Archiv fur Anatomie und Pltysiologie, 1850, p. 308.
^llnd., 1885, Suppl. Bd., p. 111.

102 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tliat the imiscle protoplasm becomes active before any outward manifestation
occurs. Tliat this view is correct has been proved by electrical observations.

When mnsclt' protoplasm jiasst'S from a state of rest to one of acti(»n it
undergoes an alteration in electrical condition. This change can be detected by
the galvanometer (Fig. 58, p. 135) or by the capillary electrometer (Fig. 59,
p. 136). Burdon Sanderson^ has foinid that by the aid of the latter instru-
ment an alteration of the electrical condition of the muscle of a frog can be
detected within 0.0025 second after the stimulus has been applied to it. Since
some slight interval of time nuist have been lost even by this delicate method,
it would seem that muscle protoplasm begins to be active at the instant it is
stimulated.

According to this view, muscle-substance has no latent period ; neverthe-
less we can still speak of the latent period of the muscle as a whole. It will
be necessary, however, to distinguish between the electrical latent j)criod and
the mechanical latent period : by the former we mean the time which ela])ses
between the moment of excitation and the first evidence obtainable of a change
in the electrical condition of the muscle ; by the latter, the time between exci-
tation and the earliest evidence of movement which can be observed. In the
case of the striated muscles of a frog the electrical latent period is about 0.0025
second, and the mechanical about 0.004 second. Mendelssohn^ estimated the
mechanical latent period of the muscles of man to be about 0.008 second.
There can be little doubt, however, that this figure is too large.

Bernstein^ found that if a normal frog's muscle be excited indirectly,
by the stimulation of its nerve, the mechanical latent period is somewhat
longer than when it is directly excited. Of course a certain length of time is
required to transmit the excitation through the length of nerve intervening
between the point stimulated and the muscle fibres. If this time be deducted,
there still remains a balance of about 0.003 second, which can only be ac-
counted for on the assumption that the motor nerve end-plates require time to
excite the muscle-fibres. The motor end-plates are therefore said to have a
latent period of 0.002-0.003 second.

The latent period, and the time required for the rise and fall of the myo-
graph curve, are found to be very different not only for the nmscles of differ-
ent animals, but even for the different muscles of the same animal. Moreover,
the time relations of the contraction process in each muscle are altered by a
great variety of conditions.

Before considering the effect of various influences upon the character of the
muscle contraction, let us give a glance at the finer structure of the muscle,
and the change of form which the microscopic segments of the mnsclc-fibre
undergo during contraction.

2. Optical Properties of Striated Muscle during Rest and Action. —
An ordinary striated muscle is composed of a great number of very long

* Centralblatl fur Physiologic, July 5, 1890, vol. iv.

* Archiv de Physiologie, 1880, 2d series, vol. vii. p. 197.

' TJntertuchungen iiber den Erregungsvorgang im Nerven und MiisktlsifStem, 1871.

GENERAL PHYSIOLOGY OP MUSCLE AND NERVE.

103

muscle-cells, fibres as they are called, arranged side by side in hiindles, the
whole being bound together by a fine connective-tissue network. Kik li muscle-
fibre consists of a very delicate elastic sheath, the sarcolennna, wiiich is com-
pletely filled with the muscle-substance. Under the microscope the fibres are
seen to be striped by alternating light and dark transverse bands, and on (bcus-
ing, the difference in textiu'c which this suggests is found to extend through
the fibres, /. c. the light and dark bands correspond to little disks of substances
of diifereut degrees of translucency. More careful study with a high power,
shows under certain circumstances other

cross markings (see Fig. 36, ^1), the light ^ -^

band is found to be divided in halves by
a fine dark line, Z, and parallel to it is z-
another faint dark line, n, while the dark q
baud, Q, is found to have a barely per- ^I
ceptible light line in its centre.

The fine dark lines, Z, which run
through the middle of the light bauds,
were for a time supposed to be caused by
delicate membranes (Krause's membrane),
which were thought to stretch through o
the fibre and to divide it into a series of q..

little compartments, each of which had .

exactly the same construction. Kuehne

chanced to see a minute nematode worm fig. 36— schema of histological structure of

•I • "J 1 ui 1 muscle-fibre: ^, resting fibre as seen bv ordinary

moving along inside a muscle-fibre, and ug^t; U. resting fibre seen by polarized light; c,
observed that it encountered no obstrUC- contracting fibre by ordinary light ; D, contract-
ing fibre by polarized light.

tion, such as a series of membranes, how-
ever delicate, would have caused. As it moved, the particles of muscle-sub-
stance closed in behind it, the original structure being completely recovered.
This observation did away with the view that the fibre is divided into com-
partments, but the arrangement shown in Figure 36, A, repeats itself through-
out the length of the fibre and indicates that it is made up of a vast succession
of like parts.

Muscle-substance consists of two materials, which differ in their optical
peculiarities and their reaction to stains. If a muscle-fibre be examined by
polarized light, it is found that there is a substance in the dark bands which
refracts the light doubly, is anisotropic, while the bulk of the substance in the
light bands is singly refractive, isotropic {B, Fig. 36). The anisotropic sub-
stance is found to stain with haematoxylin, while the isotropic is not thus
stained ; on the other hand, the isotropic substance is often colored by chloride
of gold, which is not the case with the anisotropic. By means of these reac-
tions it has been possible to ascertain something as to the arrangement of these
substances within the muscle-fibre, though the ultimate structure has not been
definitely decided. It appears that the isotropic material is the sarcoplasma,
which is distributed throughout the fibre and holds imbedded within it the

104 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

particles of the anisotropic substance, these particles liaviug a definite arrange-
ment. Striate<^l inuscle-fihros jircst'iit not only cross markings, but under
favorable conditions longitudinal striations, these being most evident in the
dark bands. These longitudinal striations are looked upon with great interest
as indicating that the particles of anisotropic material are arranged in long
chains as incomplete fibrillae. According to this view the muscle-fibre is com-
j)Ose(i of semifluid isotropic substance, in which are the j)articles of anisotropic
material, arranged to form vast numbers of parallel fibrillae of like structure,
and so placed as to give the effect of transverse disks (Z, n, Q, Fig. 36).

AVhen a striated muscle contracts, each of its fibres becomes shorter and
thicker, and the same is true of the dark and light disks of which the fibres
are composed. If we examine a muscle-fibre which has been fixed by osmic
acid at a time when part of it was contracting, we see that in the contracted
part the light and dark bauds have both become shorter and wider, but that
the volume of the dark bands (Q, Fig. 36, C) has increased at the expense of
the light bands.

Further, the dark bands are seen to be lighter and the light bands darker
in the contracted part, while examination with polarized light shows that
though the anisotropic substance does not seem to have changed its position,
(Fig. 36, D), the original dark bands have less and the lighter bands greater
refractive power. These appearances would seem to be explained by Engel-
mann's view that contraction is the result of imbibition of tiie more fluid part
of the sarcoplasm by the anisotropic substance ; the cause of the imbibition is
the liberation of heat by chemical changes which occur at the instant the
muscle is excited. Eno-elmann ^ has shown that dead substance containing:
anisotropic material, such as a catgut string, can change its form, by imbi-
bition of fluid under the influence of heat, and give a contraction curve in
many respects similar to that to be obtained from muscle. This theory of
the method of action of the muscle-substance, though attractive, can be
accepted only as a working hypothesis, and is not to be regarded as proved.
Various other theories have been advanced to explain the connection between
the chemical changes which undoubtedly occur during contraction and the
alteration of form, but none have been generally accepted. Enough has been
said to show that the contraction of the muscle as a whole is the result of
a change in the minute elements of the fibrilla", and that the various condi-
tions which influence the activity of the process of contraction must act chiefly
through alterations produced in these little mechanisms.

3. Elasticity of Muscle. — The elasticity and extensibility of muscle are
of great importance, for by every form of muscular work tlie muscle is sub-
jected to a stretching force. Elasticity of muscle is the property by virtue of
which it tends to preserve its normal form, and to resist any external force
w'hich would act to alter that form. The shape of muscles may be altered by
pressure, but the change is one of form and not of bulk ; since muscles are
largely made up of fluid, their compressibility is inconsiderable. The elasticity

* Ueber den Ursprung der Muskelkraft, Leipzig, 1R93.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 105

of muscles is slight hiit (jiiito perfect, by which is meant that a muscle yields
reiidily to a stretching force, but on the removal of the force quickly recovers
its normal form. Most of the experiments upon muscle elasticity have been
made after the muscle had been removed from the body, hence under abnormal
conditions. Under these circumstances it is found that if a number of equal
weights be added to a suspended muscle, one after the other, the extension pro-
duce<l is not, like that of an inorganic body
such as steel spring, proportional to the weight,
but each weight stretches the nuiscle less than
the preceding. If the weights be removed
in succession, an elastic recovery is observed,
which, although considerable, is incomplete.
li the change in the length be recorded by
a lever attached to the muscle, the surface
being moved along just the same amount after
each weight is added or removed, a curve is
obtained such as is shown in Fig. 37, h.
Above this is a record taken in a similar way
from a piece of rubber (a). The rubber resem-
bles a steel spring in that equal weights stretch
it to like amounts, but the elastic recovery,
though more complete than that of the muscle,
is imperfect.

In such an experiment it is found that the
full effect of adding the weights, or removing
them from the muscle, does not occur immedi-
ately, but when a weight is added there is a
gradual yielding to the stretching force, and, on the removal of a weight, a
gradual I'ecovery of form under the influence of the elasticity. This slow
after-action makes it difficult to say just what is to be considered the proper
curve of elasticity of muscle, especially as the physiological condition of the
muscle is always changing. The elasticity of muscles is dependent on normal
physiological conditions, and is altered by death, or by anything which causes
a change in the normal constitution of the muscles, as the cutting off of the
blood-supply. The dead muscle is less extensible and less elastic than the
normal living muscle. Heating, within limits, increases, and cooling decreases
the elasticity. Contraction is accompanied by increased extensibility, i. e.
lessened elasticity, and the changes caused by fatigue lessen the elasticity. It
is interesting to note in this connection that the elasticity is decreased by weak
acid solutions and increased by weak alkaline solutions (Brunton and Cash).^

The elasticity of a muscle within the normal body is witiiout doubt more

perfect than that of an isolated muscle, and suffices to preserve the tension of

the muscle under all ordinary conditions. The muscles are attached to the

bones under elastic tension, as is shown by the separation of the ends in case

^ Philosophical Transactions, 1884, p. 197.

Fig. 37. — a, Curve of extensibility
and elasticity of a rubber band ; 6, curve
of extensibility and elasticity of a sar-
torius muscle of a frog. The weights
employed were 10 grams each. The
same length of time was allowed to
pass between the adding and subtract-
ing of the weights.

106 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a muscle be cut. This elastic tension is veiy l:iv<)ral)le to tlic acti(jn of (he
muscle, as it takes up the slack and ensures that at the instant tiic muscle
begins to shorten the effect of the change shall be (juickly inij)artccl to the
bones which it is its function to move. The extensibility of the nniscle is
a great protection, lessening the danger of ruj)ture of the nmscle-fibres and
ligaments, and the injury of joints Avhen tiie nuiscles contract suddenly and
vigorously, or when they are subjected to sudden strains by external foi-ces.
The importance of extensibility and elasticity to muscles which act as antag-
onists is evident, ^yhen a muscle suddenly contracts against a resisting ft)rce
such as the inertia of a heavy weight, the energy of contraction, wdiich puts the
muscle on the stretch, is temporarily stored in it as elastic force, and as the
weight yields to the strain, is given out again ; thus the effect of the contrac-
tion force is tempered, the application of the suddenly developed energy being
prolonged and softened.

4. Influences which Afi'ect the Activity and Character of the Con-
traction.— ((/) The Character of the Musdc. — Attention has been called to
the fact that irritability and conductivity may be different not only in different
kinds of muscle-tissue, and in muscles of different animals, but even in similar
kinds of muscle-tissue in the different muscles of the same animal; the same
may be said of contractility. Although irritability, conductivity, and contrac-
tility are to be regarded as different properties of muscle protoplasm, they are
usually found to be developed to a corresponding degree in each muscle.
Those forms of muscle which require for their excitation irritants of slow and
prolonged action, are found to conduct slowly and to make slow and long-
drawn-out contractions, and muscles which are excited by irritants acting
rapidly and briefly are noted for the quickness with which they contract
and relax.

Differences in the activity of the contraction process are made evident
by the duration of single contractions of different forms of muscle-tissue.
The duration of the contraction of the striated muscles of different animals
differs greatly, e. g. of the frog -^ second, of the turtle 1 second, of certain
insects only ^^ second. Even muscles of apparently the same kind in the

Ppctornlis major

Omohyoid //[^\ — ..(^intvUh ^^^^

i ••••'•-•«•■•'••• 1

Fig. 38.— Records of maximal isotonic contractions of four diflerent muscles from a turtle, each
weighted with 30 grams : Pectoralis major ; omohyoid ; gracilis ; palmaris. The dots mark i second, and
the longer marks seconds (after Cash). 2

same animal exhibit different degrees of activity. Cash ^ reports the following
differences in the duration of the contractions of different striated muscles of
a frog in fractions of a second: Hyoglo.'^sus, 0.205; rectus abdominis, 0.170;
gastrocnemius, 0.120 ; semimembranosus, 0.108 ; triceps femoris, 0.104. Sim-
» Arcldv fur Anatntnie und Physiologic, 1880, suppl. VA., p. 147. * Op. cit., p. 157.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 107

ilar differences are found to exi.st between different muscles in other aninuds
— in tlio turtle, for instance, as is shown by tlic niyoj^ranis in Fig. 38.

It is interesting; to eoiniect the rate of the contraction ])rocess in different
muscles with their function. The omohyoid muscle of the turtle is capable of
comparatively rapid contractions, and the action of this muscle is to draw back
the head beneath the i)rojecting shell; the pectoralis, on the other hand,
although strong, contracts slowly ; it is a muscle of locomotion and has to
move the heavy body of the animal. Unstriated muscles, which are remark-
able for the slowness and the duration of their contractions, are found chiefly
in the walls of the intestines, blood-vessels, etc., which require to remain in a
state of continued contraction for considerable periods and do not need to alter
rapidly. It is the business of the heart-muscle to drive fluids often against
considerable resistance, and a strong, not too rapid, slightly prolonged contrac-
tion, such as is peculiar to it, would be best adapted to its function. The bulk
of the muscles of ihQ bodies of warm-blooded animals are capable of rapid
contraction and relaxation, but the rate normal to the muscle is found to vary
with the form of work to be done. The muscles which control the vocal
organs, for instance., have a very rapid rate of relaxation as well as of con-
traction. The muscles which move the bones appear to have different rates
of contraction and relaxation according to the weight of the parts to be moved ;
those which control the lighter parts, as the hand, being capable of rapid con-
tractions, while those which have to overcome the inertia of heavier parts, to
which rapidity of action would be a positive disadvantage, react more slowly.
In general, where rapid, brief, and vigorous contractions are required, pale
striated muscles are found; where more prolonged contractions are needed,
red striated muscles occur. The accompanying myograms (Fig. 39) illustrate

Fig. 39.— .4, maximal contractions of the gastrocnemius medialis of the rabbit (pale muscle), weighted
■with 50, 100, 300, and 500 grams ; B, maximal contractions of the soleus of the rabbit (red muscle), weighted
with 50, 100, and 200 grams (after Cash).

the difference in the rate of contractions of pale and red striated muscles of
the rabbit.

Pale and red striated fibres are found united in the same muscle in certain
instances, and in these cases it is supposed that the former, which are capable

108

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of" very rapid and powerful but short-lived contractions start the moveiueiit,
while the slower red muscles continue it.

(6) Effect of Tension on the Extent and Course of the Contraction. — As we
have seen, the rate of the contraction of an ordinary striated muscle is much
too rapid to be followed by the eye, and to study the course of the chan<re in
form it is necessary to employ some i<ind of recordini; mechanism. Every
mechanical device for recording the movements of the muscle has inertia, and,
if given motion, acquires momentum. Both of these factors would tend to
alter the shape of the record, and the more, the greater the weight of the re-
cording apparatus.

A weight, or tension, can be applied to a muscle in various ways, and the
form of the contraction will be correspondingly changed. If a muscle is made
to work with a considerable weight hanging on it, we speak of it as loaded ;
if the weight be connected with the muscle, but so supported that it does
not pull on it until the muscle begins to siiorten, the muscle is said to be after-
loaded ; if the weight is the same throughout the contraction, as when the
muscle has only to lift a light weight, ajiplied close to the axis of the lever, the
contraction is said to be isotonic ; if on the other hand the contracting muscle
is made to work against a strong s]^ring, so that it can shorten very little, i. e.
has almost the same length throughout the contraction, the contraction is said

to be isometric. The shape of the
myogram recorded as a residt of
the same stimulus would evidently
be very different in these four
cases. The effect of a weight to
alter the myogram is illustrated in
the record given in Figure 40.
Increasing the weight prolonged
the latent period, and lessened the
height and duration of the con-
tractions.

The alterations liable to occur
in the form of the myogram as a
result of the mechanical condi-
tions under wiiicli the work is
done are —

(1) Prolongation of fJie latent
2')eriod. There can be no move-
ment of the lever until the inertia
of the weight has been overcome,
and the first effect of the contrac-
tion is to stretch the muscle, a
part of the energy of contraction being changed to elastic force, which on the
recoil assists in raising the weight.

(2) Alteration in the shape of the ascending limb of the myograph curve. The

Fig. 40— Effect of the weight upon the form of tlie
myogram. The gastrociieinius muscle of a frog excited
by maximal breaking induction shocks five times, tlie
weight being increased after each contraction, and in the
intervals supported at the normal resting length of the
muscle; i.e. the muscle was after-loaded: 1, muscle
weighted only with very liglit lever; 2, weight five
grams ; 3, ten grams ; 4, twenty-five grams ; 5, fifty grams.
The perpendicular line marks the moment of excitation.
The time is recorded at the bottom of the curve by a
chronograph, actuated by a tuning-fork vibrating r>0 times
per second.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 109

weight will either lessen the rate at which the curve rises and decrease the
height, or, if the weight be not great, it may acquire a velocity from the energy
suddenly imparted to it by the muscle, which will carry the record higher than
the absolute contraction of the muscle.

(3) lliefdll of the curve may be altered. The weight, suddenly i'reed by the
rapidly relaxing muscle, may acquire a velocity in falling which will stretch
the muscle-tissue, carry the record lower than the actual relaxation of the
muscle would warrant, and lead to the development of artificial elastic after-
oscillations.

These sources of error can be in part overcome by the employment of an
exceedingly light, stiif writing-lever, and by bringing the necessary tension on
the muscle by placing the extending weight very near the axis of the lever, so
that it shall move but little and hence acquire little velocity.

(c) Effect of Rate of Excitation on Height and Form of Muscular Contrac-
tion.— If a muscle be excited a number of times by exactly the same irritant
and under the same external conditions, the amount and course of each of
the contractions should be exactly the same, provided the condition of the
muscle itself remains the same. The condition of the muscle is, however,
altered every time it is excited to contraction, and each contraction leaves
behind it an after-effect. This altered condition is not permanent ; as we have
seen, increased katabolism is accompanied by increased anabolism, and, if the
excitations do not follow each other too rapidly, the katabolic changes occur-
ring in contraction are compensated for by anabolic changes during the suc-
ceeding interval of rest. Normally, a muscle, under the restorative influence
of the blood, rapidly recovers from the alterations produced by the contraction
process, and, therefore, if not excited too frequently, will give, other things
being equal, the same response each time it is called into action. The best
illustration of this is the heart, which continues to beat at a regular rate
throughout the life of the individual. Tiegel found that one of the skeletal
muscles of a frog, while in the normal body, can make more than a thousand
contractions in response to artificial stimuli without showing fatigue; finally
the effect of the work shows itself in a lessening of the power to contract.
Every muscle contains a surplus of energy-holding compounds and also sub-
stances capable of neutralizing waste products, and even a muscle which has
been separated from the rest of the body retains for a considerable time the
ability to recover from the effects of excitation. It is evident that when a
muscle is excited repeatedly, a certain interval of rest must be permitted
between the succeeding excitations if its normal condition is to be maintained,
and that the more extensive the chemical changes produced by the excita-
tions the longer must be the periods allowed for recovery. This being the
case, the rate of excitation and consequent length of the interval of rest Mill
have a great effect upon the condition of the muscle and its capacity for work.

(1) Effect of Frequent Excitations on the Height of Separate Muscular
Contractions. — Other things being equal, the height to Avhich a muscle can con-
tract Avheu excited by a given irritant can be taken as an index of its capacity

110

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

to do work, and if a muscle be excited many times in succession, the eifect of
action upon the strengtli of the contraction process, the endurance, and the
coming on of fatigue can be estimated from tlie lieight of the succeeding con-
tractions. One might expect that ev'cry contraction would tend to fatigue and
to leaseu the power of the muscle, but almost tiie first effect of action is to
increase the irritability and mobility of muscle protoplasm.

Introdndovy and Staircase Coni factions. — The jjcculiar effect of action to
increase muscular activity was first observ^ed by Bowditch,' when studying
the effect of excitations upon the heart. He found that repeated excitations
of equal strength applied to the ventricle of a frog's heart caused a series of
contractions each of which was greater than the preceding. If the contrac-
tions were recorded on a regularly moving surface, the summits of the succes-
sive contractions were seen to rise one above the other like a flight of steps.
This peculiar phenomenon received the name of the " staircase contractions "
(see Fig. 41).

■^ -^-g^-

FiG. 41.— staircase contractions of a frog's ventricle in response to a series of like stimuli, written on
a regularly revolving drum by the float of a water manometer connected with the chamber of the
ventricle (after Bowditch). The record is to be read from right to left.

This effect of repeated excitations was later observed by Tiegel,^ on the
skeletal muscles of frogs; by Rossbach,^ on the muscles of warm-blooded
animals, and by many others on various forms of contractile protoplasm.

The following series of contractions (Fig. 42), which closely resembles the
above, was obtained from the gastrocnemius muscle of a frog, excited at a
regular rate by a series of equal breaking induction shocks.

Fig. 42.— Staircase contractions of gastrocncmins muscle of a ft'og, excited once every two seconds by
strong breaking induction shocks.

The contractions in Figure 42 did not begin to increase in height imme-
diately ; on the contrary, each of the first four contractions was slightly lower
than the one which preceded it. A decline in the height of the first three or

* Berichte der kbniglichen sdchsischen Gesellschafl der Wissenschaft, 1871. ' Ibid., 1875.

' Pfluger's Archiv, 1882, 1884, Bd. xiii., xv.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. Ill

four contractions is the rule when a normal resting nuisele is called into action
(see Figs. 43 and 46), and these contractions at the beginning of a series have
received the name of the " introductory contractions." The introductory con-
tractions appear to indicate that the first effect of action is to lessen irritability,
or that anabolic changes are too slow to compensate for katabolic changes, and
each of the first few contractions leaves behind it a fatigue effect. It is not
long, however, before the influence of activity to heighten anabolism and
increase irritability shows itself in the growth of the height of the succeeding
contractions, and the " staircase contractions" are observed. This growth of the
height of contractions nuist necessarily reach a limit, and the amount of
increase is found to gradually lessen until the succeeding contractions have the
same height. Sometimes the full height of the staircase is not reached before
more than a hundred contractions have been made. These maximal contractions
may be repeated many times ; sooner or later, however, an antagonistic effect of
the work manifests itself and the height of the contractions begins to lessen.

Effect of Fatigue.— A. decline in the height of the contractions is an
evidence of fatigue, and indicates that anabolism is failing to keep pace with

66 contractions.

Rest. 1-30 100 200 300 400 500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

Fig. 43.— Effect of fatigue on the height of muscular contractions. The figure is a reproduction of
parts of a record of over 1700 contractions made by an isolated gastrocnemius muscle of a frog. The con-
tractions were isotonic, the weight being about 20 grams. The stimuli were maximal breaking induction
shocks, and were applied directly to the muscle, at the rate of 25 per minute. Between the first group of
66 contractions and the following groups a rest of five minutes was given ; after this rest the work was
continued without interruption for about one and a half hours. The second group of contractions, that
immediately following the period of rest, contains the first twenty contractions of the new series; the
next group the 100th to the 110th ; the next the 200th to the 210th, and so on.

katabolism. From this time on, the height of the succeeding contractions
continually lessens, and often with great regularity, so that a line drawn so as to

112 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

connect the .summits of the declining contractions, the "curve of fatigue," as
it is called, may be a straight line. In the experiment, parts of" tiie record of
which are reproduced in Figure 43, an isolated gastrocnemius mascle of a frog
Mas excited with maximal breaking induction shocks at the rate of 25 times
a minute for about one and one-half hours ; the contractions were isotonic, and
the total weight of lever and load did not exceed 20 grams ; the records of
the succeeding contractions were recorded on a slowly moving cylinder. The
experiment consisted of two parts — in the first G6 contractions, in the second
over 1700 contractions were made; an interval of rest of five minutes was
permitted between the two series.

In the fii'st part of the experiment there was a decline in the height of the
contractions for the first five contractions, the " introductory contractions,"
then during the next sixty-one contractions a gradual rise in the height of the
contractions, the " staircase contractions." These phenomena repeat themselves
in the second part of the experiment, that following the interval of rest. The
contractions at the beginning of the second series were not so high as those at
the end of the first series, though somewhat higher than those seen at the
beg-innint; of the first series ; the rest of five minutes was not sufficient to
entirely do away with the stimulating influence of the preceding work. The
contractions of the second series took the following course: The first four
introductory contractions gradually declined, then eame the staircase contrac-
tions, which continued to rise until the 100th contraction, when a gradual
lessening of the height of the contractions began. This decline continued
throughout the long series of more than 1 700 contractions given in the record,
and, had the experiment been continued, would have undoubtedly gone on
until the power was completely lost. The curv'e of fatigue was not a straight
line, but fell somewhat more rapidly during the early part of the work than
toward the end.

That the peculiar changes in the height of the contractions which occur in
the early part of an experiment such as that which we have described are not
abnormal, and the result of the artificial conditions under which the work is
done, is shown not only by the fact that they are observed when a muscle
which has its normal blood-supply is rhythmically excited to a large number
of contractions, but by the personal experience of every one accustomed to
violent nuiscular exercise. E%'eryone is conscious that he cannot put out the
greatest muscular effijrt until he has "warmed up to the Mork." The runner
precedes the race by a short run ; the oarsman takes a short pull before going
to the line ; in all the sports one sees the contestants making movements to
" limber up " before they enter upon the work of the game. These prelim-
inarv movements are performed not only to put the muscles in better condition
for action, but to ensure more accurate co-ordination — that is to say, the facts
ascertained for the muscle can be carried over to the central nervous system.
The finelv adjusted activities of the nerve-cells which control the muscles reach
their perfection only after repeated action.

In such experiments as that recorded in Figure 43 the record shows to

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 113

a remarkable degree the fact tliat at any given time the muscle has a definite
capacity tor work. A suitable explanation of this is lacking. The corre-
spondence in the height of the contractions of the same gronj), and the difFer-
euce in the height of ditlerent groups of contractions, must be attributed to the
existence within the muscle-cell of some automatic mechanism which regulates
the liberation of energy and which has its activity greatly influenced by the
alterations which result from action. Whether this supposed automatic regu-
latory mechanism controls both the preparation of the final material from
which the energy displayed by the muscle is liberated, and the amount of the
explosive change which results from the application of the irritant, cannot be
definitely said.

(2) Effect of Frequent Excitations upon the Form of Separate Contractions.
— The effect of activity is not only observable in the change in the height
of the muscular contractions, but in the length of the latent period, in the rate
at which the muscle shortens, and, above all, in the rate at which the muscle
relaxes. The effect of a large number of separate contractions, made in quick
succession, upon the rate at which the muscle changes its form during contrac-
tion, is illustrated in the myograms reproduced in Figure 44.

Fig. 44.— Effect of excitation upon the form of separate contractions. In this experiment the records
of the muscular contractions were taken upon a rapidly revolving drum. The muscle was the gas-
trocnemius of the frog ; the contractions were isotonic ; the weight was very light, about 10 grams ; the
stimuli were maximal breaking induction shocks ; and the rate of stimulation was twenty-three per
minute. 1 marks the first contraction ; 2, the 100th ; 3, the 200th ; 4, the 300th. The muscle was excited
automatically by an arrangement carried by the drum, and the excitation was always given when a
definite part of the surface of the drum was opposite the point of the lever Avhich recorded the con-
tractions.

In Figure 44 only the l.st, 100th, 200th, and 300th contractions were re-
corded. The perpendicular line marks the point at which the stimulus was
given. In this experiment the latent period for each of the succeeding con-
tractions is seen to be longer ; the height is lessened ; the rise of the curve of
contraction is slowed and the curve of relaxation is even more prolonged. These
and certain other changes are to be observed in the records of Figure 45, which
were taken in an experiment made under the same conditions as the last, except

8

114 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

that the rate of excitation was 80 per minute, instead of 23, as in the preced-
ing experiment, and the record of every 50th contraction was recorded.

Fig. 45.— Effect of frequent excitation on the form of separate contractions. The method employed
to obtain this record is the same as in the preceding experiment, except that the drum is revolving more
rapidly, and every 50th contraction is recorded : 1 marks the first contraction ; 2, the 50th : 3, the 100th ;
4, the 150th ; 5, the 200th ; 6, the 250th ; 7, the 300th.

A comparison of the first with tlie 50th contraction gives a number of
points of interest. The stimulating effect of action upon the contraction pro-
cess is shown by the fact that the latent period of the 50th (2 of Fig. 45) is
shorter than that of the first, the rise of the curve is somewhat steeper, and the
height is considerably greater. It is noticeable, however, that the crest is pro-
longed, and consequently the total length of the contraction is increased. In
considering the greater activity of the contraction process of this 50th con-
traction as compared with the first, we must recall that it represents one
of a series of staircase contractions, such as we noticed in Figure 43. If
we examine the 100th contraction (3 of Fig. 45) we see the evidences of the
beginning of fatigue; although the latent period is nearly as quick as in the
first, the rise of the curve is less rapid, the height is less, and rate of relaxation
is very much slowed. Tiie.se changes are to be seen in a more mark(>d degree
in the 150th contraction (4 of Fig. 45), and the prolongation of the crest of
the contraction and the decreased rate of relaxation are particularly noticeable.
The same sort of differences are to be observed in the later contractions. By
still more rapid rates of excitation these alterations in the contraction curve
are not only exaggerated, but develop more quickly, and play a very important
part in producing the peculiar form of continued contraction known as tetanus.

(3) Effect of Frequent Excitations to Produce Tetanus. — As we have seen, the
normal muscle the first time that it is excited relaxes almost as quickly as it
contracts, but if it be excited rhythmically a number of times a minute, gradu-
ally loses its power of rapid relaxation. The tendency to remain contractefl
begins to show itself in a prolongation of the crest of the contraction curve,
even before fatigue comes on, and increases for a considerable time in spite of
the effect of fatigue in lessening the height of the contractions. If a skeletal mus-
cle of a frog be excited many times, at a rate of about once every two seconds,
the gradual increase in the duration of the contractions will have the effect of
preventing the muscle from returning to its normal length in the intervals be-

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 115

tween the suocecdiug stimuli, for contraction will be excited before relaxation
is complete. As is shown in the record of the experiment reproduced in Figure
46, there will come a time in the work when the base-line connecting the lower
extremities of the succeeding myograms will be seen to rise in the form of a
curve, the change being at first gradual, then more and more rapid, and then
again gradual (see 6, Fig. 46). The eifect of the change in the power to relax
is to make it appear as if the muscle were the seat of two contraction j)rocesses,
the one acting continuously, the other intermittently in response to the suc-
cessive excitations. Such a condition as that exhibited in section c, Figure 46,
is spoken of as an incomplete tetanus, complete tetanus being a condition of
continuous contraction caused by rhythmical excitations, in which none of the
separate contraction movements are visible. In complete tetanus the muscle
writes an unbroken curve.

Fig. -16.— Effect of frequent stimuli to gradually produce incomplete tetanus. Series of isotonic con-
tractions of a gastrocnemius muscle of a frog, excited once every two seconds by strong breaking induc-
tion shocks. Only a part of the record is shown, 70 contractions have been omitted between the end of the
section marked a and the beginning of section b, and 200 contractions between the end of section 6 and the
beginning of e. The increase in the extent of the relaxations seen at the close of the record was due
to the slowing of the rate of excitations at that time.

The slowing of the relaxation of the muscle and consequent state of con-
tinued shortening which is to be seen in the latter part of the above experiment
is termed " contracture." The amount of contracture increases, within limits,
with the increase in the strength and rate of excitation. The intensity and

116 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

rate of stinuilatiou required for the production of tiiis condition depends \tx^
largely u])on tlie character of the muscle, and its condition at the time. In
the experiment recorded in Figure 47 the deviloj^nent of the condition of con-

FiG. 47.— Effect of frequent excitations to gradually produce tetanus. Experiment on a gastrocnemius
muscle of a frog, similar to the last. The weight was only in grams. The rate of excitation was 100 per
minute. Tliis muscle had been worked a short time before this series of contractions was taken, and, as
a result, the introductory and staircase contractions were absent and contracture began much sooner
than in the experiment recorded in Figure 45. The record in section 6 is a continuation of that in
section a.

tracture was more marked than in the above experiment, and the resulting con-
dition of continued contraction caused first incomplete and finally complete
tetanus.

Although frequent excitations appear to be essential to the development of
contracture, it is doubtful whether it is to be considered a fatigue effect, since

Fig. 48.— Development and fatigue of contracture. Exi>eriment on a gastrocnemius muscle of a frog.
The weight was 10 grams. As in the preceding experiments strong maximal breaking induction shocks
were used to excite. The rate of excitation was 5 per second. The record appears as a silhouette for the
reason that the drum was moving very slowly.

the contracted state which it produces may be increasing at the time that fatigue
is lessening the height of the ordinary contraction movements, and since the

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 117

form of coutraction peculiar to contracture is itself seen to lessen as fatigue
becomes excessive. Both of these facts are illustrated in Figure 47, but are
more strikingly shown in Figure 48, in which a more rapid rate of excitation
was used.

The record in Figure 48 shows many points of interest : a to h, a rapidly
developing staircase, which is accompanied by a rising of the base line, which
indicates that contracture began to make itself felt from the moment the work
began ; 6 to c, a rapid and then a gradual fall in the height of contractions
due to fatigue effects ; c to d, a rise in the top of the curve in spite of the
lessening height of the contractions, due to the increasing contracture ; d to e,
a gradual fall of the curve of incomplete tetanus, due to the effect oi fatigue
on the contracture ; e, complete tetanus, but continued gradual decline in the
height of the curve under the influence of fatigue.

The following experiment. Figure 49, differs from those whicli have preceded
it, in that the muscle, instead of being directly excited, was stimulated indirectly
by irritation of its nerve. Each shock applied to the nerve was represented
by a separate contraction process in the muscle. The experiment illustrates
well the combined effect of the staircase and the contracture to raise the height

Fig. 49.— Development of incomplete tetanus and contracture, by indirect stimulation. A gas-
trocnemius muscle of a frog was indirectly stimulated by breaking induction shocks, of medium
strength, applied to the sciatic nerve. The rate was about 8 per second, as shown by comparison of the
seconds traced at the bottom of the figure with the oscillations caused by the separate contractions. The
weight was somewhat heavier than in the preceding experiment. The drum was revolving much faster
than in the other experiments, hence the difference in the apparent duration of the contractions.

of the contractions. On account of the more rapid rate of excitation, the
contracture came on more quickly than in the preceding experiments ; it did
not become sufficient during the few seconds that this experiment lasted to
prevent the separate relaxations from being seen, and an incomjjlete tetanus
was the result.

In the experiment the record of which is given in Figure 50, the muscle was
directly stimulated, and the rate of excitation was rapid, 33 per second. Not
even this rate sufficed to cause complete tetanus, and the crest of the curve
shows fine waves, which represent the separate contractions the combined effect
of which resulted in the almost unbroken curve seen in the record. Had the
rate been a little more rapid, no waves could have been detected and the tetanus
would have been complete from the start. The effects of the staircase and con-
tracture are merged into one another, and a very rajiid high rise of the curve
of contraction is the re.sult. It is noticeable that the summit of the curve is
rising throughout the experiment, owing to the increasing contracture.

118 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

It is evident that the condition of contracture whidi is developcHl in a
rapidlv stimulated muscle will tend to maintain a condition of continuous oon-

FiG. 50.— Effect of rapid excitations to produce tetanus. Experiment with a gastrocnemius muscle
of a frog, excited directly, with breaking induction shocks of medium strength, at the rate of 33 per
second. The weight was about 15 grams. The drum was moving much more slowly than in the pre-
ceding experiment. The time record gives fiftieths of a second.

traction, there being no opportunity for the muscle to relax in the intervals
between the succeeding excitations.

4. Explanation of the Great Height of Tetanic Contractions. — We have
now to seek an explanation of the fact that a muscle when tetanized will con-
tract much higher than it will as a result of a single excitation. As we have
seen, repeated excitations cause, in the case of a fresh muscle, a gradual increase
in irritability and consequently a gradual rise in the height of the succeeding
contractions, but the staircase sooner or later reaches its upper limit, and will
not alone account for the great shortening which occurs in tetanus.

Efect of Two Rapidli/ Following Excitations. — Helmholtz was the first to
investigate the effect of rate of excitation on the height of combined contrac-
tions. For the sake of simplicity, he excited a muscle with only two breaking
induction shocks, of the same strength, and observed the effect of varying the
interval between these two excitations. He concluded that if the second stim-
ulus is given during the latent period of the first contraction, the effect is the
same as if the muscle has received but one shock ; if the second shock be applied
at some time during the contraction excited by the first, the second contraction
behaves as if the amount of contraction present when it begins were the resting
.state of the muscle, i. e. the condition of activity caused by the first shock has
no influence on the amount of activity cau.sed by the second, but the lieight
of the second contraction is simply added to the amount of the first contraction
present. Were this rule correct, as a result of this summation, if the second
contraction occurred when the first was at its height, the sum of the two con-
tractions would be double the height of either contraction taken by itself.

Helmholtz' conclusion, that the condition of activity awakened by the first

excitation has no effect upon that caused by the second excitation, has not been

substantiated by later observers. Von Kries ' has found that the presence of

the first contraction hastens the development of the contraction process result-

* Archil' fiir Anatomic und Physiologic, 1888.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 119

ing from the second excitation ; and Von Frey ^ has ascertained that Helm-
holtz's rule of summation applies only to weighted muscles. In the case of
unweighted muscles the summation effect is greatest when the second contrac-
tion starts during the period of developing energy caused by the first excita-
tion, /. €. during the rise of tiie first contraction. If the second contraction

Fig. 51.— a schema of the effect of double excitations upon the gracilis muscle of a frog, by differ-
ent intervals of excitation. To obtain this figure, the results of diflerent experiments were super-
imposed (after Von Frey).

starts during the period of relaxation of the first, the second may be not even
as high as when occurring alone (see Fig. 51).

The fact that the second contraction is higher if it starts during the ascent
of the first, may be explained as due to a summation of the condition of ex-

FiG. 52.— Effect of support on height of contractions (after Von Frey) : o, gastrocnemius muscle of a
frog, separate contractions, tetanus, separate contractions, and group of supported contractions ; weight
10.5 grams ; 6, the same, by weight of 0.5 grams.

citation awakened by the two irritants, and hence the liberation of a greater
amount of energy. Nevertheless, the increased irritability, indicated by stair-
case contractions, and the summation of excitation effects which occur by rapidly
repeated excitations, shown by the above experiment, do not suffice to wholly
explain the great shortening of the muscle seen in tetanus. Helmholtz' idea,
' Archiv fiir Awxtomie und Physiologic, 1888, p. 213.

120 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

that there is a support atfordeJ by the first contraction to the second, nuist
also phiy an important part, and we mnst turn to this for the completion of the
explanation of the great height acquired by the tetanus curve.

Efed of Support on the Heic/ht of Contractions. — Von Kries ' and Von
Frey - found that, in general, the shorter the distance the muscle has. to raise
a .weight, the higher it can contract, and that if a muscle be excited at a regu-
lar rate, and the support for the weight be raised between each of the succeed-
ing contractions, at a certain height of the support the contractions may be
as high as during tetanus (see Fig. 52). This effect can be got with a fresh
muscle when the interval between the excitations is such that there can be no
summation in Helmholtz' sense.

The importance of this discovery to our understanding of tetanus is very
great, for it has been found that if an unsupported muscle be rapidly excited,
effects are observed which closely resemble those obtained by the aid of a sup-

FiG. 53.— Effect of a gradually Increasing rate of excitation. Excitation of a gastrocnemius muscle
of a frog with breaking induction shocks of medium strength. Tlic time was recorded directly, by a
tuning-fork making 100 vibrations per second. The rate of excitation was gradually increased, and
then gradually decreased. The ascending curve, a-b, shows the effect of increasing, and the descending
curve, c-d, of decreasing the rate of stimulation. Excitation was given by means of a special mechanism
•for interrupting the primary circuit of an induction apparatus and at the same time short-circuiting the
making shocks. This interrupter was run by an electric motor which was allowed to speed up slowly,
and was slowed down gradually.

port; this we have seen in the experiments recorded in Figures 47, 48, p. llf).
After a certain amount of excitation, a change occurs in the condition of a
muscle, owing to which it acts as if it had received an upward push, and as
if a new force had been developed within it, which aids the ordinary con-
^ Archivfiir Anatomic und Physiologic, 1886. ^ Ibid., 1887.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 121

traction process in raising the weight. The new aid to high contraction is
the support afforded by the developing condition of contracture.

5. Effect of Gradually Increasing the Rate of Excitation. — One of the
most instructive methods of exciting tetanus is to send into the nmscle a series
of breaking induction shocks of medium intensity, at a gradually increasing
rate. The record of such an experiment has been reproduced in Figure 53.

At the beginning of the experiment, a, one complete contraction with a
wave of elastic after-vibration was recorded ; this was followed by two con-
tractions of less height, " introductory contractions ;" then came three contrac-
tions each of which was higher than the preceding, "staircase contractions;"
these were followed by three contractions, which, in spite of the developing
contracture, were of less height, " fatigue eflfect." The rate of excitation at
this place was about 17 per second. From this point on, the developing con-
tracture supported the muscle more and more and the contraction waves became
less and less, until finally, when the rate had become 36 a second, the effect
of the separate stimuli could scarcely be detected, although the curve continued
to rise. This is as far as the record shows, but the rate was increased still
further, and the contraction curve continued to rise, although less and less,
until finally an almost straight, unbroken line was drawn. After a little time
this was seen to begin to fall, the contracture yielding to the effect of fatigue.

As the drum had nearly revolved to the place at which the experiment had
been begun, the rate of excitation was then slowly decreased. With the lessen-
ing rate, the curve fell more and more rapidly, and oscillations began to show
themselves. The character of the record during the rest of the experiment is
shown in the curve e^, Figure 53. At c the rate was about 1 7, and at d it
was so slow that separate contractions were recorded, nevertheless the curve as
a whole kept up. Indeed, even after the excitation had altogether ceased, the
muscle maintained a partially contracted state for a considerable time, on
account of the contracture effect, which only gradually passed off.

6. Summary of the Effects of Rapid Excitation ichich produce Tetanus. —
Muscle-tetanus is the result of the combined action of a great many different
factors, but the essential condition is that the muscle shall be excited at short
intervals, so that the eflPect of each contraction shall have an influence on the
one to follow it. This influence is exerted in several different ways: 1. In-
crease of irritability resulting from action, and leading to the production of
staircase contractions ; 2. Summation of excitation effects, as when each of the
succeeding stimuli begins to act, before the contraction process excited by its
predecessor has ceased ; 3. Support given by the contracting muscle to itself,
especially the support offered by contracture.

7. Number of Excitations required to Tetanize. — The number of stimuli per
second required to tetanize a muscle depends largely on the nature of the
muscle, for this decides the character of the separate contractions, and, through
them, the effect of their combined action.

The duration of the separate contractions, and the tendency of the muscle
to enter into contracture, are the predominant factors in determining the result.

122 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Complete tetanus can only be obtained in the ease of a fresh muscle, when the
interval between succeeding stimuli is shorter than is required for the muscle
to reach its maximal contraction by a single stimidus. Thus the prolonged
contractions of smooth muscles permit of the development of a form of tetanus
by successive closures of the galvanic current at intervals of several seconds.
Tlie contraction of some of the muscles of the turtle may last nearly a second,
and two or three excitations a second suffice to tetanize. Tetanus of the red
(slowly contracting) striated muscles of the rabbit can be obtained by 10 exci-
tations per second, while 20-30 per second are required to tetanize the pale
(active) striated muscles (Kronecker and Sterling). 100 stimuli per second
are needed to tetanize the muscles of some birds (Richet), and over 300 per
second would be required to tetanize the muscles of some insects (Marey).
Strange to say, the heart-muscle cannot be tetanized ; if it replies at all to
frequent excitations, it gives the simple contractions characteristic of the heart-
beat. Any influence which will prolong the contraction process will lessen the
rate of excitation required to tetanize.

8. Effect of Exceedingly Rapid Excitations. — The question arises. Is there an
upper limit to the rate of excitation to which muscles wall respond by tetanus?
There is no doubt that this is the case, but there is a difference of opinion as
to what the limit is, and how it shall be explained.

Striated muscles and nerves can be excited by rates at which our most deli-
cate chronographs fail to act. The muscle ceases to be tetanized by direct exci-
tation at a rate by w'hich it can still be indirectly excited through its nerve.
The highest rate for the nerve has been placed at from 3000 to 22,000 by differ-
ent observers,^ and this wide difference is probably attributable to the methods
of excitation employed. That such different results should have been reached
is not strange, if we recall the many conditions upon which the exciting power
of the irritant depends. As a rule, when the rate of excitation is so high that
tetanus fails, a contraction is observed when the current is thrown into the
nerve, and often another when it is withdrawn from the nerve. A satisfactory
explanation for this, as well as for the failure of the tetanus, is at present lack-
ing.

9. Relative Intensity of Tetanus and Single Contractions. — The amount that
a muscle is capable of shortening, when tetanized by maximal excitations, and
the strength of the tetanic contraction, depends very largely on tiie kind of
muscle. For example, pale striated muscles, although capal)le of higher and
more rapid single contractions than the red striated, do not show as great an
increase in the height and strength of contractions when tetanized as do the
red ; the latter, which are very rich in sarcoplasma, liave likewise the greater
endurance. Gruetzner has called them " tetanus muscles," since they seem to
be particularly adapted to this form of contraction. Fick found that human
muscles when tetanized develop ten times the amount of tension, by isometric

' Kronecker and Sterling: Archiv fiir Anatomic und Phijsiologie, 1878, and Jouinial nf Phi(i^i-
ology, 1880, vol. i. Von Fray und Wiedermann : Berichte der sdchsischen Gesellschafi der H'tsse/i-
sctuift, 1885. Roth : PflUget^s Archiv, 1888.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 12.]

contractions, tluit they give by single contractions; and in this respect they
can be said to resemble red striated muscles. The following relations have
been found to exist between separate contractions and tetanus in certain muscles :
triceps and gastrocnemius of the frog, 1 : 2 or 3 ; the corresponding muscles of
the turtle, 1:5; hyoglossus and rectus abdomiualis of the frog, 1 : 8 or 9.^ It
is evident that no just estimate of the part played by different groups of muscles
in the movement of the body can be reached without a careful analysis of the
nature of the contractions peculiar to each of the muscles participating in the
movement.

Both the height and strength of the tetanus is controlled by the intensity
of the stimulus. A strong stimulus not only causes the separate contractions
of which the tetanus is composed to be higher, but is favorable to the develop-
ment of all the other factors which have been described as entering into the pro-
duction of tetanus. All normal physiological contractions are supposed to be
tetani, and everyone is conscious of the wonderful accuracy with wdiich he can
grade the extent and strength of his voluntary movements. The remarkable
shading of the intensity of action observable in co-ordinated movements must
find its explanation in the adjustment of protoplasmic acti\'ity in the nerve-
cells of the central nervous system.

10. Continuous Contractions caused by Continuous Excitation. — Attention
has been already called to the fact that under certain circumstances a form of
continuous contraction may be excited by a continuous constant electric current.
If the current be very strong, the short closing contraction may be followed by
a more or less continuous contraction — the closing (or Wundt's) tetanus, and
the short opening contraction may be follow^ed by another continuous contrac-
tion, which only gradually passes off — the opening (or Hitter's) tetanus. This
form of contraction is quite readily excited in normal human muscles, both by
direct and indirect excitation. The term " galvanotdnus " is sometimes em-
ployed for the continuous contraction of human muscles excited by the con-
tinuous flow of a constant current.

The closing tetanus originates at the kathode, and the opening tetanus at
the anode. The contraction process may spread rapidly from the point of
origin to the rest of the muscle, or, if the muscle be in an abnormal state, or be
dying, the contraction may remain localized as a circumscribed swelling, or
welt. Although a continuous contraction caused by the constant current is
spoken of as tetanus, it is a matter of doubt wliether it is a true tetanic condi-
tion, for the term tetanus is limited to an apparently continuous contraction
resulting from many frequently repeated stimuli. Von Frey ^ expresses the
view that the continuous contraction which follows the closing of the contin-
uous constant current is a form of tetanus. It is certainly true that the
closing tetanus often shows irregular oscillations, suggestive of a more or less
intermittent excitation. This might be attributed to irregular chemical changes
produced in the muscle-substance by the electricity and leading to irregular

^ Biedermann : Ekktrophysiologie, p. 109.

* Archiv fiir Anatomie und Physiologic, 1885, p. 55.

124 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

contractions ot" the diliercnt iibres, the combined action of which produces a
more or less regular continued contraction. Another view w(Hild be that con-
tracture niitjht be produced under tiie influence of the changes caused by the
electric current, and a condition result similar to that which causes the pro-
longed contractions which are characteristic of poisoning with veratria, etc.
(see p. 128).

{d) Normal Fhysiologkal Contractions. — All normal physiological contrac-
tions of muscles are regarded as tetani. Even the shortest possible voluntary
or reflex movements are considered to be too long to be single contractions.
Inasmuch as we can artificially excite muscles to continuous contraction only
by means of a series of rapidly following stimuli, we find it hard to explain
continuous contractions on any otiier basis, and hence the view that tlie exci-
tation sent by the nerve-cells to muscles has always a rhythmic character, and
that the normal motor-nerve impulse is a discontinuous rather than continuous
form of excitation. The view is probably correct, but cannot be considered as
proved. The evidence in favor of it is as follows.

Muscle-sounds, Tremors, etc. — During voluntary muscular contractions the
muscle gives out a sound, which would imply that its finest particles were not
in a state of equilibrium, but vibrating. By delicate mechanisms it has been
possible to obtain records of voluntary and reflex contractions which showed
oscillations, although the contraction of the muscle appeared to the eye to be
continuous. If the surface of a muscle be exposed and be wet and glistening,
the light reflected from it duriftg continued contractions is seen to flicker, as
if the surface were shaken by fine oscillations. The tired muscle passes from
apparently continuous contraction to one exhibiting tremors, and muscular
tremors are observed under a variety of pathological conditions.

With these facts in mind, a number of observers have endeavored to dis-
cover the rate at which the muscle is normally stimulated. Experiments in
which muscles have been excited to incomplete tetanic contractions by induced
currents, interrupted at different rates, have shown that the muscle follows the
rate of excitation with a corresponding number of vibrations, and dot>s not
show a rate of vibration peculiar to itself. Further, it has been ascertained
that the sound given out by a muscle excited to complete tetanus, i. e. an
apparently continuous contraction, corresponds to the rate at which it is ex-
cited. Apparently, any rate of oscillations detected in a muscle during normal
physiological excitation would be an indication of the rate of discharge of
impulses from the central nerve-cells.

Wollaston was the first to observe that a muscle gives a low dull sound
when it is voluntarily contracted, and that this sound corresponds to a rate of
vibration of 36 to 40 per second. It may be heard with a stethoscope placed
over the contracting biceps muscle, for instance, or if, when all is still and the
ears are stopped, one vigorously contracts his masseter muscles. Helmholtz
placed vibrating reeds consisting of little strips of paper, etc., on the muscle,
and found that only those which had a rate of vibration of 18 to 20 per
second were 'thrown into oscillation when tlie muscle was voluntarily contracted.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 125

This observation imlicatcd iJiat the iiiiLsele had a rate ol" vibration of" 18 to 20
per second, a rate too slow to be recognized as a tone. He conclnded that the
tone heard from the voluntarily contracted muscle was the overtone, instead
of the true muscle-tone. The consideration that the resonance tone of the
ear itself corresjx^nds to 36 to 40 vibrations per second, makes it question-
able whether the muscle-sound should be accepted as evidence of the rate of
normal physiological excitation ; nervetheless, the experiments with the
vibrating reeds remain to indicate 18 to 20 per second to be the normal
rate.

Within the last few yeai-s a number of researches bearing upon this question
have been publisiied, and the results of these point to a still slower rate of vol-
untiiry excitation, varying from 8 to 12 per second according to the muscle on
which the experiment is made. Loven' discovered in the tetanus excited in
frogs poisoned with strychnia, and in voluntary contractions, both by mechani-
cal methods and by recording the electrical changes occurring during action
with the capillary electrometer, rates of 7 to 9 per second. Horsley and
Schafer^ excited the brain cortex and motor tracts in the corona radiata and the
spinal cord of mammals by induction shocks, at widely differing rates, and
recorded the resulting muscular contractions by tambours placed over the
muscles. They observed oscillations in the myograms obtained which had a
rate of 8 to 12 per second, the average being 10. The rate of oscillations was
quite independent of the rate of excitation, and oscillations of the same rate
were seen by voluntary and by reflex contractions. TunstalP found by the use
of tambours, in experiments on voluntary contractions of men, a rate of 8 to 13
per second, with an average of 10. Griffiths* likewise used the tambour
method, and studied the effect of tension on the rate of oscillations in voluntarily
contracted human muscles. He observed rates varying from 8 to 19, the rate
being increased with an increase of weight up to a certain point, and beyond this
decreased. The oscillations became more extensive as fatigue developed. Von
Kries by a similar method found rates varying with different muscles, but
averaging about 10.

It is not easy to harmonize the view that 8 to 13 excitations per second
can cause voluntaiy tetani, when it is possible for the expert pianist to make
as many as 10 or 11 separate movements of the finger in a second. It is,
indeed, a common observation that a muscle can be slightly and continuously
voluntarily contracted, and, at the same time, be capable of making additional
short rapid movements. Von Kries would explain this as due to a peculiar
method of innervation, while Biedermann favors Gruetzner's^ view that the
muscle may contain two forms of muscle-substance, one of which is slow to
react, resembling red muscle-tissue, and maintains the continuous contraction,
the other, of more rapid action, being responsible for the quicker movements.
Although the evidence is, on the whole, in favor of the view that all normal

* Centralblatt fiir medicinische Wissenschaft, 1881. ^ Journal of Physiology, 1886, vii. p. 96.
^ Journal of Physiology, 1886, vii. p. 114. * Journal of Physiology, 1888, ix. p. 39.

'" Pfliigers Archiv, 1887, Bd. 41, S. 277.

126 ^iV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

contractions of voluntary nniscles are tetanic in character, there is a great deal
which remains to be explainetl.

Efect of Arflficial compared ivlth Normal Stimulation. — Experiment shows
that, with the same strength of irritant, a muscle contracts more vigorously
when irritated indirectly, through its nerve, than when it is directly stimulated.
Rosenthal describes the following experiment : If the nerve of muscle A be
allowed to rest on a curarized muscle B, and an electric shock be applied in
such a way as to excite nerve A and muscle B to the same amount, muscle A
will be found to contract more than muscle B.

Further, it has been found that muscles respond more vigorously to volun-
tary excitations than to any artificial stimulus which can be applied to either
the nerve or muscle. This shows itself, not only in the fact that a muscle can
by voluntary stimulation lift much larger weights than by electrical excitation,
but that after a human muscle has been fatigued by electrical excitations it
can still respond vigorously to the will. An illustration of this is given in
Figure 54,

<,<'»<'<»«;

Fig. 54.— Voluntary excitations are more effective than electrical. The flexor muscles of the second
finger of the left hand of a man were excited first voluntarily, a, then electrically, a-h, and then volun-
tarily, h. The electrical excitation consisted of series of induction shocks, which were applied once
every two seconds, during about half a second, the spring interrupter of the induction coil vibrating
23 times per second. Each time the muscle contracted it raised a weight of one kilogram. Each of the
contractions recorded, whether the result of electrical or voluntary excitation, was a short tetanus.

Fatigue of Voluntary Muscular Contractions. — Mosso and his pupils have
done a large amount of work upon the fatigue of human muscles when excited
by voluntary and artificial stimuli under varying conditions. The results at
which they arrived all favor the view that human muscles differ but little from
thase of warm-blooded animals, and that the facts which have been ascertained
by experiments upon cold-blooded animals, such as the frog, can be accej)ted
with but slight modifications for the muscles of man. In the experiment
recorded in Figure 55 we see the effect of repeated tetanic contractions, excited
by electricity, to fatigue a human muscle. Normal voluntary contractions, if
frequently repeated, provided the muscle has to raise a considerable weight,
likewi.se cause fatigue.

It is doubtful whether, in an experiment such as is shown in Figure 55, the
loss of the power to rai.se the weight is due to fatigue of the muscles. It is
more likely that the decline in power is really due to fatigue of the central

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 127

nerve-cells by which the muscles are excited to action duriug voluntary mus-
cular work.^ This fact, that the nerve-cells give out before the muscles, ex-
plains the apparent contradiction, that a muscle fatigued by electric excitations
can be voluntarily contracted, and when the power to voluntarily contract the

< mmfn

Fig. 55.— EflFect of fatigue on voluntary muscular contractions. The flexor muscles of the second
finger of left hand were voluntarily contracted once every two seconds, and always with the utmost
force. The weight raised was four kilograms.

muscles has been stopped by fatiguing voluntary work the mu.scles will respond
to electrical excitation. It is undoubtedly of advantage to the body that the
nerve-cells should fatigue before the muscles, for the muscles are thereby pro-
tected from the injurious effects of overwork, and are always ready to serve the
brain.^ It may be added that nerve-cells not only fatigue more quickly, but
recover from fatigue more rapidly than the muscles.

(e) Effect of Temperature upon 3fuscular Contraction. — Heat, within certain
limits, increases the irritability and conductivity of muscle-tissue, and at the
same time has a favoring influence upon those forms of chemical change which
liberate energy. The effect of a rise of temperature, as shown by the myo-
gram, is a shortening of the latent period, an increase in the height of contrac-
tion, and a quickening of the contraction and relaxation, the whole curve being
shortened. Of course there is an upper limit to this favoring action, since, at a
certain temperature, about 45° C. for frog's muscle and about 50° C. for the
muscles of warm-blooded animals, heat-rigor begins, and this change is accom-
panied by a loss of all vital properties. Cold can be said, in general, to pro-
duce effects the opposite of those of heat; as the muscle is cooled, the latent
period, the contraction, and the relaxation, are all prolonged.

Nevertheless, the effect of temperature is not a simple one (see Fig. 56). If

^ Lombard : Archives Italiennes de Biologie, xiii. p. 1 ; or American Journal of Psychology,
1890, p. 1 ; Journal of Physiolocjy, 1892, p. 1 ; 1893, p. 97.
=■ Waller : Brain, 1891, p. 179.

128

.l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

durinu: tliu cooling process a striated muscle; ot' a irog ho irritated from lime to
time with single induction shocks, the height of tiie contractions (h)es not con-
tinually grow less as one would expect.' The maximal height is obtained at
30° C, the height above this point l)eing somewhat less, the irritabilitv les-
sening as the coagulatiou-point is approached; from 30° C. to 19° C. the
height continually decreases, but from 19° to 0° C. the height increases, while
below 0° C. it again becomes less, until at the freezing-point of muscle no con-
traction is obtained. The cause of these peculiar phenomena is not definitely
understood.

Fig. 56.— Schema of effect of temperature on height and form of contraction curve : a, contraction at
19° C. ; b, c, d, e,f, contractions made at intervals, each one at a lower temperature; g, h, contractions
at higher temperatures than 19° C, h being made when the temperature was 30° C. ; i, k, I, show a different
series of contractions, made as the temperature was increased from 30° C. toward the point at which the
muscle-substance coagulates (after Gad and Heymans).

(J) Effect of Drugs and Chemicals upon Jfuscular Contraction. — Certain drugs
and chemicals have a marked effect upon the irritability and conductivity of
mu.scles, and these effects must nece.ssarily find expression in the amount of con-
traction which would be excited by a given irritant. In addition to this, it is
worthy of notice that the character of the contraction may be altered.

The drug which has the rao.st striking effect upon the form of contraction is
veratria. A few drops of a one per cent, solution of the acetate of veratria, in-
jected beneath the skin of a frog whose brain has first been destroyed, in a few
minutes alters qompletely the character of the reflex movements ; the muscles

Fig. 57.— Myogram of muscle poisoned with veratria and that of a normal muscle ; a, myogram from a
normal gastrocnemius muscle of a frog— the waves at the close are due to the recoil of the recording lever;
b, myogram from a gastrocnemius muscle poisoned with veratria, recorded at the same part of the drum.

are still capable of rapidly contracting, but the contractions are cramp-like,
the power to relax being greatly lessened. The poison acts upon the muscle-
substance. If a muscle poi.soned with veratria be isolated and connected with
^ Gad und Heymans: Archivfur Anatomic und Physiologic, 1890, p. 73.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 129

a inyograpli, a contraction excited by a single induction shock will show a rise
as rapid and as high as normal, but the fall of the curve will be greatly pro-
longed (see Fig. 57).

Often the crest of the curve will exhibit a notch, which shows that relaxa-
tion may begin and be checked by a second contraction process which carries
the curve up again and holds it there for a considerable time. In the above
experiment the contracture etiect followed the primary contraction immediately.
If the muscle be frequently excited, the characteristic prolongation of the
contraction disappears, and the curve becomes normal ; but if the muscle be
allowed to rest, there is a return of the condition. Both high and low tempera-
tures act like exercise to prevent this peculiar effect of veratria from showing
itself.

Barium salts, and to a less degree calcium and strontium, act similarly to
veratria to prolong the relaxation of the muscle without lessening the rapidity
and height of the contraction. Potassium and ammonium salts act to kill the
muscle, and, as the death-process develops, excitation produces prolonged local-
ized contractions. This effect seems to be quite different from that of veratria,
being accompanied by a rapid lessening of the power of the muscle. Sodium
salts in strong solution may increase the irritability and induce fatigue, which
is always accompanied by a prolongation of the curve of relaxation.

The condition of continued contraction caused by veratria is a form of
"contracture." The true natm*e of the condition is still under discussion;
the fact that the veratria contracture passes off if the muscle is worked, shows
that it is not in the nature of a fatigue effect. Since more heat is produced
during contracture than during rest (Fick and Boehme), it is to be regarded as
an active contraction process and not an increase of elasticity. The fact
that the crest of the veratria curve often exhibits a notch, and that the second
rise, leading to the prolonged ridge, may be higher than the primary rise, has
been interpreted to mean that the muscle contains two different forms of muscle-
tissue which, like the pale (rapid) and red (slower) striated muscles of the rab-
bit, have different rates of contraction. The first rise is supposed to be due to
the quicker and the second to the slower form of muscle. A similar double
crest is seen in the contraction curves of muscles the irritability of which
has been heightened by sodium carbonate, and indeed in the curves from
muscles of normal frogs after their irritability has been increased by frequent
excitations.

Liberation of Energy by the Contracting' Muscle. — The law of con-
servation of energy applies no less to the living body than to the inanimate
world in which it dwells. Every manifestation of life is the result of the
liberation of energy which was stored in the body in the form of chemical
compounds. When a muscle is excited to action it undergoes chemical
changes, which are accompanied by the conversion of potential to kinetic en-
ergy. This active energy leaves the muscle in part as thermal energy, in part
as mechanical energy, and, to a slight extent, under certain conditions, as elec-
trical energy. In general, the sum of the liberated energy is given off as heat
9

130 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

or niotiou. The proportion in whicii these two forms of energy shall be pro-
duced by a muscle may vary within wide limits, according to the state of the
muscle and the conditions under which the work is done. Fick * states that
if the nmscle works against a very heavy weight, ])ossibly \ of the liberated
energy may be obl^iiucd as mechanical work, but if the weight be light not
more than ^^ of the chemical energy is given off in this form, the muscle
working no more economically than a steam engine. The flict that always a
part, and often the whole, of the mechanical energy developed by the muscle
is converted to thermal energy within the nuiscle, and leaves it as heat, makes
it the more difficult to determine in what proportion these two forms of
energy were originally produced. Moreover, if Engelmann's view be correct,
that the change of form exhibited by the muscle is the result of the imbibition
of the fluid of the isotropic substance by the anisotropic material, this change
being brought about by the heat which is liberated within the muscle, we nmst
consider potential energy to be set free first as heat, a part of which is after-
ward changed to mechanical energy, which in part, at least, is again changed
to heat.

lAbeixdion of Mechanical Energy. — In estimating the amount of mechanical
energy liberated by a muscle, we observe the amount of physical work which
it accomplishes, /. e. the amount of mechanical energy which it imparts to ex-
ternal objects. If a muscle by contracting raises a weight, it gives energy to
the weight, the amount being exactly that which the weight in falling through
the distance which it was raised by the muscle can impart as motion, heat, etc.,
to the objects with which it comes in contact. The measure of the mechanical
work done by the contracting muscle is the product of the weight into the height
to which it is lifted. For example, if a muscle raises a weight of 5 grams,
10 millimeters, it does 50 grammillimeters of work.

The amount of work which a muscle can do depends on the following con-
ditions :

(rt) The kind of muscle. The muscles of warm-blooded animals are stronger
than those of cold-blooded animals ; a human muscle can do two to three
times the amount of work of an equal amount of frog's muscle. The muscles
of certain insects have even greater strength.^

(6) nie quantity of muscle-substance and the arrangement of the fibres. The
power of a muscle to do mechanical work, the absolute muscular force, is esti-
mated by the weight which, brought upon the muscle at the instant it begins to
contract, prevents it from shortening but does not stretch it, /. e. one which ex-
actly balances the contractile force of the muscle when it is excited to a maxi-
mal tetanic contraction. It is evident that the amount of force which can be
developed will depend on the amount of contractile substance and on the
arrangement of the fibres. Since the force which can be developed by a contract-
ing muscle depends largely on the arrangement of the microscopic contractile
mechanisms of which it is composed, it is found best, for purposes of compari-

* Fick: Pfluger's Archiv, 1878, xvi. p. 85.

* Hermann : Handbuch der Physiologie, 1879, Bd. i. p. 64.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 131

son, to state tlie strength ot'u tnusclc and its capacity to do work, fur tlie unit
of bulk, one cubic centimeter, or the unit of weight of muscle-substance, one
gram. Thus, the absolute nuiscular force of frog's muscle is estimated to
be about 3 kilograms per cubic centimeter, and of human muscle to be 8 to 10
kilograms per cubic centimeter. Fick states that the maximal amount of ex-
ternal work of which frog's muscle is capable is 1 grammeter per gram of
m uscle-substance.

(c) The condition of the muscle. Any of the influences which lessen the
irritability of the muscle — lack of blood, fatigue, cold, etc. — decreases the power
to liberate energy, and any influence which heightens the irritability is favora-
ble to the work. The effect of tension to heighten irritability has already been
referred to and is of especial interest in this connection, since the very re-
sistance of the weight is, within limits, a condition favorable to the liberation
of the energy required to overcome the resistance. This will be referred to
again.

(d) The strength and character of the stimulus. The liberation of energy is,
up to a certain point, the greater, the stronger the excitation. Furthermore,
rapidly repeated excitations are much more effective than single excitations,
because a series of rapidly following stimuli, both by altering the irritability and
by inducing the form of contraction known as tetanus, act to produce powerful
and high contractions. Bernstein states that the energy developed by the
muscle increases with the increase of the rate of excitation from 10 to 50 per
second, at which rate the contraction power may be double that called out by a
single excitation.

(e) The method of contraction and the mechanical conditions under which the
work is done. Inasmuch as mechanical work is measured by the product of
the weight into the height to which it is lifted, an unweighted muscle in con-
tracting does no work ; a muscle, however vigorously it may contract, if it be
prevented from shortening, does no work; finally, a muscle which raises a
weight and then lowers it again when it relaxes, does not alter its surround-
ings as the tot result of its activity, and hence does no work. Although no
mechanical work is accomplished under these circumstances, physiological work
is being done, as is evidenced by the fatigue produced. Unquestionably mechani-
cal energy is developed within the muscle in all these cases, but it is all con-
verted to heat before it leaves the muscle.

The amount of weight is an important factor in determining the extent to
which a muscle will shorten when excited by a given stimulus, and, therefore,
the quantity of work which it will accomplish. If a muscle be after-loaded,
i. e. if the weight be supported at the normal resting length of the muscle, and
the muscle be excited to a series of maximal contractions, the weight being in-
creased to a like amount before each of the succeeding excitations, there is, in
general, a gradual lessening in the height of the contractions, but the de-
crease in height is not proportional to the increase of the weight. The
decrease in the height of contractions is, as a rule, more rapid at the beginning
of the series than later, though at times an opposite tendency may show itself

132 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

aud the increasing weights temporarily increase the irritability and therefore
increase the amount of shortening. The effect of tension to increase the activ-
ity of the contraction process is seen if a muscle which is connected with a
strong spring or heavy weight be excited to isometric contractions and in
the midst of a contraction be suddenly released ; the muscle under such cir-
cumstances is found to contract higher than when excited by the same stimulus
without bcintr sul))ected to tension. The effect of tension on the activitv of
muscular contractions is to be clearly seen in the case of the heart muscle.
A rise of pressure of the fluid within the isolated heart of a frog increases
the strength as well as the rate of the beat.

If the weight be gradually increased, although the height of the contrac-
tions is lessened, the work will for a time increase, and a curve of work (con-
structed by raising ordinates of a length corresponding to the work done,
from points on an abscissa at distances proportional to the weights em-
ployed), will be seen to rise. After the weight has been increased to a cer-
tain amount the decline in the height of contractions will be so great that the
product of the weight into the height will begin to decrease, and the curve of
work will fall, until finally a weight will be reached which the contracting
muscle can just support at, but not raise above, its normal resting length. As
has been said, this weight will be a measure of the absolute muscular force.

Example.

Load Height of lift Work

(grams). (millimeters). (grammillimeters).

0 13 0

30 11 330

60 9 540

90 7 630

120 5 600

150 3 450

180 2 360

210 0 0

In the above experiment 30 grams Avas added to the muscle after each
contraction ; as the weight was increased up to 90 grams the amount of
work was increased, with greater weights the amount of work was lessened.

Liberation of Thermal Energy. — Energy leaves the body as mechanical
energy only when by its movements the body imparts energy to surrounding
objects. Most of the energy liberated within the body leaves it as heat ; even
during violent muscular exercise five times more energy may be expended as
heat than as mechanical energy, and the dispro])ortion may be even greater
than this. So great is the production of heat during exercise, that, in spite
of the great amount leaving the body, the temperature of an oarsman has been
found to be increased, during a race of 2000 meters, from 37.5° C. to 39°
or 40° C

It is exceedingly difficult to ascertain M'ith accuracy on the warm-blooded
animal the exact relation of heat-production to muscular contraction. The

^ Geo. Kolb: Physiology of Sport, translated from the German, 2d edition, London, 1892.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 133

best results have been obtained by experiments on isolated muscles of cold-
blooded animals. Helmholtz observed the temperature of a muscle of a
frog to be increased by tetanus lasting a couple of minutes 0.14° to 0.18°
C. ; Heidenhain saw a change of 0.005° C. result from a single contraction ;
and Fick ascertained that a fresh, isolated muscle of a frog can by a single
contraction produce per gram of muscle-substance enough heat to raise
3 milligrams of water 1° C* To obtain evidence of the slight changes
of temperature which occur in such small masses of muscle-tissue it is
necessary to employ a very delicate instrument, such as a thermopile or a
bolometer.

The thermopile consists of strips of two dissimilar metals, united at their extremities,
so as to form a series of thermo-electric junctions. If there be a difference of temperature
at two such junctions, a difference of electric potential is developed, which causes the
flow of an electric current. If the current be passed through the coils of wire of a
galvanometer its amount can be measured, and the extent of the change in tempera-
ture at one of the junctions, the other remaining constant, can be estimated. In the
more sensitive instruments, several thermo-electric junctions are used. The amount of
current depends largely on the metals employed, antimony and bismuth being a very
sensitive combination.

The action of the bolometer is based on the fact that the resistance of a wire to the
passage of an electric current changes with its temperature.

The amount of heat developed within the muscle by direct conversion of
potential to thermal energy, and the amount formed indirectly, through con-
version of mechanical to thermal energy, has been made a subject of careful
study by Heidenhain,^ Fick and his pupils,^ and others, the experiments being
made chiefly with isolated muscles of frogs.

In general, the stronger the stimulus and the greater the irritability of the
muscle — in other words, the more extensive the chemical changes excited in
the muscle — the greater the amount, not only of mechanical, but of thermal
energy liberated. Increase of tension, which is very favorable to muscular
activity, greatly increases the heat-production. As the weight is increased,
both the amount of heat developed and the work are increased, but the libera-
tion of heat reaches its maximum and begins to decline sooner than the amount
of work, i. e. with large weights the muscle works more economically ; similarly,
as the muscle is weakened by fatigue the heat-production lessens sooner than
the work.

Muscle-tonus and Chemical Tonus. — During waking hours, the cells
of the central nervous system are continually under the influence of a shower
of weak nervous impulses, coming from the sensory organs all over the body;*
moreover, activity of brain-cells, especially emotional forms of activity, leads

1 Fick : Pfluger's Archiv, 1878, xvi. p. 89.

* Mechanische Leistung, Wdrmeentwicklung und Stoffumsatz bei der Muskelthdtigkeit, Leipzig,
1864.

^ Myothermische Untersuchungen aus den physiologischen Laboratorium zu Zurich und Wurzburg,
Wiesbaden, 1889.

* Brondgeest : Archiv fur Anatomic und Physiologic, 1860, p. 703; Hermann, Ibid., 1861,
p. 350.

134 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

to au ovorliow ot" nervous impuLses to the spinal cord and an increased irrita-
bility, o)', if stronger, excitation of motor uerve-cells. If, when one is quietly
sitting and reading, he turns his attention to the sensory impressions which
are coming at every moment from all over the body to the brain, notes the
temperature of different parts of the skin, the pressure of the clothes, etc.,
upon different parts, the light reflected from neighboring objects, and the slight
sounds about him, he will recognize that the central nervous system is all the
time subject to a vast number of excitations, which, because of their very
repetition, are ordinarily disregarded by the mind, but which arc, nevertheless,
all the time influencing tiic nerve-cells. The effect of this multitude of affer-
ent stimuli, in spite of their feebleness, is to cause the motor cells of the cord
to continually send delicate motor stimuli to the muscles. These cause the
muscle to keep in the state of slight but continued contraction which gives the
tension ])eculiar to waking hours, and which is called viusclc-tonus. That
such a tension exists is made evident by the change in attitude which occurs
when the relaxation accompanying sleep comes on. The effect of brain activ-
ity to cause muscular tension is, likewise, most easily recognized by observing
the relaxation of the muscles which occurs when mental excitement ceases.

Muscle-tonus, like every form of muscular contraction, is the result of chem-
ical change, and the liberation of energy. But little of this energy leaves the
body as mechanical energy, most of it being given off as heat.

This view is by no means universally accepted, and many physiologists
believe in a production of heat by the muscles, as a result of nervous influences,
independent of contraction. It is thought that a condition of slight but con-
tinuous chemical activity resulting in the production of heat may be maintained
in the muscles by intermittent but frequent reflex excitations, a condition which
has been called chemical tonus} That the chemical activity of muscles is kept
up by small stimuli from the spinal cord is shown by the fact that if the nerves
be severed, or the nerve-ends be poisoned by curare, the muscle absorbs less
oxygen and gives off less carbon dioxide than when at rest under normal
conditions.^

The theory of a reflex chemical tonus independent of contraction implies
the existence of special nervous mechanisms for the exciting of chemical
changes in the muscles which shall result in the liberation of energy as heat,
independent of the change of form of the muscle. The question of the exist-
ence of special nervous mechanisms controlling heat-production — heat-centres,
as they are called — will be considered in another part of this book.

E. Electrical Phenomena in Muscle and Nerve.

The active muscle liberates three forms of energy : mechanical work, heat,
and electricity. The active nerve makes no visible movements, gives off no
recognizable quantity of heat, but exhibits changes in electrical condition quite

^ Roehrig und Zuntz: Pfluger's Archiv, 1871, Bd. iv. ; Pfliiger: PiUUjei^s Archiv, 1878, xviii.
p. 247.

'^ Zuntz: Pfluger's Archiv, 1876, xii. 522; Colasanti, Ibid., 1878, xvi. p. 57.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 135

comparahk' to those observed in the aetive niusele. The electrieal changes in
nerves are the only evidence of activity which we can observe, aside from the
effect of the nerve on the organ whicli it excites ; tliey are therefore of great
interest to ns.

Electrical energy, like all forms of active energy, is the result of a trans-
formation of potential or some form of kinetic energy. In the case of the
muscle, as of an electric battery, we find electricity to be associated with chemi-
cal change, and believe it to be liberated from stored potential energy. In the
case of nerves no chemical change can be detected during action, and hence we
are at a loss to explain the devolopment of electricity. We can only say that
it is the result of some chemical or physical process which we have as yet failed
to discover.

Although activity of nerve and muscle is found to be associated with elec-
trical change, we must not suppose functional activity to be in any sense an
electrical process. The movements of a man may be interpreted from the move-
ments of his shadow, but they are very different phenomena; the activity of
the nerve and muscle is indicated by the electrical changes accompanying it,
but they may be independent processes. Certainly the irritating change which
is transmitted along the nerve and which
excites the muscle to action, although ac-
companied by electrical changes, is not
itself an electric current.

Electrical energy is exhibited not only
by active nerve and muscle, but during
the activity of a great variety of forms
of living matter. It may be detected in
gland-cells, in the cells of many of the
lower animal organisms, and even plant-
cells. The amount of electrical energy
developed in animal tissues may be far
from trivial. Although delicate instru-
ments are necessary to observe the elec-
trical changes in nerve and muscle, as
the great internal resistance of the tissues
causes the currents to be small, we find in
certain fish special electric organs, which
appear to be modified muscle-tissue, and

Fig. 58.— Schema of galvanometer: n, s, north
and south poles of astatic pair of magnets ; m,
compensating magnet, held by friction on the
which are capable of discharging a great staff, and capable of being approached to, or ro

amount of electrical energy when excited
through their nerves. So intense is the
action of this electrical apparatus that it
can be used as a weapon of defence and
offence.

1. Methods of Ascertaining the Electrical Condition of a Muscle or a Nerve.—
If the electric tension of any two parts of an object differs, the instant they are joined an

tated with reference to, the suspended magnet ;
X, mirror; /, fibre supporting the magnets; c, c,
c, c, coils of wire to carry the electric current
near to the magnets, the upper coils being wound
in the opposite direction to the lower ; e, e, non-
polarizable electrodes applied to the longitudinal
surface and cross section of a muscle.

136

A^^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

electric current will flow from the point where the tension is greater to that where it is less.
The presence, direction of flow, and strength of an electric current can be detected by an
instrument calleil a iralvanometer. If any two parts of a muscle or nerve, as e, e, Figure
58, be connected by suitable conductors witli the coils, c, c, of a galvanometer, and if there
be a difiereiice in the electric potential of the twu jiarts examined, an electric airrent will
be indicated by the instrument. In such tests all extra sources of electricity are to be
avoided, therefore the electrodes applied to the muscle must be non-polarizable.

The Galvanometer — An ordinary form of galvanometer consists of a magnet suspended
bj' an exceedingly delicate fibre of silk, or quartz, and one or more coils, composed of many
windings of pure copper wire, placed vertically near the magnet and in the plane of the mag-
netic meridian. If an electric current be allowed to flow through the wire, it influences the
magnetic field about it, and, if the coils be close to the suspended magnet, cau.ses the
magnet to deviate from the plane of the magnetic meridian in one or the other direction,
according to the direction of the flow of the current. In the more delicate instruments the
influence of the earths magnetism is lessened by the use of two magnets of as nearly as pos-
sible the same strength, placed so as to point in opposite directions, and fastened at the
extremities of a liglit rod. As each magnet tends to point toward the north, they mutually
oppose each other, and therefore the effect of the earth's magnetism is partly compensated.
Still another magnet may be brought near this "astatic" combination, and by opposing the
action of the earth's magnetism make the arrangement even more delicate. In the Thomp-
son galvanometer, the rod connecting the needles bears a slightly concave mirror, from
which a beam of liglit can be reflected on a scale. Or a scale may be placed so that its
image falls on the mirror, and the shghtest movement of the magnet may be read in the
mirror by a telescope.

The galvanometer is very sensitive to the presence of electric currents. Another appa-
ratus which is even more responsive to changes in electric potential of short duration is
the capillary electrometer.

The capillarrj electrometer (Fig. 59) consists of a glass tube ia) drawn out to form
a very fine capillary, the end of which dips into a glass cup with parallel sides (/) contain-
ing a 10 per cent, solution of sulphuric acid. The
upper part of the tube is connected bj' a thick-
walled rubber tube with a pressure-bulb containing
mercury (c). As the pressure-bulb is raised, the
mcrcurj' is driven into the capillary, the flow being
opposed by the capillary resistance. By a suffi-
cientlj' great pres.sure. mercury may be driven to the
extremity of the capillar^' and all the air expelled.
When the pressure is relieved the mercurj' rises
again in the tube, drawing the sulphuric acid after
it. The colunm of mercur>' will come to rest at a
point where the pressure and the capillary force just
balance. Seen through the microscope (e), the end
of the column of mercury, where it is in contact
with the sulphuric acid appears as a convex menis-
cus (d). Any alteration of the surface tension of
the meniscus causes the mercury to move with
great rapidity in one direction or the other along
the tube ; and a verj'^ slight difference of electric
potential suffices to cause a change in surface ten-
sion of the mercurj'-sulphuric acid meniscus. A i)latinum wire ftised into the glass tube
(a), and another dipped into a little mercury at the bottom of the cup holding the acid,
permit the mercury in the capillary and the acid to be connected with the body the elec-
tric condition of which is to be examined. If the mercury and acid be connected with
two points of different electric potential, as g and /; of muscle M, the mercury will instantly

Fig. 59.— Schema of capillary electrometer.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 137

move from tlie direction of greater to that of lesser tension, descending deeper into the
tube if the pressure be raised on tlie mercury side, or lowered on the acid side, and vice
versa. As seen through the micnjscope the picture is reversed {d), and the movements
of the mercury appear to be in the opposite direction to that stated. The extent of the
movements of the mercury column can be estimated by a scale in the eyepiece. More-
over, the movement of the mercury can be recorded ijhotographicully, \>y placing a strong
light behind the column of mercury, and letting its shadow fall thnjugh a slit in the wall
of a dark chamber, upon a sheet of sensitized i)aper stretched over the surface of a revolv-
ing drum or a sensitized plate moved by clockwork or other suitable mechanism. This
instrument, of which there are a number of different forms besides that originally devised
by Lippmann, is very delicate, recording exceedingly slight differences in electrical poten-
tial.

2. Currents of Rest. — A normal resting nerve or muscle presents no dif-
ferences in electric tension and gives no evidence of electric currents, wherefore
we say it is iso-electric. If any part of the structure be injured, its electrical
condition is forthwith changed, and if the injured portion and some normal
part be connected with a galvanometer, an electric current is observed to flow
from the normal region to the point of injury. These muscle-currents were
discovered at about the same time by Matteucci and Du Bois-Reymond, and
the latter wrote a now celebrated treatise upon the electrical phenomena to be
observed in the nerve and muscle undei' varying conditions.^

Directions of Currents of Rest. — If a striated muscle, with long parallel
fibres, such as the sartorius or the semimembranosus of a frog, be prepared
with care not to injure the surface, and then be given a cylindrical shape by
cutting off the two ends at right an-
gles to the long axis, the piece will
present two cross sections of injured
tissue and a normal longitudinal sur-
face (see Fig. 60). If non-polarizable
electrodes, connected with the coils of
wire of a galvanometer, be applied to
various parts of such a piece of mus-
cle, it will be found that all points on
the longitudinal surfaces are positive
in relation to all points on the cross
sections, but that the differences of
tension will differ according to the
points which are compared. Suppose
that the cylinder be divided into
equal halves by a plane parallel to the
cut ends. Points on the line bound-
ing this plane, the equator, show the

greatest positive tension, and the forther other points on the longitudinal sur-
face are from the equator the less their tension. Points on the cross section
show a negative tension, and this lessens from the centre to the periphery of
' Untersuchungen vber thierische Ekktricitdt, Berlin, 1849.

Fig. 60.— Schema to show the direction of cur-
rents to be obtained from muscle. The schema
represents a cylindrical piece of muscle with nor-
mal longitudinal surface (a, c and 6, d), and two
artificial cross sections (a, b and c, d). The position
of the equator is shown by line e. The unbroken
lines connect points of different potential, and the
arrows show the direction which the currents
would take were these points connected with a
galvanometer. The broken lines connect points
of equal potential from which no current would be
obtained.

138 AN AMERICAN TEXT-BOOK OF I'HV.SIOLOaY.

the cross section. Points on the cross section equidistant from the centre, or
on the longitudinal surface equidistant from the equator, have the >amc poten-
tial and give no current, while points placed nnsymmetrieally give a current.
Splitting the cylinder by separation of the parallel fibres gives j)ieces of nuis-
cle M Inch show the same electrical juMuliarities, and without doubt the same
would be true of separate muscle-fibres or pieces of fibres.

Theories as to Cause of Ounrnts of Best — Du Bois-Reymond, impressed by
the facts which he had ascertained as to the direction of action of the electro-
motive forces exhibited by the muscle, tried to explain the difference in elec-
trical tension of the surface and cross section on the supjiosition that the
muscle was composed of electro-motive molecules which presented differences
in electric tension similar to those shown by the smallest particles of muscle
which it is possible to study experimentally. Further, he considered these dif-
ferences in tension, and the consequent electric currents, to exist within the
normal muscle — the longitudinal surface and normal cross section, i. e. the
point where the muscle-fibre joins the tendon, having the same sort of differ-
ence in electric potential as the normal longitudinal surface and the artificial
cross section. When the muscle is injured the balance of the electro-motive
forces within is lost, and they are revealed. It is difficult to refute such a
theory by experiment, because our instruments only record differences in tension
at points on the surface of the muscle to which we can apply the electrodes.
We cannot say that there is an absence of electric tension or lack of electric
currents within the normal resting muscle ; we can only say that there is no
direct experimental evidence of the existence of such currents.

Another theory of the electrical phenomena observed in muscle, and one
which has found many adherents, was advanced by Hermann.^ According to
Hermann's view there are no differences in electric potential and no electric
currents within the normal muscle; the "current of rest" is a "current of
injury," a "demarcation current," i. e. it is due to chemical changes occurring
in the dying muscle-tissue at the border line between the injured and living
muscle-tissue.

Although the greatest differences in potential are observed when many muscle-
fibres are injured, as when a cut is made completely through a muscle, injurv
to any part causes that part to become negative as compared with the rest.
Even an injurv to a tendon causes a difference in potential. It is exceedingly
difficult, therefore, to expose a muscle M'ithout injuring it ; but this can be done
in the case of the heart ventricle, and Engelmann showed that this gives no cur-
rent when at rest, although a current is found as soon as any part is hurt, the
part becoming immediately negative in relation to other uninjured parts. In
experiments on isolated, long, parallel-fil)red muscles, the current which is
caused by the injury of one extremity is found to fade away only very gradu-
ally (it may last forty-eight hours or more), and this current can be strength-
ened but little by new injuries. In the case of the heart-muscle the current
caused by cutting off a piece of the ventricle soon disappears, but another cur-
1 Handbuch der Physiologic, 1879, Bd. i. p. 226.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 139

rent ot" ocuinl strength is got if a new section be made by cutting off the tissue
injured by the lirst cut. In tiie case of the long-fibred muscles the death
process gradually progivsses the length of the injured fibres, while in the case
of the heart-niuscle, in which the cells are very short, the death processes are
limited to the injun-d cells, and on their death the current disappears; when a
new cut is made other cells are injured and again a strong current is obtained.

Dead tissue gives no current ; normal resting living tissue gives no current ;
dying tissue is electrically negative as compared with normal living tissue.

Hering has carried Hermann's view that electrical change is the result of
chemical action still further. He considers that the condition of negativity is
an evidence of katabolic (breaking-down) chemical processes and that anabolic
(building-up) chemical processes are accompanied by a positive electrical change.
Like Du Bois-lieymond, he believes that the normal resting muscle may be
the seat of electro-motive forces Avhich do not manifest themselves as long as
the diflferent parts are in like condition.

Current of Red of a Nerve. — Xerves like muscles show no electric currents
if normal and resting, but give a demarcation current if injured, the dying por-
tion being negative to normal parts, and the direction of the currents is the
same as in injured muscle. Gotch and Horsley^ ascertained the electro-motive
force in the nerve of a cat to be 0.01 of a Daniell cell and of an ape only 0.005,
while in the spinal nerve-roots of the cat it was 0.025, and in the tracts of the
spinal cord of the cat 0.046 and of the ape 0.029. Larger currents are
obtained from uon-medullated nerves, probably because a non-medullated
nerve contains a larger number of axis-cylinders than a medullated nerve of
the same size. The current of injury of a nerve lasts only a short time. The
death process which is the immediate result of the injury proceeds along the
nerve only a short distance, perhaps to the first node of Ranvier, and when it
has ceased to advance the current fails ; a new injury of the nerve causes
another demarcation current as strong as the first.

Hering found that a nerve like a muscle could be excited by its own cur-
rent, provided the circuit between the longitudinal and fresh cross section of an
irritable nerve was rapidly closed.

3. Currents of Action in Muscle. — Just as the dying tissue of nerves is
electrically negative as compared with normal tissue, so active nerve- and
muscle-tissue is electrically negative as compared with resting tissue.

Du Bois-Reymond discovered that if the normal longitudinal surface and
injured cut end of a muscle were connected with a galvanometer and the muscle
were tetanized, the magnet swung back in the opposite direction to the deflec-
tion which it had received from the current of rest. This backward swing of
the magnet was not due to a lessening of the current of rest, for if the effect
of the current of rest on the galvanometer were compensated for by a battery
current of equal strength and of opposite direction, so that the needle stood at
0, and the muscle were then tetanized, there was a deviation of the needle
in the opposite direction to that given it by the current of rest. Du Bois-
1 Philosophical Transactio7is, 1891, B., vol.182, pp. 267-526.

Fig. 6L— Secondary tetanus.

140 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

Reymond called this current of action the negative variation current. This
negative variation current was found to last as long as the muscle coiitinucd in
tetanus. On the cessation of the stimulus the current subsided more or less
rapidly and the needle returned more or less completely to the position given it
by the current of rest before the excitation. Tiie return was rarely complete,
and by repeated excitations there was a gradual lessening of the current of
rest, the amount varying with the extent of the preceding irritation.

Secondary Tetanus. — Matteucci and Du Bois-Reyraond (1842) both dis-
covered the phenomenon which Du Bois-Rcymond called secondary tetanus.

If two nerve-muscle preparations be
''''•^^•~-^'' — ^ 1:^ made, and the nerve of prejiaration B

„._/ — r^v^^ \\^ be laid on the muscle of preparation

A, when the nerve of A is stimulated,
not only the muscle of A but the
muscle of B will twitch (see Fig. 61).
If nerve A be excited by many
rapidly following induction shocks so
that muscle A enters into tetanus,
muscle B will also be tetanized. The phenomenon is not due to a spread of
the irritating electric current through nerve and muscle A to nerve B, for the
tetanus of both muscles stops if nerve A be ligated ; moreover, a secondary
tetanus is obtained in case tetanus of muscle A is called out by mechanical
stimuli, such as a series of rapid light blows, applied to nerve A.

Du Bois- Reymond considered " secondary tetanus " a proof of the discon-
tinuity of the apparently continuous contraction of tetanus, for muscle B could
only have been excited to tetanus by rhythmic excitations from A. Each of
the rapidly following excitations applied to A was the cause of a separate con-
traction process and a separate current of action in B ; the separate contractions
combined to produce the tetanus of 7>, but the separate currents of action did
not fuse, although they caused a continuous negative variation of the slowly
moving magnet of the galvanometer.

The correctness of this view has been shown by experiments with the capil-
lary electrometer, which approaches the " physiological rhcoscopc," as the
nerve-muscle preparation is called, in its sensitiveness to rapid changes in elec-
trical potential.

Burdon Sanderson ^ has obtained, by photographically recording the move-
ments of the column of mercury of the capillary electrometer (see Fig. 59,
p. 136), beautiful records of the changes of electric potential which occur when
an injured muscle is tetanized.

The record in Figure 62 shows, first, a series of negative changes resulting
from the separate stinmli. It is these which cause secondary tetanus and
which produced the negative variation current disclosed by the galvanometer
in the experiments of Du Bois-Reymond. Second, there is a more permanent
negative change, likewise opposed to and lessening the effect of the negative
^ Journal of Physiology, 1895, vol. xviii. p. 717.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 141

chan^i' at tlie part where the tissue is dying, and called by Sanderson " the
diniiuntional effect." This continuous negative change is probably attributable
to the presence of a continuous contraction process, perhaps the contracture
which we observed in studying the tetanus curve (see Fig. 49). This " diniinu-

Fin. 02. — Recc^rd of cliaii^es in eleetrif' potential in a tetanized injured muscle of a fro^'. The leadiuK-
off non-polarizable electrodes connected with the capillary electrometer touched the normal longitud-
inal and injured cut surface of the muscle. The muscle was tetanized by an induction current applied
to its nerve, the rate of interruptions being 210 per second. A rise of the curve indicates an electrical
change of opposite direction to that caused by the injury. The diminution of the current of injury,
which was less than in some other experiments, was 0.008 volt. The time record at the bottom of the
curve was obtained from a tuning fork making 500 double vibrations per second (after Burdon San-
derson).

tional effect " is only to be observed upon an injured muscle, since it repre-
sents a difference in potential between the normally contracting and the injured,
imperfectly contracting muscle-substance. AYhen all parts of the muscle are
normal and contracting to an equal amount, the electrical forces would be
everywhere of the same nature, balance one another, and give no external
evidence. Although the diminutional effect is only to be observed upon the
injured muscle, the temporary negative changes which follow each excitation
are to be observed on the normal muscle. To understand this we must con-
sider the diphasic current of action.

Diphasic Current of Action. — If a normal muscle be locally stimulated by
a single irritation, either directly or indirectly through its nerve, the part
excited will be the first to become active and electrically negative, and this
condition will be taken on later by other parts. Our methods only permit us
to observe the relative condition of the parts of the muscle to which the elec-
trodes are applied, the changes in the intermediate tissue failing to show them-
selves. If an electrode be applied near the place where the uninjured
muscle is stimulated. A, and another at some distant point, B, and these
electrodes be connected with a capillary electrometer, a diphasic electrical
change will be observed to follow each stimulation. At the instant the irritant
is applied the muscle-substance at A will become suddenly negative with
respect to that at B ; when the spreading irritation wave has reached B, that
part too wnll tend to be negative, and an electrical equality will be temporarily
established ; finally, B continuing to be active after A has ceased to act, B
will be negative in respect to A. Since the Avave of excitation spreads along
the fibres in both directions from the point irritated, each excitation will cause
two such diphasic electrical changes.

142 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

If the muscle has beeu injured at i>, the dyiiii^ libre.s lliere will react but
poorly to the stimulus, and therefore the anta<ronistic influence of the nej^ative
change at B will incompletely compensate for the negativity at A, and hence
only a single phase due to the condition of negativity at A will be seen.

The normally beating heart shows diphasic currents of action : in the first
phase the base, where the contra(;tion process starts, is negative to the apex,
and in the second phase the apex is negative to the base. In case the heart be
injured, the negative change corresponding to action fails at the injiu'cd part,
and therefore a single and because not antagonized more prolonged negative
change is observed. Under certain conditions a trii)hasic change is observed,
which need not be discussed here. AV^aller ^ has succeeded in recording the
electrical changes which accompany the beat of the human heart.

These diphasic changes of the electric condition are sufficiently strong and
rapid in the mammalian heart to excite the nerve of a nerve-muscle prepara-
tion, and the muscle will be seen to give one, or, if the heart is uninjured,
sometimes two, contractions every time the heart beats.

Bernstein 2 found the time between the two portions of diphasic change to
be proportional to the distance between the Icading-off electrodes, and to cor-
respond to a rate of transmission the same as that of the wave of excitation
as revealed by the spread of the contraction process (in the muscle of the frog
3 meters per second). Hermann,'* by using cord electrodes on the human fore-
arm, found the rate of spread of the active process by the voluntary contraction
of human muscle to be from 10 to 13 meters per second. Du Bois-Reymond
dip])ed a finger of each hand into fluid contained in cups connected with a
galvanometer. If the muscles of one arm were vigorously contracted, a
deflection of the magnet was seen. This was probably due to electric currents
from the glands of the skin and not from the contracting muscles. Bernstein
found that the negative change began at the instant of excitation, /. e. during
what was considered the latent period, and hence he thought that it preceded the
contraction process and rei)resented the excitation process. It is now believed
that the katabolic chemical changes which result in the development of the
three forms of energy, heat, motion, and electricity, have little or no latent
period, but begin at the instant the irritant acts, being practically synchronous
with the excitation process (see p. 101). The condition of negativity is con-
sidered not to result from an irritation process preceding the contraction, but
to be associated with the contraction process itself, and this view is supported
by the discovery that the negative state continues throughout the contraction.
Sanderson and Page* saw the diphasic change which accompanies the beat of
the heart last throughout the contraction.

Lee^ found the dijihasic change which occurs when the skeletal muscle of

' Archiv fiir Anatomie unci Physiolor/ie, 1890; physiol. Abtheil., p. 187.

^ Untersuchuncjen iiber den Erregunfjsvorgung im Nerven- und Muskel-systeme, 1871.

' Handbuch der Physiologie, 1879, i. 1, p. 224.

* Journal of Physiology, 1879, vol. ii., p. 396.

^ Archiv fiir Anatomie und Physiologic, 1887, p. 204.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 143

a frog is excited by a single stinmlus to continue as long as the muscle remains
active, including the period relaxation ; in some cases it lasted from 0.05 to
0.06 second. Sandei*son, as we have seen (see Fig. 62), tetanized injured
skeletal nuiscles of the frog, and found not only a series of negative variations
corresponding to the contraction processes which resulted from the separate
excitations, but a continuous negative variation, the diminutional effect, which
developed comparatively slowly and lasted after the irritant had ceased to act.
All these facts unite to point to the conclusion that the negative electrical
change w'hich develops when a muscle is excited to action is associated with
the contraction process.

4. Currents of Action in Nerves. — In general, the facts which have been
stated with regard to the current of action in muscles apply to nerves. When
a normal nerve is excited a negative change is forthwith developed at the
stimulated point and passes thence in both directions along the nerve at the
same rate as the nerve impulse. This change is diphasic, first the part excited
and later distant parts showing the negative change. If the nerve be injured,
and the normal surface be compared with the dying or dead cross section, the
second phase is absent. If the nerve be frequently excited, each excitation
awakens a separate current of action. The duration of the negative change
caused by a .single stimulus varies in different conditions from 0.007 to 0.023
second. The strength of the current of action likewise varies, but under
favorable conditions may be twice as great as the current of rest,^ and Hering
has shown that it is capable of exciting another nerve to action. Nerve-cells
and muscles are more sensitive to nerve impulses than our instruments are to
the accompanying electrical changes, nevertheless a negative change may be
observed to accompany a nerve impulse which has been caused by the excita-
tion of the nerve by nerve-cells.

Du Bois-Reymond observed with the galvanometer a lessening (" negative
variation") of the demarcation current ("current of rest") when in strychnia-
poisoning the spinal motor nerve-cells were exciting the motor nerves vigor-
ously and causing cramp-like tetanic muscular contractions. Gotch and
Horsley ^ applied electrodes connected with a capillary electrometer to periph-
eral nerves, spinal nerve-roots, and tracts of motor fibres within the spinal
coi'd, and di.scovered that if the cortical brain-cells in the motor zones were
excited, the nerves showed currents of action corresponding in rate to the dis-
charge of motor impulses from these brain-cells, e. g. if the epileptiform con-
vulsions were occurring at the time, the capillary electrometer revealed changes
of potential of like rate in the nerves.

As far as has been ascertained the nerve impulse has the same general cha-
racteristics in all forms of nerves, medullated and non-medullated, sensory,
inhibitory and motor, and except as regards strength, rhythm, etc. is the same
whether they be excited artificially or normally by a nerve-cell or sen.sory end-
organ. In every case the impulse appears to be accompanied by a current of

' Biedermann : Elektrophysiologie, 1895, p. 666.

* Philosophical Transactions, 1891, vol. 182, pp. 267-526.

144 AN A3fUBICAN TEXT-BOOK OF PHYSIOLOGY.

action, e.g. light falling on the retina of" the eye of a frog causes a negative
variation of the current of rest of the optic nerve.

F. Chemistry of Muscle and Nerve.

1. Chemistry of Muscji.e.

Muscles contain about 75 j)art,s water and 25 parts solids; nearly 21 parts
of the solids are proteids, the remaining 4 parts consisting of fats, extractives,
and salts.

Little is known concerning the chemistry of living muscle; the instability
of the complex jnolecules which makes possible the rapid development of energy
peculiar to muscles renders exact analysis impossible. The manipulations
essential to chemical analysis necessarily alter and kill the muscle protoplasm.

Death of the muscle is ordinarily associated with a peculiar chemical change
known as rigor mortis. To understand the chemical composition of muscle it
is necessary that we should consider the nature of this change.

1. Rigor Mortis. — Rigor mortis, the rigidity of death, is the result of a
chemical chung(i in the substance of a muscle by which it is permanently
altered, its irritability and other vital properties being irretrievably lost. The
change is manifested by a loss of translucency, the muscle becoming opaque, and
by a gradual contraction, accompanied by a development of heat and acidity,
and resulting in the muscle being stiff and firm to the touch, less elastic, and
less extensible. Whenever muscle dies it undergoes this change.

Conditions which Influence the Development of Rigor. — Ordinarily on the
death of the body the muscle enters into rigor slowly — the muscle-fibres are
involved one after the other, and through the gradual contraction and harden-
ing of the antagonistic muscles the joints become fixed and the body acquires
the rigidity which we associate with death. Rigor usually affects the different
parts of the body in a regular order, from above downward, the jaw, neck,
trunk, arms, and legs being influenced one after the other. The jjosition taken
by the body is generally determined by the weight of the parts and the rela-
tive strength of the contractions of the muscles.

The time required for the appearance of rigor is very variable. It is deter-
mined in part by the nature of the muscle, its condition at the moment of
death, and the temperature to which it is subjected. The muscles of warm-
blooded animals enter into rigor more quickly than those of cold-blooded
animals; of the warm-blooded animals, pale muscles more quickly than red,
and the flexors before the extensors ; of the cold-blooded animals, frog's muscles
more quickly than those of the turtle. In general, the more active the muscle
protoplasm, the more rapid are the chemical changes which it undergoes, and
amongst these the coagulation of rigor mortis.

The condition of the muscle plays a very important part in determining the
onset of rigor. If the muscles are strong and vigorous and death of the body
has come suddenly, rigor develo])s slowly ; if the muscles have been enfeebled
by disease or fatigued by great exertion shortly before death, it comes rapidly.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 145

In till' case of wasting diseases rigor comes quickly, is poorly developed, and
passes off' quickly ; when the muscles are fatigued at the time of" death, as in
the case of a hunted animal, it comes (juickly. We hear of soldiers found dead
on the field of battle grasping the sword, as if the muscular contractions of life
had been continued by the contractions of death. In the case of certain dis-
eases of the spinal cord and brain, too, rigor may come so ra})idly that the
limbs may maintain the position which they had at the time of death, " cata-
leptic rigor," as it has been called. The coming on of rigor is particularly
striking in the case of diseases which, like cholera, are accompanied by violent
muscular cramps and lead to a rapid death. It is not uncommon, in such
cases, for the contractions of rigor to cause movements which may mislead a
watcher into supposing the dead man to be still alive. This idea is favored by
the fact that the body may remain warm, owing to the heat which is produced
in the muscles as a result of the chemical changes occurring during rigor.
The post-mortem muscular contractions and the rise of temperature observed
in such eases are only excessive manifestations of what always occurs on the
death of the muscle. The movements are probably due, in part, to the rapidity
with which the muscles contract in rigor, and in part to the fact that the
antagonistic muscles are not affected at the same time to the same degree.
Whether the contractions are partly excited by changes accompanying the
death of the motor nerve-cells in the central nervous system is uncertain, but
not impossible. Muscles are still able to respond by contractions to stimuli
coming to them through the nerve, even after rigor has become quite pro-
nounced, probably because the coagulation process attacks the different fibres
at different rates, and certain of the fibres are still alive and irritable after the
others are dead and coagulated.

Many observers favor the view that the central nervous system influences
muscles after the death of the body as a whole, and by weak stimuli resulting
from the changes in the nerve-cells excites chemical changes in the muscles
which favor the coming on of rigor.^ In proof of this it is stated that cura-
rized muscles enter into rigor more slowly than non-curarized. Undoubtedly
stimulation of the nerve, or, indeed, anything which would excite a muscle to
action, tends to put it in a condition favorable to the coming on of rigor ;
whether the influence exerted by the central nervous system is more than this
is very questionable.

Temperature has a marked influence on the development of rigor mortis.
Cold delays and warmth favors, 38°-40° C. being most favorable. Since rigor
is the result of a chemical change, these effects of temperature are what one
would have expected. Other forms of chemical change which are attributable
to ferment action are found to be the most vigorous at a temperature of about
40° C.

In general, it may be said that rigor in warm-blooded animals comes on
in from ten minutes to seven hours after death, although some state that it
may come as late as eighteen hours. It lasts anywhere from one to six days.
^ Brown-Sequard : Archives de Physiologie, 1889, p. 675.
10

146

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

The sooner it conies on, the sooner it goes off. The stiffness can be broken up
artificially by forced movements of the part?^, and when thus destroyal does
not return, provided the rigor was complete at the time.

The Clause and Xature of the Contraction of Rigor 3Ior( is. — Tlie most likely
explanation of the contraction of the dying muscle is that it is the result of
the coagulation of a part of the semi-fluid muscle-substance within the sarco-
lemma. This was suggested by Bruecke, and Kuehne proved that such a
coagulation change takes place, by showing that the semi-fluid muscle-sub-
stance, " the muscle-plasma," if expressed from the frozen muscle, coagulates on
being warmed. The coagulation is a chemical change attributed to the action
of a ferment, the myosin ferment, which is thought to be formed at the death
of the muscle.

Another, though less generally accepted view, is that the contraction of the
muscle seen in rigor is of the same nature as ordinary muscular contractions.^
Prolonged muscle ct)ntractions are ol)served when a muscle is greatly fatigued
or subjected to such a drug as veratria (see p. 128), and there are many points
of resemblance between the contraction of normal and dying muscle — viz. the
change of form, the production of heat, the formation of sarcolactic acid, the
using up of oxygen and the production of carbon dioxide, and the fact that
the dying and presumably coagulating muscle is, like normal contracting mus-
cle, electrically negative as compared with normal resting muscle. To this
may be added that, as has been said, the muscle continues to be irritable even
when rigor is quite advanced, and that it enters into rigor more quickly if left
in connection with the central nervous system.

On the other hand, one cannot fail to be impressed with the differences
between the two forms of contraction.

Normal Contracting Musdc.
Contains uncoagulated myosinogen.
Is translucent.
Is soft and flexible.
Is no less elastic than in repose.
Is more extensible than in repose.
Contracts rapidly.
Fatigues rapidly and reTaxes.

Muscle contracting by Rigor Mortis.
Contains coagulated myosin.
Is opaque.
Is firm and stiff.
Is less elastic than before.
Is less extensible than before.
Contracts very slowly, as a rule.
Remains contracted a long time.

Furthermore, it may be added that normal contractions only occur A\hen
the irrital)le muscle is stimulated, while a mu.scle can enter into rigor when its
irritability has been taken away by subjecting it to oxalate solutions,^ also,
when it has been curarizod and so shut out from all nervous influences.^

Rigor is not confined to the voluntary mu.scles, though it is less easily
observed in the case of most involuntary muscles. The heart enters rapidly
into rigor, with the formation of sarcolactic acid. The non-striated muscle
of the stomach and ureters, too, has been .seen to undergo this change.

' Hermann : Handbuch dtr Physiologie, 1879, Bd. i. p 146.
* Howell : Journal of Physiology, 1893, vol. xiv. p. 476.
' Nagel : Pjliiger's Archiv, vol. Iviii. S. 279.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 147

The passini^ ott' of rigor mortis is usually accompanied by beginning
decomposition, and, indeed, it is generally supposed that the decomposition is
the cause of" softening of the muscle. This is denied by certain observers, and
it is stated that rigor may pass off when the presence of putrefactive organisms
is excluded by special aseptic precautions.

The Chemical Changes which accompany the Development of Rigor. — Rigor
mortis is characterized by the coagulation of a part of the muscle-substance ;
this can be prevented by a temperature a little below 0° C. Cold, although
temporarily depriving the muscle of its irritability, does not, unless extreme and
long-continued, kill the muscle protoplasm. Frogs can be frozen stiff and
recover their activity when they thaw out. Indeed, this probably happens not
infrequently to the frogs hibernating in holes in the banks of ponds. Since cold
prevents coagulation without destroying the life of the muscle protoplasm, we
can by its aid isolate the living muscle-substance from the nerves, blood-
vessels, connective tissue, and sarcolemna of the muscle, but as soon as we
begin to analyze it it loses its living structure. This method of obtaining
muscle-plasma was introduced by Kuehne^ in the study of the muscles of frogs,
and was later employed with slight modifications by Halliburton^ for the mus-
cles of warm-blooded animals. The blood was washed out of the vessels with
a stream of 0.6 per cent, sodium-chloride solution at 5° C. ; the irritable mus-
cles were then quickly cut out and frozen in a mixture of ice and salt at
12° C The frozen muscle was then cut up finely in the cold, and a yellowish,
somewhat viscid, and faintly alkaline muscle-plasma was squeezed out. This
fluid was found to coagulate in twenty to thirty minutes at a temperature of
40° C. ; if the temperature were lower the coagulation was slower. The clot,
which was jelly-like and translucent, contracted slowly aud in a few hours
squeezed out a few drops of serum. The coagulated material formed in the
clot is called myosin. It dissolves readily in dilute neutral saline solutions,
as a 10 per cent, solution of sodium chloride or a 5 per cent, solution of mag-
nesium sulphate, and its saline solutions are precipitated in an excess of water
or by saturation with sodium chloride, magnesium sulphate, or ammonium
sulphate ; it has, in short, the characteristics of a globulin. Chittenden and
Cummins state that it has the following composition: C 52.82, H 7.11. X
16.17, S 1.27, O 22.03.

Halliburton, in studying the coagulation of mu.scle, followed for the sake of
comparison the methods which have been employed in the study of coagulation
of blood. He found that muscle-plasma, like blood-plasma, is prevented from
coagulating not only by cold, but by neutral salts, such as magnesium sulphate,
sodium chloride, and sodium sulphate ; and further, that the salted plasma if
diluted coagulates.

The points of resemblance between the coagulation of myosin and fibrin
suggest a similar cause, and Halliburton succeeded in obtaining from muscles
coagulated by long standing in alcohol a watery extract, which greatly hastened

' UntersHckungen iiber das ProtopUwna, Leipzig, 1864.
^ Journal of Physiology, 1887, vol. viii. p. 134.

148 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the coagulation of nmscle-plasina and myosin solutions, llo cailc^d the sub-
stance thus obtained myosin ferment. The extract obtained contained an
albumose which was eitluM- the ferment or held it in close combination. The
pure ferment has not been isolated. The myosin ferment is not the same as
fibrin ferment, since neither can do the w(;rk of the other. Moreover, fibrin
ferment is destroyed at 75°-80° C. and myosin ferment is not destroyed till
100° C.

In several respects there is a close resemblance between th(! bcluivior of
blood- and muscle-plasma, but the coatrulated products differ. Kuehne found
that myosin could be dissolved by a dilute saline solution, and that, on further
dilution, it w^as reprecipitated. Halliburton observed that a saline solution of
myosin, diluted twenty times with water, gave a precipitate which could be
dissolved in a 5 per cent, magnesium-sulphate solution, and then by the addi-
tion of water be made to recoagulate. In these respects myosin differs markedly
from fibrin. Fil)rin is dissolved only with difficulty in dilute saline solutions
and cannot be recoagulated. Myosin also differs from fibrin by its greater
solubility in dilute HCl.

Moreover, the chemical change which results in the formation of myosin is
different from that which produces fibrin. The clotting of muscle-plasma and
the formation of myosin is accompanied or closely followed by the production
of an acid, while no such change occurs during the coagulation of blood-plasma.
In the earlier stages of clotting the acidity may be due in part to acid potassium
phosphate, but the final acidity is chiefly due to lactic acid. The source of the
lactic acid has not been definitely made put. The view that it comes from
glycogen is made questionable by Boehm's^ observation that the amount of
glycogen is not lessened in rigor, and is corroborated by the observation that
the muscles of starving animals become acid when entering into rigor, although,
as Bernard found, they contain no glycogen. Boehme concluded that the
sarcolactic acid is formed from the proteids, and this is accepted by other good
observers.

Some writers have thought the coagulation of the muscle was the result of
the formation of an acid by the dying muscle. This is unlikely, although the
presence of acid, like that of many other substances, quinine, caflfein, digitaliu,
veratrin, hydrocyanic acid, ether, chlorofi)rm, etc.,^ may hasten the process.
This may account for the rapidity with which rigor comes on in fatigued
muscles.

2. Constituents of Muscle-serum and Changes resulting from Con-
traction.— Muscle-serum can be most readily obtained by mincing a muscle
in rigor mortis and expressing the fluid. The proteids of the serum can be
separated by the degrees at which they undergo heat-coagulation.

The method of fractional heat-coagulation was employed by Halliburton'
to determine the proteids of muscle. He found the following :

^ Pfiiiyer' s Arckiv, 1880, Bd. xxiii. S. 44. " Ilalliburton : Phyi^iological Chemistry, p. 414.
■' Journal of Physiology, viii. pp. 184-186.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 149

Name. Temperature of coagulation.

Proteids obtained from ) Paramyosinogen 47° V,

the dissolved clot . . t- Myosinogen 5G° C

Y> J • 1 1 , • ] ,• ( Mvoglobulin 63° C.

Proteids obtainetl irom ^ - >-'

muscle-serutn

Myo-albiimin 73° C.

iMyo-albumose (not coagulated by heat).

The proteids of the serum can also be (listinguished by their sohibilities in
neutral salt-solutions of various strengths. The myoglobulin resembles .serum-
globulin, although precipitated at 63° C. instead of 73° C. The myo-albumin
is apparently identical with serimi-albumin.

To these proteids we must add the pigment haemoglobin. Another })ig-
ment, myohsematiu, is also found. It is not unlikely that the.se pigments have
here as elsewhere a respiratory fimction.

Nitrogenous Extractives. — The chief nitrogenous extractive is creatin ; in
addition to this we find small amounts of creatinin and of various xanthin
bodies, as xanthin, hypoxanthin, carnin, and sometimes traces of urea, uric
acid, taurin, and glycocoil. The chemical nature of these bodies need not be
considered here. Physiologically they may be regarded as waste products
which result from the partial oxidation of the proteids of muscle during the
katabolic processes which are continually occurring even in the resting muscle
protoplasm. Monari has shown that the amount of creatin and creatinin is
increased by the wear and tear of muscular work, although the proteids of the
well-fed muscle probably supply but little of the energy which is set free.^

The non-nitrogenous constituents of muscle are fats, glycogen, inosit, sugar,
and lactic acid.

Fats are usually found in intermuscular connective tissue, but there is little
within the normal fibre. It is doubtful whether fat plays any direct part in
the ordinary metabolic processes involved in the action of muscles, although
it is probable that if more available sources of energy are lacking it may, like
the proteids, be altered and employed. Under pathological conditions large
amounts of fat may be found inside the sarcolemma ; in phosphorus-poisoning
the degenerated muscle protoplasm may be replaced by fat in the form of fine
globules.

Glycogen is found in very variable amounts in different muscles. The work
of many observers has shown that it is here, as in the liver, a store of carbo-
hydrate material, and is employed by the muscle, either directly or after con-
version into some other body, as a source of energy. The quantity, which is
rarely more than | per cent., lessens rapidly during muscle work.

Sugar is found in muscles in small quantities only, nevertheless it probably
plays an important part, for Chauveau and Kaufmann, by studying the levator
labii .superioris of the horse, found that the muscles take sugar from the blood,
and that they take more during action than rest. The sugar which the mus-

1 Fick und Wislicenns: VierteJjahresschrift der Ziiricher Nnturfornchenden Gesellschafi, 1865,
Bd. X. p. 317 ; Pettenkofer und Voit : Zeitschrift far Bioloc/ie, 1866, ii. ; Voit : [bid., 1876, vi.
S. 305.

150 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cle takes during rest is for the most part stored as glycogen.' Altliough sugar
is considered a source of muscle-energy, the exact way in which it is employed
is doubtful.

Inovganio Constituents of Muscle. — Amongst the bases, potassium has the
greatest prominence, and sodium next ; magnesium, calcium, and small amounts
of iron are also found. Of the acids, phosphoric is present in the largest quan-
tities.

Gases of Muscle. — No free oxygen can be extracted, but carbon dioxide
may be obtained, in part free and in part in combination. A little nitrogen
can also be extracted. The amount of carbonic acid varies greatly with the con-
dition of the muscle ; for instance, it is much increased by muscle work. Mus-
cles take up oxygen from the blood freely, especially when active, and
when removed from the body may absorb small amounts from the air.
More oxygen is taken up by the muscle during rest than is liberated as
carbon dioxide, but during action the reverse is the case.^ Oxygen is not
retained as free oxygen, but is stored in some combination more stable than
oxyha^moglobiu. It is by virtue of the combined oxygen that the muscle is
enabled to do its work, but the process is not one of simple oxidation. That
muscles hold oxygen in available combinations was shown by Hermann, who
ascertained that a muscle can contract hundreds of times in an atmosphere
free from oxygen, and produce water and carbon dioxide.

II. Chemistry of Nerves.

Most of our ideas concerning the chemistry of nerves are based on analysis
of the white and gray matter of the central nervous system. The white matter
is largely made up of fibres and supporting tissue and the gray matter of nerve-
cells. The peripheral nerve-fibres are simply a continuation of the structures
in the central nervous system ; the active part of the fibre, the axis-cylinder, is
an outgrowth of the cytoplasm of a nerve-cell, and the surrounding medullary
sheath a continuation of the material which sheaths the axis-cylinder while in
the brain and cord. It is ])robable, therefore, that the chemistry of the axis-
cylinder approaches to that of the nerve-cell of which it is a branch, and the
chemistry of the medullary substance is the same outside as inside the central
nervous system.

The white matter of the brain of the ox, which is largely made up of nerve-
fibres, is composed of about 70 parts water and 30 parts solids, about one-half
the latter being cholesterin, about a quarter proteids and connective-tissue sub-
stance, and about a quarter complex fatty bodies, neuro-keratin, salts, chiefly
potassium salts and phosphates, and traces of xanthin, hypoxanthin, etc.

The nerve-fibre has a delicate sheath, the neurilemma, the exact constitution

' C5jn/5/e.s rendus de la Sociefe de Biologie, 1886, civ.

" Ludwig und Sczelkow : Sitzungsberichte den k. A/cad. Wien, 1862, Bd. xlv. Abthl. 1 ; and
Ludwig und Schmidt : Silzungaberkhte den math.-phys. Classe d. k. Sachs. Gesethchrtft drr Witsen-
schdft. 1868, Bd. xx. ; Regnault and Reiset: Annates de Chimie el de Physique, 1849, 3 me s^r.,
xxvi. ; Pfliiger: Pjluger's Archiv, 1872, vi. ; and others.

GENERAL PHYSIOLOGY OF MUSCLE AND NERVE. 151

of which is unknown, but which is supposed to resemble tlie sarcolemma and
to be composed of" a substance similar to elastin. The fibres are bound together
by connective tissue which on boiling gives gelatin. Within the neurilemma is
the medulkiri/ sheath, which is composed of two elements — viz. (1) neuro-kera-
tin, a material similar to the horny substance of epithelial structures, which
forms a sort of loose trellis, or network, and probably acts as a supporting
framework to the fibre ; (2) a white, highly refracting, semi-fluid material,
which fills the meshes of the ncuro-keratin network, and which is composed
largely of protagon and cholesterin combined with fatty bodies. Protagon is
a complex pli()sj)horized nitrogenous compound, which many observers believe
to contain lecithin and cerebrin. Both lecithin and cerebrin are fatty bodies
possessing nitrogen, and the former phosphorus. These and some other com-
plex fatty bodies ])robably exist in addition to protagon in the medullary sub-
tance. The formation of the "myelin forms" seen in the medulla of dead
nerves is attributed to lecithin. The axis-cylinder probably contains most of
the proteids of the fibre, chiefly globulins, mixed with complex fatty bodies.

The reaction of the normal living fibre is neutral or slightly alkaline. It
is said to become acid after death, but this change is not known to accompany
functional activity. Indeed, nothing is known of the physiological import of
the chemical constituents of the nerve-fibre or of the chemical changes which
occur in the axis-cylinder when it develops or transmits the nerve impulse.
The peculiar chemical composition of the medullary substance would suggest
that it has a more important function than simply to protect the axis-cylinder.
Some have attributed to it nutritive powers, and others have supposed it helped
to insulate : it is certain that the axis-cylinder can develop and transmit the
nerve impulse without the aid of the medullary sheath, for there is a large
class of important nerves — the non-medullated nerves — in which it is lacking.

III. SECRETION.

A. General Considerations.

The term secretion is meant ordinarily to apply to the liquid or semi-
liquid products formed by glandular organs. On careful consideration
it becomes evident that the term gland itself is widely applied to a variety
of .structures differing greatly in their anatomical organization — .so much so,
in fact, that a general definition of the term covering all cases becomes
very indefinite, and as a con.sequence the conception of what is meant by a
secretion becomes correspondingly extended.

Considered from the most general standpoint we might define a gland
as a structure composed of one or more gland-cells, epithelial in character,
which forms a product, the .secretion, which is discharged either upon a
free epithelial surface such as the skin or mucous membrane, or upon the
closed epithelial surface of the blood- and lymph-cavities. In the former ca.se
— that is, when the .secretion appears upon a free epithelial surface communi-
cating with the exterior, the product forms what is ordinarily known as a
secretion ; for the sake of contrast it might be called an external secretion.
In the latter case the secretion according to modern nomenclature is designated
as an internal secretion. The best-known organs furnishing internal .secretions
are the liver, the thyroid, and the pancreas. It remains pcssible, however,
that any organ, even tho.se not po.ssessing an epithelial structure, such as
the muscles, may give off' substances to the blood comparable to the internal
secretions — a possibility which indicates how indefinite the distinction between
the processes of .secretion and of general cell-metabolism may become if the
analysis is carried sufficiently far. If we consider only the external secretions
definition and generalization become much easier, for in these cases the secret-
ing surface is always an epithelial structure which, when it pos.'ses.ses a certain

organization, is designated as

rr^TO W • / • )♦)• /-T-T^JjJj / •/v^T^T^rr I ' \\lL. a gland. The type upon which

~~^^^^^^^^^\^^^l^^^^^^^^^=zpo^ these secreting surfaces arecon-

^^~^ structed is illustrated in Figure

Fig. 63.— Plan of a secreting membrane. /ir> mi ^ • ^ *•

63. The type consists or an
epithelium placed upon a basement membrane, while upon the other side of
the membrane are blood-capillaries and lymph-spaces. The secretion is
derived ultimately from the blood and is discharged upon the free epithelial
surface, which is suppo.sed to communicate with the extei-ior. The nuicous
membrane of the alimentary canal from stomach to rectum may be considered,

152

SECRETION.

153

if we neglect tlie existence of tlie villi and crypts, as representing a secreting
surface constructed on this type. If we suppose such a membrane to become

22333333^

M^

Fig. 64.— To illustrate the simplest form of a tubular and a racemose or acinous gland.

invaginated to form a tube or a sac possessing a definite lumen (see Fig. 64),
we have then what may be designated technically as a gland.

It is obvious that in this case the gland may be a simple pouch, tubular or
saccular in shape (Fig. 65), or it may attain a varying degree of complexity by
the elongation of the involuted portion and the development of side branches

SSJJS

Fig. 65.— Simple alveolar gland of the
amphibian skin (after Flemming).

Fig. 66.— Schematic representation of a lobe of a
compound tubular gland (after Flemming).

(Fig. 66). The more complex structures of this character are known sometimes
as compound glands, and are further described as tubular, or racemose (saccular),
or tubulo-racemose, according as the terminations of the invaginations are
tubular, or saccular, or intermediate in shape.^ As a matter of fact we find
the greatest variety in the structure of the glands imbedded in the cutaneous
and mucous surfaces, a variety extending from the simplest form of crypts or
tubes to very complicated organs possessing an anatomical independence and
definite vascular and nerve-supplies as in the case of the salivary glands
or the kidney. In compound glands it is generally assumed that the terminal
portions of the tubes alone form the secretions, and these are designated as the
the acini or alveoli, while the tubes connecting the alveoli with the exterior are
known as the ducts, and it is supposed that their lining epithelium is devoid
of secretory activity.

The secretions formed by these glands are as varied in composition as the
glands are in .structure. If we neglect the case of the so-called reproductive

' Flemming has called attention to the fact that most of the so-called compound racemose
glands, salivary glands, pancreas, etc., do not contain terminal sacs or acini at the ends of the
system of ducts ; on the contrary, the final secreting portions are cylindrical tubes, and such
glands are better designated as compound tubular glands.

154 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

glands, the ovary and testis, whose I'ight to the desiguutiou of" glauds is doubt-
ful, we may say that the secretions in the mammalian body are liquid or semi-
liquid in character and are composed of water, inorganic salts, and various
organic compounds. With regard to the last-mentioned constituent the secre-
tions differ greatly. In some cases the organic substances present are not found in
the blood, and furthermore they may be specific to a particular secretion, so that
we must suppose that these constituents at least are constructed in the gland
itself. In other cases the organic elements may be present in the blood, and
are merely eliminated from it by the gland, as in the case of the urea found in
the urine. Johannes MUller long ago made this distinction, and spoke of secre-
tions of the latter kind as excretions, a term which we still use and which car-
ries to our minds also the implication that the substances so named are waste
products whose retention would be injurious to the economy. Excretion as
above defined is not a term, however, which is capable of exact aj)plication to
any secretion as a whole. Urine, for example, contains some constituents which
are probably formed within the kidney itself, e. g. hij)puric acid; while, on
the other hand, in most secretions the water and inorganic salts are derived
directly from the blood or lymph. So, too, some secretions — for example, the
bile — carry off waste products which may be regarded as mere excretions, and
at the same time contain constituents (the bile salts) which are of immediate
value to the whole organism. Excretion is therefore a name which we may
apply conveniently to the process of removal of waste products fi-om the botly,
or to particular constituents of certain secretions, but no fundamental distinc-
tion can be made between the method of their elimination and that of the
formation of secreted products in general. Owing to the diversity in com-
position of the various external secretions and the obvious difference in the
extent to which the glandular epithelium participates in the process in different
glands, a general theory of secretion cannot be formulated. The kinds of
activity seem to be as varied as is the metabolism of the tissues in general.

It was formerly believed that the formation of the secretions was de-
pendent mainly if not entirely upon the physical processes of filtration, im-
bibition, and diffusion. The basement membrane Avitli its liuing epithelium
was supposed to constitute a membrane through which various products of the
blood or lymph passed by filtration and diffusion, and the variation in com-
position of the secretions was referred to differences in structure and chemical
properties of the dialyzing membrane. The significant point about this view
is that the epithelial cells were supposed to play a passive part in the process ;
the metabolic processes within the cytoplasm of the cells were not believed to
affect the composition of the secreted product. As compared with this view
the striking peculiarity of modern ideas of secretion is, perhai)S, the import-
ance attributed to the living structure and properties of the epithelial cells.
It is believed generally now that the glandular epithelium takes a direct part
in the production of some if not all of the constituents of the secretions. The
reasons for this view will be brought out in detail further on in describing the
secreting processes of the separate glands. Some of the general facts, how-

SECRETION. 155

ever, whidi infiiieiiced physiologists in coming to this conclusion are as
follows :

Microscopic examination has demonstrated clearly that in many cases parts
of the epithelial cell-substance can be followed into the secretion. In the
sebaceous secretion the cells seem to break down completely to form the mate-
rial of the secretion ; in the formation of mucus by the goblet cells of the
mucous membrane of the stomach and intestines a portl(^n of the cytoplasm
after undergoing a mucoid degeneration is extruded bodily from the cell to
form the secretion ; in the mammary glands a portion of the substance of the
epithelial cells is likewise broken off and disintegrated in the act of secretion,
while in other glands the material of the secretion is deposited within the cell
in the form of visible granules which during the act of secretion may be
observed to disappear, apparently by dissolution in the stream of water passing
through the cell. Facts like these show that some at least of the products of
secretiou arise from the substance of the gland-cells, and may be considered as
representing the results of a metabolism within the cell-substance. From
this standpoint, therefore, we may explain the variations in the organic
constituents of the secretions by referring them to the different kinds of
metabolism existing in the different gland-cells. The existence of distinct
secretory nerves to many of the glands is also a fact favoring the view of
an active participation of the gland-cells in the formation of the secretion.
The first discovery of this class of nerve-fibres we owe to Ludwig, who (in
1851) showed that stimulation of the chorda tympani nerve causes a strong
secretion from the submaxillary gland. Later investigations have demon-
strated the existence of similar nerve-fibres to many other glands — for
example, the lachrymal glands, the sweat-glands, the gastric glands, the
pancreas. It is asserted also that, in some cases at least, the increased
secretion is accompanied by an elevation in temperature of the gland, \vhich
speaks for an increased metabolic activity. Moreover, there is considerable
evidence, which will be given in the proper place, to show that the secretory
fibres are of two kinds, one controlling the production of the organic elements,
and one increasing the flow of water and inoi'ganic salts. Recent microscopic
work indicates that the secretory fibres end in a fine plexus between and round
the epithelial cells, and we may infer from this that the action of the nerve-
impulses conducted by these fibres is exerted directly upon the gland-cells.

The formation of the water and inorganic salts present in the various
secretions offers a problem the general nature of which may be referred to ap-
propriately in this connection, although detailed statements must be reserved
until the several secretions are specially described. The problem involves,
indeed, not only the well-recognized secretions, but also the lymph itself as
well as the various normal and pathological exudations. Formerly the occur-
rence of these substances was explained by the action of the physical processes
of filtration and diffusion through membranes. With the blood under a con-
siderable pressure and with a certain concentration in salts on one side of the
basement membrane, and on the other a liquid under low pressure and differ-

156 .l.V AMEIilCAX TEXT- HOOK OF PHYSIOLOGY.

ing iu chemical coniposititm, it would s^eein inevitable that water .should Hltor
through the membrane and that processes of osmosis would be set up, further
ehanjxinix the nature of the secretion. Upon this theory the water and salts iu
all secretions were regarded merely as transudatory products, and so far as they
were concerned the epithelium was supposed to act simply as a dead membrane^
This theory has not proved entirely acceptable for various reasons. It has
been shown that living membranes offer considerable resistance to filtration
even when the liquid pressure on one side is much greater than on the other.
Tigerstedt ^ and Santessen, for instance, found that a lung taken fi-om a frog
just killed gtive no filtrate when its cavity was distended l)y liquid under a
pressure of 18 to 20 centimeters, providetl the liquid used was one that did
not injure the tissue. If, however, the lung-tissue was killed by heat or other-
wise, filtration occurred readily under the same pressure. In some glands,
also, the formation of the water and salts, as has been said, is obviously under
the control of nerve-fibres, and this fact is difficult to reconcile with the idea
that the epithelial cells are merely passive filters. In glands like the kidney,
and in other glands as well, it has been shown that the amount of water and
salts does not increase in proportion to the rise of blood-pressure within the
capillaries, as should happen if filtration were the sole agent at work, and
furthermore, certain chemical substances when injected into the blood may
increase the flow of water in the secretion to an extent that cannot be well
accounted for in any other way than by supposing that they act as chemical
stimuli to the epithelial cells.

While, therefore, it cannot be denied that the anatomical conditions pre-
vailing in the glands are favorable to the processes of filtration and osmosis,
and while no one is justified in denying that these processes do actually occur
and seem to account in part for the appearance of the water and inorganic
salts, it seems to be clear that iu the present condition of our knowledge these
factors alone do not suffice to explain all the phenomena connected with the
secretion of water and salts. We must suppose that the epithelial cells are
actively concerned in the process. The way in which they act is not known ;
various hypotheses have been advanced, but none of them meets all the facts
to be explained, and at present it is customary to refer the matter to the vital
projjerties of the cells — that is, to the peculiar j)hysical or chemical properties
connected with their living structure.

We may now pass to a consideration of the facts known with regard to the
physiology of the different glands considered merely as secretory organs.
The functional value of the secretions will be found described in the sections
on Digestion and Nutrition.

B. Mucous AND Albuminous (Serous ) Types of Glands ; Salivary

Glands.

Mucous and Albuminous Glands. — Heidenhain rwognized two types
of glands, the mucous and the ali)umin()us, basing his distinction upon the
' Mittheil. vom physiol. Lab. de.s Carol, mfrl.-chir. InstittUs in Stockholm, 1885.

SECRETION. 157

character of" tlie secretion uiul u[)()n the histological appearance of the secreting
cells. The classification as originally made was applied only to the salivary
glands and to similar glands fonnd in the mucous membranes of the mouth
and (esophagus, the air-passages, conjunctiva, etc. The chemical difference
in the secretions of the two types consists in the fact that the secretion of the
albuminous (or serous) glands is thin and watery, containing in addition to
possible enzymes only water, inorganic salts, and small quantities of albumin ;
while tluit of the mucous glands is stringy and viscid owing to the presence
of mucin. As examples of the albuminous glands we have the parotid in
man and the mammalia generally, the submaxillary in some animals (rabbit),
some of the glands of the mucous membrane of the mouth and nasal cavities,
and the lachrymal glands. As examples of the mucous glands, the submaxil-
lary in man and most mammals, the sublingual, the orbital, and some of the
glands of the mucous membrane of the mouth-cavity, oesophagus, and air-
passages. The histological appearance of the secretory cells in the albuminous
glands is in typical cases markedly different from that of the cells in the
mucous glands. In the albuminous glands the cells are small and densely
filled with granular material, so that the cell outlines, in preparations from the
fresh gland, cannot be distinguished (see Figs. 70 and 72). In the mucous
glands, on the contrary, the cells are larger and much clearer (see Fig. 73).
In microscopic preparations of the fresh gland the cells, to use Langley's
expression, present the appearance of ground glass, and granules are only
indistinctly seen. Treatment with proper reagents brings out the granules,
which are, however, larger and less densely packed than in the albuminous
glands, and are imbedded in a clear homogeneous substance. Histological
examination shows, moreover, that in some glands, e. g. the submaxillary
gland, cells of both types occur. Such a gland is usually spoken of as a
mucous gland, since its secretion contains mucin, but histologically it is a
mixed gland. The terms mucous and albuminous or serous, as applied to the
entire gland, are not in fact perfectly satisfactory, since not only do the mucous
glands usually contain some secretory cells of the albuminous type, but albu-
minous glands, such as the parotid, may also contain cells belonging to the
mucous type. The distinction is more satisfactory when it is applied to the
individual cells, since the formation of mucin within a secreting cell seems to
present a definite histological picture, and we can recognize microscopically a
mucous cell from an albuminous cell althouo-h the two mav occur together in
a single alveolus.

Goblet Cells. — The goblet cells found in the epithelium of the intestine
afford an interesting example of mucous cells. The epithelium of the intes-
tine is a simple columnar epithelium. Scattered among the columnar cells are
found cells containing mucin. These cells are originally columnar in shape
like the neighboring cells, but their protoplasm undergoes a chemical change
of such a character that mucin is produced, causing the cell to become swollen
at its free extremity, whence the name of goblet cell. It has been shown that
the mucin is formed with the substance of the protoplasm as distinct granules

158

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

of a large size, and that the ainount ui' iniicin iiiereases gradually, forcing the
micleus aud a small part of the unchanged protoplasm toward the base of the
cell. Eventually the mucin is extruded bodily into the lumen of the intestine,
leaving behind a partially empty cell with the nucleus and a small remnant of
protoplasm (see Fig. 67). The complete life-history of these cells is imper-

FiG. 67.— Formation of secretion of mucus in the goblet cells: ^, cell containing mucin; 5, escape of
the mucin ; C, after escape of the mucin (after Paneth).

fectly known. According to Bizzozero^ they are a distinct variety of cell and
are not genetically related to the ordinary granular epithelial cells by which
they are surrounded. According to others, any of the columnar epithelial cells
may become a goblet cell by the formation of mucin within its interior, and
after tiie mucin is extruded the cell regenerates its proto])lasm and becomes
again an ordinary epithelial cell. However this may be, the interesting fact
from a physiological standpoint is that these goblet cells are genuiue unicellular
mucous glands; moreover, the deposition of the mucin in the form of definite
granules within the protoplasm gives histological proof that this material is
produced by a metabolism of the cell-substance itself. It will be found that
the mucin cells in the secreting tubules of the salivary glands exhibit similar
appearances. So far as is known, the goblet cells do not possess secretory
nerves.

Salivary Glands.

Anatomical Relations. — The salivary glands in man are three in num-
ber on each side — the parotid, the submaxillary, and the sublingual. The
parotid gland communicates with the mouth by a large duct (Stenson's duct)
which opens upon the inner surface of the cheek opposite the second molar
tooth of the upper jaw. The submaxillary gland lies below the lower jaw,
and its duct (Wharton's duct) opens into the mouth-cavity at the side of the
frsenum of the tongue. The sublingual gland lies in the floor of the mouth
to the side of the frseuum and opens into the mouth-cavity by a number (8 to
20) of small ducts, known as the ducts of Rivinus. One larger duct which
runs parallel with the duct of Wharton aud opens separately into the mouth-
cavity is sometimes present in man. It is known as the duct of Bartholin
and occurs normally in the dog. In addition to these three pairs of large
glands a number of small glands belonging both to the albuminous and the
* Arckivfiir mihroskopische Anatomie, 1893, vol. 42, p. <S2.

SECRETION.

159

mucous types are found imbedded in the mucous membrane of the mouth and
tongue. The secretions of these glands contribute to the formation of the
saliva.

The course of the nerve-fibres supplying the large salivary glands is interest-
ing in view of the physiological results of their stimulation. The description
here given applies especially to their arrangement in the dog. The parotid gland
receives its fibres from two sources — first, cerebral fibres which originate in the
glosso-pharyugeal or ninth cranial nerve, pass into a branch of this nerve known
as the tympanic branch or nerve of Jacobson, thence to the small superficial
petrosal nerve, through which they reach the otic ganglion. From this gan-
glion they pass by way of the auriculo-temporal branch of the inferior max-

Inferior maxillary
' branch of fifth

Glosso-pharyngeal
nerve

Fig. 68.

Petroii^
ganglion

-Schematic representation of the course of the cerebral fibres to the parotid gland.

illary division of the fifth cranial nerve to the parotid gland. (A schematic
diagram showing the course of these fibres is given in Figure 68.) A second

FariaJ

Inferior maxillary
branch of fifth

Branches
to tongue

Branches to submaxil-
lary and sublingual ganglion

Fig. 69.— Schematic representation of the course of the chorda tympani nerve to the submaxillary gland.

supply of nerve-fibres is obtained from the cervical sympathetic nerve, the
fibres reaching the gland ultimately in the coats of the blood-vessels. The

160 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

submaxillary (and tiic subliumial) uiaiuls receive their nerve-lihro also from
two sources. The cerebral fibres arise from the brain in the facial nerve and
pass out in the chorda tympani branch (Fij^. 69). This latter nerve, after
emerging from the tympanic cavity throntrh the Glaserian fissure, joins the
lingual nerve. After running with this nerve for a >hort distance, the secre-
tory (and vaso-dilator) norve-Hbres destined for the sul)maxillarv and sublin-
gual glands branch off and pass to the glands, following the course of the
ducts. Where the chorda tympani fibres leave the lingual there is a small
ganglion which has received the name of submaxillary ganglion. The nerve-
fibres to the glands pass through this ganglion, but Langley has shown that
only those destined for the sublingual gland really connect with the nerve-
cells of the ganglion, and he suggests therefore that it should be called the
sublingual instead of the submaxillary ganglion. The nerve-fibres for the
submaxillary gland make connections with nerve-cells within the hilus of the
gland itself. The submaxillary and sublingual glands receive also sympa-
thetic nerve-fibres, which after leaving the superior cervical ganglion pass to
the glands in the coats of the blood-vessels.

Histolog-ical Structure. — The salivary glands belong to the type of com-
pound tubular glands, as Flemming has pointed out. That is, the secreting
portions are tubular, in shape, although in cross sections these tubes may
present various outlines according as the plaue of the section passes through
them. The parotid is described usually as a typical serous or albuminous
gland. Its secreting epithelium is composed of cells which in the fresh con-
dition as well as in preserved specimens contain numerous fine granules (see
Figs. 70 and 72, A). Heideuhain states that in exceptional cases (in the
dog) some of the secreting cells may belong to the mucous type. The base-
ment membrane is composed of flattened branched connective-tissue cells, the
interstices between which are filled by a thin membrane. The submaxillary
gland differs in histology in different animals. In some, as the dog or cat,
all the secretory tubes are composed chiefly or exclusively of epithelial cells
of the mucous type (Fig. 73). In man the gland is of a mixed type, the
secretory tubes containing both nuicous and albuminous cells. The sublingual
gland in man also contains both varieties of cells, although the mucous cells
predominate. It follows from these histological characteristics that the secre-
tion from the submaxillary and sublingual glands is thick and mucilaginous as
compared with tl.at from the j)arotid.

In the mucous glands another variety of cells, the so-called demilunes or
crescent cells, is frequently met with ; and the physiological significance of
these cells has been the subject of much discussion. The demilunes are cres-
cent-shaped granular cells lying between the mucous cells and the basement
membrane, and not in contact, therefore, with the central lumen of the tube
(see Fig. 73). According to Heideuhain these demilunes are for the purpose
of replacing the nuicous cells. In consecjuence of long-continued activity the
raucous cells may disintegrate and disappear, and the demilunes then develop
into new mucous cells. According to other views the demilunes represent

SECRETION. 161

merely an inactive stage of ordinary mucous cells, or the basal protoplasmic
part of a mucous cell, or, finally, a distinct secretory cell of the albuminous
type.

The secreting tubules of the salivary glands each possess a distinct lumen
round which the cells are arranged. In addition a number of recent observers,
making use of the Golgi method of staining, have apparently demonstrated
that in the albuminous glands the lumen is continued as fine capillary spaces
running between the secreting cells.^ The statement is also made that from
these secretion capillaries small side-branches are given oif which penetrate
into the substance of the cell, making an intracellular origin of the system of
ducts; this point, however, needs confirmation. In the mucous glands similar
secretion capillaries are found only in connection with the demilunes. This
latter fact supports the view that the demilunes are not simply inactive forms
of mucous cells, but cells with a specific functional activity. It is an un-
doubted fact that the salivary glands possess definite secretory nerves which
when stimulated start the formation of secretion. This fact indicates that
there must be a direct contact of some kind between the gland-cells and the
terminations of the secretory fibres. The nature of this connection has been
the subject of numerous investigations, the results of which were for a long time
negative or untrustworthy. Quite recently, however, the application of the
useful Golgi method has led to satisfactory results. The ending of the nerve-
fibres in the submaxillary and sublingual glands has been described by a num-
ber of observers.^ The accounts differ somewhat as to details of the finer
anatomy, but it seems to be clearly established that the secretory fibres from
the chorda tympani end first round the intrinsic nerve-ganglion cells of the
glands, and from these latter cells axis-cylinders are distributed to the
secreting cells, passing to these cells along the ducts. The nerve-fibres termi-
nate in a plexus upon the membrana propria of the alveoli, and from this
plexus fine fibrils pass inward to end on and between the secreting cells. A
more elaborate description of the final termination of the secretory fibres is
given by DogieP for the lachrymal gland, which is a gland belonging to the
albuminous type. It would seem from these observations that the nerve-
fibrils do not penetrate or fuse with the gland-cells, as was formerly supposed,
but form a terminal network in contact with the cells, following thus the
general schema for the connection between nerve-fibres and peripheral tissues.

Composition of the Secretion, — The saliva as it is found in the mouth
is a mixed secretion from the large salivary glands and the numerous
smaller glands scattered over the mucous membrane of the mouth. It is a
colorless or opalescent, turbid, and mucilaginous liquid of weakly alkaline re-
action and a specific gravity of about 1003. It may contain numerous flat
cells derived from the epithelium of the mouth, and the peculiar spherical cells
known as salivary corpuscles, which seem to be altered leucocytes. The im-

^ Laserstein: Pfluger's Archiv fur die r/esammte Physiologic, 1893, Bd. 55, p. 417.
^ See Huber : Journal of Experimental Medicine, 1896, vol. i. p. 281.
^Archiv fiir mihroscopische Anatomic, 1893, Bd. xlii. S. 632.
11

162 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

purtimt coustituents of the secretion are mucin, a diastatic enzyme known as
ptyaliu, traces of albumin and of potassium sulphocyanide, and inorganic salts
such as potassium and sodium chloride, potassium sulphate, sodium carbonate,
and calcium carbonate and ])hospluite. The average jjroportions of these con-
stituents is given in the following analysis by Hanunerbaeher :

Water, 994.203

Solids :

Mucin and epithelial cells, 2.202

Ptvalin and albumin, 1.390

Inorganic salts, 2.205

5.797

1.000.000
(Potassium sulphocyanide, 0.041.)

Of the organic constituents of the saliva the albumin exists in small and varia-
ble quantities, and its exact nature is not determined. Tlie mucin gives to the
saliva its roi)y, mucilaginous character. This substance belongs to the group
of combined proteids, glyco-proteids (see section on Chemistry), consisting of a
proteid combined with a carbohydrate group. The physiological value of this
constituent seems to lie in its ])hysical pro})erties, as described in the section on
Digestion. The most interesting constituent of the mixed saliva is the pty-
alin. This body belongs to the group of enzymes or unorganized ferments,
whose general and .specific properties are described in the section on Digestion.
It suffices here to say only that ptyalin belongs to the dia.static group of enzymes,
whose specific action is to convert the starches into sugar by a process of
hydrolysis. In some animals (dog) jityalin seems to be normally absent from
the fresh saliva. An interesting fact with reference to the saliva is the large
quantity of gases, particularly COg, which may be obtained from it when
freshly secreted. In an analysis by Pfliiger of the saliva from the submaxil-
lary gland the following figures were obtained : COj, 65 per cent., of which
42.5 per cent, was in the form of carbonates ; N, 0.8 per cent. ; O, 0.6 per
cent. For the parotid secretion Kiilz reports : CO2, 66.7 per cent., of which
62 per cent, was in combination as carbonate ; N, 3.8 per cent. ; O, 1.46 per
cent.

The secretions of the parotid and submaxillary glands can be obtained easily
by inserting a cannula into the openings of the ducts in the mouth. The secre-
tion of the sublingual can only be obtained in sufficient quantities for analysis
from the lower animals. Examination of the separate secretions shows that the
main difference lies in the fact that the parotid saliva contains nonuicin, while
that of the submaxillary and especially of the sublingual gland is rich in
mucin. The parotid saliva of man seems to be particularly rich in ptyalin as
compared with that of the submaxillary, while the secretion of the latter and
of the sublingual gland give a stronger alkaline reaction than the parotid
saliva.

The Secretory Nerves. — The exi.stence of secretory nerves was discovered
by Ludwig in 1851. He found that stimulation of the chorda tympani nerve
caused a flow of saliva from the submaxillary gland. He established also

SECRETION. 163

several important facts with regard to the pressure and composition of the
secretion whicli will be referred to presently. It was afterward shown that
the salivary glands receive a double nerve-supply, in part by way of the
cervical sympathetic and in part through cerebral nerves, as briefly described
on {). 159. It was discovered also that not only are secretory fibres carried
to the glands by these paths, but that the vaso-raotor fibres are contained in
the same nerves, and the arrangement of these latter fibres is such that the
cerebral nerves contain vaso-dilator fibres which cause a dilatation of the small
arteries in the glands and an accelerated blood-flow, while the sympathetic
carries vaso-constrictor fibres whose stimulation causes a constriction of the
small arteries and a diminished blood-flow. The eflect upon the secretion of
stimulation of these two sets of fibres is found to vary somewhat in different
animals. For purposes of description we may confine ourselves to the effects
observed on dogs, since most of our fundamental knowledge upon the subject
is derived from Heidenhain's ' experiments upon this animal. If the chorda
tympani nerve is stimulated by weak induction shocks the gland begins to
secrete promptly, and the secretion, by proper regulation of the stimuli, may
be kept up for hours. The secretion thus obtained is thin and watery, flows
freely, is abundant in amount, and contains not more than 1 or 2 per cent, of
total solids. At the same time there is an increased flow of blood through
the gland. The whole gland takes on a redder hue, the veins are distended,
and if cut the blood that flows from them is of a redder color than in the
resting gland, and may show a distinct pulse — all of which points to a dilata-
tion of the small arteries. If now the sympathetic fibres are stimulated, quite
different results are obtained. The secretion is relatively small in amount,
flows slowly, is thick and turbid, and may contain as much as 6 per cent, of
total solids. At the same time the gland becomes pale, and if the veins be
cut the flow from them is slower than in the resting gland, thus indicating
that a vaso-constriction has occurred.

The increased vascular supply to the gland accompanying the abundant
flow of "chorda saliva" and the diminished flow of blood during the scanty
secretion of " sympathetic saliva " suggest naturally the idea that the whole
process of secretion may be at bottom a vaso-motor phenomenon, the amount
of secretion depending only on the quantity and pressure of the blood flowing
through the gland. It has been shown conclusively that this idea is erro-
neous and that definite secretory fibres exist. The following facts may be
quoted in support of this statement : (1) Ludwig showed that if a mercury
manometer is connected with the duct of the submaxillary gland and the
chorda is then stimulated for a certain time, the pressure in the duct may
become greater than the blood-pressure in the gland. This fact shows that
the secretion is not derived entirely by processes of filtration from the blood.
(2) If the blood-flow be shut off completely from the gland, stimulation of
the chorda will still give a secretion for a short time. (3) If atropin is

^ Pfliiger's Archiv fiir die gesammte Physiologie, 1878, Bd. xvii. p. 1 ; also in Hermann's Haml-
huch der Physiologie, 1883, Bd. v. Th. 1.

164 AN AMEIUCAN TEXT-BOOK OF PHYSIOLOGY.

injected into tlie gland, stimulation of the chorda will cause vascular dilata-
tion but no secretion. This may he explained by supposing that the atropiu
paralyzes the secretory but not the dilator fibres. (4) Hydrochlorate of qui-
nine injected into the gland gives vascular dilatation but no secretion. In
this case the secretory fibres are still irritable, since stimulation of the chorda
gives the usual secretion.

A still more marked diffei'ence between the effect of stimulation of the
cerebral and the sympathetic fibres may be observed in the case of the parotid
gland in the dog. Stimulation of the cerebral fibres alone in any part of
their course (see Fig. 68) gives an abundant thin and watery saliva, poor in
solid constituents. Stimulation of the sympathetic fibres alone (provided the
cerebral fibres have not been stimulated shortly before (Langley) and the tym-
panic nerve has been cut to prevent a reflex effect) gives usually no perceptible
secretion at all. But in this last stimulation a marked effect is jn-oduced upon
the gland, in spite of the absence of a visible secretion ; this is shown by the
fact that subsequent or simultaneous stimulation of the cerebral fibres gives a
secretion very unlike that given by the cerebral fibres alone, in that it is very
rich indeed in organic constituents. The amount of organic matter in the
secretion may be tenfold that of the saliva obtained by stimulation of the
cerebral fibres alone.

Another important and suggestive set of facts with regard to the action of
the secretory nerves is obtained from a study of the differences in composition
of the secretion following upon variations in tlie strength of stimulation of the
nerves.

Relation of the Composition of the Secretion to the Strength of Stimulation. —
If the stimulus to the chorda be gradually increased in strength, care being
taken not to fatigue the gland, the chemical composition of the secretion is
found to change with regard to the relative amounts of the water, the salts,
and the organic material. The water and the salts increase in amount with the
increased strength of stimulus up to a certain maximal limit, which for the
salts is about 0.77 per cent. Increase of stimulus beyond this point has no
further effect, the amount of water and salts remaining constant. It is im-
portant to observe that this effect may be obtained from a perfectly fresh
gland as well as from a gland which had previously been secreting actively.
With regard to the organic constituents the precise result obtained depends
on the condition of the gland. If previous to the stimulation the gland was
in a resting condition and unfiitigued, then increased strength of stimulation
is followed at first by a rise in the ])ercentage of organic constituents, and this
rise in the beginning is more marked than in the case of the salts. But
with continued stimulation the increase in organic material soon ceases, and
finally the amount begins actually to diminish, and may fall to a low point
in spite of the stronger stimulation. On the other hand, if the gland in the
beginning of the experiment had been previously worked to a considerable
extent, then an increase in the stimulating current, while it increases the
amount of water and salts, may have either no effect at all upon the organic

SECRETION. 165

constituents or cause only a temporary increase, quickly followed by a fall.
Similar results may be obtained from stimulation of the cerebral nerves of
the parotid gland. The above facts led Heidenhain to believe that the con-
ditions determining the secretion of the organic material are different from
those controlling the water and salts, and he gave a rational explanation of
the differences observed, in his theory of trophic and secretory fibres.

Theory of Trophic and Secretory Nerve-fibres. — This theory supposes
that two physiological varieties of nerve-fibres are distributed to the salivary
glands. One of these varieties controls the secretion of the water and inor-
ganic salts and its fibres may be called secretory fibres proper, while the other,
to which the name trophic is given, causes the formation of the organic con-
stituents of the secretion, probably by a direct influence on the metabolism in
the cell. Were the trophic fibres to act alone, the organic products would be
formed within the cell but there would be no visible secretion, and this is
the hypothesis which Heidenhain uses to explain the results of the experi-
ment described above upon stimulation of the sympathetic fibres to the parotid
of the dog. In this animal, apparently, the sympathetic branches to the parotid
contain exclusively or almost exclusively trophic fibres, while in the cerebral
branches both trophic and secretory fibres proper are present. The results of
stimulation of the cerebral and sympathetic branches to the submaxillary gland
of the same animal may be explained in terms of this theory by supposing that
in the latter nerve trophic fibres preponderate, and in the former the secretory
fibres proper.

It is obvious that this anatomical separation of the two sets of fibres along the
cerebral and sympathetic paths may be open to individual variations, and that
dogs may be found in which the sympathetic branches to the parotid glands
contain secretory fibres proper, and therefore give some flow of secretion on
stimulation. These variations might also be expected to be more marked when
animals of different groups are compared. Thus Langley ^ finds that in cats the
sympathetic saliva from the submaxillary gland is less viscid than the chorda
saliva, just the reverse of what occurs in the dog. To apply Heidenhain's
theory to this case it is necessary to assume that in the cat the trophic fibres
run chiefly in the chorda. An interesting fact with reference to the secretion
of the parotid in dogs has been noted by Langley and is of special interest,
since, although it may be reconciled with the theory of trophic and secretory
fibres, it is at the same time suggestive of an incompleteness in this theory.
As has been said, stimulation of the sympathetic in the dog causes usually no
secretion from the parotid. Langley ^ finds, however, that if the tympanic
nerve is stimulated just previously, stimulation of the sympathetic causes
a secretory flow from the parotid. One may explain this in terms of the
theory by assuming that the sympathetic does contain a few secretory fibres
proper, but that ordinarily their action is too feeble to start the flow of water.
Previous stimulation of the tympanic nerve, however, leaves the gland-cells in

1 Journal of Physiology, 1878, vol. i. p. 96.

2 Ibid., 1889, vol. X. p. 291.

166 ^.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a more irritable condition, so that the few secretory fibres proper in the sym-
pathetic branches are now effective in producing a flow of water.

Theories of the Action of Trophic and Secretory Fibres. — The way
in which the trophic fibres act has been briefly indicated. Tiiey may be sup-
posed to set up metabolic changes in the protoplasm of the cells, leading to the
formation of certain definite products, such as mucin or ptyalin. That such
changes do occur is abundantly showu by microscopic examination of the rest-
ing and the active gland, the details of which will be given presently. In
general these changes may be supposed to be katabolic in nature ; that is, to
consist in a disassociation or breaking down of the complex living material
with the formation of the simpler and more stable organic constituents of the
secretion. There is evidence to show that these gland-cells during activity
form fresh material from the nourishment supplied by the blood ; that
is, that anabolic or building-up processes occur along with the katabolic
changes. The latter are the more obvious and are the changes which are
usually associated with the action of the trophic nerve-fibres. It is possible,
also, that the anabolic or growth changes may be under the control of separate
fibres for which the name anabolic fibres would be appropriate. Satisfactory
proof of the existence of a separate set of anabolic fibres has not yet been
furnished.

The method of action of the secretory fibres proper is difficult to under-
stand. At present the theories suggested are very speculative, and a detailed
account of them is scarcely appropriate in this place. Heidenhain's own view
may be mentioned, but it should be borne in mind that it is only an hy-
pothesis, the truth of which is far from being demonstrated. The theory starts
from the fact that no more water leaves the blood-capillaries than afterward
appears in the secretion ; that is, no matter how long the secretion continues,
the gland does not become oedematous nor does the velocity of the lymph-
stream in the lymphatics of the gland increase. This being the case, we must
suppose that the stream of water is regulated by the secretion, that is, by the
activity of the gland-cells. If we suppose tiiat some constituent of these cells
has an attraction for water, then, while the gland is in the resting state, water
will be absorbed from the basement membrane ; this in turn supplies its loss
from the surrounding lymph, and the lymph obtains the same amount of
water from the blood. As the amount of water in the cell increases a point is
reached at which the osmotic tension comes to an equilibrium, and the diffu-
sion stream from blood to cells is at a standstill. The water in the cells
does not escape into the lumen of the tubule or of the secretion capillaries,
because the periphery of the cell is modified to form a layer offering
considerable resistance to filtration. The action of the secretory fibres
proper consists in so altering the structure of this limiting layer of the cells
that it offers less resistance to filtration ; consequently the water under tension
in the cells escapes into the lumen, and the osmotic pressure of its substance
again starts up a stream of water from capillaries to cells, which continues as
long as the nerve-stimulation is effective.

SECRETION. 167

Recent work by Runvicr, Drasch, Biedenniinn, and others lias called atten-
tion to an interesting phenomenon occurring in gland-cells during secretion
which when better known will possibly throw light upon the formation of the
water stream under the influence of nerve-stimulation. Ranvier^ describes
in both serous and mucous cells the formation of vacuoles within the proto-
plasmic substance. These vacuoles are particularly abundant after nerve-
stimulation. They seem to contain water, and if they behave as they do in
the protozoa — and this is indicated by the observations of Drasch ^ upon the
glands in the nictitating membrane in the frog — they would seem to form a
mechanism sufficient to force water from the cells into the lumen.

Histological Changes during Activity. — The cells of both the albu-
minous and mucous glands undergo distinct histological changes in conse-
quence of prolonged activity, and these changes may be recognized both in
preparations from the fresh gland and in preserved specimens. In the parotid
gland Heidenhain studied the changes in stained sections after hardening in
alcohol. In the resting gland (Fig. 70) the cells are compactly filled with

Fig. 70.— Parotid of the rabbit, in the resting condition (after Heidenhain),

granules which stain readily and are imbedded in a clear ground substance
which does not stain. The nucleus is small and more or less irregular in out-
line. After stimulation of the tympanic nerve the cells show but little altera-
tion, but stimulation of the sympathetic produces a marked change (Fig. 71).
The cells become smaller, the nuclei more rounded and the granules are more
closely packed. This last appearance seems, however, to be due to the hard-
ening reagents used. A truer picture of what occurs may be obtained from a
study of sections of the fresh gland. Langley,^ who first used this method,

^ Ccmiptes rendus, cxviii., 4, p. 168. ^ Archivfiir Anatomie und Physiologie, 1889, S. 96.
^Journal of Physiology, 1879, vol. ii. p. 260.

168

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

describes his results as follows: When the animal is in a fasting condition the
cells have a granular appearance throughout their substance, the outlines of

Fig. 71.— Parotid of the rabbit, after stimulation of the sympathetic (after Heidenhain).

the different cells being faintly marked by light lines (Fig. 72, ^1). When
the gland is made to secrete by giving the animal food, by injecting pilocarpin,
or by stimulating the sympathetic nerves, the granules begin to disappear from

■^#^ ^^^0^"

C D

Fig. 72.— Parotid gland of the rabbit in a fresh state, showing portions of the secreting tubules : .i4, in
a resting condition ; B, after secretion caused by pilocarpin ; C, after stronger secretion, pilocarpin and
stimulation of sympathetic ; D, after long-continued stimulation of sympatlietic (after Langley).

the outer borders of the cells (Fig, 72, B), so that each cell now shows an outer
clear border and an inner granular one. If the .stimulation is continued the
granules become fewer in number and are collected near the lumen and the mar-

SECRETION.

169

gins of the cells, the oloar zone increases in extent and the cells become smaller
(Fig. 72, C, D). Evidently the granular material is used up in some way to
make the organic material of the secretion. Since the ptyalin is a conspicuous
organic constituent of the secretion, it is assumed that the granules in the rest-
ing gland contain the ptyalin, or rather a preliminary material from which the
ptyalin is constructed during the act of secretion. On this latter assumption
the granules are frequently spoken of as zymogen granules. During the act
of secretion two distinct processes seem to be going on in the cell, leaving out
of consideration for the moment the formation of the water and the salts. In
the first place the zymogen granules undergo a change such that they are forced
or dissolved out of the cell, and, second, a constructive metabolism or an-
abolism is set up, leading to the formation of new protoplasmic material from
the substances contained in the blood and lymph. The new material thus
formed is the clear, non-granular substance, which appears first toward the
basal sides of the cells. We may suppose that the clear substance during the
resting periods undergoes metabolic changes, whether of a katabolic or anabolic
character cannot be safely asserted, leading to the formation of new granules,
and the cells are again ready to form a secretion of normal composition. It
should be borne in mind that in these experiments the glands were stimulated
beyond normal limits. Under ordinary conditions the cells are probably never
depleted of their granular material to the extent represented in the figures.

In the cells of the mucous glands changes equally marked may be observed
after prolonged activity. In stained sections of the resting gland, according
to Heidenhain, the cells are large and clear (Fig. 73), with flattened nuclei

Fiu.Tii.— Mucous gland; Submaxillary .jf dog, rest- Fiu. 74.— Mucous gland, submaxillary of dog
ing stage. after eight hours' stimulation of the chorda tym-

pani.

placed well toward the base of the cell. When the gland is made to secrete
the nuclei become more spherical and lie more toward the middle of the cell,
and the cells themselves become distinctly smaller. After prolonged secretion
the changes become more marked (Fig. 74) and, according to Heidenhain,
some of the mucous cells may break down completely, the demilune cells
increasing in size and forming new mucous cells. According to most of the

170 AN AMERICAN TEXT-BOOK OF PIIYHIOLOGY.

later observers, however, the mucous cells do not actually disintegrate, but
form again new material during the ])eriod of rest as was described for the
goblet cells of the intestine. In the mucous as in the allmminous cells ob-
servations upon pieces of tiic fresh gland seem to give more rcliabh; results
than those uj>on preserved specimens. Langley ' has shown that in the fresh
mucous cells of the submaxillary gland numerous large granules may be
discovered, about 125 to 250 to a cell. These granules are comparable to
those found in the goblet cells, and may be interpreted as consisting of
mucin or some ])reparatory material from which mucin is formed. The
granules are sensitive to reagents ; addition of water causes them to swell up
and disappear. It may be assumed that this happens during secretion, the gran-
ules becoming converted to a mucin-mass which is extruded from the cell.

Action of Atropin, Pilocarpin, and Nicotin upon the Secretory
Nerves. — The action of drugs upon the salivary glands and their secretions
belongs properly to pharmacology, but the effects of the three drugs men-
tioned are so decided that they have a peculiar physiological interest. Atro-
pin in small doses injected either into the blood or into the gland-duct
prevents the action of the cerebral fibres (tympanic nerve or chorda tympani)
upon the glands. This effect may be explained by assuming that the atropin
paralyzes the endings of the cerebral fibres in the glands. That it does not
act directly upon the gland-cells themselves seems to be assured by the inter-
esting fact that with doses sufficient to throw out entirely the secreting action
of the cerebral fibres, the sympathetic fibres are still effective when stimulated.
Pilocarpin has directly the opposite effect to atropin. In minimal doses it
sets up a continuous secretion of saliva, which may be explaiued upon the
supposition that it stimulates the endings of the secretory fibres in the gland.
Within certain limits these drugs antagonize each other — that is, the effect of
pilocarpin may be removed by the subsequent application of atroj)in and vice
veisa. Nicotin, according to the experiments of Langley,^ prevents the action
of the secretory nerves, not by action on the gland-cells or the endings of the
nerve-fibres, but by paralyzing the nerve-ganglion cells through which the
fibres pass on their way to the gland. If, for example, the superior cervical
ganglion is painted with a solution of nicotin, stimulation of the cervical
sympathetic below the gland will give no secretion ; stimulation, however, of
the fibres in the ganglion or between the ganglion and gland will give the
usual effect. By the use of this drug Langley is led to believe that the cells
of the so-called submaxillary ganglion are really intercalated in the course
of the fibres to the sublingual gland, while the nerve-cells with which the
submaxillary fibres make connection are found chiefly in the hilus of the
gland itself.

Paralytic Secretion. — A remarkable phenomenon in connection with the
salivary glands is the so-called paralytic secretion. It has been known for a
long time that if the chorda tympani is cut the submaxillary gland after a cer-

' Journal of Physiology, 1889, vol. x. p. 433.

* Proceedings of the Royal Society, London, 1889, vol. xlvi. p. 423.

SECRETION. 171

taiu lime, one to three days, begins to secrete slowly and the secretion contin-
ues uninterruptedly for a long period — as long, perhaps, as several weeks — and
eventually the gland itself undergoes atrophy. Langley ^ states that section of
the chorda on one side is followed by a continuous secretion from the glands
on both sides ; the secretion from the gland of the opposite side he designates
as the auti paralytic or anti lytic secretion. He believes that this continuous
secretion is due to the fact that the irritability of the nerve-cells in the secretion
centre (see below) in the medulla, as well as of the nerve-cells in the gland
itself, is so much increased that the venosity of the blood itself is sufficient to
throw them into continuous activity. It is difficult, however, to understand
why section of the chorda should have any such effect as this upon the medul-
lary centre, especially as it is kuown that section of the secretory fibres in the
sympathetic docs not give a similar result. A more plausible explanation is
the one suggested by Bradford,^ namely, that the salivary glands receive through
their cerebral nerves certain fibres which may be called anabolic, whose action
is to cause suspension or inhibition of the katabolic changes in the gland-cells —
probably, according to Bradford, by acting on the local nerve-ganglion cells in
the gland. When these fibres are removed by section there is nothing to
hold the katabolic processes in the gland in check, and as a result we get a
continuous secretion and a wasting of the gland.

Normal Mechanism of Salivary Secretion. — Under normal conditions
the flow of saliva from the salivary glands is the result of a reflex stimulation of
the secretory nerves. The sensory fibres concerned in this reflex must be
chiefly fibres of the glosso-pharyngeal and lingual nerves supplying the mouth
and tongue. Sapid bodies and various other chemical or mechanical stimuli
applied to the tongue or mucous membrane of the mouth will produce a flow
of saliva. The normal flow during mastication must be effected by a reflex of
this kind, the sensory impulse being carried to a centre and thence transmitted
through the efferent nerves to the glands. It is found that section of the
chorda prevents the reflex, in spite of the fact that the sympathetic fibres are
still intact. No satisfactory explanation of the normal functions of the secre-
tory fibres in the sympathetic has yet been given. Since the flow of saliva is
normally a definite reflex, we should expect a distinct salivary secretion centre.
This centre has been located by physiological means in the medulla oblon-
gata ; its exact position is not clearly defined, but possibly it is represented by
the nuclei of origin of the secretory fibres which leave the medulla by way of
the facial and glosso-pharyngeal nerves. Owing to the wide connections
of nerve-cells in the central nervous system we should expect this centre to be
affected by stimuli from various sources. As a matter of fact it is known that
the centre and throuo-h it the o-lands mav be called into activitv bv stimula-
tion of the sensory fibres of the sciatic, splanchnic, and particularly the vagus
nerves. So, too, various psychical acts, such as the thought of savory food and
the feeling of nausea preceding vomiting, may be accompanied by a flow of saliva,

^ Proceedings of the Royal Society, I^ondon, 1 885, No. 236.
^ Journal of Physiology, 1888, vol. ix. p. 287.

172 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the effect in this case being due probably to stimulation of tiie secretion centre
bv nervous impulses descending from the higher nerve-centres. Lastly, the
medullary centre may be inhibited as well as stimulated. The well-known
effect of fear, embarrassment, or anxiety in producing a parched throat may
be supposed to arise in this way by the inhibitory action of nerve-impulses
arisino- in the cerebral centres.

Electrical Changes in the Gland during Activity. — It has been shown
that the salivary as well as other glands suffer certain changes in electric
potential during activity which are comparable in a general way to the
" action currents " observed in muscles and nerves (see section on Muscle and
Nerve). Bradford ' has apparently shown that stimulation of the secretory
fibres proper causes the surface of the gland to become negative to the hilus,
while stimulation of the trophic fibres gives the reverse effect. Stimulation
of a mixed nerve, therefore, such as the chorda, gives a diphasic effect. The
theories bearing upon the causes of these electrical changes are too intricate
and speculative to enter upon here. The reader is referred to a recent account
by Biedermann^ for further details.

0. Pancreas ; Glands of the Stomach and Intestines.

Anatomical Relations of the Pancreas. — The pancreas in man lies in
the abdominal cavity behind the stomach. It is a long, narrow gland, its
head lying against the curvature of the duodenum and its narrow extremity
or tail reaching to the spleen. The chief duct of the gland (duct of Wirsung)
usually opens into the duodenum, together with the common bile-duct, about
eight to ten centimeters below the pylorus. In some cases, at least, a smaller
duct may enter the duodenum separately somewhat lower down. The points at
which the ducts of the pancreas open into the duodenum vary considerably in
different animals. For instance, in the dog there are two ducts, the larger of
which enters the duodenum separately about six to seven centimeters below
the pylorus, while in the rabbit the main duct opens into the duodenum over
thirty centimeters below the pylorus. The nerves of the pancreas are derived
from the solar plexus, but physiological experiments which will be described
presently show that the gland receives fibres from at least two sources, through
the vagus nerve and through the sympathetic system.

Histological Characters. — The pancreas, like the salivary glands, belongs
to the compound tubular type. The cells in the secreting portions of the
tubules, the so-called alveoli, resemble the serous or albuminous type, and are
usually characterized by the fact that the outer portion of each cell, that is,
the part toward the basement membrane, is composed of a clear non-granular
substance which takes stains readily, while the inner portion turned toward
the lumen is filled with conspicuous granules. In addition to this type of
cell, which is the characteristic secreting element of the organ, the pancreas
contains a number of irregular masses of cells of a different character (bodies
of Langerhans). These latter cells are clear and small, frequently have ill-
^ Journal of Physiology, 1887, vol. viii. p. 86. ^ Elektrophysiologie, Jena, 1895-

SECRETION. 173

defined cell-bodies, but coutain nuclei whicii stain readily with ordinary
reagents. By some these cells are supposed to be immature secreting cells of
the ordinary pancreatic type. By others it is thought that they are a separate
type of cell and take some special part in the secretory functions of the pan-
creas. Nothing definite, however, is known as to their physiological import-
ance.

In the pancreas, as in the salivary glands, the latest histological methods
have apparently demonstrated that the lumen of each secreting tubule is con-
tinuous with a system of intercellular secretion capillaries lying between the
secretory cells, and according to some observers sending terminal capillaries
into the very substance of the gland-cells.

Composition of the Pancreatic Secretion. — The pancreatic secretion is
a clear alkaline liquid which in some animals (dog) is thick and mucilaginous.
Its physical characters seem to vary greatly, even in the same animal, accord-
ing to the duration of the secretion or the time since the establishment of the
fistula by which it is obtained (see p. 238). In a newly made fistula in the
dog the secretion is thick, but in a permanent fistula it becomes much thinner
and more watery. The main constituents of the secretion are three enzymes,
a large percentage of proteid material the exact nature of which is not known,
some fats, soaps, a slight amount of lecithin, and inorganic salts. The strongly
alkaline nature seems to be due chiefly to sodium carbonate, which may
be present in amounts equal to 0.2 to 0.4 per cent. The three enyzmes are
known respectively as trypsin, a proteolytic ferment ; amylopsin, a diastatic
ferment, and steapsin, a fat-spliting ferment. The action of these enzymes
in digestion is described in the section on Digestion.

Action of the Nerves on the Secretion of the Pancreas. — In animals
like the dog, in which the process of digestion is not continuous, the secretion
of the pancreas is also supposed to be intermittent. A study of the flow of
secretion as observed in cases of pancreatic fistula indicates that it is connected
with the beginning of digestion in the stomach, and is therefore probably a
reflex act. Until recently, however, little direct evidence had been obtained
of the existence of secretory nerves. Stimulation of the medulla was known
to increase the flow of pancreatic juice and to alter its composition as regards
the organic constituents, but direct stimulation of the vagus and the sympa-
thetic nerves gave only negative results. Lately, however, Pawlow' and some
of his students have been able to overcome the technical difficulties in the w.ay,
and have given what seems to be perfectly satisfactory proof of the existence of
distinct secretory fibres comparable in their nature to those described for the
salivary glands. The results that they have obtained may be stated briefly as
follows : Stimulation of either the vagus nerve or the sympathetic causes, after
a considerable latent period, a marked flow of pancreatic secretion. The failure
of other experiments to get this result was due apparently to the sensitiveness of
the gland to variations in its blood-supply. Either direct or reflex vaso-con-

^Pawlow: Dii Bois-Reymond's Archiv fiir P%s^ioio^ie, 1893, Suppl. Bd. ; Mett: 76;^/., 1894;
Kudrewetsky : Ibid., 1894.

174 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

strictiou of the pancreas prevents the action of tlio secretory nerves uj)on it.
Thus stimulation of the sympathetic j^ives usually no effect upon the secretion,
because vaso-constrictor fibres are stimulated at tiie same time, but if the sym-
pathetic nerve is cut five or six days previously, so as to give the vaso-con-
strictor fibres time to degenerate, stimulation will cause, after a long latent
period, a distinct secretion of the ])ancreatic juice.

Accepting the theory of secretory and trophic fibres j)roposed for the sali-
vary glands, the experiments upon the variations in pancreatic secretion follow-
ing upon stimulation of the vagus and sympathetic respectively seem to indi-
cate that in the sympathetic trophic fibres are more abundant, and in the vagus
the secretory fibres proper. The long latent period elaj)sing between the time
of stimulation and the effect upon the flow is not easily understood. The
authors quoted give no satisfactory explanation of this curious fact, but sug-
gest that it may be due to the presence of definite inhibitory fibres to the
gland, which are stimulated simultaneously with the secretory fibres and thus
hold the secretion in check for a time. No indepeudent proof of the presence
of inhibitory fibres is furnished.

Histological Changes during Activity. — The morphological changes in
the pancreatic cells have long been known and have been studied satisfac-
torily in the fresh gland as well as in preserved specimens. The general
nature of the changes is the same as that described for the salivary gland,
and is illustrated in Figures 75, 76, and 77. If the gland is removed from
a dog which has been fasting for about twenty-four hours and is hardened
in alcohol and sectioned and stained, it will be found that the cells are filled
with granules except for a narrow zone toward the basal end, which is marked
off more clearly because it stains more deeply than the granular portion (Fig.
75). If, on the contrary, the gland is taken from a dog which had been fed

Fig. 7.').— Pancreas of the dog during hunger ; preserved in alcohol and stained in carmine

(after Heidenhain).

six to ten hours previously, the non-staining granular zone is nuich reduced in
size, while the clearer non-granular zone is enlarged (Fig. 76). The increase
in size of the non-granular zone does not, however, entirely compensate for

8ECBETION.

175

the loss of the granular material, so that the cell as a whole is smaller in
size than in the gland from the fasting animal. It seems evident that during
the honi-s immediately following a meal — that is, at the time when we know

Fig. 76.— Pancreas of dog during first stage of digestion ; alcoiiol, carmine (after Heidenliain).

that the gland is discharging its secretion, the granular material is being used
up. After the period of most active secretion — that is, during the tenth to
the twentieth hour after a meal in the case of a dog fed once in twenty-four

Fig. 77.— Pancreas of dog during second stage of digestion; alcohol, carmine (after Heidenhain).

hours — the gland-cells return to their resting condition (Fig. 77). New gran-
ules are formed, and finally, if the gland is left unstimulated they fill the
entire cell except for a narrow margin at the basal end.

Similar results are reported by Kiihne* and Lea from observations made
upon the pancreas cells in a living rabbit. In the inactive gland the outlines

^ TJnter«ux.hungen aus dem physiologischen Insiitut des Universitdts Heidelberg, 1882, Bd. ii.

176 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of the iudividiial cells are not clearly distinguishable, but it can be seeu that
there are two zones, one clear and homogeneous on the side toward the basement
membrane, and one granular on the side toward the lumen. During activity
the secretory tubules show a notched appearance corresponding to the positions
of the cells, the outlines of the cells become more distinct, the granular zone
becomes smaller, and the homogeneous zone increases in width. It should Im;
stated also tiiat in this latter condition the basal zone of the cells shows a dis-
tinct striation. From these appearances we must believe that, as in the case
of the salivary gland, a part at least of the organic material of the secretion is
formed from the granules of the inner zone, and that the granules in turn are
formed within the cells from the homogenous material of the outer zone.

Enzyme and Zymogen. — The observations just described indicate that the
enzymes of the pancreatic secretion are derived from the granules in the cells,
but other facts show that the granules do not contain the enzymes as such, but
a preparatory material or mother-substance to which the name zymogen
(enzyme-maker) is given. This belief rests upon facts of the following kind :
If a pancreas is removed from a dog which has fasted for twenty-four hours,
when, as we have seen, the cells are heavily loaded with granules, and a glycerin
extract is made, very little active enzyme will be found in it. If, however,
the gland is allowed to stand for twenty-four hours in a warm spot before the
extract is made, or if it is first treated with dilute acetic acid, the glycerin ex-
tract will show very active tryptic or amylolytic properties. Moreover, if an
inactive glycerin extract of the perfectly fresh gland is treated by various
methods, such as dihition with water or shaking with finely divided platinum-
black, it becomes converted to an active extract capable of digesting proteid
material. These results are readily explained upon the hypothesis that the
granules contain only zymogen material, which during the act of secretion, or
by means of the methods mentioned, may be converted into the corresponding
enzymes. As the three enzymes of the pancreatic secretion seem to be distinct
substances, one may suppose that each has it own zymogen to which a distinc-
tive name might be given. The zymogen which is converted into trypsin is
frequently spoken of as trypsinogen.

Normal Mechanism of Pancreatic Secretion. — After the establishment
of a pancreatic fistula it is possible to study the flow of secretion in its rela-
tions to the ingestion of food. Experiments of this kind have been made,
and show that in animals like the dog, in which sufficient food may be taken
in a single meal to last for a day, the flow of secretion is intimately connected
with the reception of food into the stomach and its subsequent digestive
changes. The time relations of the secretion to the ingestion of food are
shown in the accompanying chart (Fig. 78). The secretion begins immedi-
ately after the food enters the stomach, and increases in velocity up to a cer-
tain maximum which is reached some time between the first and the third hour
after the meal. The velocity then diminishes rapidly to the fifth or sixth
hour, after which there may be a second smaller increase reaching its maxi-
mum about the ninth to the eleventh hour. From this point the secretion

SECRETION.

177

diminishes in quantity to the sixtoentli or seventeenth hour, when it has
practically reaclucl the zero point. In man, in whom the meals normally
occur at intervals of five to six hours, this curve of course would have a dif-
ferent form. The interestincr fact, however, that the secretion starts very soon

o — , -^ 3 -^ — s — b — y s 9 'io~^' /2 15 /v 15 Jb 17 a

Fig 78 -Curve of the secretion of pancreatic juice during digestion. The figures along the abscissa
represent hours after the beginning of digestion; the figures along the ordinate represent the quantity
of this secretion in cubic centimeters. Curves of two experiments are given (after Heidenhain).

after the beginning of gastric digestion is probably true for human beings, and
gives strong indication that the secretion is a reflex act.

Recently a number of experiments have been reported which strengthen
the view that the normal secretion of the pancreas is reflexly excited by
stimuli acting upon the mucous membrane of the stomach or intestine.
Gottlieb^ finds that in rabbits the pancreatic secretion is very greatly accel-
erated by stimulants such as oil of mustard, pepper, acids, or alkalies intro-
duced into the stomach or duodenum, and Dolinsky,^ working upon dogs
under more favorable. experimental conditions finds that acids are particularly
eifective in arousing the pancreatic flow ; on the contrary, alkalies in the
stomach diminish the pancreatic secretion. Dolinsky believes that the normal
acidity of gastric secretion is perhaps the most effective stimulus to the pan-
creatic gland, and that in this way the flow of gastric juice in ordinary diges-
tion starts the pancreatic gland into activity. Whether the acid acts after
absorption into the blood, or stimulates the sensory fibres of the raucous mem-
brane and thus reflexly affects the pancreas through its secretory nerves, is not
definitely known, but the probabilities are in favor of the latter view. It is
probable also that the acid acts mainly upon the sensory fibres of the mucous
membrane of the duodenum rather than upon the gastric membrane.
1 Arehiv flir ejcperimentelle Pathologic und Phainimkologie, 1894, Bd. 33, p. 273.
* Archives des Sciences biologiques, St. Petersburg, 1895, vol. iii. p. 399.
12

178 J.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

AVe are justitied from these experiments in believing that tlie nieclianisra
of the pancreatie secretion is closely analogous to that c(mtrolling the salivary
glands. It is usually stated, however, that the pancreas still continues to
secrete after all its extrinsic nerves have been severed. The experiments
uj)c)n which this statement rests are not entirely satisfactory, since, owing to
the way in which the nerve-fibres reach the organ in the walls of the blood-
vessels, it is difficult to be sure that all the nerve-fibres are actually severed,
and moreover it is probable that if the gland contiiuies to secrete after removal
of its extrinsic nerves, the flow is of the nature of a paralytic secretion, which
in time would be followed by a wasting of the gland. More experimental
work is required upon this point.

Glands of the Stomach.

Histolog-ical Characteristics. — The glands of the gastric mucous mem-
brane belong practically to tlie type of simple tubular glands ; for, although
two or more of the simple tubes may possess a common opening or mouth,
there is no system of ducts such as prevails in the compound glands, and the
divergence from the simplest form of tubular gland is very slight. Each of
these glands possesses a relatively wide mouth, lined with the columnar epi-
thelium found on the free surface of the gastric membrane, and a longer, nar-
rower secreting part, which penetrates the thickness of the mucosa and is lined
by cuboidal cells. The glands in the pyloric end of the stomach differ in gen-
eral appearance from those in the fundic end, and are especially characterized
by the fact that they possess only one kind of secretory cell, while the fundic
glands contain two apparently distinct types of cells (Fig. 81). The lumen in the
latter glands is lined by a continuous layer of short cylindrical cells to which
Heidenhain gave the name of chief-cells. These cells are apparently concerned
in the formation of pepsin, the proteolytic enzyme contained in the gastric secre-
tion. In addition there are present a number of cells of an oval or triangular
shaj)e which are placed close to the basement membrane and do not extend quite
to the main lumen of the gland. These cells, which are not found in the pyloric
glands, are known by various names, such as border-cells, parietal cells, oxyntic
cells, etc. The last-mentioned name has been given to ihem because of their
supposed connection with the formation of the acid of the gastric secretion. The
nature and function of these border-cells have been the subject of much discus-
sion. From the histological side they have been interpreted as representing
either immature forms of the chief-cell, or else the active modification of this
cell. Recent work, however, seems to have demonstrated that they form a
specific type of cell, and probably therefore have a specific function. An
interesting histological fact in connection with the parietal cells is that, in the
human stomach at least, they frequently contain several nuclei, five or six,
and some of these seem to be derived from ingested leucocytes. They are
interesting also in the fact that they contain distinct vacuoles which seem to
appear some time after digestion has begun, reach a maximum size, and then
gradually grow smaller and finally disappear. I^ike the similar phenomenon

SECRETION. 179

described for other oland-cells (p. 167), tliis appearance is possibly connected
with the formation of the secretion.

The duct of a gastric gland was formerly supposed to be a simple tube
extending the length of the gland. A number of recent observers, however,
have shown, by the use of the Golgi stain, that this
view is not entirely correct, at least not for the glands
in the fundus in which border-cells are present. In
these glands the central lumen sends offside channels
which pass to the border-cells and there form a net-
work of small capillaries which lie either in or round
the cell.' An illustration of the duct-system of a
fundic gland is given in Figure 79. If this work
is correct it would seem that the chief-cells com-
municate directlv with the central lumen, but that fig. tu— Ducts and secretion
the border-cells have a system of secretion capillaries ^f "f ^« ^o parietal oeiis.

J i Gland from the fundus of cat s

of their own, resembling in this respect the demi- stomach (after Langendorff
lunes of the mucous salivary glands (p. 161). This

fact tends to corroborate the statement previously made, that the border-cells
form a distinct type of cell whose function is jirobably different from that
of the chief-cells.

Composition of the Secretion of the Gastric Mucous Membrane. —
The secretion as it is poured out on the surface of the mucous membrane is
composed of the true secretion of the gastric glands together with more or less
mucus, which is added by the columnar cells lining the surface of the mem-
brane and the mouths of the glands. In addition to the mucus, water, and
inorganic salts, the secretion contains as its characteristic constituents hydro-
chloric acid and two enzymes — namely, pepsin which acts upon proteids, and
reuniu which has a specific coagulating effect upon tiie casein of milk. For an
analysis of the gastric secretion of the dog see p. 161. According to Heiden-
hain,^ the secretion from the pyloric end of the stomach is characterized by the
absence of hydrochloric acid, although it still contains pepsin. This statement
rests upon careful experiments in which the pyloric end was entirely resected
and made into a blind pouch which was then sutured to the abdominal wall
to form a fistula. In this way the secretion of the pyloric end could be obtained
free from mixture with the secretion of any other part of the alimentary canal.
By this means Heidenhaiu found that the pyloric secretion is an alkaline liquid
containing pepsin. This fact forms the strongest evidence for Heidenhain's
hypothesis that the HCl of the normal gastric secretion is produced by the
"border-cells" of the fundic glands and the pepsin by the "chief-cells," since
HCl is formed only in parts of the stomach containing border-cells, whereas
the pepsin is produced in the pyloric end, where only chief-cells are present.

Evidence of this character is naturally not very convincing, and the hypoth-

1 Langendorff and Laserstein : Pflugei-'s Archiv fur die gesammte Physiohgie, 1894, Bd. Iv. S.
578.

* Archiv fiir die gesammte Physiologic, 1878, Bd. xviii. S. 169, also Bd. xix.

180 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

esis, especially that part ooniiectinj^ the border-eell.s with the turmatiou of
HCl, cau ouly be accepted provisionally until further investigation confirms
or disproves it. It should be stated that the alkalinity of the secretion obtained
from the pyloric glands by Heidenhain's method has been attributed by some
authors to the abnormal conditions j)revailing, especially to the section of the
vagus fibres which necessarily results from the operation. Contejean ' asserts
that the reaction of the pyloric membrane under normal conditions is acid in
spite of the absence of border-cells.

Influence of the Nerves upon the Gastric Secretion. — It has been very
difficult to obtain direct evidence of the existence of extrinsic secretory nerves
to the gastric glands. In the hands of most experimenters, stimulation of the
vagi and of the syrapathetics has given negative results, and, on the other
hand, section of these nerves does not seem to prevent the formation of the
gastric secretion. There are on record, however, a number of observations
which point to a direct influence of the central nervous system on the secre-
tion. Thus Bidder and Schmidt found that in a hungry dog with a gastric
fistula (page 225) the mere sight of food caused a flow of gastric juice ; and
Richet reports a case of a man in whom the oesophagus was completely oc-
cluded and in whom a gastric fistula was established by surgical operation.
It was then found that savory foods chewed in the mouth produced a marked
flow of gastric juice. There would seem to be no other way of explaining the
secretions in these cases except upon the supposition that they were caused by a
reflex stimulation of the gastric mucous membrane through the central nervous
system. These cases are strongly supported by some recent experimental
work on dogs by Pawlow ^ and Schumowa-Simanowskaja. These observers
used dogs in which a gastric fistula had been established, and in which, more-
over, the oesophagus had been divided in the neck and the upper and lower
cut surfaces brought to the skin and sutured so as to make two fistulous
openings. In these animals, therefore, food taken into the mouth and subse-
quently swallowed escaped to the exterior through the upper oesophageal
fistula, without entering the stomach. Nevertheless this " fictitious meal,"
as the authors designate it, in the case of certain foods (meats), brought about
an increased formation of gastric juice, although, curiously enough, other foods,
such as milk and soup, gave negative results. If in such animals the two
vagi were cut, the " fictitious meal " no longer caused a secretion of the gas-
tric juice, and this fact may be considered as showing that the secretion
obtained when the vagi were intact was due to a reflex stimulation of the
stomach through these nerves. Finally, these observer were able to show
that direct stimulation of the vagi under proper conditions causes, after a long
latent period (six or seven minutes), a marked secretion of gastric juice. A
satisfactory explanation of the unusually long latent period is not given.

Taking these results together, we nuist believe that the vagi send secretory
fibres to the gastric glands, and that these fibres may be stimulated reflexly

* Archives de Physiologic, 1892, p. 554.

' Du Bois-Reymond^ s Archiv fiir Physiologic, 1895, S. 53.

SECRETION. 181

through the sensory nerves of i\w. numtli, unci probably also by psychical
states.

Normal Mechanism of Secretion of the Gastric Juice. — Our know-
ledge of the means by which the flow of gastric secretion is caused during
normal digestion, and of the varying conditions which influence the flow, is
as yet quite incomplete. Some notable experiments recently made by Pawlow '
and Khigine, together with older experiments by Heidenhain,^ have, however,
thrown some light upon this difficult problem, and have, moreover, opened
the way for further experimental study of the matter. Heidenhain cut out
a part of the fundus of the stomach, converted it into a blind sac, and brought
one end of the sac to the abdominal wall so as to form a fistulous opening to
the exterior. The contiiuiity of the stomach was established by suturing the
cut ends, but the fundic sac was completely separated from the rest of the
alimentary canal. He found that under these conditions the ingestion of
ordinary food caused a secretion in the isolated and empty fundic sac, the
secretion beginning fifteen to thirty minutes after the food was taken, and
continuing until the stomach was empty. The ingestion of water caused a
temporary secretion in the fundus, while indigestible material such as liga-
mentum nuchse gave no secretion at all. Heidenhain's interpretation of these
experiments as applied to normal secretion was that in ordinary digestion we
must distinguish between a primary and a secondary secretion. The pri-
mary secretion depends upon the mechanical stimulus of the ingested food,
and is confined to the spots directly stimulated ; the secondary secretion begins
after absorption from the stomach is in progress, and involves tiie whole
secreting surface. In the experiments related above, the secretion from the
isolated fundus was a part of this secondary secretion. The stimulus in this
case would seem to be a chemical one, consisting of some of the })roducts
absorbed from the stomach, which either acts directly on the gastric glands
or indirectly on the intrinsic nerve-centres of the stomach.

Khigine has made similar experiments, but altered the operation so that the
isolated fundic sac retained its normal nerve-supply, which in Heidenhain's
operations was apparently injured. The results which he obtained are much
more complete than any hitherto reported. He was able in the first place to
determine the effect of various diets upon the amount of gastric secretion, upon
its acidity, and upon its digestive power, using the secretion from the isolated
fundic sac as typical of what was going on in the rest of the stomach in which
the food was actually in process of digestion. One of his curves showing the
effect of a mixed diet (milk, 600 cubic centimeters ; meat, 100 grams ; bread, 100
grams) is reproduced in Figure 80. It will be seen that the secretion began
shortly after the ingestion of food (seven minutes) and increased rapidly to a
maximum which it reached in two hours. After the second hour the flow
decreased rapidly and nearly uniformly to about the tenth hour. The acidity
also rose slightly between the first and second hours, and then fell gradually.

* Khigine: Archives des Sciences biologiques, St. Petersburg, 1895, vol. iii. p. 461.
^ Hermann's Hanclbuch der Physiologic, 1883, Bd. v. S. 114.

182

^.Y AMEBICAy TEXT-BOOK OF PHYSIOLOGY.

The digestive power showed ii striking increase between the second and
third hours. The author gives other tables showing the effect of a meat diet,
a milk diet, a bread diet, etc., which .seem to .sliow that a meat diet j)romotes

th(i greatest flow of .secretion,
while the bread diet gives a
secretion of more than usual
digestive power.

Khigine attempted to deter-
mine the effect of various chemi-
cal substances, found in food
or occurring during digestion,
upon the flow of the secretion,
hoping by this means to throw
.some light upon the nature of
the normal .stimulus in ordinary
gastric digestion. lie obtained
practiciilly negative results with
acids, alkalies, and neutral .salts;
none of these substances when
introduced into the stomach had
any decisive effect upon the se-
cretion in the isolated fundus.
Water, however, was quite ef-
fective ; the ingestion of 500
cubic centimeters produced a
marked and fairly long-con-
tinned secretion of gastric juice.

Fig. 80.— Diagram showing the variation in quantity of But, SO far as his experiments
gastric secretion in the dog after a mixed meal : also the .

variations in acidity and in digestive power (after Khigine). "^^'^"1 5 peptone IS, yWT excellence,

the chemical .stimulus to the
gastric glands. The peptones caused an unusual secretion of gastric juice,
although the closely related products of digestion known as proteoses (see p.
230) had little or no effect. It remains unsettled, however, how the water
and the peptones act— whether they arc ab.sorbed, as Heidenhain thought, and
act as chemical stimuli to the glands or the intrin.sic ganglia of the stomach, or
whether, as Khigine believes, they are direct and as it were .specific nerve-
stimuli to the .sen.sory nerve-fibres of the mucous membrane, and thus produce
a reflex effect upon the efferent secretory nerves to the gastric glands. The
latter view would be more in accord with the mechanism of .secretion as we
know it in the salivary glands and pancreas, but it cannot be .^aid to have
been demonstrated as yet.

Histological Changes in the Gastric Glands during Secretion.— The
cells of the ga.stric glands, especially the .'^o-called chief-cells, show di.^^tinct
changes as the result of ])rolonged activity. Upon preserved specimens taken
from dogs fed at intervals of twenty-four hours, Heidenhain found that in the

e

50.3

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Quantity in
cubic centi-
meters.

Milk, Meat, Bread,
600 c.c. 100 gr. 100 gr.

10
8
6
4
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0.576
0.528
0.480
0.432

18

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0.384 1 16

/

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0.336
0.288
0.240
0.192
0.144
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0.048

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\1
10
8
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1

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Acidity.

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SECRETION.

183

fasting condition the chief-cells were large and clear, that during the first six
hours of digestion the chief-cells as well as the border-cells iiicreased in size,
but that in a second period extending from the sixth to the fifteenth hour, the
chief-cells became gradually smaller, svhile the border-cells remained large or
even increased in size. After the fifteenth hour the chief-cells increased in
size, gradually passing back to the fasting condition (see Fig. 81).

FIG. 81.-Glands of the fundus (clog) : A and A\ during hunger resting condition ; B ^"^^"f f ^ /^^
stage of digestion ; C and D, the second stage of digestion, showing the diminution m the sue of the
" chief" or central cells lafter Heidenhain).

Langley ' has succeeded in following the changes in a more satisfactory
way by observations made directly upon the living gland. He finds that the
chief-cells in the fasting stage are charged with granules, and that during
digestion the granules are used up, disappearing first from the base ot the
cell, which then becomes filled with a non-granular material. Observations
similar to those made upon the pancreas demonstrate that these granules
represent in all probabilitv a preliminary material from which the gastric
enzymes are made during the act of secretion. The granules, therefore, as in
the other glands, mav be spoken of as zymogen granules, the preliminary
material of the pepsin being known as pepsinogen and that of the rennin
sometimes as pexiuogen.

1 Journal of Physiology, 1880, vol. iii. p. 269.

184 ^iV' AMERICAN TEXT- BOOK OF PHYSIOLOGY.

Glands of the Intestine. — At the very beginiiiug of the intestine in the
immediate neighborhood of the pylorus is found a small area of mucous mem-
brane containing distinct tubular glands known usually as the glands of
Bruuuer. These glands resemble closely in arrangement those of the pyloric
end of the stomach, with the exception that the tubular duct is more branched.
The secreting cells are similar to those of the pyloric glands of the stomach.
Little is known of their secretion. According to some authors it contains
pepsin. The amount of secretion furnished by these glands would seem to
be too small to be of great importance in digestion. Throughout the length
of the small and large intestine the well-known crypts of Lieberkiihn
are found. These structures resemble the gastric glands in general appear-
ance, but not in the character of the epithelium. The epithelium lining the
crypts is of two varieties — the goblet cells, whose function is to form nmcus,
and columnar cells with a characteristic striated border. The chany;es in the
goblet cells during secretion and the probability of a relationship between them
and the neighboring epithelial cells has been discussed (see p. 157).
Whether or not the crypts form a definite secretion has been much debated.
Physiologists are accustomed to speak of an intestinal juice, " succus entericus,"
as being formed by the glands of Lieberkiihn, but practically nothing is known
as to the mechanism of the secretion. The succus entericus itself, however it
may be formed, can be collected by isolating small loops of the intestine and
bringing the ends to the abdominal wall to form fistulous openings. The
secretion thus obtained contains diastatic and also inverting ferments, the action
of which is described on p. 247. Histologically, the cells in the bottom of
the crypts do not possess the general characteristics of secreting cells.

D. Liver ; Kidney.

The liver is a gland belonging to the compound tubular type. The
hepatic cells represent the secretory cells and the bile-ducts carry off the
external secretion, which is designated as bile. In addition it is known that
the liver-cells occasion important changes in the material brought to them
in the blood, and that two important compounds, namely, glycogen and urea,
are formed under the influence of these cells and afterward are given off to
the blood-stream. The liver, then, furnishes a conspicuous example of a
gland which forms simultaneously an external and an internal secretion. In
this .section we have to consider only certain facts in relation to the external
secretion, the bile.

Histological Structure. — The general histological relations of the hepatic
lobules need not be repeated in detail. It will be remembered that in each
lobule the hepatic cells are arranged in columns radiating from the central
vein, and that the intralobular capillaries are .so arranged with reference to
the.se columns that each cell is practically brought into contact with a mixed
blood derived in part from the portal vein and in jiart from the hepatic
artery.

As a gland making an external secretion, the relations of the liver-cells to

SECRETION. 185

the ducts and to the nervous system are important j)oints t(j be determined.
The bile-ducts can be traced without difficulty to the fine interhjbular branches
running round the periphery of the lobules, but the finer branches or bile-
capillaries springing from the interlobular ducts and jjenetrating into the in-
terior of the lobules luive been difficult to follow with exactness, especially as to
their connection with the interlobular ducts on the one hand, and with the
liver-cells on the other. The bile-capillaries have long been known to pene-
trate the columns of cells in the lobule in such a way that each cell is in con-
tact with a bile-capillary at one point of its periphery, and with a blood-capil-
lary at another, the bile- and blood-cai)illaries being separated from each other
by a portion of the cell-substance. But whether or not intracellular branches
from these capillaries actually penetrate into the substance of the liver-cells
has been a matter in dispute. Kuppfer contended that delicate ducts arising
from the capillaries enter into the cells and end in a small intracellular vesicle.
As this appearance was obtained by forcible injections through the bile-ducts,
it was thought by many to be an artificial product ; but recent observations
with staining reagents tend to substantiate the accuracy of Kuj)pfer's obser-
vations and confirm the belief that normally the system of bile-ducts begins
within the liver-cells in minute channels which connect directly with the
bile-capillaries.

Two questions with reference to the bile-ducts have given rise to considerable
discussion and investigation : first, the relationship existing between the liver-
cells and the lining epithelium of the bile-ducts; second, the presence or ab-
sence of a distinct membranous wall for the bile-capillaries. Different opin-
ions are still held upon these points, but the balance of evidence seems to show
that the bile-capillaries have no proper wall. They are simply minute tubular
spaces penetrating between the liver-cells and corresponding to the alveolar lu-
men in other glands. Where the capillaries join the interlobular ducts the liver-
cells pass gradually or abruptly, according to the class of vertebrates examined,
into the lining epithelium of the ducts. From this standpoint, then, the liver-
cells are homologous to the secreting cells of other glands in their relations to
the general lining epithelium. Several observers (MaCallum,^ Berkeley,^ and
Korolkow^) have claimed that they are able to trace nerve-fibres to the
liver-cells, thus furnishing histological evidence that the complex processes oc-
curring in these cells are under the regulating control of the central nervous
system. According to the latest observers (Berkeley, Korolkow) the terminal
nerve-fibrils end between the liver-cells, but do not actually penetrate the sub-
stance of the cells, as was described in some earlier papers. If these observa-
tions prove to be entirely correct they would demonstrate the direct effect of
the nervous system on some at least of the manifold activities of the liver-
cells. So far as the formation of the bile is concerned we have no satisfactory
physiological evidence that it is under the control of the nervous system.

Composition of the Secretion. — The bile is a colored secretion. In

' MaCalluru : Quarterly Journal of the Microscopical Sciences, 1887, vol. xxvii. p. 439.

^ Berkeley : Anatomvicher Anzeiger, 1893, Bd. viii. S. 769. ^ Korolkow : Ibid., S. 750.

186 AN AMERICAN TEXT-BOOK OF I'll YSIOLOGY.

luotit caruivorous aninmls it is golden red, while in the herbivora it is green,
the diflPerence depending on the character and quantity of the pigments. In
man the bile is usually stated to f()lk)\v the carnivorous ty})e, showing a red-
dish or brownish color, although in some cases apparently the green predomi-
nates. The characteristic constituents of the bile are the pigments, bilirubin in
carnivorous bile and bilivcnlin in herbivorous bile, and the bile acids or bile-
salts, the sodium salts of glycocholic or taurocholic acid, the relative proportions
of the two acids varying in different animals. In addition there is present a
considerable quantity of a mucoid nucleo-albumin, a constituent which is not
formed in the liver-cells, but is added to the secretion by the mucous membrane
of the bile-ducts and gall-bladder; and small quantities of cholesterin, lecithin,
fats, and soaps. The inorganic constituents comprise the usual salts — chlorides,
phosphates, carbonates and sulphates of the alkalies or alkaline earths. Iron
is found in small quantities, combined probably as a phosphate. The secre-
tion contains also a considerable though variable quantity of COg gas, held in
such loose combination that it can be extracted Avith the gas-pump without the
addition of acid. The presence of this constituent serves as an indication of
the extensive metabolic changes occurring in the liver-cells. Quantitative
analyses of the bile show that it varies greatly in composition even in the same
species of animal. Examples of this variability are given in the analyses
quoted in the section on Digestion (p. 261), where a brief account will also be
found of the origin and physiological significance of the different constituents.
The Quantity of Bile Secreted. — Owing to the fact that a fistula of the
common bile-duct or gall-bladder may be established upon the living animal
and the entire quantity of bile be drained to the exterior without serious detri-
ment to the animal's life, we possess numerous statistics as to the daily quantity
of the secretion formed. Surgical operations upon human beings (see p. 261
for references), made necessary by occlusion of the bile-passages, have furnished
similar data for man. In round numbers the quantity in man varies from 600
to 800 cubic centimeters per day, or, taking into account the weight of the
individuals concerned, about 8 to 16 cubic centimeters for each kilogram of
body-weight. Observations upon the lower animals indicate that the secretion
is proportionally greater in smaller animals. This fact is clearly shown in the
following table, compiled l)y Ileidenhain ' for three herbivorous animals:

Sheep. Rabbit. Guinea-pig.

Ratio of bile-weight for 24 liours to body-weiglit . . . 1 : 37.5 1 : 8.2 1 : 5.6

Ratio of bile-weight for 24 hours to liver-weight . . . 1.507 : 1 4.064 : 1 4.467 : 1

There .seems to be no doubt that the bile is a continuous secretion, although
in animals possessing a gall-bladder the .secretion may be stored in this reser-
voir and ejected into the duodenum only at certain intervals connected with
the processes of digestion. The movement of the bile-stream within the
system of bile-ducts — that is, its actual ejection from the liver, is al.^o probably
intermittent. The observations of Copeman and Winston on a human patient

^ Hermann's Handbuch dei- Physiologie, vol. v. Thl. 1, p. 253.

SECRETION. 187

with a biliary fistula showed that the secretion was ejected in spirts, owing
doubtless to contractions of the muscular walls of the larger bile-ducts. But
though continuously formed within the liver-cells, the flow of bile is subject
to considerable variations. According to most observers the activity of secre-
tion is definitely connected with the period of digestion. Somewhere from the
third to the fifth hour after the beginning of digestion there is a very marked
acceleratit)n of the flow, and a second maximum at a later period, ninth to
tenth hour (Iloppe-Seyler), has been observed in dogs. The mechanism con-
trolling the accelerated flow during the third to the fifth hour is not perfectly
understood. It would seem to be correlated with the digestive changes occur-
ring in the intestine, but whether the relationship is of the nature of a reflex
nervous act, or whether it depends on increased blood-flow through the organ
or upon some action of the absorbed products of secretion remains to be deter-
mined. It has been shown that the presence of bile in the blood acts as a
stimulus to the liver-cells, aud it is highly probable that the absorption of bile
from the intestine which occurs during digestion serves to accelerate the secre-
tion ; but this circumstance obviously does not account for the marked increase
observed in animals with biliary fistulas, since in these cases the bile does not
reach the intestine at all. Some imperfect observations by Bidder and Schmidt
indicate that the total quantity of bile varies with the character of the food,
being larger upon a meat diet than when the subject is fed exclusively upon
fats. Exact data as to the effect of the different food-stuffs are lacking.

Relation of the Secretion of Bile to the Blood-flow in the Liver. —
Numerous experiments have shown that the quantity of bile formed by the
liver varies more or less directly with the quantity of blood flowing through
the organ. The liver-cells receive blood from two sources, the portal vein
and the hepatic artery. The supply from both these sources is probably essen-
tial to the perfectly normal activity of the cells, but it has been shown that bile
continues to be formed, for a time at least, when either the portal or the arterial
supply is occluded. However, there can be little doubt that the material actually
utilized by the liver-cells in the formation of their external and internal secre-
tions is brought to them mainly by the portal vein, and that variations in the
quantity of this supply influences directly the amount of bile produced. Thus,
occlusion of some of the branches of the portal vein diminishes the secretion ;
stimulation of the spinal cord diminishes the secretion, since, owing to the large
vascular constriction produced thereby in the abdominal viscera, the quantity of
blood in the portal circulation is reduced ; section of the spinal cord also dimin-
ishes the flow of bile or may even stop it altogether, since the result of such an
operation is a general paralysis of vascular tone and a general fall of blood-
pressure aud velocity ; stimulation of the cut splanchnic nerves diminishes the
secretion because of the strong constriction of the blood-vessels of the abdom-
inal viscera and the resulting diminution of the quantity of the blood in the
portal circulation ; section of the splanchnics alone, however, is said to increase
the quantity of bile, in dogs, since in this case the paralysis of vascular tone
is localized in the abdominal viscera. The effect of such a local dilatation of

188 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the blood-vessels would be to diniinish the resistance alonj:; the intestinal
paths, and thus lead to a greater flow of blood to that area and the portal
circulation.

In all these cases one might suppose that the greater or less quantity of
bile formed depended oidy on the blood-pressure in the capillaries of the liver
lobules — that so far at least as the water of the bile is concerned it is produced
by a process of filtration and rises and fiills with the blood-pressure. That
this simple mechanicid explanation is not sufficient seems to be proved by the
fact that the pressure of bile within the bile-ducts, although comparatively
low, may exceed that of the blood in the portal vein. While it is not possible,
therefore, to exclude entirely the factor of filtration, it is evident that the
quantity of secretion depends largely on the mere quantity of blood flowing
by the cells in a unit of time.

The Existence of Secretory Nerves to the Liver. — The numerous
experiments that have been made to ascertain whether or not the secretion
of bile is under the direct control of secretory nerves have given unsatisfactory
results. The experiments are difficult, since stimulation of the nerves supply-
ing the liver, such as the splanchnic, is accompanied by vaso-motor changes
which alter the blood-flow to the organ and thus introduce a factor which in
itself influences the amount of the secretion. So far as our actual knowledge
goes, the physiological evidence is against the existence of secretory nerve-
fibres controlling the formation of bile. On the other hand, there are some
experiments,' although they are not perfectly conclusive, which indicate that
the glycogen formation within the liver-cells is influenced by a special set of
glyco-secretory nerve-filn-es. This fact, however, does not bear directly upon
the formation of bile.

Motor Nerves of the Bile-vessels. — Doyon ^ has recently shown that the
gall-bladder as well as the bile-ducts is innervated by a set of nerve-fibres
comparable in their general action to the vaso-constrictor and vaso-dilator
fibres of the blood-vessels. According to this author, stimidatiou of the
peripheral end of the cut splanchnics causes a contraction of the bile-ducts
and gall-bladder, while stimulation of the central end of the same nerve, on
the contrary, brings about a reflex dilatation. Stimulation of the central end
of the vagus nerve causes a contraction of the gall-bladder and at the same
time an inhibition of the sphincter muscle closing the opening of the common
bile-duct into the duodenum. These facts need confirmation, perhaps, on the
part of other observers, although they are in accord with what is known of
the actual movement of the bile-stream. The ejection of bile from the gall-
bladder into the duodenum is produced by a contraction of the gall-bladder,
and it is usually believed that this contraction is brought about reflexly from
some sensory stimulation of the mucous membrane of the duodenum or
stomach. The result of the experiments made by Doyon would indicate that
the afferent fibres of this reflex pass upward in the vagus, while the efferent

' Moral and Dufoiirt: Archives de Physiologit, 1894, p. 371.
"^ Archives de Physiologic, 1894, p. 19.

SECRETION. 189

fibres to the ^all-bladdor riiii in tho splanchnics and reach the liver through
the seniihuiar plrxns.

Normal Mechanism of the Bile-secretion. — Bearing in mind the fact
tliat our knowledge of the secretion of bile is in many respects incomplete,
and that any theory of the act is therefore only provisional, wa might picture
the processes concerned in the secretion and ejection of bile as f<)llo\vs: The
bile is steadily formed by the liver-cells and turned out into the bile-capil-
laries ; its quantity varies with the quantity and composition of the blood
flowing through the liver, but the formation of the secretion depends upon
the activities taking place in the liver-cells, and these activities are independ-
ent of direct nervous control. During the act of digestion the formation of
bile is increased, owing probably to a greater blood-flow through the organ
and to the generally increased metabolic activity of the liver-cells occasioned
by the inflow of the absorbed products of digestion. The bile after it gets
into the bile-ducts is moved onward partly by the accumulation of new bile
from behind, the secretory force of the cells, and partly by the contractions
of the walls of the bile-vessels. It is stored in the gall-bladder, and at inter-
vals during digestion is forced into the duodenum by a contraction of the
muscular walls of the bladder, the process being aided by the simultaneous
relaxation of a sphincter-like layer of muscle which normally occludes the
bile-duct at its opening into the intestine; both these last acts are under the
control of a nervous reflex mechanism.

Efifect of Complete Occlusion of the Bile-duct. — It is an interesting
fact that wdien the flow of bile is completely prevented by ligation of the bile-
duct, the stagnant liquid is not reabsorbed by the blood directly, but by the
lymphatics of the liver. The bile-pigments and bile-acids in such cases may
be detected in the lymph as it flows from the thoracic duct. In this way they
get into the blood, producing a jaundiced condition. The way in which the
bile gets from the bile-ducts into the hepatic lymphatics is not definitely known,
but probably it is due to a rupture, caused by the increased pressure, at some
point in the course of the delicate bile-capillaries.

Kidney.

Histology. — The kidney is a compound tubular gland. The constituent
uriniferous tubules composing it may be roughly separated into a secreting
part comprising the capsule, convoluted tubes, and loop of Henle, and a col-
lecting part, the so-called straight collecting-tube, the epithelium of Avhich is
assumed not to have any secretory function. AVithin the secreting part the
epithelium differs greatly in character in different regions ; its peculiarities
may be referred to briefly here so far as they seem to have a physiological
bearing, although for a complete description reference must be made to some
work on Histology.

The arrangement of the glandular epithelium in the capsule with reference
to the blood-vessels of the glomerulus is worthy of special attention. It will
be remembered that each Malpighiau corpuscle consists of two principal parts,

190

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a tuft of blood-vessels, the glonierulu.s, ami an onvel()j)iiii^ exj)an.sion of the
uniferous tubule, the capsule. The glomerulus is a remarkable structure (see
Fig. 82, A). It consists of a small afferent artery which after entering the
glomerulus breaks up into a number of capillaries, which, though twisted
together, do not anastomose. These capillaries unite to form a single etlerent
vein of a smaller diameter than the afferent artery. The whole structure,

Fig. S2.— Portions of the various divisions of the uriniferous tubules drawn from sections of human
kidney : A, Malpighian body ; x, squamous epithelium lining the capsule and reflected over the glomer-
ulus ; I/, :, afferent and efferent vessels of the tuft : e. nuclei of capillaries ; n, constricted neck marking
passage of capsule into convoluted tubule ; B, proximal convoluted tubule ; C, irregular tubule ; D and
F, spiral tubules ; E, ascending limb of Henle's loop; G, straight collecting tubule (Piersol).

therefore, is not an oidinary capillary area, but a rete mirabile, and the phys-
ical factors are such that within the capillaries of the rete there must be a
greatly diminished velocity of the blood-stream owing to the great increase
in the width of the stream-bed and a high blood-pressure as compared with
ordinary capillaries. Surrounding this glomerulus is the double-walled capsule.
One wall of the caj>sule is closely adherent to the capillaries of the glomerulus;
it not only covers the structure closely, but dips into the interior between the
small lobules into which the glomerulus is divided. This layer of the capsule
is composed of flattened ondothelial-like cells, the glomerular epithelium, to
which great imjiortance is now attached in the formation of the secretion. It
will be noticed that between theinteriorof the blood-vessels of the glomerulus and
the cavity of the capsule which is the beginning of the uriniferous tubule there
are interposed only two very thin layers, namely, the epithelium of the capil-
lary wall and the glomerular epithelium. The apparatus would seem to afford
most favorable conditions for filtration of the liquid ]>arls of the blood. The
epithelium clothing the convoluted portions of the tubule, including under this
designation the so-called irregular and spiral portions and the loop of Henle, is
of a character quite different from that of the glomerular epithelium (Fig. 82, B,
C, D, E, F, G). The cells, speaking generally, are cuboidal or cylindrical, proto-
plasmic, and granular in appearance ; on the side toward the basement mem-
brane they often show a peculiar striation, while on the lumen side the extreme

SECRETION. 191

periphery presents a compact border wliicli in some cases shows a cilia-like
striation. These cells have the general appearance of active secretory struc-
tures, and recent theories of urinary secretion attribute this importance to them.

Composition of Urine. — The chemical composition of the urine is very
complex, as we should expect it to be when we remember that it contains most
of the end-products of the varied metabolism of the body, its importance in
this respect being greater than the other excretory organs such as the lungs, skin,
and intestine. The secretion is a yellovvish liquid which in carnivorous ani-
mals and in man has normally an acid reaction, owing to the presence of acid
salts (acid sodium and acid calcium phosphate), and an average specific gravity
of 1017 to 1020. The quantity formed in twenty-four hours is about 1200 to
1700 cubic centimeters. In the very young the amount of urine formed is
proportionately much greater than in the adult. The normal urine contains
about 3.4 to 4 per cent, of solid material, of which over half is organic mate-
rial. Among the important organic constituents of the urine are the follow-
ing : urea, uric acid, hippuric acid, xanthin, hypoxanthin, guanin, creatinin
and aromatic oxy- acids (para-oxypheuyl ])ropionic acid and para-oxyphenyl
acetic acid, as simple salts or combined with sulphuric acid) ; phenol, paracre-
sol, pyrocatechin and hydrochinon, these four substances being combined with
sulphuric or glycuronic acid ; indican or indoxyl sulphuric acid ; skatol sul-
phuric acid ; oxalic acid ; sulphocyanides, etc. These and other organic con-
stituents occurring under certain conditions of health or disease in various
animals, are of the greatest importance in enabling us to follow the metab-
olism of the body. Something as to their origin and significance will be
found in the section on Nutrition, while their purely chemical relations
are described in the section on Chemistry.

Among the inorganic constituents of the urine may be mentioned sodium
chloride, sulphates, phosphates of the alkalies and alkaline earths, nitrates, and
carbon dioxide gas partly in solution and partly as carbonate. In this section
we are concerned only with the general mechanism of the secretion of urine,
and in this connection have to consider mainly the water and soluble inorganic
salts and the typical nitrogenous excreta, namely, urea and uric acid.

The Secretion of Urine. — The kidneys receive a rich supply of nerve-
fibres, but most histologists have been unable to trace any connection between
these fibres and the epithelial cells of the kidney tubules. Berkeley^ has, how-
ever, recently discovered nerve-fibres passing through the basement membrane
and ending between the secretory cells.

The majority of purely physiological experiments upon direct stimulation of
the nerves going to the kidney are adverse to the theory of secretory fibres, the
marked effects obtained in these experiments being all explicable by the changes
produced in the blood-flow through the organ. Two general theories of urinary
secretion have been proposed. Ludwig held that the urine is formed by the
simple physical processes of filtration and diffusion. In the glomeruli the
conditions are most favorable to filtration, and he supposed that in these struc-
' The Johns Hopkins Hospital Bulletin, vol. iv., No. 28, p. 1.

192 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tares water filtered tlirough from tlie blood, earrying with it not only the iu-
orgauic salts, but also the specific elements (urea) of the secretion. There was
thus formed at the beginning of the uriniferous tubules a complete but diluted
urine, and in the subsequent passage of this liquid along the convoluted tubes
it became concentrated by ditfusion with the lymph surrounding the outside
of the tubules. So far as the latter part of this theory is concerned it has
not been supported by actual experiments; recent histological work (see below)
seems to indicate that the epithelial cells of the convoluted tubules have a
distinct secretory function, and that they give material to the secretion rather
than take from it.

Bowman's theory of urinary secretion, which has since been vigorously
supported and extended by Heidenhain, was based apparently mainly on his-
tological grounds. It assumes that in the glomeruli water and inorganic salts
are produced, while the urea and related bodies are eliminated through the
activity of the epithelial cells in the convoluted tubes.

Elmiinaiion of Urea and Related Bodies. — Numerous facts have been
discovered which tend to support the latter part of Bowman's theory — namely,
the participation of the cells of the convoluted tubules in the secretion of the
specific nitrogenous elements. In birds the main nitrogenous element of the
secretion is uric acid instead of urea, and it is possible, owing to the small solu-
bility of the urates, to see them as solid deposits in microscopic sections of the
kidney. When the ureters are ligated the deposition of the urates in the kid-
ney may become so great as to give the entire organ a whitish appearance.
Nevertheless histological examinations of a kidney in this condition shows that
the urates are found always in the tubes and never in the Malpighian corpus-
cles. From this result we may conclude that the uric acid is eliminated
through the epithelial cells of the tubes. Heidenhain has shown by a striking
series of experiments that the cells of the tubes possess an active secretory
power. In these experiments a solution of indigo-carmine was injected into
the circulation of a living animal after its spinal cord had been cut to reduce
the blood-pressure and therefore the rapidity of the secretion. After a certain
interval the kidneys were removed and the indigo-carmine precipitated in situ
in the kidney by injecting alcohol into the blood-vessels. It was found that
the pigment granules were deposited in the convoluted tubes, but never in the
^Malpighian corpuscles.

Still further proof of definite secretory functions on the part of the cells
of the tubules is given by the results of recent histological work upon the
changes in the cells during activity. Van der Stricht* and Disse'* both
describe definite morphological changes in the epithelial cells of the convoluted
tubes and ascending loop of Henle which they connect with the functional
activity of the cells. The details of the descriptions diifer, but the two authors
agree in finding that the material of the secretion collects in the interior of the

' Comptes rendua, 1891, and Travail du Lahoratoire d'Histolugie de I' Unircrsile dr Gand, 1892.
" Referate und Beitrage zur ATiatomie und Entwickelungsgesckichte (anatomische Hefte), Merkel
and Bonnet, 1893.

SECRETION. 193

cell to form a vesicle wliicii is alterwurcl (iiseliarged into the lumen of the cell.
According to Disse the inactive cells are small and granular, and toward the
lumen show a striated border of minute processes, while the lumen of the tube
is relatively wide. As the fluid secretion accumulates in the cells it may be
distinguished as a clear vesicular area near the nucleus. The cells enlarge
and project toward the lumen, which becomes smaller; the striated border dis-
appears. Finally the swollen cells fill the entire canal, and the liquid secre-
tion is emptietl from the cells by filtration. Van dcr Stricht believes that the
vesicles rupture the cells and thus are cast out into the lumen. In hmgitudinal
sections various stages in the process may be seen scattered along the length
of a single tubule.

Seo-etion of the Water and Salts. — There seems to be no question that the
elimination of N^iiter together with inorganic salts, and probably still other
soluble constituents, takes place chiefly through the glomerular epithelium.
This supposition is made in both the general theories that have been men-
tioned. It has, however, long been a matter of controversy, in this as in
other glands, whether the water is produced by simple filtration or whether
the glomerular epithelium takes an active part of some character in setting up
the stream of water. The problem is perhaps simpler in this case than in the
salivary glands, since the direct participation of secretory nerves in the process
is excluded. On the filtration theory the quantity of urine should vary
directly with the blood-pressure in the glomerulus. This relationship has
been accepted as a crucial test of the validity of the filtration theory, and
numerous experiments have been made to ascertain whether it invariably
exists. Speaking broadly, any general rise of blood-pressure in the aorta will
occasion a greater blood-flow and greater pressure in the glomerular vessels
provided the kidney arteries themselves are not simultaneously constricted to
a sufficient extent to counteract this favorable influence ; whereas a general fall
of pressure should have the opposite influence both on pressure and velocity of
flow. It has been shown experimentally that if the general arterial pressure
falls below 40 or 50 millimeters of mercury, as may happen after section of
the spinal cord in the cervical region, the secretion of the urine will be greatly
slowed, or suspended completely. Constriction of the small arteries in the
kidney, whether effected through its proper vaso-constrictor nerves or by par-
tially clamping its arteries, causes a diminution in the secretion and at the
same time in all probability a fall of pressure within the glomeruli and a
diminution in the total flow of blood. On the other hand, dilatation of the
arteries of the kidney, whether produced through its vaso-dilator fibres or by
section or inhibition of its constrictor fibres, augments the flow of urine and
at the same time probably increases the pressure within the glomerular capil-
laries, and also the total quantity of blood flowing through them in a unit of
time. From these and other experimental facts it is evident that the amount
of secretion and the amount of pressure wathin the glomerular vessels do often
vary together, and this relationship has been used to prove that the water of
the secretion is obtained by filtration from the blood-plasma. But it will be

13

194 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

observed that the qiumtity of secretion varies not only with the ])ressure of
the l)K)o(l within the glomeruli, hut also with the (jnantity ol" blood flowing
through them. Heidenhain has insisted that it is this latter factor and not
the intracapillary pressure which determines the quantity of water secreted.
He believes that the glomerular epithelial cells possess the property of actively
secreting water, and that they are not sim])ly passive filters ; that the forma-
tion, in other w^ords, is not a simple mechanical process, but a more complex
one depending upon the living structure and proj)crties of the epithelial cells.
In support of this view he quotes the fact that partial compression of the
renal veins quickly slows or stops altogether the flow of urine. Compression
of the veins should raise the pressure within the vessels of the glomeruli, and
upon the filtration hypothesis should increase rather than diminish the secre-
tion. It has been shown also that if the renal artery is compressed for a
short time so as to completely shut off the blood-flow to the kidney the
secretion is not only suspended during the closure of the arteries but for a
long time after the circulation is re-established. According to Tiegerstedt,
if the renal artery is ligated for only half a minute the activity of the
kidney is suspended for three-quarters of an hour. This fact is difficult to
understand if the glomerular epithelium is simply a filtering membrane, but
it is easily explicable upon the hypothesis that the epithelial cells are actively
concerned in the production of the water.

Much of the recent work upon the secretion of urine tends to support
Heidenhain's opinion. Munk ^ and Senator made careful experiments upon
excisecl kidneys which were kept alive and in functional activity by an arti-
ficial supply of blood, and w^ere able to show that the quantity of the secretion
depended less on the blood-})ressure than on the rate of flow. So, numerous
experiments upon the action of diuretics ^ such as NaCl, KNO3, and cafFein
seem to have shown distinctly that the increased flow of blood caused by these
substances cannot be explained upon the filtration hy})othesis, and that we
must suppose that they have a specific action upon the kidney-cells, particularly
the epithelial cells covering the glomeruli.

We may assume, therefore, until the contrary is proved, that the larger
Ipart of the water and inorganic salts of the urine is secreted at the capsular
[end of the uriniferous tubule by a definite action of the living epithelial cells.
It must be borne in mind, however, that some water and probably also some
of the inorganic salts are secreted at other parts of the tubule along with the
elimination of the nitroo-enous wastes. It is of interest to add that the most
important of the abnormal constituents of the urine under pathological con-
ditions, such as the albumin in albuminuria, the ha?moglobin in htemoglo-
biuuria, and the sugar in glycosuria, seem likewise to escape from the blood
into the kidney tubules through the glomerular epithelium.

Theoretical Considerations. — Granting that the glomerular epithelium

^ Virchow's Archiv fur pathologische Anatornie nnd Phy^olocfie, etc., M. cxiv., 1888.
* See Von Scliroeder: Archiv fur exper. Pathologie und PharmakoL, Bd. xxiv. S. 85, and
Dreser, Ibid., 1892, Bd. xxix. S. 303.

SECRETION. 195

takes an active part in directing the stream of water from the blood to the
uriniferous tubules, it is natural to ask by what mechanism this action is
effected. The problem is essentially similar to that already encountered in
explaining the flow of water in other glands (see p. 166). There is as yet no
satisfactory explanation given. It is to be supposed that this property is
dependent upon some physical or chemical reaction of the substance of the
cell, and involves the existence of no form of energy not already known to us
in other ways ; but what tlie nature of these reactions is must be left for
future work. The extent of the activity seems to depend mainly on the
quantity of blood flowing through the glomeridi. The greater the quantity
of blood, the greater will be the quantity of water brought to the cells, and
the more complete also the supply of needful oxygen. In addition, substances,
such as the inorganic salts, which occur normally in the blood, or other sub-
stances which may be introduced therapeutically, may act as chemical irritants
to these cells, and thus increase their secretory activity. The normal stimulus
to the epithelial cells of the convoluted tubules, using the term convoluted to in-
clude the actively secreting parts, seems to be the presence of urea and related
substances in the blood (lymph). That the elimination of the urea is not a simple
act of diffusion seems to be clearly shown by the fact that its percentage in the
blood is much less than in the urine. In some way the urea is selected from
the blood and passed into the lumen of the tubule, and although we have
microscopic evidence that this process involves very active changes in the sub-
stance of the cells, there is no adequate theory of the nature of the force which
attracts the urea from the surrounding lymph. The whole process must be
rapidly effected by the cell, since there is normally no heaping up of urea in
the kidney-cells; the material is eliminated into the tubules as quickly as it
is received from the blood. The rate of elimination increases normally with
the increase in the urea in the blood, as would be expected upon the assump-
tion that the urea itself acts as the physiological stimulus to the epithelial
cells.

The Blood-flow through the Kidneys. — It will be seen from the dis-
cussion above that, other conditions remaining the same, the secretion of the
kidney varies with the quantity of blood flowing through it. It is therefore
important at this point to refer briefly to the nature and especially the regula-
tion of the blood-flow through this organ, although the same subject is referred
to in connection with the general description of vaso-motor regulation (see
Circulation). It has been shown by Landergren^ and Tiegerstedt that the
kidney is a very vascular organ, at least when it is in strong functional activ-
ity such as may be produced by the action of diuretics. They estimate that
in a minute's time, under the action of diuretics, an amount of blood flows
through the kidney equal to the weight of the organ ; this is an amount from
four to nineteen times as great as occurs in the average supply of the other
organs in the systemic circulation. Taking both kidneys into account, their
figures show that (in strong diuresis) 5.6 per cent, of the total quantity of
^ Skandinavisches Archiv fur Physiologie, 1892, Bd. iv. S. 241.

196 AX AMERICAN TEXT- BOOK OF PHYSIOLOGY.

blood sent out ut" the lott liourt in a laimite may pass tlirougli tlic kiJueys,
although the coiubineil weight of these organs makes only 0..")6 per cent, of
that of the body.

The richness of the supply of vaso-iuotor nerves to the kidney and tiie con-
ditions which bring them into activity are fairly well known, owing to the use-
ful invention of the oncometer by Roy.' This instrument is in principle a
plethysmograph especially modified for use upon the kidney of the living
animal. It is a kiilney-shaped box of thin brass made in two parts, hinged at
the back, and with a clasj) in front to hold them together. In the interior of
the box thin peritoneal membrane is so fastened to each half that a layer of olive
oil may be placed between it and the brass walls. There is thus formed in
each half a soft pad of oil upon which the kidney rests. When tiie kidney,
freed as far as possible from fat and surroiniding connective tissue, but with
the blood-vessels and nerves entering at the hilus entirely uninjured, is laid in
one-half of the oncometer, and the other half is shut down upon it and tightly
fastened, the organ is surrounded by oil in a box which is liquid-tight at every
point except one, where a tube is led ofif to some suitable recorder such as a
tambour. Under these conditions every increase in the volume of the kidney
will cause a proportional outflow of oil from the oncometer, which will be
measured by the recorder, and every diminution in volume will be accompa-
nied by a reverse change. At the same time the flow of urine during these
changes can be determined by inserting a cannula into the in-eter and measur-
ing directly the outflow of urine. By this and other means it has been shown
that the kidney receives a rich supply of vaso-coustrictor nerve-fibres which
reach it between and round the entering blood-vessels. These fibres emerge
from the spinal cord chiefly in the lower thoracic spinal nerves (tenth to thir-
teenth in the dog), pass through the sympathetic system, and reach the organ
as non-medullated fibres. Stimulation of these nerves causes a contraction of
the small arteries of the kidney, a shrinkage in volume of the whole organ as
measured by the oncometer, and a diminished secretion of urine. AVhen, on
the other hand, these constrictor fibres are cut as they enter the hilus of the
kidney, the arteries are dilated on account of the removal of the tonic action
of the constrictor fibres, the organ enlarges, and a greater quantity of blood
passes through it, since the resistance to the blood-flow is diminished while
the general arterial pressure in the aorta remains practically the same. Along
with this greater flow of blood there is a marked increase in the secretion of urine.

Under normal conditions we must suppose that these fibres are brought
into play to a greater or less extent by reflex stimulation, and thus serve to
control the blood-flow through the kidney and thereby influence its functional
activity. It has been shown, too, that the kidney receives vaso-dilator nerve-
fibres, that is, fibres which when stimidated directly or reflexly cause a dilata-
tion of the arteries, and therefore a greater flow of blood through the organ.
According to Bradford,^ these fibres emerge from the spinal cord mainly in the

> See Colniheini and Roy : yircho\v& Arckiv, 1883, Bd. 92, S. 424.
^ Journal of Physiology, 1889, vol. x. p. 358.

SECRETION. 197

anterior roots ot" the eluveutli, twelf'tli, uiid tliirtceuth spinal uerves. Under
normal conditions these fibres are probably thrown into action by reflex stimula-
tion and lead to an increased functional activity. It will be seen, therefore,
that the kidneys possess a local nervous mechanism through which their
secretory activity may be increased or diminished by corresponding alterations
in the blood-supply. So far as is known, this is the only way in which the
secretion in the kidneys can be directly affected by the central nervous svstem.
It should be borne in mind, also, that the blood-flow through the kidneys,
and therefore their secretory activity, may ijc affected by conditions influ-
encing general arterial pressure. Conditions such as asphyxia, strychnin-
poisoning, or painful stimulation of sensory nerves, which cause a great
rise of blood -pressure, influence the kidney in the same way, and tend,
therefore, to diminish the flow of blood through it; while conditions which
lower general arterial pressure, such as general vascular dilatation of the skin
vessels, may also depress the secretory action of the kidney by diminishing
the amount of blood flowing thrj^ugh it.

In what way any given change in the vascular conditions of the body will
influence the secretion of the kidney depends upon a number of factors, and
their relations to one another ; but any change which will increase the differ-
ence in pressure between the l)lood in the renal artery and the renal vein will
tend to augment the flow of blood unless it is antagonized by a simultaneous
constriction in the small arteries of the kidney itself. On the contrary, any
vascular dilatation of the vessels in the kidney will tend to increase the blood-
flow through it unless there is at the same time such a general fall of blood-
pressure as is sufficient to lower the pressure in the renal artery and reduce the
driving force of the blood to an extent that more than counteracts the favora-
ble influence of diminished resistance in the small arteries.

Movements of the Ureter and the Bladder. — (See Micturition, p. 327.)

E. Cutaneous Glands ; Internal Secretions.

The sebaceous glands, sweat-glands, and mammary glands are all true epider-
mal structures, and may therefore be conveniently treated together.

Sebaceous Secretion. — The sebaceous glands are simple or compound
alveolar glands found over the cutaneous surface usually in association with the
hairs, although in some cases they occur .separately, as, for instance, on the pre-
puce and glans penis, and on the lips. When they occur with the hairs the
short duct opens into the hair-follicle, so that the secretion is passed out upon
the hair near the point where it projects from the skin. The alveoli are filled
with cuboidal or polygonal epithelial cells, which are arranged in several lay-
ers. Those nearest the lumen of the gland are filled with fatty material.
These cells are supposed to be cast off bodily, their detritus going to form the
secretion. New cells are formed from the layer nearest the basement mem-
brane, and thus the glands continue to]iroduce a slow but continuous secretion.
The sebaceous secretion, or sebum, is an oily semi-liquid material which sets
upon exposure to the air to a cheesy mass, as is seen in the comedones or pim-

198 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ple.s which so fivquently occur upon the skin from occlusion of the opening' of
the ducts. The exact composition of the secretion is not known. It contains
tats and soaps, some cholcstcrin, albuminous material, part of which is a
nuclco-alhumin often described as a casein, remnants of e|)ithenal cells,
and inorganic salts. The cholesterin occurs in combination with a fatty acid
and is found in especially large quantities in sheep's wool, from which it is
extracted and used commercially under the name of lanolin. The sebaceous
secretion from different places, or in different animals, is probably somewhat
variable in composition as well as in quantity. The secretion of the prepuce
is known as the smegma pneputii ; that of the external auditory meatus,
mixed with the secretion of the neighboring sweat-glands or cenuninous glands,
forms the well-known ear-wax or cerumen. The secretion in this place con-
tains a reddish ])igment of a bitterish-sweet taste, the composition of which has
not been investigated. Upon the skin of the newly-born the sebaceous ma-
terial is accumidated to form the vernix caseosa. The well-known ui-opvgal
gland of birds is homologous with the mammalian sebaceous glands, and its
secretion has been obtained in sufficient quantities for chemical analysis.
Physiologically it is believed that the sebaceous secretion affords a protection
to the skin and hairs. Its oily character doubtless serves to protect the hairs
from becoming too brittle, or, on the other hand, from being too easily satu-
rated with external moisture. In this way it probably aids in making the
hairy coat a more perfect protection against the effect of external changes of
temperature. Upon the surface of the skin also it forms a thin protective
layer which tends to prevent undue loss of heat from evaporation, and possi-
bly is important in other ways in maintaining the physiological integrity of
the external surface.

Sweat. — The sweat or perspiration is a secretion of the sweat-glands.
These latter structures are found over the entire cutaneous surface except in
the deeper portions of the external auditory meatus. They are particularly
abundant upon the palms of the hands and the soles of the feet. Krause
estimates that their total number for the whole cutaneous surface is about two
millions. In man they are formed on the type of simple tubular glands; the
terminal portion contains the secretory cells, and at this j)art the tube is
usually coiled to make a more or less compact knot, thus increasing the extent
of the secreting surface. The larger ducts have a thin muscular coat of invol-
untary tissue which may possibly be concerned in the ejection of the secretion.
The secretory cells in the terminal portion are columnar in shape, they possess
a granular cytoplasm and are arranged in a single layer. The amount of
secretion formed by these glands varies greatly, being influenced by the con-
dition of the atmosphere as regards temperature and moisture, as well as by
various physical and psychical states such as exercise and emotions. An aver-
age quantity for twenty-four hours is said to vary between 700 and 900 grams,
although this amount may be doubled inider certain conditions.

Composition of the Secretion. — The precise chemical composition of sweat
is difficult to determine, owing to the fact that as usually obtained it is liable

SECRETION. 1^^

t„ 1„. mixcl witl, .1,0 sebaceous secretion. Norn.ally ,t ,s a very thn, scae-
ion of low specific gravity (1004) and an all<aline react, on al hong , when
ftn^ secretecl L .-eaetion n,ay bo .M owing t<, adnnxtnre vy,tl, tl,e .e baceou
Lterial. The la,-ger ,,art of the i„o,-gauic salts eons,sts of sod.nn. el lor,, e.
tf,uall quantities of the alkaline sulphates an.l phosphates are also ,„-esont. The
o,-ga„ic eoustitneuts, though present in ,ne>-e traces arc qmte var,e<l ,n nnn,-
li Urea uric acid, e,-eatini„, arou.atic oxy- acls, etl,ereal sulphates of
pbe'nol and skatol, an.l all,u„,i„, are said to o,.cur when the sweat.ng ,s pro-
f .^ Ar«,ti„sky has shown that after the action of vapo,- baths, and as the
result of mnsenlar work, the amount of urea eli,nina.ed in tins seeret.on may
be eousidcablc (sec p. 299). Under pathologieal c„nd,t,o„s '"volv.ng a
diminished elimination of urea through the kidneys ,t has been obse vol t ha
tl.e amount found in the sweat is markedly i„c,-eased, so that crystals of ,t
„,ay be deposited upon the skin. Under perfectly normal eond,t,o„s, how-
ever it is obvious that the organic constituents are of m,nor ,mportanee. The
main fact to be considered in the secretion of sweat is the format,on o «^ ter
Secrdory Fibres to ll^ feaf-ffW^.-Definite expcr,mental proof of the
existence of sweat-uerves was fi^t obtained by Goltz' in some exi»nn,ents
npol stimulation of the sciatic uerve in «,ts. In the eat and dog, ,n wh.ch
sweat-o-lands occur only on the balls of the feet, the presence of sweat-nerves
ZZC demonst,-atcd with great ease. Electrical stimulat.on of the penphera
end of the divided sciatic nerve, if suificiently strong w,U -use v,s,ble drops
of sweat to form on the hairless skin of the balls of the feet. When the el«.
t odrarc kept at the same spot on the nerve and the stimulatron ,s ma,ntamed
he s3on soon ceases, bat' this effect seems to be due to a temporary ,njnry
of some kind to the nerve-fibres at the point of sti,nulat,on, and not to a
1,SL ft igne of the sweat-glands or the sweat-fibres, s.nce mov,ng the elee-
frdeT o a ,' w point on the nerve farther toward the pe,-,phery calls forth a
ew i rction. The secretion so formed is thin and limp,d, and has a ma,-l^
"llal ,e rllion. The anatomical «,u,-se of these fibres has been worked out
"Th cat 1 great care by Langley.^ He finds that for the h,nd fee th y
ave the spinal'cord chiefly in the first and -™"'\ '7" ^ X:: inl gS
sympathetic chain, and emerge fron, this as "^-"^''""f "*>;";" t/^^^
rami nroceeding from the sixth lumbar to the second sac al ganglion, but
ra,n, proceeo,u„ , „ i ,, (lien on the nerves of

chiefly in the seventh lumbar and h,->t sacal, ana i,ie, j
the sciatic plexus. For the fore feet the fibres leave the sp,nal cord ,n the
f!„-.ht^^th tenth thoracic nerves, enter the sympathetic cha.n, pass upward
0 l,e first thoracic ganglion, whence they are continued as non-meduUated
r whi pass out'of this ganglion by the gray --/ -"-— f ^f^
the nerves forming the brachial plexus. The act.on of the - ^ ;«^J^" 'f^

.he sweat-glands cannot be explained as » ■;j;-^ ^ '^ J Xlown

rpc^nlt of a variatou n the blood-flow. JLxpenmems lune i i

Tat! in the cat, stimulation of the sciatic still calls forth a secret.on after the

1 Archiv fur die (jesammte Physiologie, 1875, Bd. xi. S. 71.

2 Journal of Phydology, 1891, vol. xii. p. 347.

200 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

blood lias been shut otl' Iroiii the leg l)y ligation oi" the aorta, or indeed al'tc^r
the leg has been amputated for as long as twenty niiinites. So in iiiinian
beings it is known that profuse sweating may often aeeomjtany a j)allid skin,
as in terror or nausea, while on the other hand the ilushed skin of fever is
characterized by the absence of perspiration. There seems to be no doubt
at all that the sweat-nerves are genuine secretory fibres, producing the secre-
tion directly by their action on the cells of the sweat-glands. In accordance
with this physiological fact recent iiistological work has demonstrated that
special nerve-fibres are suj)plied to the glandular epithelium. According to
Arnstein ' the terminal fibres form a small branching varicose ending in con-
tact with the epithelial cells. The sweat-gland may be made to secrete in
many ways other than by direct artificial excitation of the sweat-fibres; for
example, by external heat, dyspnoea, muscular exercise^, strong emotions, and
by the action of various (b'ugs such as pilocarpin, muscarin, strychnin, nicotiu,
picrotoxin, and physostigmin. In all such cases the effect is supposed to
result from an action on the sweat-fibres, either directly on their terminations,
or indirectly upon their cells of origin in the central nervous system. In
ordinary life the usual cause of profuse sweating is a high external temper-
ature or muscular exercise. With regard to the former it is known that
the high temperature does not excite the sweat-glands immediately, but
through the intervention of the central nervous system. If the nerves going
to a limb be cut, exposure of that limb to a high temperature does not cause
a secretion, showing that the temperature change alone is not sufficient to
excite the gland or its terminal nerve-fibres. We must suppose, therefore,
that the high temperature acts upon the sensory cutaneous nerves, ]>ossibly
the heat-fibres, and reflexly stimulates the sweat-fibres. Although external
temperature does not directly excite the glands, it should be stated that it
affects their irritability either by direct action on the gland-cells or, as is more
likely, upon the terminal nerve-fibres. At a sufficiently low temperature the
cat's paw does not secrete at all, and the irritability of the glands is increased
by a rise of temperature up to about 45° C

Dysj)noea, nmscular exercise, emotions, and many drugs aflPeet the secretion,
probably by action on the nerve-centres. Pilocarpin, on the contrary, is
known to stimulate the endings of the nerve-fibres in the glands, while atropin
has the opposite effect, completely paralyzing the secretory fibres.

Siveat-centres in the Central Nervous Si/sfem. — The fact that secretion of
sweat may be occasioned by stimulation of afferent nerves or by direct action
upon the central nervous system, as in the case of dyspnoea, implies the exist-
ence of physiological centres controlling the secretory fibres. The precise loca-
tion of the sweat-centre or centres has not, however, been satisfactorily deter-
mined. Histologically and anatomically the arrangement of the sweat-fibres
resembles that of the vaso-constrictor fibres, and, reasoning from analogy, one
might suppose the existence of a general sweat-centre in the medulla compara-
ble to the vaso-constrictor centre, but positive evidence of the existence of such

^ Anaiomiacher Ameiger, 1895, Bd. x.

SECRETION. 201

an arraiii^i'ment is lacking. It lias Ikcm shown than when the medulla is
separated t'roni the cord hv a sctition in the cervical or thoracie region the
action of dyspnoea, or ot" various sudorific drugs suj)p(jsed to act on the cen-
tral nervous system, may still cause a secretion. On the evideuce of* results
of this character it is assumed that there are spinal sweat-centres, but whether
these arc few in number or represent simply the various nuclei of origin of the
fibres to different regions is not definitely known. It is })ossil)le that in addi-
tion to these spinal centres there is a general regulating centre in the medulla.

Mammary Glands.

The mammary glands are undoubtedly epidermal structures comparable iu
development to the sweat- or the sebaceous glands. Whether they are to be
homologized with the sweat- or with the sebaceous glands is not clearly deter-
mined. In most animals they are compound alveolar glands, and their acinous
structure and the rich albuminous and fatty constituents of their secretion
would seem to suggest a relationship to the sebaceous glands. But the histo-
logical structure of their alveoli with its single layer of epithelium points
rather to a connection with the sweat-glands. Whatever may have been their
exact origin in the primitive mammalia, there seems to be no question that
they were deriv^ed in the first place from some of the ordinary skin-glands
which at first simply opened on a definite area of the skin, but without a dis-
tinct mamma or nipple, as is seen now in the case of the monotremes. Later
in the phylogenetic history of the gland the separate ducts united to form
one or more larger ones, and these opened to the exterior upon the protrusion
of the skin known as the nipple. The number and position of the glands
vary much in the different mammalia. In man they are found in the thoracic
region and are normally two in number. The milk-ducts do not unite to
form a single canal, but form a group of fifteen to twenty separate systems,
each of which opens separately upon the surface of the nipple. Before preg-
nancy the secreting alveoli are incompletely formed, but during pregnancy
and at the time lactation begins the formation of the alveoli is greatly acceler-
ated by proliferation of the epithelial cells.

Composition of the Secretion. — The general appearance and composi-
tion of the milk are well known. Microscopically milk consists of a liquid
portion, or plasma, in which float an innumerable multitude of fine fat-drop-
lets. The latter elements contain the milk-fat, which consists chiefly of neutral
fats, stearin, palmitin, and olein, but contains also a small amount of the fats
of butyric and caproic acid as well as slight traces of other fatty acid com-
pounds and small amounts of lecithin, cholesterin, and a yellow pigment. Upon
standing, a portion of these elements rises to the surface to form the cream. The
milk-plasma holds in solution important proteid and carbohydrate compounds
as well as the necessary inorganic salts. The proteids are casein, belonging to
the group of nucleo-albumins ; lactalbumin, which closely resembles the serum-
albumin of blood, and lacto-globulin, which is similar to the paraglobulin of
blood : the two latter proteids occur in much smaller quantities than the casein.

202

AX AMERICAN TEXT-BOOK OF rilVSIOLOGY.

The chief carbohydrate in niilU is the iiiilk-siigar or hictosc. Ilaminarsteii '
has succeeded iu isolating from the mammary gland a nucleo-protcid (-ontain-
ing a reducing group. He designates this suhstance as nncleo-glyco-proteid.
It seems possible that a compound of this character might serve as the parent
substance for both tlie casein and the lactose of the secretion. The mineral
constituents are varied and, considered quantitatively, show an interesting rela-
tionship to the mineral composition of the body of the suckling (see p. 296).
The fact that the inorganic salts of the milk vary so widely in quantitative
composition from those of the blood has been used to show that they are not
derived from the blood by the simple mechanical processes of filtration or
dialysis, but are secreted by the epitlielial (^ells of the gland. Traces of
nitrogeneous excreta, such as urea, creatiu, and oreatinin, are also found in
the milk-plasma, together with some lecithin and cholesterin and a small
amount of citric acid occurring as citrate of calcium.

Histolog-ical Changes during Secretion. — The simple fact that sub-
stiinces are foinid in the milk which do not occur in the blood or lymph is
sufficient proof that the epithelial cells are actively concerned in the process
of secretion. Histological examination of the gland during lactation confirms

fully tliis a 'priori deduction, and enables
us to understand the probable origin of
some of the important constituents.^ In
the resting gland during the period of
gestation, or in certain alveoli during
lactation, the alveoli are lined by a single
layer of flattened or cuboidal cells, which
have only a single nucleus, present a
granular appearance, and have few or
no fat-globules in them (Fig. 83).
When such alveoli enter into the active
formation of milk the epithelial cells
increase in height, projecting in toward the lumen, the nuclei divide, and as a

Fig. 83.— Section through the middle of two
alveoli of the mammary gland of the dog ; con-
dition of rest (after Heidenhain).

A

Fig. 84.— Mammary gland of dog, showing the formation of the secretion : A, medium condition of
growth of the epithelial cells ; B, a later condition (after Heidenhain).

rule (Steinhaus^) each cell contains two nuclei (Fig. 84). Fat-droplets de-
velop in the cytoplasm, especially in the free end of the cell, and according to

' Zeitschrift fiir physiologische Chemie, 1894, Bd. xix. S. 19.

^ See Heidenhain: Hermann's Handbuch (hr I'hj/xiologie, 18S3, Bd. v. S. 381.

^ Du Bok-ReymoncVs Archiv fiir Phi/siolnrjle, 1892, Siippl. Bd., p. 54.

SECRETION. 203

Steiiihaus the uuclous nearest the lumen uiulergoe-s a fatty metamorphosis.
According to the same author the granular material in the cytoplasm also
undergoes a visible change; the granules, which in the resting cell are
spherical, elongate during the stage of activity to threutls that take on a
spirochneta-like form. The acme of this phase of development is reached by
the solution or disintegration of a portion of the end of the cell; the frag-
ments being discharged into the lumen of the alveolus. The debris of this
disintegrated portion of the cell helps to form the secretion ; part of it goes
into solution to form, probably, the albuminous and carbohydrate constituents,
while the fat-droplets are set free to form the milk-fat. Apparently the basal
portion (jf the cell regenerates its cytoplasm and thus continues to form new
material for the secretion. In some cases, however, the whole cell seems to
undergo dissolution, and its place is taken by a new cell formed by karyo-
kinetic division of one of the neighboring epithelial cells. The origin of the
peculiar colostrum corpuscles found in the milk during the first few days
of its secretion has been explained differently by different observers. Heid-
enhain traces them to certain epithelial cells of the alveoli which at this
time become rounded, develop numerous fat-droplets, and are finally dis-
charged bodily into the lumen, although he was not able to actually trace
the intermediate steps in the process. Steinhaus, on the contrary, thinks
that these corpuscles are derived from the wandering cells of the connective
tissue (^Mastzellen) which at the beginning of lactation are very numerous,
but seem to undergo fatty degeneration and elimination in the secretion of
the newly active gland.

Control of the Secretion by the Nervous System. — There are indica-
tions that the secretion of the mammary glands is under the control, to some
extent at least, of the central nervous system. For instance, in women during
the period of lactation cases have been recorded in which the secretion was
altered or perhaps entirely suppressed by strong emotions, by an epileptic
attack, etc. This indication has not received satisfactory confirmation from
the side of experimental physiology. Eckhard ^ found that section of the
main nerve-trunk supplying the gland, the external spermatic, caused no dif-
ference in the quantity or quality of the secretion. Rohrig^ obtained more
positive results, inasmuch as he found that some of the branches of the exter-
nal spermatic supply vaso-motor fibres to the blood-vessels of the gland and
influence the secretion of milk by controlling the local blood-fiow in the
gland. Section of the inferior branch of this nerve, for example, gave in-
creased secretion, while stimulation caused diminished secretion, as in the
case of the vaso-constrictor fibres to the kidney. These results have not been
confirmed by others — in fact, they have been subjected to adverse criticism —
and they cannot, therefore, be accepted unhesitatingly.

Mironow^ reports a number of interesting experiments made upon goats.

^ See Heidenhain : Hermann's Handbuch der Physiologic, Bd. v. Thl. 1. S. 392.
* Virchovfs Archiv far pathologische Anatomic, etc., 1876, Bd. 67, S. 119.
'^ Archives des Sciences biologiques, St. Petersburg, 1894, vol. iii. p. 353.

204 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

He foiiud that artilicial stiiuulation of sensory nerves causes a diiiiinution iu
the amount of secretion, thus oonlinninu- the opinion IjasctI upon observations
upon tlie Imman heinj;-, that in some way tlie central nervous system exerts au
inriuenee on the mammary gland. When the mammary glands are com-
pletely isolated from their connections with the central nervous system, stimu-
lation of an afferent nerve no longer influences the secretion. Mirouow
states also that although section of the external spermatic on one side does not
influence the secretion, section of this nerve on both sides is followed bv a
marked diminution, and the same result is obtained when the gland cm one
side is completely isolated from all nervous connections. The diminution of
the secretion in these cases comes on very slowly, after a number of days, so
that the effect cannot be attributed to the removal of definite secretory fibres.
Moreover, after apj)arently complete separation of the gland from all its
extrinsic nerves, not oidy does the secretion, if it was previously present, con-
tinue to form although in less quantities, but in operations of this kind upon
pregnant animals the glands increase in size during pregnancy and become
functional after tlie act of parturition.

Experiments, therefore, as far as they have been carried, indicate that
the gland is under the regulating control of the central nervous system, either
through secretory or vaso-motor fibres, but that it is essentially an automatic
organ. The bond of connection between it and the uterus seems to be, in part
if not entirely, through the blood rather tiian through the nervous system.
It should be added that Arnstein ' has described a definite connection between
the nerve-fibres and the epithelial cells of the gland. If this fact is corrobo-
rated it would amount to an histological proof of the existence of special
secretory fibres, but the physiological evidence for the same fact is either
negative or unsatisfactory.

Normal Secretion of the Milk. — As was said in speaking of the his-
tology of the gland, the secreting alveoli are not fully formed until tiie first
pregnancy. During tlie period of gestation the epithelial cells multiply, the
alveoli are formed, and after parturition secretion begins. At first the .secre-
tion is not true milk, but a liquid differing in composition and known as the
colostrum ; this secretion is characterized microscopically by the existence of
the colostrum corpuscles, which seem to be wandering cells that have under-
gone a complete fatty degeneration. After a few days the true milk is formed
in the manner already described. According to Rohrig the secretion is con-
tinuous, but this statement needs confirmation. As the liquid is formed it
accumulates in the enlarged galactophorous ducts, and after the tension has
reached a certain point further secretion is apj)arently inhibited. If the ducts
are emptied, by the infant or othcrwi.se, a new secretion begins. The emptying
of the ducts, in fact, seems to con.stitute the normal physiological stimulus to
the gland-cells, but how this act affects the secreting cells, whether reflexly or
directly, is not known. When the child is weaned the .secretion under normal
conditions soon ceases and the alveoli undergo retrograde changes, although
' Anatomischer Anzeiger, 1895, Bd. x. S. 410.

SECRETIOiX. 205

they do not return completely to the condition they were in before the first
pregnancy.

Inteunal Secretions.

According to tiie definition proposed on p. 152, the term internal secretion
is here used to mean a specific substance or substances formed within a gland-
ular organ and given off to the blood or lymph. As was said before, it is
difficult to make a distinction between these iuternal secretions and the waste
products of metabolism generally so far as method and place of formation
and elimination are concerned. Every active tissue gives off waste products
which are borne off in the lymph and blood, but as generally employed the
term internal secretion is not meant to include all such products, but only the
materials produced in distinctly glandular organs which are more or less
specific to those organs, and which are su})pose(l to have a general value to
the body as a whole. The idea of an internal secretion seems to have been
first advocated by Brown-S^quard in the course of some work upon extracts
of the testis. Within the last few years the terra has been frequently used,
especially in connection with the valuable and interesting work done upon the
pancreas and the so-called blood-vascular or ductless glands, the thyroids,
adrenals, pituitary body, and spleen. In almost all cases our knowledge of
the nature and importance of these internal secretions is in a formative stage ;
the literature, however, of the subject is already very great, and is increasing
rapidly, while speculations are numerous, so that constant contact with current
literature is necessary to keep pace with the advance in knowledge. In this
section only an outline of the subject can be attempted.

Liver. — It has not been customary to speak of the liver as furnishing an
internal secretion, but two of the products formed within this organ are so
clearly known and their method of production is so typical of what is sup-
posed to be the mechanism of internal secretion, that it is desirable both for
the sake of convenience and consistency to include them under this general
heading. Glycogen (CgHjoOg)!! is formed within the liver-cells from the
sugars and proteids brought to them in the blood of the portal vein, and in
many cases the presence of this glycogen can be demonstrated microscopically
within the cells. From time to time, however, the glycogen within the cell
is converted into dextrose by a process of hydration,

CeHjoOg + H2O = CgHiPei

and the sugar so formed is by a secretory process of some kind given off to
the blood to serve for the metabolism of the other tissues of the body, es-
pecially the nuiscles. This elimination of its stored glycogen on the part of
the liver may be regarded as a case of internal secretion. (For further details
concerning glycogen, its properties and functions, see p. 266 and the section
on Chemistry.) A second substance which is formed under the influence
of the liver-cells and is then eliminated into the blood is urea. Urea constitutes
the chief nitrogenous end-product of the metabolism of the proteid tissues ; it

206 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

is eliininiited from the body bv tlie kidneys, but it is known not to be formed
in these organs. Modern investigations (see p. 000) have seemed to show con-
clusively that this substance is formed mainly within the liver from some
antecedent substance (carbamate of ammonia) which arises in the proteid tissues
generally, but is not prepared for final elimination until in the liver or else-
where it is converted into urea. Here again the liver-cells perform a metab-
olism for the good of the organism as a whole, and the act of passing out
the urea into the blood may be regarded as an internal secretion. It is quite
possible that in still other ways the liver-cells add to the blood elements of
importance to the tissues of the body — as, for example, in the conservation and
distribution of the iron of broken-down hiemoglobin (see p. 275), or in the syn-
thetic combination of the products of putrefaction formed in the intestines (indol,
skatol, phenol, etc.) with sul])huric acid (see p. 263); but concerning these mat-
ters our knowledge is not yet sufficiently definite to make positive statements.
Pancreas. — The importance of the external secretion, the pancreatic juice,
of the pancreas has long been recognized, but it was not until 1889 that Von
Mehring' and Minkowski proved that it furnishes also an equally important
internal secretion. These observers succeeded in extirpating the entire pan-
creas without causing the immediate death of the animal, and found that in
all cases this operation was followed by the appearance of sugar in the urine
in considerable quantities. Further observations of their own and other experi-
menters have corroborated this result and added a number of interesting facts
to our knowledge of this side of the activity of the pancreas. It has been
shown that when the pancreas is completely removed a condition of glycosuria
inevitably follows, even if carbohydrate food is excluded from the diet. More-
over, as in the similar pathological condition of glycosuria or diabetes mellitus
in man there is an increase in the quantity of urine (])olyuria), and of urea,
and an abnormal thirst and hunger. These symptoms in cases of complete
extirpation of the pancreas are followed by emaciation and muscular weak-
ness, which finally end in death in about two weeks or less. If the pancreas
is incompletely removed the glycosuria may be serious, or slight and transient,
or absent altogether, depending upon the amount of pancreatic tissue left.
According to the experiments of Von Mehring and Minkowski on dogs, a
residue of one-fourth to one-fifth of the gland may be sufficient to prevent the
appearance of sugar in the urine. The portion of pancreas left in the body
may suffice to prevent glycosuria, partly or completely, even though its con-
nection with the duodenum is entirely interrupted, thus indicating that the
suppression of the pancreatic juice is not responsible for the glycosuria. The
same fact is shown more conclusively by the following experiments: Glycos-
uria after coni]>lete removal of the pancreas from its normal connections may
be prevented by grafting a portion of the pancreas elsewhere in the abdominal
cavity or even under the skin. The ducts of the gland may be completely
occluded by ligature or by injection of paraffin without seriously disturbing

' Archiv fur exper. Pathologic uml Pharmakoloi/ie, 1890, Bd. xxvi. S. 371. See also Minkow-
ski, Ibid., 1893, Bd. xxxi. S. 85, for a more complete account.

SECRETION. 207

the healthy eoudition of the aninial. In the last experiment it is said that
the normal secreting tubules of the glaud undergo atrophy.

We must believe from these experiments that the pancreas produces a sub-
stance of some kind which is given off to the blood or lymph and which is
either necessary for the normal consumption of sugar in the body, or else, as
is held by some,' normally restrains the output of sugar from the liver and
other sugar-producing tissues of the body. What this material is and how it
acts has not yet been determined satisfactorily. It is interesting and sugges-
tive to state in this connection that post-mortem examination in cases of dia-
betes mellitus in the human being has shown that this disease is associated in
some instances with obvious alterations in the structure of the pancreas.

The Thyroid Body. — The thyroids are glandular structures found in
all the vertebrates. In the mammalia they lie on either side of the trachea
at its junction with the larynx. In man they are united across the front of
the trachea by a narrow band or isthmus, and hence are sometimes spoken
of as one structure, the thyroid body. In some of the lower mammals
{e. g. dog) the isthmus is often absent. The thyroids in man are small
bodies measuring about 50 millimeters in length by 30 millimeters in width ;
they have a distinct glandular structure but possess no ducts. Histological
examination shows that they are composed of a number of closed vesicles vary-
ing in size. Each vesicle is lined by a single layer of cuboidal epithelium,
while its interior is filled by a homogeneous glairy liquid, the colloid substance
which is found also in the tissue between the vesicles lying in the lymph-
spaces. This colloid substance is regarded as a secretion from the epithelial
cells of the vesicles, and Biondi,^ Laugendorff,^ and Hiirthle* claim to have
followed the development of the secretion in the epithelial cells by micro-
chemical reactions. While the interpretation of the microscopical appearances
given by these authors is not identical, they agree in believing that the colloid
material is formed within some or all of the epithelial cells, and is eliminated
into the lumen with or without a disintegration of the cell-substance. More-
over, Langeudorff and Biondi believe that the colloid material is finally dis-
charged into the lymphatics by the rupture of the vesicles. The composition
of the colloid is incompletely known.

Parafhi/roids. — The parathyroids are a pair of small bodies lying lateral or
posterior to the thyroids, and in some animals (rat) they are apparently con-
tained within the substance of the thyroids. They are quite unlike the thyroids
in structure, consisting of solid masses or columns of epithelial-like cells which
are not arranged to form acinous vesicles. According to Schaper* these bodies
are not always paired, but may have a multiple origin extending along the
common carotid in the neighborhood of the thyroids. Experimental investi-
gations seem to show that these bodies are probably immature structures

^ See Kaufmann : Archives de Physiologie normale et pathologique, 1895, p. 210.

" Berliner Klhmche Wochenschrift, 1888. ' Archiv fur Physiologie, 1889, Suppl. Bd.

* Pflilger''s Archiv fib- die gesammte Physiologie, 1894, Bd. Ivi. S. 1.

* Archiv fiir mikroskopische Anatomic, 1895, Bd. xlvi. S. 500.

208 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

which are capable of Jissiiming the fimetions of the thyroids to a greater or
less extent when tlie.se latter are removed or injured.

Acce^'imri/ Thyroids. — In addition to tlie paratliyi-oids a variable number of
accessory thyroids have been described by dillerent observers, occurring in the
neck or even as far down as the heart. Tliese bodies possess the structure of
the tliyroid, and presumably have the same function. After removal of the
thyroids they may suffice to prevent a fatal result.

Functions of the Thyroids. — Very great interest has been excited within
recent years with regard to the functions of the thyroids. In 1856 SchifF
showed that in dogs complete extirpation of the two thyroids is followed by the
death of the animal ; and within the last few years similar results have been
obtained by numerous observers. Death is preceded by a number of character-
istic symptoms, such as muscular tremors, which may pass into spasms and con-
vulsions, cachexia, emaciation and a more or less marked condition of apathy.
The muscular phenomena seem to proceed from the central nervous system,
since section of the motor nerves protects the muscles from the irritation. The
metabolic changes may also be due primarily to an alteration in the condition
of the cord and brain. Similar results have been obtained in cats. Among the
herbivorous animals it was at first stated that removal of the thyroids does not
cause death ; but so far as the rabbit is concerned Gley ' has shown that if care
be taken to remove the parathyroids also, death is as certain and more rapid
than in the case of the caruivora ; and a similar result has been obtained upon
rats by Christiani. It is still asserted, however, that in sheep, horses, and birds
the glands may be removed without serious injury to the animal. Cases have
been reported also in which dogs have recovered after complete thyroidectomy,
but these cases are rare and may be explained probal)ly by the presence of acces-
sory thyroids which remain after the operation. It has been observed, too, that
the operation is more rapidly and certainly fatal in young animals than in old
ones. In the monkey as well as in man the evil results following the removal
of the glands develop more slowly than in the lower animals, and give rise to
a series of symptoms resembling those of myxoedema in man. Among these
symptoms may be mentioned a pronounced anaemia, diminution of muscular
strength, failure of the mental powers, abnormal dryness of the skin, loss of
hairs, and a peculiar swelling of the subcutaneous connective tissue. Physiol-
ogists have shown that in the case of dogs the fatal results following thyroid-
ectomy may be mitigated or entirely obviated by grafting a portion of the
gland under the skin or in the peritoneal cavity. If the piece grafted is suffi-
ciently large the animal recovers apparently completely from the operation.
So also in removing the thyroids, if a small portion of the gland, or the para-
thyroids, be left undisturbed the fatal symptoms do not develop. In human
beings suffering from myxoedema as the result of loss of function of the thy-
roids it has been abundantly shown that injections of thyroid extracts, or
feeding the fresh gland, restores the individual to an approximately normal
condition,

' Archives de Physiologic normale et Palhologiqtie, 1892, p. 135.

SECRETION. 209

It follows from these various ohscrv^iitions that the thyroid glauds play a
very important part of soMie kind in the general metabolism of the body.
Two views prevail as to the general nature of their function.^ According to
some the office of the thyroids is to remove some toxic substance which nor-
mally accumulates in the blood as the result of the body-metabolism. If the
thyroids are extirpated this substance then increases in quantity and produces
the observed symptoms by a ])rocess of auto-toxicatiou. In support of this
view there are numerous observations to show that the blood, or urine, or
muscle-juice of thyroidectoraized animals has a toxic effect upon sound animals.
These latter results, however, do not appear to be marked or invariable, and
in the hands of some experimenters have failed altogether. The second view
is that the thyroids secrete a material, a true internal secretion, which after
getting into the blood plays an important and indeed essential part in the
metabolic changes of some or all of the organs of the body, but especially the
central nervous system. In support of this view we have such facts as these :
Injections of thyroid extracts have a beneficial and not an injurious influence;
there is microscopic evidence to show that the epithelial cells participate
actively in the formation of the colloid secretion and that this secretion
eventually reaches the blood by way of the lymph-vessels; the beneficial
material in the thyroid extracts may be obtained from the gland by methods
which prove that it is a distinct and stable substance formed in the gland, as
we might suppose would be the case if it formed part of a definite secretion.
This latter fact, indeed, amounts to a proof that the important function of the
thyroids is connected with a material secreted within its substance ; but it may
still be questioned, perhaps, whether this material acts by antagonizing toxic sub-
stances produced elsewhere in the body or by directly influencing the body-
metabolism. Much work has been done to isolate the beneficial material of the
thyroid, particularly in relation to the therapeutic use of the gland in myxce-
deraa and goitre. The mere fact that feeding the gland acts as well as injecting
its extracts shows the resistant nature of the substance, since it is evidently not
injured by the digestive secretions. It has been shown also by Baumann ^
that the gland material may be boiled for a long period with 10 per cent, sul-
phuric acid without destroying the beneficial substance. This observer has
succeeded in isolating from the gland a substance to which the name thyro-
iodin is given, which is characterized by containing a relatively large per-
centage (9.3 per cent, of the dry weight) of iodine, and which preserves in
large measure the beneficial influence of thyroid extracts in cases of myxoe-
dema and parenchymatous goitre. This notable discovery shows that the thy-
roid tissue has the power of forming a specific organic compound of iodine, and
and it is possible that its influence upon body-metabolism may be connected
with this fact. In a later communication by Baumann and Roos^ it is stated
that the thyroiodin is contained within the gland mainly in a state of combi-

' SeeSchaefer : " Address on Physiology," annual meeting of the British Medical Association,
London. July-A'.igiist, 1895.

2 Zeitschr'ift fur physiologische Chemie, 1896, Bd. xxi. 8. 319. ^ Ibid., S. 481.

14

210 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

nation with protoid bodies, from wliicli it may be separated by digestion with
trastric juice or bv boilintr witii acids. Most of the sul)stance is combined with
an albuminous proteid to wiiicii th(y give the name thyroicxhilbiimin, while
a smaller part is united with a globulin-like proteid. In this paper still more
favorable reports of the beneficial action of this substance are reported, and
there can be but little doubt that the authors have succeeded in isolating the
reallv effective substance of thyroid extracts. A future ])aper upon the chemi-
cal nature of thyroiodiu is promised, Friiukel has also isolated a basic body
— thyreo-antitoxiu — to which he gives the formula CgHnNjOj, which also
shows to some extent the beneficial efi'eet of the thyroid extracts. Drechsel ^
has succeeded in isolating two crystalline basic bodies one of which is apparently
identical with that described by Friinkel. Both of these bodies are said to have
a beneficial influence when administered to thyroidectomized animals. Drechsel
suggests that there may be three separate substances formed in the thyroid
which are of value to the body, and that corresponding to these the tliyroids
may exert a threefold effect upon body-metabolism. Gourlay states that he
has succeeded in proving the presence of a nucleo-albumin in the thyroids, and
showing by microchemical reactions that this substance is present in the
colloid secretion.

Adrenal Bodies. — The adrenal bodies — or, as they are frequently called
in human anatomy, the suprarenal capsules — belong to the group of ductless
glands. Their histology as well as their physiology is incompletely known.
It was shown first by Brown-S6quard (1856) that removal of these bodies is
followed rapidly by death. This result has been confirmed by many experi-
menters, and so far as the observations go the effect of complete removal is
the same in all animals. The fatal effect is more rapid than in the case of
removal of the thyroids, death following the operation usually in two to three
days, or, according to some accounts, within a few hours. The symptoms pre-
ceding death are great prostration and muscular weakness, and marked dimi-
nution in vascular tone. These symptoms are said to resemble those occurring
in Addison's disease in man, a disease which clinical evidence has shown to be
associated with pathological lesions in the suprarenal capsules. It has been
expected, therefore, that the results obtained for thyroid treatment of myx-
cedema might be repeated in cases of Addison's disease by the use of adrenal
extracts. These expectations seem to have been realized in part, but complete
and satisfactory reports are yet lacking. The physiology of the adrenals has
usually been explained upon the auto-toxication theory. The death that comes
after their removal has been accounted for upon the supposition that during
life they remove or destroy a toxic substance produced elsewhere in the body,
possibly in the nniscular system. Oliver ^ and Schaefer, however, have recently
given reasons for believing that this organ forms a peculiar substance which
has a very definite physiological action especially upon the muscular system.
They find that aqueous extracts of the medulla of the gland when injected into

» CeniralbluU fiir Pbymoloijie, 1S96, Bd. ix.. Xo. 24.
^ Journcd of Physiology, 1895, vol. xviii. p. 230.

SECRETION. 211

the blood of a livini; animal have a romarkal)lo influence upon the heart,
blood-vessels, and skeletal muscles. The contractions of the latter are pro-
lono-ed, somewhat as after the action of veratrin. Upon the blood-vessels
the extracts cause a strong vascular contraction, giving an enormous increase
in blood-pressure, and upon the heart muscles also, if the vagus nerves have
been previously cut, there is a similar stimulating action manifested by an
increase in the strength and frequency of the beats. These effects are obtained
with very small doses of the extracts. Schaefer states that as little as 5|
milligrams of the dried gland may ])roduce a maximal effect upon a dog weigh-
ing 10 kilograms. The effects produced by such extracts are quite temporary
in character. In the course of a few minutes the blood-pressure returns to
normal, as also the heart-beat, showing that the substance has been destroyed
in some way in the body, although where or how this destruction occurs is not
known. According to Schaefer the kidneys and the adrenals themselves are
not responsible for this prompt elimination or destruction of the injurious
substance. It is possible that the substance in question may be continually
secreted under normal conditions by the adrenal bodies and play a very import-
ant part with reference to the functional activity of the muscular tissue.

Pituitary Body. — It is stated that complete removal of the pituitary body
causes death, accompanied by symptoms which resemble somewhat those fol-
lowing thyroidectomy, such as muscular tremors and spasms, apathy, etc. A
number of observers, therefore, have supposed that physiologically the pitui-
tary body is related to the thyroids, and is able to vicariously assume, to a
greater or less extent, the functions of the latter. The work upon this organ
has not, however, made sufficient progress to euable any satisfactory statements
to be made concerning its po.-sible functional value.

Testis. — Some of the earliest work upon the effect of the internal secretions
of the glands was done upon the reproductive glands, especially the testis, by
Browu-Sequard.^ According to this observer extracts of the fresh testis when
injected under the skin or into the blood may have a remarkable influence
upon the nervous system. The general mental and physical vigor and espe-
cially the activity of the spinal centres are greatly improved, not only in cases
of general prostration and neurasthenia, but also in the case of the aged.
Brown-Sequard maintained that this general dynamogenic effect is due to
some unknown substance formed in the testis and subsequently passed into
th« blood, although he admitted that some of the same substance may be
found in the external secretion of the testis, i. e. the spermatic liquid. More
recentlv PoehP asserts that he has prepared a substance, spermin, to which he
gives the formula CgHi^Ng, which has a very beneficial effect upon the metab-
olism of the body. He believes that this spermin is the substance which
gives to the testicular extracts prepared by Brown-S^quard their stimulating
effect. He claims for this substance an extraordinary action as a physiologi-
cal tonic. Tiie precise scientific value of the results of experiments with the

' Sfie Archives de Phyaiologie normale et pathologique, 1889-92.
^ See Zeitschrift fur klinkche Medicin, 1894, Bd. 26, S. 133.

212 A.\ AMKIUCAX TEXT-BOOK OF PHYSIOI.OOY.

testicular extracts eaiinot bo estimated at present, in spite of tlie large litera-
ture upon the subject; we must wait for more detailed and exact experiments,
which doubtless will soon be made, (^nite recently Zoth ' tiud alsoPregel*
seem to have obtained exact objective proof, by means <jf ergograjdiic records,
of the stimulating action of the testicular extracts upou the neuro-niuscular
apparatus in man. They find that injections of the testicular extracts cause not
oidy a diminution in the muscular and nervous fatigue resulting from muscu-
lar work, but also lessen the subjective fatigue sensations. The fact that the
internal secretion of the testis, if it exists at all, is not absolutely essential to
the life of the body as a whole, as in the case of the thyroids, adrenals, and
pancreas, naturally makes the satisfactory determination of its existence and
action a more difficult task.

* Imager's Arckivfur die gesammle Physiologic, 1896, Bd. 62, 8. 335. ^ Ibid., S. 379.

IV. CHEMISTRY OF DIGESTION AND NUTRITION.

A. Definition and Composition of Foods-. Nature of Enzymes.

Speaking broadlv, what we eat aud drink for the purpose of nourish-
ing the body constitutes our food. A person in adult life who has reached
his maximum growth, and whose weight remains practically constant from
year to vear, must eat and digest a certain average quantity of food daily to
keep himself in a condition of health and to prevent loss of weight. In
such a case we may say that the food is utilized to repair the wastes of the body
—that is, the destruction of body-material which goes on at all times, even
during sleep, but which is increased by the physical aud psychical activities
of the waking hours— and in addition it serves as the source of heat, mechanical
work, and other forms of energy liberated in the body. In a person who is
growing— one who is, as we say, laying on flesh or increasing in stature— a
certain portion of the food is used to furnish the energy and to cover the wastes
of the bodv, while a part is converted into the new tissues formed during
growtli. The material that we eat or drink as food is for the most part in an
insoluble form, and, moreover, it has a composition differing oftentimes very
widely from that of the tissues which it is intended to form or to repair. The
object of the processes of digestion carried on in the alimentary tract is to
change this food so that it may be absorbed into the blood, and at the same
timelo to alter its composition that it can be utilized by the tissues of the body.
For we shall find, later on, that certain foods— eggs, for example— which are
verv nutritious when taken into the alimentary canal and digested cannot be
used at all by the tissues if injected at once, unchanged, into the blood. Tiie
food of mankind is most varied in character. At different times of the year
and in different parts of the world the diet is changed to suit the necessities of
the occasion. When, however, we come to analyze the various animal and
vegetable foods made use of bv mankind, it is found that they are all com-
posed of one or more of five or six different classes of substances to which the
name food-stuff)^ or alimentarv principles has been .given. To ascertain the
nutritive value of any food, it must be analyzed and the percentage amounts of
the different food-stuffs contained in it must be determined. The classification
of food-stuffs usually given is as follows :

^ 213

214 AX AMERICAN TEXT-BOOK OF rilV/SIOLOG V.

f Wak'r;
Inorganic salts;

Proteids (or proteid-containing bodies) ;
Food-stnffs. i Albuminoids (a group of bodies resembling j)rotei<ls, but
liaviug in some respects a dillereut nutritive valuej;
Carboliydrates;
Fats.

What is known witli regard to the specific nutritive value of each of these
substances will be given later ou, after the processes of digestion have been
described. A few general remarks, however, at this place will serve to give
the proper standpoint froui which to begin the study of the chemistry of
digestion and nutrition.

Wafer and >S(i/ts. — Water and salts we do not commonly consider as foods,
but the results of scientific investigation, as well as the experience of life,
show that these substances are absolutely necessary to the body. The tissues
must maintain a certain composition in water and salts in order to function
normally, and, since there is a continual loss of these substances in the various
excreta, they must continually be replaced in some way in the food. It is to
be borne in mind in this connection that water and salts constitute a part of
all our solid foods, so that the body gets a partial supply at least of these
substances in everything we eat.

Proteids. — The composition and different classes of proteids are described
from a chemical standpoint in the section ou The Chemistry of the Body.
Different varieties of proteids are found in animal as well as in vegetable
foods. The chemical composition in all cases, however, is approximately the
same. Physiologically, they are supposed to have equal imtritive values out-
side of differences in digestibility, a detail which M'ill be given later. The
e&sential use of the proteids to the body is that they supply the material from
M'hieh the new' proteid tissue is made or the old proteid tissue is repaired,
although, as we shall find when we come to discuss the subject more thor-
oughly (p. 285), proteids are also extremely valuable as sources of energy to
the body. Inasmuch as the most important constituent of living matter is the
proteid part of its molecule, it will l)e seen at once that proteid food is an
absolute necessity. Proteids contain nitrogen, and they are frequently spoken
of as the mirocjenou>^ foods; carl )()hyd rates and fats, on the contrary, do not
contain nitrogen. It follows inunediately from this fact that fats and carbo-
hydrates alone could not suffice to make new protoplasm. If our diet con-
tained no proteids, the tissues of the body woidd gradually waste away
and death from starv^ation would result. All the food-stuffs are necessary
in one way or another to the preservation of perfect health, but proteids,
together with a certain proportion of water and inorganic salts, are absolutely
necessary for the bare maintenance of animal life — that is, for the formation
and preservation of living protoplasm. Whatever else is contained in our
food, proteid of some kind must form a part of our diet. The use of

CHEMISTRY OF DIGESTION AND NUTRITION. 215

the otiier food-stutls is, as we shall see, more or less accessory. It may be
worth while to recall here the familiar fact that in respect to the nutritive
importance of proteids there is a wide difference between animal and vegetable
life. What is said above applies, of course, only to animals. Plants can,
and for the most part do, build uj) their living protoplasm upon diets con-
taining no proteid. With some exceptions which need not be mentioned here,
the food-stuff's of the great group of chlorophyll-containing plants, outside of
oxygen, consist of water, CO2, and salts, the nitrogen being found in the last-
mentioned constituent.

Alhuminoich. — Gelatin, such as is found in soups or is used in the form of
table-gelatin, is a familiar example of the albuminoids. They are not found
to any important extent in our raw foods, and they do not therefore usually
appear in the analyses given of the composition of foods. An examination of
the composition and properties of these bodies (see section on The Chemistry
of the Body) shows that they resemble closely the proteids. Unlike the fats
and carbohydrates, they contain nitrogen, and they are evidently of complex
structure. Nevertheless, tliey cannot be used in place of proteids to build
protoplasm. They are important foods without doubt, but their value is similar
in a general way to that of the non-nitrogenous foods, fats and carbohydrates,
rather than to the so-called " nitrogenous foods," the proteids.

Carbohydrates. — We include among carbohydrates the starches, sugars,
gums, and the like (see Chemical section) ; they contain no nitrogen. Their
physiological value lies in the fact that they are destroyed in the body and a
certain amount of energy is thereby liberated. The energy of muscular work
and of the heat of the body comes largely from the destruction or oxidation
of carbohydrates. Inasmuch as we are continually giving off energy from
the bodv, chiefly in the form of muscular work and heat, it follows that
material for the production of this euergy must be taken in the food. Carbo-
hydrates form perhaps the easiest and cheapest source of this energy. They
constitute the bulk of our ordinary diet.

Fats. — In the group of fats we include not only what is ordinarily under-
stood by the term, but also the oils, animal and vegetable, which form such a
common part of our food. Fats contain no nitrogen (see Chemical section).
Their use in the body is substantially the same as that of the carbohydrates.
Weight for weight, they are more valuable than the carbohydrates as sources
of energy, but the latter are cheaper, more easily digested, and more easily
destroyed in the body. For these reasons we find that under most conditions
fats are a subsidiary article of food as compared with the carbohydrates. From
the standpoint of the physiologist, fats are of special interest because the
animal body stores up its reserve of food material mainly in that form. The
history of the origin of the fats of the body is one of the most interesting
parts of the subject of nutrition, and it will be discussed at some length in its
proper place.

As has been said, our ordinary foods are mixtures of some or all of the
food-stuffs, together with such things as flavors or condiments, whose nutritive

216

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

value is of u .special character. Curefiil analyses have been luatle of the
different articles of food, mostly of the raw or uncooked footls. As might
be expected, the analyses on recoi-d diffei- more or less in the percentages
assigned to the various constituents, but almost any of the tables published
give a just idea of the fundamental nutritive value of the common foods.
For details of separate analyses reference may be made to some of the larger
works upon the composition of foods.' The subjoined table is one compiled
by Munk from the analyses given by Konig :

Composition of Foods.

In 100 parts.

Water.

Meat 76.7

i^gffs 73.7

Cheese 36-60

Cow's milk 87.7

Human milk 89.7

Wheat dour 13.3

Wlieat bread 35.6

Eye flour 13.7

Rye bread , 42.3

Rioe 13.1

Corn 13.1

Macaroni j 10.1

Pea^, beans, lentils . . . . i 12-15

Potatoes 75.5

Carrots j 87.1

Cabbages i 90

Mushrooms 73-91

Fruit ! 84

Proteid.

Fat.

Carbohydrate.

Digestible. ' Cellulose.

20.8

12.6

25-33

3.4

2.0

10.2

7.1

11.5

6.1

7.0

9.9

9.0

23-26

2.0

1.0

2-3

4-8

0.5

1.5
12.1
7-30
3.2
3.1
0.9
0.2
2.1
0.4
0.9
4.6
0.3

0.2
0.2
0.5
0.5

0.3

3-7

4.8

5.0
74.8
55.5
69.7
49.2
77.4
68.4
79.0
49-54
20.6

9.3

4-6

3-12

10

0.3
0.3
1.6
0.5
0.6
2.5
0.3
4-7
0.7
1.4
1-2
1-5
4

Ash.

1.3
1.1
3-4
0.7
0.2
0.5
1.1
1.4
1.5
1.0
1.5
0.5
2-3
1.0
0.9
1.3
1.2
0.5

An examination of this table will show that the animal foods, particularlv
the meats, are characterized by their small percentage in cari)ohvdrate and bv
a relatively large amount of proteid or of proteid and fat. A\'ith regard to
the last two food-stuffs, meats differ very much among themselves. Some
idea of the limits of variation may be obtained from the following table,
taken chieflv from Kouitj's analyses:

Reef, moderately fat
Veal, fat .....
Mutton, moderately fat

Pork, lean

Ham, salted . . . .
Pork (bacon), very fat*
Mackerel *

Water.

73.03
72.31
75.99
72.57
62.58
10.00
71.6

Proteid.

20.96
18.88
17.11
20.05
22.32
3.00
18.8

Fat.

5.41
7.41
5.77
6.81
8.68
80.50
8.2

Carbohydrate.

0.46
0.07

Ash.

1.14

1.33

1.33

1.10

6.42

6.5

1.4

The vegetable foods are distinguished, as a rule, by their large percentage
in carbohydrates and the relatively small amounts of proteids and fats, as seen,
for example, in the composition of rice, corn, wheat, and potatoes. Neverthe-

' Konig, Die Menschlichen Kahrungx und Oemtssmittel, 3d ed., 1889 ; Parke's Manual of Prac-
tical Hycjiene. section on Food.

* .\twater: The Chemistry of Foods and Nutrition, 1887.

CHEMISTRY OF DIGESTION AND NUTRITION. 217

less, it will be nulitvd that the ])ro[K)rtiuii of proteid in soiuc oi" the vegetables
is not at all iusiguiticaut. They are charaeterized by their excess in carbohy-
drates rather than by a deficiency in proteids. The composition of peas and
other legtiniinous foods is remarkable for the large percentage of proteid,
which exceeds that found in meats. Analyses such as are given here are
indispensable in determining the true nutritive value of foods. Nevertheless,
it must be borne in mind that the chemical composition of a food is not alone
sufficient to determine it^^ j)recise value in nutrition. It is obviously true that
it is not what we eat, but what we digest and absorb, that is nutritious to the
body, so that, in addition to determining the proportion of food-stuffs in any
given food, it is necessary to determine to what extent the several constitu-
ents are digested. This factor can be obtained only by actual experi-
ments; a number of results bearing upon this point have been collected which
will be spoken of later. It may be said here, however, that in general
the proteids of animal foods are more completely digestible than are those
of vegetables, and Mith them, therefore, chemical analysis comes nearer to
expressing directly the nutritive value.

The physiology of digestion consists chiefly in the study of the chemical
changes which the food undergoes during its passage through the alimentary
canal. It hajjpens that these chemical changes are of a peculiar character.
The peculiarity is due to the fact that the changes of digestion are effected
through the agency of a group of bodies known as enzymes, or unorganized
ferments, whose chemical action is different from that of the ordinary reagents
with which we have to deal. It will save useless repetition to give here
certain general facts that are known with reference to these bodies, reserving
for future treatment the details of the action of the specific enzymes found in
the different digestive secretions.

Enzymes. — Enzymes, or unorganized ferments, or unformed ferments, is
the name given to a group of bodies produced in animals and plants, but not
themselves endowed with the structure of living matter. The term ^inorganizcd
or unformed ferment was formerly used to emphasize the distinction between
these bodies and living ferments, such as the yeast-plant or the bacteria.
" Enzyme," however, is a better name, and is coming into general use.
Enzymes are to be regarded as dead matter, although produced in living
protoplasm. Chemically, they are defined as complex organic compounds con-
taining nitrogen. Their exact composition is unknown, as it has not been
found possible heretofore to obtain them in pure enough condition for analysis.
Although several elementary analyses are recorded, they cannot be considered
reliable. It is not known whether or not the enzymes belong to the group of
proteids. Solutions of most of the enzymes give some or all of the general
reactions for proteids, but there is always an uncertainty as to the purity of
the solutions. With reference to the fibrin ferment of blood, one of the
enzymes, observations have recently been made which seem to show that it
at least belongs to the group of combined proteids, uucleo-albumins (for
details see the section on Blood). But even should this be true, we are

218 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

not justified in making any general application of this i'act to the whole
group.

Clasfiijication of Enzymes. — Enzymes are classified according to the kind
of" reaction they produce — namely :

1. Proteolytic enzymes, or those acting upcjn protcids, converting them to a
soluble modification, peptone or proteose. As examples of this group we have
in the animal body pepKin of the gastric juice and trypsin of the pancreatic
juice. In plants a similar enzyme is found in the pineapple familv (bromelin)
and in the papaw (papain).

2. Amylolytie enzyme.s, or those acting upon the starches, converting them
to a soluble form, sugar, or sugar and dextrin. As examples of this group
we have in the animal body pttycdin, found in saliva, amylop.S'in, found in
pancreatic juice, and in the liver an enzyme capable of converting glycogen
to sugar. In the plants the best-known example is diastase, found in
germinating seeds. This particular enz\'me has been known for a long time
from the use made of it in the manufacture of beer. In fact, the name " dias-
tase " is frequently used in a generic sense, " the diastatic enzymes," to cha-
racterize the entire group of starch-destroying ferments.

3. Fat-splitting enzymes, or those acting upon the neutral fats, breaking
them up into glycerin and the corresponding fatty acid. The best-known
example in the animal body is found in the pancreatic secretion ; it is known
usually as steapsin, altli<uigh it has been given several names. Similar
enzymes are known to occur in a number of seeds.

4. Inverting enzymes, or those having the property of converting the double
into the single sugars — the di-saccharides, such as cane-sugar and maltose, into
the mono-saccharides, such as dextrose and levulose. Two enzymes of this
character have been found in the animal body, one acting upon cane-sugar and
one on maltose. They are usually spoken of as invertin or inverting enzymes.
A similar enzyme may be obtained from the yeast-plant.

5. Coagulating enzymes, or those acting upon soluble proteids, precipitating
thera in an insoluble form. As examples of this class we have fibrin ferment
(thrombin), formed in shed blood, and rennin, the milk-curdling ferment of the
gastric juice. An enzyme similar to rennin ha? been found in pineapple-juice.

These five classes comprise the groups of enzymes that are known to occur
in the animal body. One or more examples of each group take part in the
digestion of food at some time during its passage through the alimentary canal.
Two other important groups of enz^-mes which are not formed in the animal
body may be mentioned briefly in this connection for the sake of completeness :

6. Glucoside-sjjlitting enzymes, or those acting upon the glucosides, giving a
carbohydrate as one of the products of decomposition. Examples: emulsin,
found in bitter almonds ; myrosin, in mustard-seeds.

7. Urea-splitting enzymes, or those acting upon urea, converting it to ammo-
nium carbonate ; found in many bacteria, especially in those normally occur-
ring in the urine.

A great number of general reactions have been discovered, applicable, with

CHEMISriiV OF DIGESTION AND NUTRITION. 219

ail exct'i)ti()ii here and there, to the whole j^i-oiip of enzymes. Amon<r these
reactions the f'oHowing are the most useful or si<^nificant :

1. SolubUity. — The enzymes are all soluble in water. They are also solu-
ble in glycerin, this being the most generally useful solvent for obtaining
extracts of the enzymes from the organs in which they are formed.

2. Effect of Temperature. — In a moist condition they are all destroyed by
temperatures below the boiling-point; 60'^ to 80° C. are the limits actually
observed. Very low temperatures retard or even suspend entirely (0° C.) their
action, without, however, destroying the enzyme. For each enzyme there is
a temperature at which its action is greatest.

3. Incompleteness of Action. — With the exception perhaps of the coagulat-
ing enzymes, they are characterized by the fact that in any given solution they
never completely destroy the substance upon which they act. It seems that
the products of their activity, as they accumulate, finally prevent the enzvmes
fi'om acting further ; when these products are removed the action of the enzyme
begins again. The most familiar example of this very striking peculiarity is
found in the action of jiepsin on proteids. The products of digestion in this
case are peptones and proteoses, and when they have reached a certain concen-
tration they prevent any further proteolysis on the part of the pepsin.

4. Relation of the Amount of Enzyme to the Effect it Produces. — With most
substances the extent of the chemical change produced is proportional to the
amount of the substance entering into the reaction. With the enzymes this is
not so. Except for very small quantities, it may be said that the amount of
change caused is independent of the amount of enzyme present, or, to state the
matter more accurately, " with increasing amounts of enzymes the extent of
action also increases, reaching a maximum with a certain percentage of enzyme;
increase of enzyme beyond this has no effect."^ This fact was formerly inter-
preted to mean that the enzyme is not used up — that is, not permanently altered
— by the reaction which it causes. This belief, indeed, must be true substan-
tially, but it has been found practically that a given solution of enzyme cannot
be used over and over again indefinitely. It is generally believed now that,
although an enzyme causes an amount of change in the substance it acts upon
altogether out of proportion to the amount of its own substance, neverthe-
less it is eventually destroyed ; its action is not unlimited. Whether this using
up of the enzyme is a necessary result of its activity, or is, as it were, an acci-
dental effect from spontaneous changes in its own molecule, remains unde-
termined.

Theories of the Manner of Action of the Enzymes. — It is now^
known that with the possible exception of the coagulating enzymes the action
of the enzymes is that of hydrating agents ; they produce their effect by what
is known as hydrolysis ; that is, they cause the molecules of the substance
upon which they act to take up one or more molecules of water; the resulting
molecule then splits or is dissociated, with the formation of two or more sim-
pler bodies. This is one of the most significant facts in connection with the

' Tanimann : Zeitschrift fur physiologiache Chemie, xvi., 1892, p. 271.

220 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

action of tlie eDzynies; it is well illustrated by the action of invertin on cane-
sugar, as follows :

C.,H,A.+H,0 = C«H„(), + CJi.A

Cane-suKar. Dextrose. Levulose.

In what way enzymes cause the substances they act u})()ii to take up water is
unknown. The fact that they are not themselves used up in tlic reaction j)rc>-
portionally to the change they cause formerly influenced physiologists and chem-
ists to explain their effect as due to catalyfiis, or contact action. In its original
sense this designation meant that the molecules of enzyme act by their mere
presence or contiguity, but it need scarcely be said that a statement of this
kind does not amount to an explanation of their manner of action ; to say they
"act by catalysis " means nothing in itself Efforts to explain their action
have resulted in a number of hypotheses, a detailed account of which would
hardly be appropriate here. It may be mentioned that two ideas have found
most general acceptance : one, that the vibrations of the molecules of enzyme
set into more rapid vibration the molecules of the substance acted upon, thus
leading to the taking up of water and to the subsequent splitting ; the other idea
is that the enzyme enters into a definite chemical reaction, in which, however,
it plays the part of a carrier or go-between, so that, although the enzyme is
directly concerned in producing a chemical change, the final outcome is that it
remains in its original condition. A number of chemical reactions of this
general character are known, in which some one substance passes through a
cycle of changes, aiding in the production of new compounds, but itself
returning always to its first condition ; for example, the ])art taken by HjSO^
in the manufacture of ether from alcohol, or the successive changes of haemo-
globin to oxyhsemoglobin and back again to haemoglobin after giving up its
oxygen to the tissues. Perhaps the most suggestive reaction of this character
is the one quoted by Chittenden ^ to illustrate this very hypothesis as to the
manner of action of enzymes, as follows : Oxygen and carbon monoxide gas,
if perfectly dry, will not react upon the passage of an electric spark. If,
however, a little aqueous vapor is present, they may be made to unite readily,
with the formation of COj. The water in this case, without doubt, enters
into the reaction, but in the end it is re-formed, and the final result is as
though the water had not directly participated in the process. The reactions
supposed to take place are explained by the following equations :

CO + 2H2O + O2 = CO (OH), + HA-

H2O, -f CO = COfOH)^.

2CO(OH)2 = 2CO2 4- 2HoO.

B. Salivary Digestion.

The first of the digestive secretions with which the food comes into contact
is ftaliva. This liquid is a mixed secretion from the six large salivary glands
(parotids, submaxillaries, and sublinguals) and the smaller nuicous and serous
* Cartwright Lectures, Medical Record, New York, April 7, 1894.

CHEMISTRY OF DIGESTION AND NUTRITTON. 221

glands which ojx'ii into the nioiitli. The physic )logicul uiiattjiiiy of these
ghuuls and the mechanism l)y wliicli the secretions are produced and regulated
will be found described fully in the section on Secretion ; we are concerned
here only with the composition of the secretion after it is formed, and with its
action upon foods.

Properties and Composition of the Mixed Saliva. — Filtered saliva is a
clear, viscid, transparent liquid. As obtained usually from the mouth, it is
more or less turbid, owing to the presence in it, in suspension, of particles
of food or of detached cells from the epithelium of the mouth. A some-
what characteristic cell contained in it in small numbers is the so-called
" salivary corpuscle." These bodies are probably leucocytes, altered in struc-
ture, which have escaped into the secretion. So far as is known, they have no
physiological value. The specific gravity of the mixed secretion is on an aver-
age 1003, and its reaction is normally alkaline. The total amount of secretion
during twenty-four hours varies naturally with the individual and the condi-
tions of life; the estimates made vary from 300 to 1500 grams. Chemically, in
addition to the water, the saliva contains mucin, ptyalin, albumin, and inor-
ganic salts. The proportions of these constituents are given in the ibllowing
analysis (Hammerbacher) :

In 1000 parts.

Water 994.203

Solids :

Mucin (and epithelial cells) 2.202 ^

Ptyalin and albumin 1.390 I 5 797

Inorganic salts 2.205 J

Potassium sulphocyanide 0.041

[

The inorganic salts, in addition to the sulphocyanide, which occurs only in
traces, consist of the chlorides of potassium and sodium, the sulphate of
potassium, and the phosphates of potassium, sodium, calcium, and magnesium ;
the earthy phosphates form about 9.6 per cent, of the total ash. Mucin is an
important constituent of saliva; it gives to the secretion its ropy, viscid cha-
racter, which is of so much value in the mechanical function it fulfils in
swallowing. This substance is formed in the salivary glands. Its formation
in the protoplasm of the cells may be followed microscopically (see the section
on Secretion). Chemically, it is now known to be a combination of a proteid
with a carbohydrate group (see section on The Chemistry of the Body). So
far as known, mucin has no function other than its mechanical use. The pres-
ence of potassium sulphocyanide (KCXS) among the salts of saliva has always
been considered interesting, since, although it occurs normally in urine as well
as in saliva, it is not a salt found commonly in the secretions of the body, and
its occurrence in saliva seemed to indicate some special activity on the part of
the salivary gland, the possible value of which has been a subject of specula-
tion. In the saliva, however, the sulphocyanide is found in such minute traces
and its presence is so inconstant that no special functional importance can be
attributed to it. It is supposed to be derived from the decomposition of
proteids, and it represents, therefore, one of the end-products of proteid metab-

222 AN AMJJRICAN TEXT-BOOK OF PHYSIOLOGY.

ollsni. rutassiuiii siilplKx-vuiiido may ho detected in saliva by adding to the
latter a (Uhite aeiduhited solution of ferric chloride, a reddish color being
produced.

Ptyalin and its Action. — From a piiysiological standj)()int the most
important constituent of saliva is liiyaVm. It is an unorganized ferment or
enzyme belonging to the amylolytic or diastatie group (p. 218) and possessing
the general properties of enzymes already enumerated. It is found in human
saliva and in tiiat of many of the lower animals — for exam})le, the j)ig and
the herbivora — but it is said to be absent in the carnivora. Ptyalin has not
been isolated in a sufficiently pure condition for satisfactory analy>is, so that
its chemical nature is undetermined ; we depend for its detection upon its
specific action — that is, its effect upon starch. Speaking roughly, we say that
ptyalin converts starch into sugar, but when we come to consider the details
of its action we find tiiat it is complicated and that it consists in a series of
hydrolytic splittings of the starch molecule ; the exact products of the reaction
depend upon the stage at which the action is interrupted. To demonstrate
the action of ptyalin on starch it is only necessary to make a suitable starch
paste by boiling some powdered starch in water, and then to add a little fresh
saliva. If the mixture is kept at a proper temperature (30° to 40° C), the
presence of sugar may be detected within a few minutes. The sugar that is
formed was for a time supposed to be ordinary grape-sugar (dextrose, CgH,^,Og),
but later experiments have shown conclusively that it is maltose (CijHgjOj,,-
HgO), a form of sugar more closely related in formula to cane-sugar (see
Chemical section). In experiments of the kind just described two facts
may easily be noticed : first, that the conversion of starch to sugar
is not direct, but occurs through a number of intermediate stages; second,
that the starch is not entirely converted to sugar under the conditions of
such experiments — namely, when the digestion is carried on in a vessel,
digestion in vitro. The second fact is an illustration of the incomplete-
ness of action of the enzymes, a general property which has already been
noticed. We may supj)ose, in this as in other cases, that the products of
digestion, as they accumulate in the vessel, tend to retard and finally to sus-
pend the amylolytic action of the ptyalin. In normal digestion, however, it
is usually the case that the products of digestion, as they are formed, are
removed by absorption, and if the above explanation of the cause of the
incompleteness of action is correct, then under normal conditions we should
expect a complete conversion of starch to sugar. Lea ^ states that if the
products of ptyalin action are partially removed by dialysis during digestion
in vitro, a much larger percentage of maltose is formed. Ilis experiments
would seem to indicate that in the body the action of the amylolytic ferments
may be c()m])lete, and that the final })roduct of their action may be maltose
alone. It will be found that this statement applies practically not to the
ptyalin, but to the similar amylolytic enzyme in the pancreatic secretion, owing
to the fact that, normally, food is held in the mouth for a short time only, and
* Jomiud of Physiology, vol. xi., 1890, p. 227.

CHEMISTRY OF DIGESTION AND NUTRITION. 223

that ptyalin tligv.stioii is soon interruptecl after the food roaches the stomacli.
Witli reference to the intorniediate stages or pnjducts in the convei'siou of
stardi to sugar it is dilHcult to give a perfectly clear account. It was formerly
thought that the starch was first converted to dextrin, and this in turn was
converted to sugar. It is now believed that the starch molecule, which is quite
complex, consisting of some multiple of 0^11,1,0,, — possibly {^'^n)Or^2ii — fi^'-'^t
takes up water, thereby becoming soluble (soluble starch, amylodcxtrin), and
then splits, with the formation of dextrin and maltose, and that the dextrin
again undergoes the same hydrolytic process, with the formation of a second
dextrin and more maltose ; this process may continue under favorable con-
ditions until only maltose is present. The difficulty at present is in isolating
the diflferent forms of dextrin that are produced. It is usually said that at
least two forms occur, one of which gives a red color with iodine, and is then;-
fore known as erythrodextrin, while the other gives no color reaction M'itli
iodine, and is termed achroodextrin. It is pretty certain, however, that there
are several forms of achroodextrin, and, according to some observers, erythro-
dextrin also is really a mixture of dextrins with maltose in varying propor-
tions. In accordance with the general outline of the process given above,
Neumeister ^ proposes the following schema, which is useful because it gives a
clear representation of one theory, but which must not be considered as satis-
factorily demonstrated (see also the section on Chemistry of the Body).

/Maltose.
Starch— soluble starch j

(amylodextrin). 1 .,, ,^

■ 'Maltose.

Erythrodextrin.

/Maltose.

Achroodextrin a. <

/Maltose.

Achroodextrin ^. .'

/Maltose,
(maltodextrin).

Achroodextrin y j

xMaltose.

This schema represents the possibility of an ultimate conversion of all the
starch into maltose, and it shows at the same time that maltose may be pres-
ent very early in the reaction, and that it may occur together with one or more
dextrins, according to the stage of the digestion. It should be said in conclu-
sion that this description of the manner of action of the ptyalin is supposed to
apply equally well to the amylolytic enzyme of the pancreatic secretion, the
two being, so far as known, identical in their properties. From the stand-
])oint of relative physiological importance the description of the details of
amylolytic digestion should have been left until the functions of the pancre-
atic juice were considered. It is introduced here because, in the natural order
of treatment, ptyalin is the first of this group of ferments to be encountered.
It is interesting also to remember in this connection that starch can be con-
verted into sugar by a process of hydrolytic cleavage by boiling with dilute
mineral acids. Although the general action of dilute acids and of amylolytic
' Lehrbuch der physiologischen Chemie, 1893, p. 232.

224 J.y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ciizynies is similar, the two processes are not identical, since in the first process
dextrose is the sugar formed, while in the second it is maltose. Moreover,
variations in tcinjierature afllect the two reactions differently.

Conditions Influencing- the Action of Ptyalin. — Tcmpcralare. — As iu
the case of the other enzymes, ptyalin is very susceptible to changes of temper-
ature. At 0° C. its activity is said to be sus})ended entirely. The intensity
of its action increases with increase of temperature from this point, and
reaches its maximum at about 40° C. If the temperature is raised much
beyond this point, the action of the ptyalin decreases, and at from 65° to
70° C. the enzyme is destroyed. In these latter points ptyalin differs from
diastase, the enzyme of malt. Diastase shows a maximum action at 50° C.
and is destroyed at 80° C.

Efect of Reaction. — The normal reaction of saliva is slightly alkaline.
Chittenden' has shown, however, that ptyalin acts as well, or even better, in
a perfectly neutral medium. A strong alkaline reaction retards or prevents
its action. The most marked influence is exerted by acids. Free hydrochloric
acid to the extent of only 0.003 per cent. (Chittenden) is sufficient to prac-
tically stop the araylolytic action of enzyme, and a slight increase in acidity not
only stops the action, but also destroys the enzyme. The latter fact is of
practical importance because it indica'tcs that the action of ptyalin on starch
must be suspended after the food reaches the stomach.

Condition of the Starch. — It is a well-known fact that the conversion of starch
to sugar by enzymes takes place much more rapidly with cooked starch — for
example, starch pas^e. In the latter condition sugar begins to appear in a
few minutes (one to four), provided a good enzyme solution is used. With
starch in a raw condition, on the contrary, it may be many minutes, or even
several hours, before sugar can be detected. The longer time required for
raw starch is partly explained by the well-known fact that the starch-grains
are surrounded by a layer of cellulose or cellulose-like material which resists
the action of ptyalin. When boiled, this layer breaks and the starch in the
interior becomes exposed. In addition, the starch itself is changed during the
boiling; it takes up water, and in this hydrated condition is acted upon more
rapidly by the ptyalin. The practical value of cooking vegetable foods is
evident from these statements without further comment.

Physiological Value of Saliva. — Although human saliva contains ptyalin,
and this enzyme is known to possess veiy energetic amylolytic properties, yet
it is probable that it has an insignificant action in normal digestion. The time
that food remains in the mouth is altogether too short to suppose that the starch
is profoundly affected by the ptyalin. It would seem that whatever change
takes place must be confined to the initial stages. After the mixed saliva and
food are swallowed the acid reaction of the gastric juice soon stops completely
all further amylolytic action. The complete digestion of the carbohydrates
takes place after the food (chyme) has reached the small intestine, under the
influence of the amylopsin of the pancreatic secretion. For these reiisons it is
' Studies/rom the Laboratory of Physiological Chemistry of Vale Collrt/e, vol. i., 1884.

CHE3IISTBY OF DIGESTION AND NUTRITION. 225

usually believed that the main value of the saliva, to the human being and to
tiiG carnivora at least, is that it facilitates the swallowing of food. It is impos-
sible to swallow perfectly dry food. The saliva, by moistening the food, not
only enables the swallowing act to take place, but its viscous consistency must
aid also iu the easy passage of the food along the oesophagus. Among the
herbivora it is probable that the longer retention of food in the mouth gives
the saliva opportunity for more complete digestive action.

C. Gastric Digestion.

After the food reaches the stomach it is exposed to the action of the secre-
tion of the gastric mucous membrane, known usually as the gastric juice. The
physiological mechanisms involved in the production and regulation of this
secretion, and the important ])art played in gastric digestion by the movements
of the stomach, will be found described in other sections (Secretion, Move-
ments of Alimentary Canal). It is sufficient here to say that the secretion
of gastric juice begins with the entrance of food into the stomach. By means
of the muscles of the stomach the contained food is kept in motion for several
hours and is thoroughly iliixed with the gastric secretion, which during this
time is exerting its digestive action upon certain of the food-stuffs. From time
to time portions of the liquefied contents, known as chyme, are forced into the
duodenum, and their digestion is completed in the small intestine. Gastric
digestion and intestinal digestion go more or less hand in hand, and usually
it is impossible to tell in any given case just how much of the food will
undergo digestion in the stomach and how much will be left to the action of
the intestinal secretions. It is possible, however,, to collect the gastric secre-
tion or to make an artificial juice and to test its action upon food-stuffs by
digestions in vitro. Much of our fundamental knowledge of the digestive
action of the gastric juice has been obtained in this way, although this has
been supplemented, of course, by numerous experiments upon lower animals
and human beings.

Methods of Obtaining- Normal Gastric Juice. — The older methods used
for obtaining normal gastric juice were very unsatisfactory. For instance, an
animal was made to swallow a clean sponge to which a string was attached so
that the sponge could afterward be removed and its contents be squeezed out ;
or there was given the animal to eat some indigestible material, to start the
secretion of juice by mechanical stimulation, the animal being killed at the
proper time and the contents of its stomach being collected. A better method
of obtaining normal juice was suggested by the famous observations of Beau-
mont^ upon Alexis St. Martin, St. Martin, by the premature discharge of
his gun, was wounded in the abdomen and stomach. On healing, a fistulous
opening remained in the abdominal wall, leading into the stomach, so that the
contents of the latter could be inspected. Beaumont made numerous interest-
ing and most valuable observations upon his patient. Since that time it has
become customary to make fistulous openings into the stomachs of dogs when-

' The Physiology of Digestion, 1833.
15

226 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ever it i.s iR'ct'ssaiy to have tlie uuniial juice lor examination. A .silver e^nula
is placed in the fistula, and at any time the plug closing the canula may be
removed and gastric juice be obtained. In some ca.ses the cesophagus has
been occluded or excised so as to prevent the mixture of saliva with the gastric
juice. Gastric juice may be obtained from human beings also in cases of vom-
iting or by means of the stomach-pump, but in such cases it is necessarily
more or less diluted or mixed with food and cannot be used for exact analvses,
although specimens of gastric juice obtained by these methods are valuable in
the diagnosis and treatment of gastric troubles.

Properties and Composition of Gastric Juice. — The normal gastric secre-
tion is a thin, colorless or nearly colorless liquid with a strong acid reaction
and a characteristic odor. Its specific gravity varies, but it is never great,
the average being about 1002 to 1003. Upon analysis the gastric juice is
found to contain a trace of proteid, probably a peptone, some mucin, and
inorganic salts, but the essential constituents are an acid (HCl) and two
enzymes, pepsin and rennin. A satisfactory analysis of the human juice has
not been reported, owing to the difficulty of getting proper specimens.
According to Schmidt,^ the gastric juice of dogs, free from saliva, has the
following composition, given in 1000 parts :

Water 973.0

Sulids 27.0

Organic substances 17.1

Free HCl 3.1

NaCl 2.5

CaClj 0.6

KCl 1.1

NH.Cl 0.5

Ca3(P0J, 1.7

Mg,(P0,)2 0.2

FePO, 0.1

Gastric juice does not give a coagulum upon boiling, but the digestive enzymes
are thereby destroyed. One of the interesting facts about this secretion is the
way in which it withstands putrefaction. It may be kept for a long time, for
months even, without becoming putrid and with very little change, if any, in
its digestive action or in its total acidity. This fact shows that the juice
possesses antiseptic properties, and it is usually supposed that the presence of
the free acid accounts for this quality.

The Acid of Gastric Juice. — The nature of the free acid in gastric juice
was formerly the subject of dispute, some claiming that the acidity is due to
HCl, since this acid can be distilled off from the gastric juice, others contend-
ing that an organic acid, lactic acid, is present in the secretion. All recent
experiments tend to prove that the acidity is due to HCl. This fact was firet
demonstrated satisfactorily by the analyses of Schmidt, who showed that if,
in a given specimen of gastric juice, the chlorides were all precipitated by
silver nitrate and tiie total amount of chlorine was determined, more was
* ITammarsten : Text-book of Physiological Chemistry (translation by Mandel), 1893, p. 177.

CHEMISTR Y OF DIGESTION AND NUTRITION. 227

found tlian could \)o held in combination by the bases present in the secretion.
Evidently, some of the chlorine luust have been present in combination with
hydroi2;en as iiydrochloric! acid. (\)uHrniat()ry evidence of one kind or another
has siuce been obtained. Thus it lias been shown that a number of color
tests for free mineral acids react with the gastric juice : methyl-violet solutions
are turned blue, contro-red s(jlutions and test-paper are changed from red to
blue, 00 tropteolin from a yellowish to a pink-red, and so on. A numl)er of
additional tests of the same general character will be found described in the
laboratory handbooks of physiology.^ It must be added, however, that lactic acid
undoubtedly occurs, or may occur, in the stomach during digestion. Its pres-
ence is usually explained as being due to the fermentation of the carbohydrates,
and it is therefore more constantly present in the stomach of the herbivora.
The amount of free acid varies according to the duration of digestion ; that is,
the secretion does not j)ossess its full acidity in the beginning, owing probably
to the fact (Heideuhain) that in the first periods of digestion, while the secre-
tion is still scanty in amount, a portion of its acid is neutralized by the
swallowed saliva and the alkaline secretion of the pyloric end of the stomach
(see the section on Secretion), Estimates of the maximum acidity in the
human stomach are usually given as between 0.2 and 0.3 per cent. The
acidity of the dog's gastric juice is greater — 0.3 to 0.58 per cent.

Origin of the HCl. — The gastric juice is the only secretion of the body con-
taining a free acid. The fact that the acid is a mineral acid makes this circum-
stance more remarkable, although other instances of a similar kind are known;
for example, Dolium galea, a mollusc, secretes a salivary juice containing free
H2SO4 and free HCl. When and how the HCl is formed in the stomach is
still a subject of investigation. Histologically, attempts have been made to show
that it is produced in the border cells of the peptic glands in the fundic end
of the stomach (see Secretion). It cannot be said, however, that the evidence
for this theory is at all convincing ; it can be accepted only provisionally.
Ingenious efforts have been made to determine the place of production of the
acid by micro-chemical methods. Substances which give color reactions with
acids have been injected into the blood, and sections of the mucous membrane
of the stomach have then been made to determine microscopically the part of
the gastric glands in which the acid is produced ; but beyond proving that the
acid is formed in the mucous membrane these experiments have given negative
results, the color reaction for acid occurring throughout the thickness of the
membrane.^ The chemistry of the production of free HCl also remains unde-
termined. No free acid occurs in the blood or the lymph, and it follows, there-
fore, that it is manufactured in the secreting cells. It is quite evident, too,
that the source of the acid is the neutral chlorides of the blood ; these are in
some way decomposed, the chlorine uniting with hydrogen to form HCl which
is turned out upon the free surface of the stomach, while the base remains

' Stirling : Outlines of Practical Physiology.

^ Friinkel : PjlUyer's ArchivfUr die gesammtePhysiologie, 1891, vol. 48, p. 63.

228 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

behiud and prubably passes back into the blood. The latter part (jf the pro-
cess, the passage of the base into the blood-current, enables us to explain in part
the facts, noticed by a number of observers, that the alkalinity of the blood is
increased and the acidity of the urine is decreased after meals. Attemj)ts to
express the reaction which takes place in the decomposition of the chlorides
are still too theoretical to merit more than a brief mention in a book of this
character. According to Ileidenhain, a free organic acid is secreted by the
cells, which acid then acts upon and decomposes the chlorides. According to
Maly, the HCl is the result of a reaction between the phosphates and the
chlorides of the blood, as expressed in the two following equations:

NaH^PO, + NaCl = NaJTPO, + HCl ; or,
SCaCl^ + 2Na2HrO, = O^IVO^)^ + 4NaCl + 2 HCl.

A recent theory by Liebermann supposes that the mass action of the COj
formed in the tissues of the gastric raucous membrane upon the chlorides,
with the aid of a nucleo-albumin of acid properties which can be isolated
from the gastric glands, may account for the production of the HCl. Although
it is customary to speak of the HCl as existing in a free state in the gastric
juice, certain differences in reaction between this secretion and aqueous solu-
tions of the same acidity have led to the suggestion that the HCl, or a part of
it at least, is held in some sort of combination with the organic (protcid) con-
stituents of the secretion, so that its })roperties are modified in some minor
points just as the properties of luemoglobin are modified by the combination in
which it is held in the corpuscles. The differences usually described are that
in the gastric juice or in mixtures of HCl and proteid the acid does not dialyze
nor distil off so readily as in simple aqueous solutions. The peptones and
proteoses formed during digestion seem to combine with the acid very readily
— so much so, in fact, that in certain cases specimens of gastric juice taken
from the stomach, although they give an acid reaction with litmus-paper, may
not give the special color reactions for free mineral acids. In such cases, hoM'-
ever, the acid may still be able to fulfil its part in the digestion of proteids.

Nature and Properties of Pepsin. — Pepsin is a typical proteolytic enzyme
which exhibits the striking peculiarity of acting only in acid media; hence
peptic digestion in the stomach is the result of the combined action of pepsin
and HCl. Pepsin is influenced in its action by temperature, as is the case with
the other enzymes ; low temperatures retard, and may even suspend, its activity,
while high temperatures increase it. The optimum temperature is stated to be
from 37° to 40° C, while exposure for some time to 80° C. results, when the
pepsin is in a moist condition, in the total destruction of the enzyme. Pepsin
has never been isolated in sufficient purity for satisfactory analysis. It may be
extracted, however, from the gastric mucous membrane by a variety of methods
and in different degrees of purity and strength. The commercial preparations of
pepsin consist usually of some form of extract of the gastric mucous membrane
to which starch or sugar of milk has been added. Laboratory preparations are
usually made by mincing thoroughly the mucous membrane and then extract-

CHEMISTRY OF DIGESTION AND NUTRITION 229

i)i<^ Tor a long time with glycerin. Glycerin extracts, if not too much diluted
witii water or blood, keep I'or an indefinite time. Purer ])re|)arations of" pepsin
have been made by what is known as " Briicke's method," in which the mucous
membrane is minced and is then self-digested with a 5 per cent, solution of
phosphoric acid. The phosj)horic acid is j)recipitated by the addition of lime-
water, and the pepsiu is carried down in the flocculent precipitate. This pre-
cipitate, after being washed, is carried into solution by dilute hydrochloric
acid, and a solution of cholesterin in alcohol and ether is added. The choles-
terin is jirecipitated, and, as before, carries down with it the pepsin. This
precipitate is collected, carefully washed, and then treated repeatedly with
ether, which dissolves and removes the cholesterin, leaving the pepsin in
aqueous solution. This method is interesting not only because it gives the
purest form of pepsin, but also in that it illustrates one of the properties of
this enzyme — namely, the readiness with which it adheres to precipitates occur-
ring in its solutions. Pepsin illustrates very well two of the general properties
of enzymes that have been described (p. 219): first, its action is incomplete, the
accumulation of the products of digestion inhibiting further activity at a certain
stage ; and, secondly, a small amount of the pepsin, if given sufKcient time and
the proper conditions, will digest a very large amount of proteid.

Artificial Gastric Juice. — In studying peptic digestion it is not necessary
for all })urposes to establish a gastric fistula to get the normal secretion. The
active agents of the normal juice are pepsin and acid of a proper strength ; and,
as the pepsin can be extracted and preserved in various ways, and the HCl can
easily be made of the proper strength, an artificial juice can be obtained at any
time which may be used in place of the normal secretion for many purposes. In
laboratory experiments it is customary to employ a glycerin extract of the gastric
raucous membrane, and to add a small portion of this extract to a large bulk of
0.2 per cent. HCl. The artificial juice thus made, when kept at a temperature of
from 37° to 40° C, will digest proteids rapidly if the preparation of pepsin is a
good one. While the strength of the acid employed is generally from 0.2 to 0.3
per cent., digestion will take place in solutions of greater or less acidity. Too
great or too small an acidity, however, will retard the process ; that is, there is
for the action of the pepsin an optimum acidity which lies somewhere between
0.2 and 0.5 per cent. Other acids may be used in place of the HCl — for example,
nitric, phosphoric, or lactic — although they are not so effective, and the opti-
mum acidity is different for each ; for phosphoric acid it is given as 2 per cent.

Action of Pepsin-Hydrochloric Acid on Proteids. — It has been known
for a long time that solid proteids, such as boiled eggs, when exposed to the
action of a normal or an artificial gastric juice, swell up and eventually pass
into solution. The soluble proteid thus formed was known not to be coagu-
lated by heat ; it was remarkable also for being more diffusible than other
forms of soluble proteids, and was further characterized by certain positive
and negative reactions which will be described more explicitly farther on.
This end-product of digestion was formerly described as a soluble proteid
with properties fitting it for rapid absorption, and the name of peptone was

230 AN AM Kit IVAN TEXT- BOOK OF J'JI YSlOIJXlY.

given to it. It was quickly found, however, that the proeess was complicated
— that in the convei-sion to so-called "peptone" the proteid under digestion
passed through a number of intermediate stages. 'J'he intermediate [)roducts
were partially isolated and were given specific names, such as acid-albumin^
parapcpfone, and propcptone. The two latter names, unfortunately, have not
always been used with the same meaning by authors, and latterly they have
fallen somewhat into disuse, although they are still frcijuentiy employed to
indicate some one or other of the intermediate stages in the formation of pep-
tones. The most complete investigation of the products of pejjtic digestion,
and of proteolytic digestion in general, we owe to Kiihne and to those who
have followed along the lines he laid down, among whom maybe mentioned
Chittenden and IS'eumeister. Their work has thrown new light upon the
whole subject and has developed a new nomenclature. In our account of the
process we shall adhere to the views and terminology of this school, as they
seem to be generally adopted in most of the recent literature. It is well,
however, to add, by way of caution, that investigations of this character are
still going on, and the views at present accepted are lial)le, therefore, to
changes in detail as our experimental knowledge increases. Without giving
the historical development of Kiihne's theory, it may be said that at present
the following steps in peptic digestion have been described : The proteid
acted upon, whether soluble or insoluble, is converted first to an acid-albumiu
(see Chemical section) to which the name si/ntonin is usually given. In arti-
ficial digestions the solid proteid usually first swells up i'rom the action of the
acid, and then slowly dissolves. Syntonin has the general })ropcrties of acid-
albumins, of which properties the most characteristic is that the albumin is
precipitated upon neutralizing the solution with dilute alkali. If, in the begin-
ning of a peptic digestion, the liquid is neutralized, a more or less abundant
precipitate of syntonin will form, the quantity depending upon the stage of
digestion. The formation of syntonin is due mainly to the action of the HCl,
although the acid seems to be much more effective in combination with pepsin
than in simple aqueous solutions of the same strength. Syntonin in turn, under
the influence of tlie pepsin, takes u}) water and undergoes hydrolytic cleavage,
with the formation of two soluble proteids known together as primary albumoses
or proteoses,^ and separately as j^trofo-profrose and Jietero-pi'oteose. Each of these
proteids again takes up water and undergoes cleavage, with the formation of
a second set of soluble proteids known as secondary proteoses, in contradis-
tinction to the primary proteoses, but to which the specific name of deniero-
proteoses is given. Finally, the deutero-proteose, or more properly the
deutero-proteoses, again undergo hydrolytic cleavage, with the formation of
what are known as peptones. Peptic digestion can go no farther than the
formation of peptones, but we shall find later that other proteolytic enzymes

' The term proteose is used by some authors in phice of the older name albumose, as it has a
more general significance. According to this nsage tlie name alhitmose is given to the proteoses
formed from albumin, rjlobiilo.'O' to those formed from globulin, etc., while proteose is a general
term applying to the intermediate products from any proteid.

CHEMISTRY OF DIGESTION AND NUTRITION. 231

(trypsin, for example) arc capable of splitting up a part of the peptones still
further. The fact that trypsin can act upon only a j)art of the peptone shows
that this latter substance is either a mixture of at least two separate although
closely-related peptones, to which the names of anti-pcjjfonc and liend-peptone^
liave been given, or it is a compound containing such hemi- and anti- groups,
and capable, under the action of trypsin, of splitting, with llu; formation of
hemi-peptone and anti-peptone (Neumeister). If we consider pej)tic digestion
alone, this distinction is unnecessary. The final products of peptic digestion
are therefore spoken of usually simply as peptones, although the name ampho-
peptone is also frequently used to emphasize the fact that two distinct varieties
of peptone are probably present. This description of the steps in peptic
digestion may be made more intelligible by the following schema, which is
modified somewhat from that given by Neumeister:^

Proteid.

I
Syntonin.

(Primary proteoses) = Proto-proteose. Hetero-proteose.

I I

(Secondary proteoses) = Deutero- proteose. Deutero-proteose.

I I

(Ampho-peptones) = Peptone. Peptone.

' Kiihne's full theory of proteolytic digestion assumes that the original proteid molecule
contains two atomic groups, the hemi- and the anti- group. Proteolytic enzymes split the mole-
cule so as to give a hemi- and an anti- compound, each of which passes through a proteose stage
into its own peptone. A condensed schema of tlie hypothetical changes would be as follows:

Proteid.

Anti-albumose. Hemi-albumose.

I I

Anti-peptone. Hemi-peptone.

Am pho-peptone.

In the detailed description of proteolysis given above, primary and secondary proteoses are pre-
sumably, according to this schema, mixtures in varying proportions of hemi- and ami- com-
pounds, or, in other words, they are arapho- proteoses. No good way of separating the anti-
from the hemi- compounds has been discovered except to digest them with trypsin. By this
means each compound is converted to its proper peptone, and by the continued action of the
trypsin the hemi-peptone is split into much simpler bodies (p. 241), only anti-peptone being left
in solution. The conception of a proteid molecule with hemi- and anti- groups and the splitting
into hemi- and anti-albumose is mainly an inference backward from the fact that there are two
distinct peptones, one of which, hemi-peptone, is acted upon by trypsin, while the other is not
so acted upon. The details of the splitting of the proteid under the influence of pepsin are still
further complicated by the fact that in some cases a part of the proteid remains undissolved, form-
ing a highly resistant substance to which the name antalhumid has been given. It has been shown
that if this substance is dissolved in sodium carbonate and then submitted to the action of trypsin,
only anti-peptone is formed, indicating that it contains none of the hemi- group. In fact, the prop-
erties of antalbuniid show that it is a peculiar modification of the anti- group which may arise dur-
ing the cleavage of the proteid molecule, and may vary greatly in quantity in different digestions.
^ Lehrbuch der physiologischen Chemie, 1893, p. 187.

232 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

According to this sclienia, peptic digestion, after the syntonin stage, consists in
a succession of liydrolytic cleavages whereby sohible i)roteids (proteoses and
peptones) are produced of smaller and smaller molecular weights. It is {jossi-
ble, of course, that the steps in this process may be moi-e nnmenjiis than those
represented in the scihema, but the general nature of the changes seems to be
established beyond question. Moreover, it is easy to understand that the
products of digestion in any given case will vary with the stage at which the
examination is made. Sufficiently early in the process one may find mainly
syntonin, or syntonin and primary proteoses ; later the deutero-proteoses and
peptones may occur alone or with mere traces of the first i)roducts. The whole
process is more or less progressive, although it must be understood that the
first and the last products may coexist in the same liquid ; that is, a part of
the original proteid may be well on toward the last stages of the action while
another part is in the first stages. It is worth enqohasizing also that in arti-
ficial digestions with pepsin, uo matter how long the action is allowed to go on,
the final product is always a mixture of peptones and proteoses (deutero-proteose).
Even when provision is made to dialyze off the peptone as it forms, thus simu-
lating natural digestion, the final result, according to Chittenden and Amerman,'
is still a mixture of proteose and peptone. The extent of peptic digestion in the
body will be spoken of presently in connection with a rdsum^ of the ])hysiology
of gastric digestion. In general, it may be said that from a physiological
standpoint the object of the whole process is to get the proteids into a form
in which they can be absorbed more easily. The properties and reactions of
peptones and proteoses will be found stated in the Chemical section. It may
serve a useful end, however, to give here some of their properties, in order to
emphasize the nature of the changes caused by the pepsin.

Peptones. — The name " peptones " was formerly given to all the })roducts
of peptic digestion after it had passed the syntonin stage — that is, to the pro-
teoses as well as the true peptones. Commercially, the word is still used in this
sense, the preparations sold as peptones being generally mixtures of ])i-oteoses and
peptones. True pe])tones, in the sense used by Kiihne, are distinguished chem-
ically by certain reactions. Like the proteoses, they are very soluble, they are
not precipitated by heating, and th(>y give a red biuret reaction (see Reactions
of Proteids, Chemical section). They are distinguished from the ])rimary pro.-
teoses by not giving a precipitate with acetic acid and potassium ferrocyanide,
and from the whole group of proteoses by the fact that they are not thrown
down from their solutions by the most thorough saturation of the liquid with
ammonium sulphate. This last reaction gives the only means for the conqilete
separation of the peptones from the proteoses. The peptones, indeed, may be
defined as being the products of proteolytic digestion which are not precipitated
by saturation of the liquid with ammonium sulphate. The validity of this
reaction has lately been called in question. It has been pointed out that,
although the primary proteoses are readily ])recipitated by this salt, the deutero-
proteoses, under certain circumstances at least, arc not precipitated, and cannot
* Journal of Physiology, vol. xiv., 1893, p. 483.

CHEMISTRY OF DIGESTION AND NUTRITION.

233

therefore be distiiiouislied or separated from the so-called " true peptones." We
must await further investigations before attempting to eome to any conclusion
ujwn this poiut. It is well to bear in mind that the change from ordinary
proteid to peptone evidently take.^^ place through a number of intermediate steps,
and the word peptone is meant to designate tiie linal product. Whether this
final product is a chemical individual with properties separating it from all the
intermediate stages is perhaps not yet fully known, but, provisionally at least, we
may adopt Kiihne's definition, outlined above, of what constitutes peptone, as it
seems to be generally accepted in current literature. Peptones are characterized
by their diffusibility, and this property is also possessed, although to a less
marked extent, by the i)roteoses. Recent work by Chittenden,^ in which he
corroborates results published simultaneously by Kiihne, shows the following
relative diffusibility of peptones and proteoses. The solutions used were approx-
imately 1 per cent. ; they were dialyzed in parchment tubes against running
water for from six to eight hours, and the loss of substance was determined
and expressed in [percentages of the original amount. Proto-proteose gave a
loss of 5.09 per cent.; deutero-proteose, 2.21 percent.; peptone, 11 percent.
Several elementary analyses of proteoses and peptones have been reported,
but they cannot be accepted as final, owing to the fact that the substances
analyzed were probably mixtures, and not chemical individuals. The follow-
ing analyses, reported by Chittenden,^ will serve to show the relative percentage
composition of these bodies :

Phyto-vUellin, a Crystallized Proteid extracted from Hemp-seed.

Mother-proteid.

Proto-vitellose.

Deutero-vitellose.

Peptone.

c

H

N

S

0

51.63
6.90

18.78

0.90

21.79

51.55
6.73

18.90

1.09

• 21.73

49.78
6.73

17.97
1.08

24.44

49.40
6.77

18.40
0.49

24.94

The most .striking differences in composition observed in passing from the
raother-proteid to the peptones are the progressive decrease in the percentage
of carbon and the increase in the percentage of oxygen. Both these facts are
in accord with the general theory that proteolysis consists essentially in a series
of hydrolytic cleavages.

Rennm.—lx\ addition to pepsin the gastric secretion contains an enzyme
which is characterized by its coagulating action upon milk. It has long been
known that milk is curdled by coming into contact with the raucous membrane
of the stomach. Dried mucous membrane of the calf's stomach, when stirred
in with fresh milk, will curdle the latter with astonishing rapidity, and this
property has been utilized in the manufacture of cheese. Hammai-sten discovered
that this action is due to the presence of a specific enzyme which exists ready
formed in the membrane of the sucking-calf's stomach, and which is present

' Journal of Physiology, vol. xiv., 1893, p. 502.

2 Cartwright Lectures, New York Medical Record, April, 1894.

234 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

in a preparatory form (rennin-zymogen) in .stomachs of all mammals. This
enzyme has been given several names; rcnniti seems preferable to any other,
and is the term most commonly employed. Remiin may he ol)taiiied from
the stomach by self-digestion of the nuicous membrane or by extracting it
with glycerin. Such extracts usually contain both pepsin and reimin, but the
two have been separated successfully, most easily by the prolonged action of
a temperature of 40° C. in acid solutions, which destroys the remiin, but not
the pepsin. Good extracts of rennin cause clotting of milk with great rapidity
at a temperature of 40° C, the milk (cow's milk), if undisturbed, setting first
into a solid clot, which afterward shrinks and presses out a clear yellowish
liquid, the whey; with human milk, however, the curd is much less firm,
being deposited in the form of loose flocculi. The whole process resembles the
clotting of blood not only in the superficial phenomena, but also in the
character of the chemical changes. Briefly, what happens is that the rennin
acts upon a soluble proteid in the milk known usually as casein, but by some
called " caseinogen," and changes this proteid to an insoluble modification which
is precipitated as the curd. The chemistry of the change is not completely
understood, and there is an unfortunate want of agreement in the terminology
used to designate the products of the action. It has been shown that, as in
the case of blood, curdling cannot take place unless lime salts are present. What
seems to occur is as follows: Casein is a complex substance belonging to the
group of nucleo-albumins, and when acted upon by rennin it undergoes hydro-
lytic cleavage, with the formation of two proteid bodies, paracasein and whey
proteid. The first of these bodies forms with calcium salts an insoluble com-
pound which is precipitated as the curd ; the second remains behind in solution
in the whey. It will be seen that this theory supposes the action to be parallel
with that occurring in blood-coagulation, where fibrin ferment causes a cleavage
of the fibrinogen molecule, a part uniting with calcium to form the insoluble
fibrin, and a part — much the smaller part — remaining in solution in the serum
as fibrin-globulin. It should be added that casein is also precipitated from
milk by the addition of an excess of acid. The curdling of sour milk in the
formation of bonnyclabber is a well-known illustration of this fact. When
milk stands for some time the action of bacteria upon the milk-sugar leads to
the formation of lactic acid, and when this acid reaches a certain concentration
it causes the ])recipitation of the casein. One might suppose that the curdling
of milk in the stomach is caused by the acid present in the gastric secretion,
but it has been shown that perfectly neutral extracts of the gastric mucous
membrane will curdle milk quite readily.

So far as our positive knowledge goes, the action of rennin is confined to
milk. Casein constitutes the chief proteid constituent of milk, and has there-
fore an important nutritive value. It is interesting to find that before its
peptic digestion begins the casein is acted upon by an altogether different
enzyme. The value of the curdling action is not at once apparent, but we
may suppose that casein is more easily digested by the proteolytic enzymes
after it has been brought into a solid form. The action of rennin goes no

CHEMISTRY OF DIGESTION AND NUTRITION 235

further tlian the curdliiitr ; the digestion of the curd is carried on by the ])ep-
sin, and later, in the intestines, by the trypsin, witli the formation of proteoses
and peptones as in the ease of other proteids.

Action of Gastric Juice on Carbohydrates and Fats. — The gastric juice
itself has no direct action upon carbohydrates; that is, it does not contain an
aniylolytic enzyme. It is possible, nevertheless, that some digestion of carbo-
hydrates goes on in the stomach, for, as has been seen, the masticated food is
thoroughly mixed with saliva before it is swallowed. The portion that enters the
stomach in the beoinning of dit»;estion, when the aciditv of the contents is small
(see p. 227), may continue to be acted upon by the ptyalin. This effect, however,
cannot be considered important, since the acidity of the contents of the stomach
must soon reach a point sufficient to suspend, and then to destroy, the ptyalin.
It should be added, however, that Lusk ^ has shown that cane-sugar can be
inverted to dextrose and levulose in the stomach. The importance of this
process of inversion, and the means by which it is accomplished, will be
described more in detail when speaking of the digestion of sugars in the small
intestine (p. 247). Upon the fats also gastric juice has no direct digestive
action. According to the best evidence at hand, neutral fats are not split in
the stomach, nor are they emulsified or absorbed. Without doubt, the heat
of the stomach is sufficient to liquefy most of the fats eaten, and the move-
ments of the stomach, together with the digestive action of its juice on the
proteids and albuminoids with which the fats are often mixed, bring about
such a mechanical mixture of the fats and oils with the other elements of the
chyme as facilitates the more rapid digestion of these substances in the intestine.

Action of Gastric Juice on the Albuminoids. — Gelatin is, from a
nutritive standpoint, the most important of the albuminoids. Its nutritive
value is stated briefly on page 215. It has been shown that this substance is
acted upon by pepsin in a way practically identical with that described for the
proteids. Intermediate products are formed similar to the albumoses, which
products have been named gelatoses^ or glutoses;^ these in turn may be con-
verted to gelatin peptones. It is stated that the action of pepsin is confined
almost, if not entirely, to changing gelatin to the gelatose stage. The pro-
teolytic enzyme of the pancreatic secretion, however carries the change to the
peptone stage much more readily.

"Why does the Stomach not Digest Itself?— The gastric secretion will
readily digest a stomach taken from some other animal, or under certain con-
ditions it may digest the stomach in which it is secreted. If, for instance, an
animal is killed while in full digestion, the stomach may undergo self-diges-
tion, especially if the body is kept warm. This phenomenon has been observed
in human cadavers. It has been shown also that if a portion of the stomach
is deprived of its circulation by an embolism or a ligature, it may be attacked
by the secretion and a perforation of the stomach-wall may result. How,

' Voit: Zeitschrift fur Biologie, vol. xxviii., 1891, p. 269.

"^ Chittenden and SoUey : Journal of Phydoloriy, vol. xii., 1891, p. 23.

^ Klug: Pjiiiger^s Archivfur die gesammte Physiologic, vol. 48, 1891, p. 100.

23(i AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

then, under normal conditions, is the stomacli j^rotectod from corrosion by its
own secretion? The (juestion has <;iven rise to much (hscussion, and in reahty
it deals with one of the fundamental properties of living matter, for the
same question nuist be extended to take in the non-di<vestion of tlie small
intestine by the alkaline pancreatic secretion, the non-digestion of the digestive
tracts of the invertebrates, and the ease of the unicellular animals in which
there is formed within the animal's protoplasm a digestive secretion which
digests foreign material, but does not att'ect the living substance of the cell.
In the particular case under consideration — namely, the protection of the
mammalian stomach from its own secretion — explanations of the following
character have been offered : It was suggested (Hunter) that the " princij)le
of life" in living things protected them from digestion. This suggestion
cannot be considered seriously at the present day, since it implies that living
matter is the seat of a special force, the so-called "vital principle," different
from the forms of energy acting uj)on matter in general. Appeals of this
kind to an unknown force in explanation of the properties of living matter
are not now permissible in the science of physiology. Moreover, it was
shown by Bernard that the hind leg of a living frog introduced into a
dog's stomach through a fistula undergoes digestion. The same thing will
happen, it may be added, if the leg is put into a vessel containing an artificial
gastric juice at the proper temperature. Bernard's theory was that the c})ithe-
lium of the stomach acts as a protection to the organ, preventing the absorp-
tion of the juice. Others believe that the mucus formed by the gastric mem-
brane acts as a protective covering ; while still another theory holds that the
alkaline blood circulating through the organ saves it from digestion, since it
neutralizes the acid of the secretion as fast as it is absorbed, and it is known
that pepsin can digest only in an acid medium. None of these ex])lanations
is sufficient. The last explanation is unsatisfactory because it does not explain
the immunity of the small intestine from digestion by the alkaline pancreatic
juice, or the protection of the infusoria from their own digestive secretion.
The mucous theory is inadequate, as we cannot believe that by this means the
protection could be as complete as it is ; and, moreover, this theory does not
admit of a general application to other cases. The epithelium theory simply
changes the problem a little, as it involves an explanation of the immunity of
the living epithelial cells. It is well known that in the dead stomach the
epithelial lining is no longer a protection against digestion, so that we are led
to believe that there is nothing j)eculiar in the composition of ejiithelial cells,
as compared with other tissues, to account for their exemption under normal
conditions. When we come to consider all the evidence, nothing seems clearer
than that the protection of the living tissue is in every case due to the jiroper-
ties of its living structure. So long as the tissue is alive, it is protected from
the action of the digesting secretion, but the ultimate physical or chem-
ical reason for this property is yet to be discovered. In the case of the
mammalian stomach it is quite probable that the lining epithelial cells are
especially modified to resist the action of the digestive secretion, but, as has

CHEMISTRY OF DldESTION AND NUTRITION. 237

just been said, they lose this property as soou as they undergo the change
from living to dead structure. The digestion of the living frog's leg in
gastric juice, and similar instances, do not affect this general idea, since, as
Bernard himself pointed out, what happens in this case is that the tissue is
first killed by the acid and then undergoes digestion. On the other hand,
Neuraeister has shown that a living frog's leg is not digested by strong pan-
creatic extracts of weak alkaline reaction, since under these conditions the
tissues are not injured by the slightly alkaline liquid. When it is said that
the exemption of living tissues from self-digestion is due to the peculiarities
of their structure, it must not be supposed that this is equivalent to referring
the whole matter to the action of a mysterious vital force. On the contrary,
all that is meant is that the structure of living protoplasmic material is such
that the action of the digestive secretion is prevented, possibly because it is not
absorbed, this result being the outcome of the physical and chemical forces
exhibited by matter with this peculiar structure. While a statement of this
kind is not an explanation of the facts in question, and indeed amounts to a
confession that an explanation is not at present possible, it at least refers the
phenomenon to the action of known properties of matter.

General Remarks upon the Physiology of the Stomach. — From the
foregoing account it will be seen that, speaking generally, the functions of the
stomach are in part to act chemically upon the proteids, and in part, by the
combined action of its secretion and its muscular movements, to get the food
into a physical condition suitable for subsequent digestion in the intestine.
The material sent out from the stomach (chyme) must be quite variable in
composition, but physically the action of the stomach has been such as to
reduce it to a liquid or semi-liquid consistency. The extent of the true
digestive action of gastric juice on proteids is not now believed to be so
complete as it was formerly thought to be. Examination of the chyme
shows that it may contain quantities of undigested or only partially digested
proteid, complete digestion being effected in the intestines. Moreover, arti-
ficial peptic digestion of proteids under the most favorable conditions shows
that only a portion is ever converted to peptone, most of it remaining in the
proteose stage. It has been suggested, therefore, that gastric digestion of
proteids is largely preparatory to the more complete action of the pancreatic
juice, whose enzyme (trypsin) has more powerful proteolytic properties. In
accordance with this idea, it has been shown that an animal can live and
thrive without a stomach. Several cases ^ are on record in ^^'llich the stomach
was practically removed by surgical operations, the oesophagus being stitched
to the duodenum. The animals did well and seemed perfectly normal. Exper-
iments of this character do not, of course, show that the stomach is useless in
digestion ; they demonstrate only that in the animals used it is not absolutely
essential. The reason for this will better be appreciated after the digestive
properties of pancreatic secretion have been studied.

^ Ludwig and Ogata/ Archiv fiir Anatomie und Physiologic, 1883, p. 89; and Carvallo and
Pachon : Archives dc Physiologic normalc et pathologique, 1894, p. 106.

238 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

D. Intestinal Digestion.

After the fond has jinssed tlir()ii<i;h the pylorio orifice of the stomach and has
entered the small intestine it undergoes its most ])rof()und digestive changes.
Intestinal digestion is carried ont mainly while the food is passing through
the small intestine, althongh, as we shall see, the process is completed during
the slower passage through the large intestine. Intestinal digestion is effected
through the combined action of three secretions — namely, the pancreatic juice,
the bile, and the intestinal juice. The three secretions act together uimn the
food, but for the sake of clearness it is advisable to consider each one separately
as to its properties and its digestive action.

Composition of Pancreatic Juice. — Pancreatic juice is the secretion of
the pancreatic gland. In man the main duct of the gland opens into the
duodenum, in common with the bile-duct, about 8 to 10 cm. below the opening
of the pvlorus. In some of the other mammals the arrangement is different :
in dogs, for example, there are two ducts, one opening into the duodenum,
together with the bile-duet, about 3 to 5 cm. below the opening of the
pylorus, and one some 3 to 5 cm. farther down. In rabbits the principal
duct opens separately into the duodenum about 35 cm. below the opening
of the bile-duct. For details as to the act of secretion, its time-relations to
the ingestion of food, its quantity, etc., the reader is referred to the section on
Secretion. Most of our exact knowledge of the properties of the pancreatic
secretion has been obtained either from experiments upon lower animals,
especially the dog and the rabbit, in which it is possible to establish a pan-
creatic fistula and to collect the normal juice, or from experiments with arti-
ficial pancreatic juice prepared from extracts of the gland. Various methods
have been used in making pancreatic fistuhie : usually the main duct of the
gland, which in the two animals named is separate from the bile-duct, is
exposed and a canula is inserted. A better method, devised by Heidenhain,
consists in cutting out the piece of duodenum into which the main duct opens
and sewing this isolated piece to the abdominal wall so as to make a permanent
fistula, the continuity of the intestinal tract in this case being re-established,
of course, by sutures. A simple method of obtaining normal pancreatic juice
from the rabbit is described by Ratchford.^ In his method the portion of
the duodenum into which the main duct opens is resected and cut open along
the border opposite to the mesenteric attachment. The mouth of the duct is
seen as a small papilla projecting from the surface of the mucous membrane.
Through the papilla a small glass canula may be passed into the duct, and the
secretion, which flows slowly, may be collected for several hours. The total
quantity olitainable by this means from a rabbit is small — about 1 c.c. — but it
is sufficient for the demonstration of some of the imiiortant properties of pan-
creatic juice, especially its action upon fats. As obtained by these methods,
the secretion is found to be a clear, colorless, alkaline liquid. The secretion
obtained from dogs is thick and glairy, and forms a coagulum upon standing,
' Journal of Phymology, vol. xii., 1891, p. 72.

CHEMISTRY OF DIGESTION AND NUTRITION.

239

while that iVoiii iiibbits is u thin, perf't'ctly colorless liquid \vhi(;ii duos not fonu
a clot. Ill dogs the secretiou from a perniaueut fistula soon becomes thinner
than it was when the fistula was first established, and this (change in its con-
sistency is accompanied by a corresponding variation in specific gravity. The
specific gravity (dog) of the juice from a tem^jorary fistula is given at 1030;
from a })ernianent fistula, at 1010 to 1011. The secretion coagulates upon
being heated, owing to the proteids held in solution, and it undergoes putre-
faction very quickly, so that it cannot be kept for any length of time. The
analysis of the secretion most frequently quoted is that given by C. Schmidt,
as follows :

Pana'ealic Juice {Dog).

Constituents.

S Water

I Solids

Orfi;anic substances

Asli

Sodium carbonate

Sodium cbloride

Calcium, magnesium, and sodium phosphates

Imme.liately after

From permanent

establishing fistula.

fistula.

900.76

980.45

99.24

19.55

90.44

12.71

8.80

6.84

0.58

3.31

7.35

2.50

0.53

0.08

The composition of normal human pancreatic juice has not been determined
completely, owing to the rarity of opportunities of obtaining the secretion.
Several partial analyses have been reported. According to Zawadsky,^ the
composition of the secretion in a young woman was as follows :

In 1000 parts.

Water 864.05

Organic substances 132.51

Proteids 92.05

Salts 3.44

The organic substances held in the secretion are in part of an albuminous
nature, since they coagulate upon heating, but the exact nature of the proteid
or proteids has not been determined satisfactorily. The most important of the
organic substances — the essential constituents, indeed, of the whole secretion —
are three enzymes acting respectively upon the proteids, the carbohydrates,
and the fats. The proteolytic enzyme is called " trypsin ;" the amylolytic
enzyme is described under different names : " amylopsin " is perhaps the best,
and will be adopted in this section ; for the fat-splitting enzyme we shall use
the term " steapsin." Owing to the presence of these enzymes the pancreatic
secretion is capable of exerting a digestive action upon each of the three im-
portant classes of food-stuffs.

Trypsin. — Trypsin is a more powerful proteolytic enzyme than pepsin.
Unlike the latter, trypsin acts best in alkaline media, but it is effective also in
neutral liquids, or even in solutions not too strongly acid. Trypsin is affected
by changes in temperature like the other enzymes, its action being retarded
by cooling and being hastened by warming. There is, however, a temperature,

' Cenlralblatl fiir Physiologie, vol.5, 1891, p. 179.

240 AA^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

which nuiy be called the optimum temperature, at which the trypsin acts most
powerfully; if, however, the temperature is I'aised to as much as 70° to 80° C,
the enzyme is destroyed entirely. Trypsin has never been isolated in a condi-
tion sufficiently pure for analysis, so that its chemical (jomposition is unknown.
Extracts containing trypsin can be made from the gland very easily and by
a variety of methods. The usual laboratory method is to mince the gland and
to cover it with glycerin for some time. In using this and other methods for
preparing trypsin extracts it is best not to take the perfectly fresh gland, but
to keep it for a number of hours before using. The reason for this is that the
enzyme exists in the fresh gland in a preparatory stage, a zymogen (see sec-
tion on Secretion), which in this case is called "' trypsinogen." Upon standing,
the latter is slowly converted to trypsin — a process which may be hastened by
the action of dilute acids and by other means. An artificial pancreatic juice
is prepared usually by adding a small quantity of the pancreatic extract to an
alkaline liquid ; the liquid usually employed is a solution of sodium carbonate
of from 0.2 to 0.5 per cent. To prevent putrefactive changes, which come on
with su(^h readiness in pancreatic digestions, a few drops of an alcoholic solution
of thymol may be added. A mixture of this kind, if kept at the proper
temperature, digests proteids very rapidly, and most of our knowledge of
the action of trypsin has been obtained from a study of the products of such
digestions.

Products of Tryptic Digestion. — Tryptic digestion resembles peptic diges-
tion in that proteoses and peptones are the chief products formed, but the two
processes differ in a number of details. The naked-eye appearances, in the first
place, are different in cases in which the proteid acted u])on is in a solid form ;
for while in the pepsin-hydrochloric digestion the; proteid swells up and grad-
ually dissolves, under the action of trypsin it does not swell, but suffers erosion,
as it were, the solid mass of proteid being eaten out until finally only the indi-
gestible part remains, retaining the shape of the original mass, but falling into
fragments when shaken. In the second jilace, the hy(h'olytic cleavages seem
to be of a more intense nature. In peptic digestion, after the syntonin stage is
passed, there is a gradual change to peptone through the intermediate primary
and secondary proteoses. Under the influence of trypsin, according to the most
recent experiments, the solid proteid undergoes a transformation directly to
secondary proteoses (deutero-proteoses), the intermediate stages being skipjied.
It was formerly thought that the solid proteid was converted first into a soluble
proteid, and that if the solution was alkaline some alkali-albumin was formed,
precipitable by neutralization, and comparable to the syntonin of pepsin-hydro-
chloric digestion. This soluble proteid was thought to be split into proteoses
of the hemi- and anti- groups which were then converted to the corresponding
peptones, according to Kiiline's schema (p. 231). There seems to be no doubt
that with the proteid most frequently used in artificial digestion — namely^
fibrin from coagulated blood — the first effect is a conversion to a soluble
globulin-like form of proteid ; but Neumeister finds that this does not happen
with other proteids, and he thinks that in the case of fibrin it is not due to a

CHEMISTRY OF DIGESTION AND NUTRITION.

241

true digestive action of trvi)siu, but to a partial solution of the fibrin by the
inorganic salts in the liquid. In general, however, the preliminary stage of
a soluble proteid is missed, as also is that of the primary proteoses. The
proteid falls at once by hydrolytic cleavage into deutero-proteoses, and these
in turn are transformed to peptones (ampho-peptones). Just at this point
comes in one of the most characteristic differences between the action of pepsin
and that of trypsin. Pepsin cannot affect further the ampho-peptones, but
trypsin may act upon the supposed hemi- constituent and split it up, with the
formation of a number of much simpler non-proteid bodies, most of which are
amido-acids. The final products of })rolonged tryptic digestion are, first, a pep-
tone which cannot further be decomposed by the enzyme and which constitutes
what is known as anti-peptone, and, second, a number of simpler organic sub-
stances, mainly amido-acids, that come from the splitting of that part of the
peptone which can be acted upon by the trypsin, and which constitutes what
is known as henii-peptone. It may be remarked in passing that hemi-peptone
has not been isolated. Ampho-peptones containing both anti- and hemi-pep-
tones are formed in peptic digestion, and they may be obtained from tryptic
digestion if it is not allowed to go too far ; anti-peptone, on the other hand,
may be obtained from tryptic digestion which has been permitted to go on until
the hemi-peptone has been completely destroyed, but no good method is known
by which hemi-peptone can be isolated from solutions containing both it and
the anti- form. The simpler products formed by the breaking up of the hemi-
peptone molecule under the influence of the trypsin can be formed, in part at
least, in the laboratory by processes which are known to cause hydrolytic
decompositions. It is probable, therefore, that these substances may be looked
upon as products of the hydrolytic cleavage of hemi-peptone. They are of
smaller molecular weight and of simpler structure than the peptone molecule
from which they are formed. A tabular list of these bodies, taken from Gam-
gee,^ is given. The list includes only those substances which have actually
been isolated ; it is possible that others exist :

Final Products {other than Peptones) of the Action of Trypsin on Albuminous and Albuminoid

Bodies.

Bodies derived from the
fatty acids.

Bases.

Organic body of unknown
composition.

Aromatic bodies.

Amido-caproic acid (leu-

cin).
Amido - valerianic acid

(biitalanin).
Amido-succinic acid (as-

partic acid).
Amido-pyrotartaric acid

(glutamic acid).
(Diamido-acetic acid?)

Lysin.

Lvsatinin.

NHa.

Tryptophan (gives a
red color on the ad-
dition of chlorine-
water, and violet
with bromine-water).

Paroxyphenylamidopro-
pionic acid (tyrosin).

Of these substances, the ones longest known and most easily isolated are leucin
(CgHigXOj) and tyrosin (CgHuNOg). The chemical composition and proper-

' A Text-book of the Physiological Chemistry of the Animal Body, 1893, vol. ii. p. 230.
16

242 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ties of those and the other products are described in the Chemical section.
Leiiciii and tvrosin have been found in the contents of tlie intestines, and it is
probable, therefore, that the splitting of the henii-peptone whieii tai<es place so
readily in artificial tryptic digestions occurs also, to some extent at least, within
the body, although we have no accurate estimates of the amount of peptone
destroved in this way under normal conditions. On the supposition that the
production of leucin, tyrosin, and the other amido- bodies is a normal result of
tryptic digestion within the body, it is interesting to inquire what physiological
value, if any, is to be attributed to these substances. At first sight the forma-
tion of these amido- bodies from the valuable peptone would seem to be a
waste. Peptone we know may be absorbed into the blood, and may then be
used to form or n'i)air })roteid tissue, or to furnish energy to the body upon
oxidation, but lcu('in and tyrosin and the other products of the breaking up
of the hemi-peptone are far less valuable as sources of energy, and so far as
we know they cannot be used to form or rej)air ]n"oteid tissue. But m'C must
be careful not to jump too hastily to the conclusion that the splitting of the
hemi-peptone is useless. It remains possible that a wider knowledge of the
subject may show that the process is of distinct value to the body, although it
must be confessed that no plausible suggestion as to its importance has yet
been made. In addition to any possible functional value which these amido-
bodies may possess, their occurrence in proteolysis is of immense interest to
the physiologist. Some of them are of a constitution simple enough to be studied
by exact chemical methods, and the hope is entertained that through them
a clearer knowledge may be obtained of the structure of the proteid molecule.
It should be added that not only are these amido- bodies found in the aliment-
ary canal as products of tryptic digestion, but that they, or some of them,
occur also in other parts of the body, especially under pathological conditions,
and that, furthermore, they occur among the products of the destruction of
the proteid molecule by laboratory methods or by the action of bacterial
organisms. The theoretical importance of the base lysatinin will be referred
to again later, when speaking of the origin of urea in the body. The processes
of tryptic digestion outlined above are represented in brief in the following
schema, taken from Neumeister : '

Proteid.

I
Deutero-albiimoses.

I
Ampho-peptone.

Anti-peptone. Hemi-peptone.

Leucin. Tyrosin. Aspartic acid. Tryptophan, etc.

It may be said in conclusion that trypsin produces pe])tone from ]>roteids more

readily than does pepsin. Under normal conditions it is probable that most

* Lehrbuch der physiologischen Ckemie, 1893, p. 200.

CHEMISTRY OF DIGESTION AND NUTRITION. 243

of the ]>rotei(l of the food receives its fiiiul preparation for absorption in the
small intestine, nnder the inlinenee of this enzyme.'

Albuminoids. — Gelatin and the other albuminoids are aeted upon by
trypsin, the produets being similar in general to those formed from the pro-
teids. As stated on page 235, pei)sin carries the digestion of gelatin mainly to
the gelatose stage; trypsin, however, produces gelatin peptones. It seems
probable, therefore, that the final digestion of the albuminoids also is effected
in the small intestine.

Aniylopsin. — The enzyme of the pancreatic secretion which acts upon
starches is found in extracts of the gland, made according to the general
methods already given, and its presence may be demonstrated, of course, in
the secretion obtained by establishing a pancreatic fistula. The proof of the
existence of this enzyme is found in the fact that if some of the pancreatic
secretion or some of the extract of the gland is mixed with starch paste, the
starch quickly disappears and maltose or maltose and dextrin are found
in its place. Amylopsin shows the general reactions of enzymes with rela-
tion to temperature, incomj)leteness of action, etc. Its specific reaction is its
effect upon starches. Investigation has shown that the changes caused by it
in the starches are apparently the same as those produced by ptyalin. In
fact, the two enzymes ptyalin and amylopsin are identical in properties as
far as our knowledge goes, so that it is not uncommon, in German liter-
ature especially, to have them both described under the name of ptyalin.
The term amylopsin is convenient, however, in any case, to designate the
special origin of the pancreatic enzyme. As to the details of its action, it is
unnecessary to repeat what has been said on page 223. The end-products
of its action, as far as can be determined from artificial digestions, are a sugar,
maltose (Ci2H220ii,H20), and more or less of the intermediate achrobdextrins,

' The details of the cleavage of the proteid molecule under the influence of pepsin

and trypsin are obviously not yet completely worked out. The general idea of Kiihne

is given briefly in a foot-note on .page 231. An important modification of the original

conception is represented in a theoretical schema given by Neumeister, which is here

reproduced. According to this diagram, each proteose, as well as the peptone produced

in an ordinary digestion, contains both hemi- and anti- groups, and is therefore an

ami)ho- compound. The relative amount of hemi- or anti- substance present at each

stage is indicated by thick or thin lines as the case may be. While proto-proteose and

the deutero-proteose and peptone arising from it are mainly composed of the hemi-

group, hetero-proteose and its subsequent stages consist chiefly of the anti- grouping.

The resistant compound, known as anti-albumid, which is split off from the proteid

molecule in greater or less quantity, seems to have only the anti- grouping; so far as it

can be converted to peptone, it yields only anti-peptone.

r Proteid molecule. "1

[Hemi- group. Anti- group.J^^

Proto-proteose. Hetero-proteose.

(Ampho-proteose.) {Ampho-proteose.) Anti-albumid.

II II I

Deutero-proteose. Deutero-proteose. Deutero-proteose.

(Ampho-proteose.) (Ampho-proteose.) (Anti-proteose.)

II i I i

Ampho-peptone. Ampho-peptone. Anti-peptone.

244 .I.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the relative amounts depending upon the completeness of digestion. As has
previously been said, there are indications tiiat under tiie favorable conditions
of natural digestion all tlie starch may be changed to maltose, but possibly
it is not necessary that the action should be so complete in order that the
carbohydrate may be absorbed into the blood, as will be shown when we come
to speak of the further action of the intestinal secretion upon maltose and the
dextrins. The amylolytic action of the pancreatic juice is extremely import-
ant. The starches constitute a large part of our ordinary diet. Tlie action of
the saliva upon them is probably, for reasons already given, of subordinate
importance. Their digestion takes place, therefore, entirely or almost entirely
in the small intestine, and mainly by virtue of the action of the amylopsin
contained in the pancreatic secretion. The action of the amylopsin is supple-
mented to some extent, apparently, by a similar enzyme formed in small
quantities in the intestinal wall itself, the nature of which will be described
presently in connection with intestinal secretion.

Steapsin. — Steapsin is the name given to a fat-splitting enzyme occurring
in the pancreatic juice. It is of the greatest importance in the digestion and
absorption of fats. The peculiar power of the pancreatic juice to split neutral
fats with the liberation of free fatty acid was first described by Bernard. His
discovery has since been corroborated for different animals, including man,
by the use of normal pancreatic juice obtained from a fistula, or by the aid of
the tissue of the fresh gland, or, finally, by means of extracts of the gland.
When neutral fats (see Chemical section for the composition of fats) are
treated with an extract containing steapsin, they take uj) water and then
undergo cleavage (hydrolysis), with the production of glycerin and the free
fatty acid found in the particular fat used. This reaction is exjjlained by the
following equation, in which a general formula for fats is used :

C3H,(aH2„,,COO)3 4- 3HP = C3H,(OH)3+ 3(aH,„,,COOH).

Fat. Glycerin. Free fatty acid.

The reaction in the case of palmitin would be —

C3H,(C\,H3,COO)3 -F 3H,0 = C3H,(OH)3 -f- 3(C\3H3,COOH).

Palmitin. Glycerin. Palmitic acid.

While this action is undoubtedly caused by an enzyme, it has not been possible
to isolate the so-called " steapsin " in a condition of even approximate purity.
As a matter of fact also, ordinary extracts of pancreas, such as the laboratory
extracts in glycerin, do Jiot usually siiow the presence of this enzyme unless
special precautions are taken in their preparation. It would seem that steapsin
is easily destroyed. With fresh normal juice or with pieces of fre.>^li pancreas
the fat-splitting effect can be demonstrated easily. One striking method of
making the demonstration is to use butter as the fat to be decomposed. If
butter is mixed with normal pancreatic juice or with pieces of fresh pancreas,
and the mixture is kept at the body-temperature, the several fats contained in
butter will be decomposed and the corresponding fatty acids will be liberated,

CHEMISTRY OF DIGESTION AND NUTRITION. 245

amoiiii; tlicm butyric acid, which is readily recognized by its familiar odor,
that ot" rancid butter. The action of steapsin, as in the case of the other
enzyiues, is very much influent-ed l)y the temperature. At the iKMly-temper-
ature the action is very rapid. The nature of the fat also influences the
rapidity of the reaction ; it may be said, in general, that fats with a high
melting-point are less readily decomposed than those with a low melting-
point. It has been shown, however, that even spermaceti, which is a body
related to the fats and whose melting-point is 53° C, is decomposed, although
slowly and imperfectly, by steapsin. The fat-splitting action of the steapsin
undoubtedly takes place normally in the intestines, but it must not be supposed
that all the fat eaten undergoes this process. On the contrary, it is believed
that a small portion only of the fats and oils is aifected by the steapsin, by far
the larger portion remaining unaffected and being absorbed into the blood as
neutral fat. What, then, is the physiological value of steapsin in the digestion
and absorption of fats? This question is difficult to answer satisfactorily if
one goes into the details. In general, however, it is commonly taught that the
small part of the fat split by the steapsin into fatty acid and glycerin helps
to emulsify the balance of the fat and thereby renders its absorption possible.
The fat-splitting action of steapsin, then, is of indirect value in digestion, and
its importance can be brought out best by describing the emulsification of fats
and the conditions bringing this emulsification about.

Emulsification of Fats. — An oil is emulsified when it is broken up into
minute globules which do not coalesce, but which remain separate and more
or less uniformly distributed throughout the medium in which they exist.
Artificial emulsions can be made by shaking oil vigorously in viscous solutions
of soap, mucilage, etc. Milk is a natural emidsion which separates partially
on standing, some of the oil rising to the top to form cream. Bernard made
the important discovery that when oil and pancreatic juice are shaken together
an emulsion of the oil takes place very rapidly, especially if the temperature
is about that of the body. The main cause of the emulsification has been
shown to be the formation of free fatty acids due to the action of steapsin,
and the union of these acids with the alkaline salts present to form soaps.
This fact has been demonstrated by experiments of the following character:
If a perfectly neutral oil is shaken with an alkaline solution (^ per cent,
sodium-carbonate solution), no emulsion occurs and the two liquids soon sepa-
rate. If to the same neutral oil one adds a little free fatty acid, or if one
uses rancid oil to begin with and shakes it with \ per cent, sodium-carbonate
solution, an emulsion forms rapidly and remains for a long time. Oil con-
taining fatty acids when shaken with distilled water alone will not giv^e an
emulsion. It has been shown, moreover, by Gad and Ratchford that with a
certain percentage of free fatty acids (5| per cent.) rancid oil and a sodium-
carbonate solution will form a fine emulsion spontaneously — that is, without
shaking. Shaking, however, facilitates the emulsification when the amount
of free acid varies from this optimum percentage. In what way the formation
of soaps in an oily liquid causes the oil to become emulsified is still a matter

240 ^liV" AMERICAN TEXT- BOOK OF PHYSIOLOGY.

of speculation. It lias hccii suf^irostod that the soaj) ioriiis a tliiii n»atin<; or
membraiu" round the small oil-drops, thus ]treventing them I'njni uuitin;^. The
splitting!; of the oil into small drops seems to be caused, in cases of spontaneous
emulsification, by the a<;t of formation of the soaj) — that is, the union of the
alkali with the fatty acid — in other cases by the mechanical shaking, or by these
two causes combined. The aj)plication of these facts to the action of the pan-
creatic juice normally in the small intestine is easily made. When the chyme,
containing more or less of liquid fat, comes into contact with the pancreatic
juice, a part of the oil is quickly sj)lit by the steaj)sin, with the formation of free
fatty acids. These acids unite with the alkalies and the alkaline salts present in
the secretions of the small intestine (pancreatic juice, bile, intestinal juice) to
form soaps. The formation of the soaps, aided, perhaps, by the peristaltic
movements of the intestine, emulsifies the remainder of the fats and thus
renders them ready for al^sorption. It has been suggested that the proteids
in solution in the pancreatic juice aid in the emulsification, but there is no
experimental evidence to show that this is the case. A factor of much more
importance is the influence of the bile. In man the pancreatic; juice and the
bile are poured into the duodenum together, and in all mammals the two secre-
tions are mixed with the food at some part of the duodenum. Now, it has
been shown beyond question that a mixture of bile and pancreatic juice will
cause a splitting of fats into fatty acids and glycerin much more rapidly than
will the pancreatic juice alone.' This effect of the bile is not due to the
presence in it of a fat-splitting enzyme of its own: the bile seems merely to
favor in some way the action of the steapsin contained in the pancreatic secre-
tion. Bile aids the emulsification possibly in another way. To be efficient as
emulsifiers the fatty acids must form soaps. The alkaline salts of the pancre-
atic juice do not appear to be in a form in which they can be used readily
for this j)urpose. It is supposed that the alkaline salts of the bile (and the
intestinal juice) are therefore made use of. TIk; mechanism of the absorption
of the emulsified fat and the importance of bile in this j)rocess will be described
subsequently.

Intestinal Secretion. — The small intestine is lined with tubular glands,
the crypts of Lieberkiihn, which are supposed to form a secretion of consid-
erable importance in digestion. To obtain the intestinal secretion, or succus
entericiis, as it is often called, recourse has been had to an ingenious operation
for establishing a permanent intestinal fistula. This operation, which usually
goes under the name of the " Thiry-Vella fistula," consists in cutting out a
small portion of the intestine without injuring its supply of blood-ve&sels or
nerves, and then sewing the two open ends of this piece into the abdominal
wall so as to form a double fistula. The continuity of the intestines is estab-
lished by suture, while the isolated loop with its two openings to the exterior
can be used for collecting the intestinal secreti<^n uncontaminated by partially-
digested food. The secretion is always small in quantity, and it must be

* Nencki : Archiv fur eiperimentelle Pathnloffie u. Pharmakologie, vol. 20, 1886, p. 367 ; Ratch-
ford : Journal of Physiology, 1891, vol. 12, p. 27.

CHEMISTRY OF DIGESTION AND NUTRITION 247

started by a stinmlus of some kliul. According to Rolimann,' it varies in
quantity in dilferent parts of the small intestine, being very scanty in the upper
])art and more abundant in the lower. The intestinal secretion is a yellowish
liquid with a strong alkaline reaction. The reaction is due to the presence of
sodium carbonate, the quantity of which is about 0.25 to 0.50 per cent. Tlier
chemical composition of the secretion has not been satisfactorily determined,
but its digestive action has been investigated with success. Upon proteids and
fats it is said to have no specific action — that is, it contains neither a proteolytic
nor a fat-splitting enzyme. The possible value of its sodium carbonate in aiding
the emulsification of fats has been referred to in the preceding paragraj)h.
Upon carbohydrates tiie secretion has an important action. In the first place,
it has been shown that it contains an amylolytic enzyme which is more abun-
dant in the upper than in the lower part of the intestine. This enzyme doubt-
less aids the amylopsin of the pancreatic secretion in converting starches to
sugar (maltose) or sugar and dextrin. What is still more important, however,
is the presence of inverting enzymes capable of converting cane-sugar (saccha-
rose) into dextrose and levulose, and of a similar enzyme capable of changing
maltose (or dextrin) to dextrose. Both of these effects are examples of the
conversion of di-saccharides to mono-saccharides.

The di-saccharides of importance in digestion are cane-sugar, milk-sugar,
and maltose. The first of these forms a common constituent of our daily diet;
the second occurs always in milk ; and the third, as we have seen, is the main
end-product of the digestion of starches. These substances are all readily
soluble, and we might expect that they would be absorbed directly into the
blood without undergoing further change. As a matter of fact, however, it
seems that they are first dissociated under the influence of the inverting enzymes
into simpler mono-saccharide compounds, although in the case of lactose this
statement is perhaps not entirely justified, our knowledge of the fate of this
sugar during absorption being as yet quite incomplete. According to some
authors, lactose is absorbed unchanged (see Chemical section). The general
nature of this change is expressed in the three following reactions:

Maltose. Dextrose. Dextrose.

Ci2H,,0„ -{- H,0 = C,H. A + C,H,A.

Cane-sugar. Dextrose. Levulose.

CioH2.p,i + H,0 = C,n,.f), + CeH, A-

Lactose. Dextrose. Galactose.

For the reactions by means of which these different isomeric forms of sugar are
distinguished reference must be made to the Cliemical section. The final stage
in the artificial digestion of starches is the formation of maltose or of a mixture
of maltose and dextrins. In the intestines, however, the process is carried
a step farther by the aid of the inverting enzymes, and the maltose, and ap]iar-
ently the dextrins also, are converted into dextrose. According to this descrip-
tion, all of the starch is finally absorbed into the blood in the form of dextrose ;

' Pfiiigei-'s Arehivfur die geaammte Physiologie, 1887, vol. 41, p. 411.

248 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and this conclusion falls in witli the iiict that the sugar found normally in the
blood exists always in the form of dextrose. With reference to the inverting
enzymes found in the small intestine, it should he added that they occur more
abundantly in the mucous membrane than in the secretion itself. Indeed, the
secretion is normally so scanty, especially in the upj)cr part of the intestine,
that it caiHiot be supposed to do more than moisten the free surface, and it is
probable that the action of the inverting enzymes takes place upon or in the
mucous membrane, as the last step in the series of digestive changes of the
carbohydrates inimediately pre{;eding their absorption.

Digestion in the Large Intestine. — Observations upon the secretions of
the large intestine have been made upon human beings in cases of anus praeter-
naturalis in which the lower portion of the intestine (rectum) was practically
isolated. These observations, together with those made upon lower animals,
unite in showing that the secretion of the large intestine is mainly composed
of mucus, as the histology of the mucous membrane would indicate, and that
it is very alkaline, and probably contains no digestive enzymes of its own.
When the contents of the small intestine pass through the ileo-csecal valve into
the colon they still contain a quantity of incompletely digested material mixed
with the enzymes of the small intestine. It is likely, therefore, that some
at least of the digestive processes described above may keep on for a time in
the large intestine ; but the changes here of most interest are the absorption
which takes place and the bacterial decompositions. The latter are described
briefly below.

Bacterial Decompositions in the Intestines. — Bacteria of different
kinds have been found throughout the alimentary canal from the mouth to
the rectum. In the stomach, howxn'er, under normal conditions, the strong
acid reaction prevents the action of those putrefactive bacteria which decompose
proteids, and prevents or greatly retards the action of those which set up
fermentation in the carbohydrates. Under certain abnormal conditions
known to us under the general term of dyspepsia, bacterial fermentation of the
carbohydrates may be pronounced, but this must be -considered as pathological.

In the small intestine the secretions are all alkaline, and it was formerly
taken for granted that the intestinal contents are normally alkaline. If this were
so the bacteria would find a favorable environment. It was supposed that putre-
faction of the proteids must certainly occur, especially during the act of tryptic
digestion, and this supposition was borne out by the extraordinary readiness of ar-
tificial pancreatic digestions to undergo putrefaction when not protected in some
way. Two recent cases ^ of fistula of the ileum at its junction with the colon in
human beings have given opportunity for exact study of the contents of the
small intestine. The results are interesting, and to a certain extent are opposed
to the preconceived notions as to reaction and proteid putrefaction which have
just been stated. They show that the contents of the intestine at the point
where they are about to pass into the large intestine are acid, provided a mixed

' Macfadyen, Nencki, and Sieber : Archiv fur expermentelle Pathologie u. Pharmakologie, 1891,
vol. 28, p. 311 ; Jakowski: Archives des Sciences biologiques, St. Petersburg, 1892, vol. 1.

CIIE3nSTBY OF DIGESTION AND NUTRITION. 249

diet is used, the acidity being due to organic acids (acetic) and being equal to
0.1 per cent, acetic acid. These acids must have come from the bacterial fer-
mentation of the carbohydrates, and a number of bacteria capable of producing
such fermentation were isolated. The products of bacterial i)utrefaction of the
proteids, on the contrary, are absent, and it has been suggested that the acid
reaction produced by the fermentation of the carbohydrates serves the useful
purpose, under normal conditions, of preventing the putrefaction of the pro-
teids. With reference, therefore, to the point we are discussing — namely, the
bacterial decomposition of the contents of the intestines — we may conclude,
upon the evidence furnished by these two cases, that in the human being, wdien
living on a mixed diet, some of the carbohydrates undergo bacterial decompo-
sition in the small intestine, but that the proteids are protected. We may
further suppose that in the case of the proteids the limits of protection are
easily overstepped, and that such a condition as a large excess of proteid in the
diet or a deficient absorption from the small intestine may easily lead to exten-
sive intestinal putrefaction involving the proteids as well as the carbohydrates.
In the large intestine, on the contrary, the alkaline reaction of the secretion
is more than sufficient to neutralize the organic acids arising from fermentation
of the carbohydrates, and the reaction of the contents is therefore alkaline.
Here, then, what remains of the proteids undergoes, or may undergo, putrefac-
tion, and this process must be looked upon as a normal occurrence in the large
intestine. The extent of the bacterial action upon the proteids as well as the
carbohydrates may vary widely even within the limits of health, and if excessive
may lead to intestinal troubles. Among the products formed in this way, the
following are known to occur: Leucin, tyrosin, and other amido-acids; indol ;
skatol; phenols; various members of the fatty-acid series, such as lactic,
butyric, and caproic acids ; sulphuretted hydrogen ; methane ; hydrogen ;
methyl mercaptan, etc. Some of these products will be described more fully
in treating of the composition of the feces. To what extent these products
are of value to the body it is difficult, with our imperfect knowledge, to say.
It has been pointed out, on the one hand, that some of them (skatol, fatty
acids, CO2, CH4, and HgS) promote the movements of the intestine, and may
be of value from this standpoint; on the other hand, some of them are
absorbed into the blood, to be eliminated again in different form in the urine
(indol and phenols), and it may be that they are of importance in the metab-
olism of the body ; but concerning this our knowledge is deficient. On the
whole, we must believe that the food in its passage through the alimentary
canal is acted upon mainly by the digestive enzymes, the so-called " unorgan-
ized " ferments, but that the action of the bacteria, or organized ferments, is
responsible for a part of the changes which the food undergoes before its final
elimination in the form of feces. These two kinds of action vary greatly
within normal limits, and to a certain extent they seem to be in inverse
relationship to each other. When the digestive enzymes and secretions are
deficient or ineffective the field of action for the bacteria is increased, and this
seems to be the case in some pathological conditions, the result being intes-

250 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tinal troubles of various kinds. The limits of normal bacterial action have
ncit been worked out satisfactorily, but it is evident that our knowledge of
digestion will not be complete until this is accomplished.

E. Absorption ; Summary of Digestion and Absorption op
THE Food-stuffs ; Feces.

In the preceding sections we have followed the action of the various
digestive secretions upon the food-stuffs as far as the formation of the supposed
end-products. In order that these products may be of actual nutritive value
to tiie body, it is necessary, of course, that they shall be absorbed into the
circulation and thus be distributed to the tissues. There are two jKjssible
routes for the absorbed products to take: they may pass immediately into the
blood, or they may enter the lymphatic system, the so-called " lacteals " of
the alimentary canal. In the latter case they reach the blood finally before
being distributed to the tissues, since the thoracic duct, into which the lym-
phatics of the alimentary canal all empty, opens into the blood-vascular system
at the junction of the left internal jugular and subclavian veins. The sub-
stances which take this route are distributed to the tissues by the blood, but
it is to be noticed that, owing to the sluggish flow of the lymph-circulation
(see section on Circulation), a relatively long time elapses after digestion
before they enter the blood-current. The products which enter the l)lood
directly from the alimentary canal are distributed rapidly ; but in this case we
must remember that they first pass through the liver, owing to the existence of
the portal circulation, before they reach the general circniation. During this
})assage through the liver, as we shall find, changes of the greatest importance
take place. The physiology of absorption is con(.'erned with the physical and
chemical means by which the end-products of digestion are taken up by the
blood or the lymph, and the relative importance of the stomach, the small
intestine, and the large intestine in this process. Leaving aside the fats,
whose absorption is a special case, the absorption of the other products of
digestion was formerly thought to be a simple physical process. The ])rocesses
of osmosis, and to a lesser extent of filtration and iml)ibition, as they are
known to occur outside the body, were supposed to account for the absorption
of all the soluble products. This belief has now given way, in large part,
to newer views, according to which the living epithelial cells take an active
]iart in absorption, acting under laws peculiar to them as living substances,
and different from the laws of diffusion, filtration, etc. established for dead
membranes. Since, however, it is highly probable that osmosis plays a ])art
in absorption, it will be convenient to give a brief definition of this process
as it occurs outside the body, in order that the use made of it in explain-
ing physiological absorption, as well as the objections to its use, may more
easily be understood.

Diffusion and Osmosis. — Certain liquids when brought into contact with
each other gradually mix, owing to the attraction of the molecules for each

CHEMISTRY OF DIGESTION AND NUTRITION. 251

other, givino- liiuilly u .solution of unilbrm coinpositiou. The [)rocess of mixing
— that is, of the passage of the molecules of one liquid into the intermoleeular
spaces of the other — is ealled "diffusion." Some liquids — water and oil, for
example — will not diffuse with each other, or, as ordinarily stated, they are not
miscihle. When two miseible li(|uids are separated by a membrane, diffusion
still takes place through the substance of the membrane ; the process under
these conditions is called "osmosis" or "dialysis," and it occurs independently
of any ditierence of pressure on the two sides. It is well to bear in mind
that, in order that osmosis may occur, it is not necessary that there should be
actual capillary pores in the membrane. We may sup[)ose such pores to be
entirely absent, and yet osmosis be possible, since the liquids in this case, or
one of them at least, may be imbibed into the substance of the membrane and
tlius be brought into contact. Imbibition, or the swelling of a membrane with
water, is, in fact, always preliminary to the process of osmosis. When two
liquids containing soluble constituents in different proportions are separated by
a membrane, the tendency is for osmosis to occur until an equable composition
is found on the two sides, diffusion equilibrium being established. This pos-
sibility cannot always be fulfilled, for the reason that some soluble substances
do not undergo osmosis, or, as we usually say, are not dialyzable. As is well
known, Graham separated soluble substances into two great classes — the crys-
talloids, comprising most of the crystalline bodies, which are dialyzable ; and the
colloids, such as gelatin, which are not dialyzable. The rapidity of osmosis of
a crystalloid is measured by some form of osmometer. The simplest form con-
sists of a glass tube the end of which is closed by a membrane — for example, a
piece of parchment. If we place a strong solution of sodium chloride in such
a tube and then bring the bottom of the membrane into contact with distilled
water, diffusion will take place, sodium chloride passing through the parchment
into the distilled water outside (exosmosis), and water passing back into the tube
(endosraosis). The weight of water which passes into the salt solution is much
greater than the weight of salt which passes into the distilled water. If the
process is allowed to go on long enough, the proportion of sodium chloride
outside and inside will be the same, but the volume of liquid inside the osmom-
eter will be increased greatly. In an experiment of this character it is not
difficult to determine \vhat weight of water passes one way through the mem-
brane for a given unit (1 gram) of the crystalloid passing the other way. On the
supposition that this ratio is constant, it was determined for a number of crys-
talloids, and represents what is known as the "endosmotic equivalent," ^^^.
As a matter of fact, the ratio is not constant : it varies among other things
with the strength of solutions used. Still the term is often used ; and it is a
convenient one, as it expresses the approximate rate of dialysis of different
substances. Colloidal substances, such as albumin solutions, which dialyze
very slightly, have been supposed to have a high osmotic equivalent, but so
far at least as the proteids are concerned this seems to be an error. Recent
work has shown that these bodies exert only a slight attraction for water.*
' See Heidenhain : Pfl'dger's Archiv fiir die gesammte Physiologie, 1894, Bd. Ivi. S. fi37.

252 AN AMERICAN TEXT-BOOK ON PHYSIOLOGY.

From this brief description it will l)e seen that osmosis supposes the existence
of two miscible liquids lyintr ou opposite sides of a membrane. In the
alimentary canal we have this arrangement. The mucous membrane rep-
resents the dialyzing membrane ; on one side is the blood or the lymph, and
on the other side are the contents of the stomach or the intestine. If in
the latter there is more sugar, let us say, than in the blood, then, according
to the principles of osmosis, the sugar will tend to dialyze through the mucous
membrane into the l)lood, and a (piantity of water (H)rresponding to its endos-
motic equivalent will pass back into the canal. The facft that the blood is
in rapid movement should promote the rapidity of dialysis, for the obvious
reason that it tends to ])rcvent an equalization in composition; just as in
ordinary osmosis, if the parchment tube containing the substance to be
dialyzed is swung in running water, the osmosis will be more comj)lete
and more rapid than when it is suspended in a given bulk of Avater which
is not changed.

With this brief exposition of the meaning of the terms diffusion, osmosis, and
dialysis, let us pass on first to a consideration of the facts known with reference
to the actual absorption that occurs in different parts of the alimentary canal.

Absorption in the Stomach. — In the stomach it is possible that there
might be absorption of the following substances: water; salts; sugars and
dextrins, which may have been formed in salivary digestion from starch, or
which may have been eaten as such ; the proteoses and peptones formed in
the })eptic digestion of proteids or albuminoids. In addition, absorption of
soluble or liquid substances — drugs, alcohol, etc. — which have been swallowed
may occur. It was formerly assumed without definite proof that the absorp-
tion in the stomach of such things as water, salts, sugars, and j)eptones was
very important. Of late years a number of actual experiments have been
made, under conditions as nearly normal as possible, to determine the extent
of absorption in this organ. These experiments have given unexpected results,
showing, upon the whole, that absorption does not take place readily in the
stomach — certainly nothing like so easily as in the intestine. The methods
made use of in these experiments have varied, but the most interesting results
have been obtained by establishing a fistula of the duodenum just beyond the
pylorus.^ Through a fistula in this position substances can be introduced into
the stomach, and if the cardiac orifice is at the same time shutoif by a ligature
or a small balloon, they can be kept in the stomach a given time, then be
removed, and the changes, if any, be noted. After establishing the fistula iu
the duodenum food may be given to the animal, and the contents of the
stomach as they pass out through the fistula may be caught and examined.
The older methods of introducing the substance to be observed into the
stomach through the oesophagus or through a gastric fistula were of little use,
since, if the substance disappeared, there was no way of deciding whether it
was absorbed or was simply passed on into the intestine.

* Compare V. Mering : Ueber die Function des 3[agens, 1S9'3 ; Edkins: Journal of Physiology,
1892, vol. 13, p. 445; Brandl: Zeitschnft fur Biologic, 1892, vol. 29, p. 277.

CHEMISTRY OF DIGESTION AND NUTRITION. 253

Water. — Experimeuts of the character just described show that water when
taken alone is practically not absorbed at all in the stomach. Von Mering's
experinu'iits especially show that as soon as water is introduced into the
stomach it begins to pass out into the intestine, being forced out in a series
of spirts by the contractions of the stomach. Within a comparatively short
time practically all the water can be recovered in this way, none or very little
having been absorbed in the stomach. For example, in a large dog with a
fistula in the duodenum, 500 cubic centimeters of water were given through
the mouth. Within twenty-five minutes 495 cubic centimeters had been
forced out of the stomach through the duodenal fistula. The result was not
true for all liquids ; alcohol, for example, was absorbed readily.

Salts. — The absorption of salts from the stomach has not been investigated
thoroughly. According to Brandl, sodium iodide is absorbed very slowly or
not at all in dilute solutions. Not until its solutions reach a concentration of
3 per cent, or more does its absorption become important. This result, if
applicable to all the soluble inorganic salts, would indicate that under ordi-
nary conditions they are practically not absorbed in the stomach, since it can-
not be supposed that they are normally swallowed in solutions so concentrated
as 3 per cent. It was found that the absorption of sodium iodide was very
much facilitated by the use of condiments, such as mustard and pepper, or
alcohol, which act either by causing a greater congestion of the mucous mem-
brane or perhaps by directly stimulating the epithelial cells.

Sugars and Peptones. — Experiments by the newer methods leave no doubt
that sugars and peptones can be absorbed from the stomach. In Von Mering's
work different forms of sugar — dextrose, lactose, saccharose (cane-sugar), maltose,
and also dextrin — were tested. They were all absorbed, but it was found
that absorption was more marked the more concentrated were the solutions.
Brandl, however, reports that sugar (dextrose) and peptone were not sensibly
absorbed until the concentration had reached 5 per cent. With these sub-
stances also the ingestion of condiments or of alcohol increased distinctly the
absorptive processes in the stomach. On the whole it would seem that sugars
and peptones are absorbed with some difficulty from the stomach.

Fats. — As we have seen, fats undergo no digestive changes in the stomach.
The process of emulsification is supposed to be a necessary preliminary step to
absorption, and, as this process takes place only after the fats have reached the
small intestine, there seems to be no doubt that in the stomach fats escape
absorption entirely.

Absorption in the Small Intestine. — The soluble products of digestion
— sugars and peptones or proteoses, as well as the emulsified fats — are mainly
absorbed in the small intestine. This we should expect from a mere a prioH
consideration of the conditions prevailing in this part of the alimentary canal.
The partially-digested food sent out from the stomach meets the digestive
secretions in the beginning of the small intestine. As we have seen, the differ-
ent enzymes of the ])ancreatic secretion act powerfully upon the three important
classes of food-stuffs, and we have every reason to believe that their digestion

254 AN A3IERICAN TEXT-BOOK OF PHYSIOLOGY.

makes rapid progress. The passage of the food along the small intestine,
although rajiid compared with its passage through the large intestine, requires
a number of hours for its completion. According to the observations made
upon a patient with a fistula at the end of the small intestine,' food begins to
pass into the large intestine in from two to five and a (piarter hours after it
lias been eaten, and it requires from nine to twenty-three hours belbre the last
portions reach the end of the small intestine ; this estimate includes, of course,
the time in the stomach. During this progress it has been converted for the
most part into a condition suitiible for absorption, and the mucous membrane
with which it is in contact is one peculiarly adapted for absorption, since its
epithelial surface is greatly increased in extent by the vast number of villi
as well as by the numerous large folds known as the " valvulse conniventes."
In addition to these considerations, however, we have abundant experimental
proof that absor])tion takes place actively in the small intestine. The ai)sorp-
tion of fats can be demonstrated microscopically, as will be described presently.
Experiments made by Rohmann ^ and others with isolated loo]>s of intestine
have shown that sugars and peptones are absorbed readily and in much more
dilute solutions than in the stomach. Moreover, in the case just referred to,
of an intestinal fistula at the end of the small intestine, a determination of
the proteid present in the discharge from the fistula, after a test-meal contain-
ing a known amount of proteid, showed that about 85 per cent, had disappeared
— that is, had been absorbed before reaching the large intestine. With refer-
ence to water and salts, it has been shown that they also are readily absorbed ;
some very interesting experiments demonstrating this fact have been reported
recently by Heidenhain in a paper which is referred to briefly on ])age 95.
It must be remembered, however, that under normal conditions the absorption
of water and salts is more or less compensated by the secretion formed along
the length of the intestine, so that when the contents reach the ileo-CcTcal valve
they are still of a fluid consistency similar to that of the chyme as it left the
stomach to enter the intestine. A consideration of the mechanism of the
absorption of flits, sugars, peptones, and water will be taken up presently,
after a few words have been said of absorption in the large intestine.

Absorption in the Large Intestine. — There can be no doubt that absorp-
tion forms an important part of the function of the large intestine. The
contents pass through it with great slowness, the average duration being given
usually as twelve hours, and while they enter through the ileo-ca?cal valve in a
thin fluid condition, they leave the rectum in the form of nearly solid feces.
This fact alone demonstrates the extent of the absorption of water. As for
the sugar and peptones, examination of the intestinal contents as they entered
the large intestine in the case of fistula cited in the preceding paragraph
showed that there may still be present an imjwrtant percentage of jiroteid
(14 per cent.) and a variable amount of sugars and fats — more than is

^ Macfadyen, Nencki, and Sieber : Arckivfiir experimentdle Pnthologie u. Phaiinakologie, 1891,
vol. 28, p. 311.

" Pfluger's Arckivfiir die gesammte Physiologie, 1887, vol. 41, j). 411.

CHEMISTRY OF DIGESTION AND NUTRITION. 255

found normally in the feces. Some of this carbohydrate and proteid under-
goes destruction by bacterial action, as has already been explained (p. 249),
but some of it is absorbed, or may be absorbed, before decomposition occure.
The power of absorption in the large intestine has been strikingly demon-
strated by the fact that various substances injected into the rectum are
absorbed and suffice to nourish the animal. P^nemata of this character are
frequently used iu medical j)ractice with satisfactory results, and careful
experimental work on lower animals and on men under conditions capable of
being properly controlled has corroborated the results of medical experience
and shown that even in the rectum absorption takes place. Without giving
the details of this work, it may be said that it is now known that proteids in
solution, or even such things as eggs beaten to a fluid mass with a little salt,
are absorbed from the rectum, and this notwithstanding the fact that no
proteolytic enzyme is found in this part of the alimentary canal. The
theoretical bearing of this fact upon the general process of absorption Avill be
brought out in the next paragraph. Fats also (such as milk-fat) and sugars
can be absorbed in the same way.

Absorption of Proteids. — As we have seen in the preceding paragraphs,
absorption of proteids takes place in the stomach and the small and large
intestines, but in all probability mainly in the small intestine. The end-
products of the digestion of proteids by the proteolytic enzymes are proteoses
and peptones. Tryptic digestion produces also leucin, tyrosin, and the related
amido- bodies, but so far as proteid has undergone decomposition to this stage
it is no longer proteid, and does not have the nutritive value of proteid. The
logical conclusion from our knowledge of proteid digestion should be that
all proteid is reduced to the form of proteoses or peptones before absorption,
and that the great advantage of proteolysis is that proteids are more readily
absorbed in this form than in any other. In the main we must accept this
conclusion. The process of proteid digestion would seem to be without mean-
ing otherwise. But we must not shut our eyes to the fact that proteid may be
absorbed in other forms than peptones or proteoses. This has been demon-
strated most clearly for the rectum and the lower part of the colon, as was
stated in the preceding paragraph. Enemata of dissolved muscle-proteid
(myosin), egg-albumin, etc. are absorbed from this part of the alimentary canal
without, so far as can be determined, previous conversion to peptones and
proteoses, and we must admit that the same power is possessed by other
parts of the intestinal tract. It is probable, for instance, that the very first
product of pepsin-hydrochloric digestion, syntonin, is capable of absorption
directly. This fact, however, does not weaken the conclusion that peptones
and proteoses are absorbed more easily than other forms of proteids, and that
they constitute the form in which the bulk of our proteid is absorbed.
Opinions as to why these forms of proteids are more easily absorbed than any
other must vary with the theory held as to the nature of absorption. It was
formerly believed that absorption is entirely a process of imbibition and
osmosis through the mucous membrane. The fact that proteoses and peptones

256 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

are more easily difFusible than are other forms of proteids harmonized with
tills theory. The ohjeet of di<»;estion, it was said, is to convert the insolnble
and non-dialyzahle j)rotci(ls into solnhle, diffusible peptones. J5ut a study of
the detail*^ of j)n)teid absorption has shown that the process cannot bo
exj)lained by the hiws of simple dialysis M'hich j^overu tlu; ])rocess of diffusion
through dead mend)ranes. l*roteids, like egg-albumin, which are practically
non-dialyzable are absorbed readily from the intestine. Moreover, when one
considers the rate of absorption of peptone from the alimentary tract, it seems
to be much too rapid and complete to be accounted for entirely by the dif-
fusibility of this substance as determined by experiments with parchment
dialyzers. It is believed, therefore, that the initial act in the absorption
of proteids is dependent in some way upon the properties of the living
epithelial cells lining the mucous membrane. It is impossible at present
to make this statement more specific. A second similar suggestion attributes
the absorption of proteids to the leucocytes found so abundantly in the
adenoid tissue of the intestine, but this has been shown by lleidenhain'
and others to be incorrect. We say, then, in brief, that the peptones and
proteoses are absorbed by a special activity of the epithelial cells. Are they
then transferred to the blood or to the lymph ? Experiments have shown
conclusively that they are transmitted directly to the blood-capillaries : liga-
ture of the thoracic duct, for example, which shuts off the entire lymjih-flow
coming from the intestine, does not interfere with the absorption of proteids.
There is one other fact of great significance in connection with this sub-
ject: the proteids are absorbed mainly, if not entirely, as proteoses and
peptones, and they pass immediately into the blood ; nevertheless, examination
of the blood directly after eating, while the process of absorption is in full
activity, fails to show any peptones or proteoses in the blood. In fact, if
these substances are injected directly into the blood, they behave as foreign,
and even as toxic, bodies. In certain doses they produce insensibility with
lowered blood-pressure, and they may bring on a condition of coma ending in
death. Moreover, when present in the blood, even in small quantities, they
are eliminated by the kidneys and are evidently unfit for the use of the tissues.
It follows from these facts that while the peptones and proteoses are being
absorbed by the epithelial cells they are at the same time changed into some
other form of proteid. What this change is has not been determined.
Experiments have shown that peptones disappear when brought into contact
with fresh pieces of the lining mucous membrane of the intestine which are
still in a living condition. The presumption is that the peptones and proteoses
are converted to serum-albumin, or at least to a native albumin of some kind,
but we have no definite knowledge beyond the fact that the peptones and
proteoses, as such, disappear. It is well to call attention to the fact that the
digestion of proteids is supposed, according to the schema already described,
to consist in a process of hydration and splitting, with the formation, probably,
of smaller molecules. The reverse act of conversion of pej)tones back to albu-
' Pji'dger's Archivfiir die (jesammtc Physiolofjie, vol. 43, 1888, supplement.

CHEMISTRY OF DIGESTION AND NUTRITION. 257

min implies, therefore, a process of dehydration and polymerization which
presumably takes place in the epithelial cells. It is at this point in the act
of absorption of protoids that our knowledge is most deficient.

Absorption of Sugars. — The carbohydrates are absorbed mainly in the
form of sugar or of sugar and dextrin. Starches are converted in the intes-
tine into maltose or maltose and dextrin, and then by the inverting enzymes
of the mucous membrane are changed to dextrose. Ordinary cane-sugar
suffers invei'sion into dextrose and levulose before absorption, and milk-sugar
possibly undergoes a similar inversion into dextrose and galactose, though less
is known of this. So far as our knowledge goes, then, we may say that the
carbohydrates of our food are eventually absorbed in the form mainly of
dextrose or of dextrose and levulose, leaving out of consideration, of course,
the small part that normally undergoes bacterial fermentation. In accordance
with this statement, we find that the sugar of the blood exists in the form
of dextrose. It is apparently a form of sugar that can be oxidized very
readily by the tissues. In fact, it has been shown that if cane-sugar is injected
directly into the blood, it cannot be utilized, at least not readily, by the tissues,
since it is eliminated in the urine ; whereas if dextrose is introduced directly
into the circulation, it is all consumed, provided it is not injected too rapidly.
The sugars are soluble and dialyzable, but, as in the case of peptones, exact
study of their absorption shows that it does not follow the known laws of
osmosis. The degree of absorption of the different sugars does not vary directly
with their diffusibility. Moreover in the small intestine at least the rate of
absorption increases with the concentration of the solution only up to a certain
point (with dextrose, 5 to 6 per cent.) at which the maximum of absorption
takes place, whereas, if it were simply a case of osmosis, the rapidity of dif-
fusion ouo;ht to increase with an increase in concentration of the solution on
one side of the membrane. For these and for other reasons it seems that the
absorption of sugars is also a special act depending, in all probability, upon
the living epithelial cells. Their absorption seems to be effected by means
similar to those used for the proteids, but the details of the act cannot be
given. As in the case of the proteids, the absorbed sugars — dextrose or dex-
trose and levulose — pass directly into the blood, and do not under normal
conditions enter the lymph- vessels. This has been demonstrated by direct
examination of the blood of the portal vein during digestion (Von Mering *),
a distinct increase in its sugar-contents being found. Examination of the
lymph show^s no increase in sugar unless excessive amounts of carbohydrates
have been eaten (Heidenhain).

Absorption of Fats. — Unlike the sugars and peptones, fats are absorbed

chiefly in a solid form — that is, in an emulsified condition. There can be no

question therefore, in this case, of osmosis ; the process of absorption must be

of a mechanical nature. The details of the jirocess have been worked out

microscopically and have given rise to numerous researches. It is unnecessary

to speak of the various theories that have been held, as it has been shown by

' Du Bois-Reymond's Archiv fiir Anaiomie und Physiologie, 1877, p. 413.
17

258 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

nearly all the rocont work that the imiiuxliato agiMit in the absorption of fats
is again the epithelial cells of the villi of the small intestine. The fat-(lroj)let8
are taken up by these cells, and can be seen microscopically after digestion in
the act of passing, or rather of being passed, through the cell-substance. Tiie
epithelial cells, in other words, ingest the fat-particles lying against their free
ends, and then pass them slowly through their cytoplasm, forcing them finally
out of the basal end of the cells into the substance, the stroma, of the villus.
Reference to the histology of the villi will show that each villus possesses
a comparatively large lymphatic capillary lying in its middle and ending
blindly, apj)areutly, near the apex of the villus. Between this central lym-
phatic— or lacteal, as it is called here — and the epithelium lies the stroma, or
main substance of the villus, which, in addition to its blood-capillaries and
plain muscle- fibres, consists mainly of lymphoid or adenoid tissue containing
numerous leucocytes. The fat-droplets have to pass from the epithelium to
the central lymphatic, for it is one of the jnost certain facts in absorption, and
one which has been long known, that the fat absorbed in an emulsified con-
dition gets eventually into the lacteals and thence is conveyed through the
system of lymphatic vessels to the thoracic duct and finally to the blood.
The name " lacteal," in fact, is given to the lymphatic capillaries of the villus
on account of the milky appearance of their contents, after meals, caused by
the emulsified fat. It should be added, however, that it has not been jiossible
to demonstrate experimentally that all the absorbed fat passes into the thoracic
duct. Attempts have been made to collect all the fat passing thiough the
thoracic duct after a meal containing a known quantity of fat, but even after
making allowance for the unabsorbed fat in the feces there is a considerable
percentage of the fat absorbed which cannot be recovered from the lymph
of the thoracic duct. While this result does not invalidate the conclusion
.stated above that the emulsified fat passes chiefly, perhaps entirely, into the
lacteals, it does indicate that there are some factors concerned in the i)rocess of
fat-absorption which are at present unknown to us. The passage of the fat-
droplets to the central lacteal is not difficult to understand. The adenoid
tissue of the stroma is penetrated by minute unformed lyniph-channels which
are doubtless connected with the central lacteal. In each villus lymph is
continually formed from the circulating blood, so that there must be a slow-
stream of Ivmpli through the stroma to the lacteal. When the fat-droplets
have passed through the epithelial cells (and basement membrane) they drop
into the interstices of the adenoid tissue and are carried in this stream into
the lacteal. The lacteals were formerly designated as the ''absorbents," under
the false impression that they attended to all the absorption going on in the
intestines, including that of peptones, sugars, and fats. It is now known that
their action under ordinary conditions is limited to the absorption of fats.

Absorption of "Water and Salts. — From what has been said (p. 252) it is
evident that absorption of water takes place very slightly, if at all, in the
stomach. Whenever soluble substances, such as peptones, sugai's, or salts, are
absorbed in this organ, a certain amount of water must go with them, but the

CIIlLMISTItV OF DIGESTION AND NUTJUTION. 259

bulk of the water passes out of the pylorus. In the small intestine absorption
of water and of inor<!;anie salts evidently takes |)laee readily, and, aeeording to
the experiments of Rohmanu and Ileidenliain already referred to, the laws
governing- their al)sorption are different from what we shoidd expect if the
process were sim])ly one of osmosis. The ditterences as regards the absorption
of salts are especially emphasized by the experiments of Heidenhain.' Making
use of an interesting method, for which reference must be made to the original
paper, Heidenhain has shown that if dilute solutions of NaCl (0.3 to 0.5 per
cent.) are introduced into an isolated loop of the small intestine, absorption of
both water and salts takes place readily, in spite of the fact that in this case
the blood is the more concentrated solution and has therefore the greater
osmotic pressure. Moreover, specimens of the animal's own blood-serum intro-
duced into an intestinal loop are also completely absorbed, although in this case
there is practically no diflPerence in composition, as regards water and salts,
between the blood of the animal and the serum introduced into the intestine.
In another paper by Heidenhain* he proved that the absorption of water in
the small intestine, when ordinary amounts are ingested, takes place entirely-
through the blood-vessels of the villus, and not through the lacteals ; when
larger quantities of water are swallowed, a small part may be absorbed through
the lacteals, as shown by the increased lymph-flow, but by far the larger
quantity is taken up directly by the blood.

In the large intestine the contents become progressively more solid as they
approach the rectum ; the absorption of water is such that the stream is
mainly from the intestinal contents to the blood, giving us a phenomenon
somew^hat similar to the absorption of water by the roots of a plant. This
process is difficult to understand upon the supposition that it is caused by
osmosis, using that term in its ordinary sense. We must suppose an active
attraction of a peculiar character for water on the part of some substance in
the epithelial cells of the wall of the large intestine.

Composition of the Feces. — The feces differ widely in amount and in
composition with the character of the food. Upon a diet composed exclu-
sively of meats they are small in amount and dark in color; with an ordinary
mixed diet the amount is increased, and it is largest with an exclusively vege-
table diet. The average weight of the feces in twenty- four hours upon a
mixed diet is given as 170 grams, while with a vegetable diet it may amount
to as much as 400 or 500 grams. The quantitative composition, therefore, will
vary greatly with the diet. Qualitatively, we find in the feces the following
things : (1) Indigestible material, such as ligaments of meat or cellulose from
vegetables. (2) Undigested material, such as fragments of meat, starch, or fats
which have in some way escaped digestion. Naturally, the quantity of this
material present is slight under normal conditions. Some fats, however, are
almost always found in feces, either as neutral fats or as fatty acids, and to
a small extent as calcium or magnesium soaps. The quantity of fat found is

^ Pjliiger's Arehiv fur die gesammte Physiologic, 1894, vol. 56, p. 579.
■■^ Ibid., vol. 43, 1888, supplement.

260 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

incrGa.«e(l by au increase of the fats in the food. (3) Products of bacterial
decomposition. The most characteristic of these pro(hicts are indol and
skatol. Tiiese two substances are formed normally in the large intestine from
the putrefaction of proteid material. They occur always together. Indol has
the formula CgH^N, and skatol, which is a methyl indol, the formula CgllgN.
They are crystalline bodies possessing a disagreeble fecal odor; this is espe-
ially true of skatol, to which the odor of the feces is mainly due. Indol and
skatol are eliminated from the body only in j)art in the feces; a certain ])r(>por-
portion of each is absorbed into the blood and is eliminated in a modified form
through the urine — indol as indican (indoxyl-sulphuric acid), from which indigo
was formerly made, and skatol as skatoxyl-sulphuric acid (see Chemical section
for further information as to the chemistry of these bodies). (4) Cholesterin,
which is found always in small amounts and is probably derived from the bile.
(5) Excretin, a crystallizable, non-nitrogenous substance to which the formula
CygHjsgSOo has been assigned, is found in minute quantities. (6) Mucus and
epithelial cells thrown off from the intestinal wall. (7) Pigment. In addition
to the color due to the undigested food or to the metallic compounds contained
in it, there is normally present in the feces a pigment, hydrobilirubin, derived
from the pigments (bilirubin) of the bile. Hydrobilirubin is formed from
the bilirubin by reduction in the intestine. (8) Inorganic salts — salts of
sodium, potassium, calcium, magnesium, and iron. The importance of the calcium
and iron salts will be referred to again in a subsequent chapter, when speaking
of their nutritive importance. (9) Micro-organisms. Great quantities of bac-
teria of different kinds are found in the feces.

In addition to the feces, there is found often in the large intestine a
quantity of gas which may also be eliminated through the rectum. This gas
varies in composition. The following constituents have been determined to
occur at one time or another: CH^, CO2, H, N, HgS. They arise mainly
from the bacterial fermentation of the proteids, although some of the N may
be derived from air swallowed with the food.

F. Physiology of the Liver and the Spleen.

The liver plays an important part in the general nutrition of the body ; its
functions are manifold, but in the long run they depend upon the properties
of the liver-cell, which constitutes the anatomical and physiological unit of the
organ. These cells are seemingly uniform in structure throughout the whole
substance of the liver, but to understand clearly the different functions they
fulfil one must have a clear idea of their anatomical relations to one another
and to the blood-vessels, the lymphatics, and the bile-duets. The histology of
the liver lobule, and the relationship of the portal vein, the hepatic artery, and
the bile-duct to the lobule, must be obtained from the text-books upon histol-
ogy and anatomy. It is sufficient here to recidl the fact that each lobule is
supplied with blood coming in part from the portal vein and in part from the
hepatic artery. The blood from the former source contains the soluble prod-
ucts absorbed from the alimentary canal, such as sugar and proteid, and these

CHEMISTRY OF DIGESTION AND NUTRITION. 261

absorbed products are submitted to the metabolic activity of the liver-cells
before reaching the general circulation. The hepatic artery brings to the liver-
cells the arterialized blood sent out into the systemic circulation from the left
ventricle. In addition, each lobule gives origin to the bile-capillaries which
arise between the separate cells and which carry off the bile formed within
the cells. In accordance with these facts, the physiology of the liver-cell falls
naturally into two parts — one treating of the formation, composition, and physi-
ological significance of bile, and the other dealing with the metabolic changes
produced in the mixed blood of the portal vein and the hepatic artery as it flows
through the lobules. In this latter division the main phenomena to be studied
are the formation of urea and the formation and significance of glycogen.

Bile. — From a physiological standpoint, bile is partly an excretion carrying
off certain waste products, and partly a digestive secretion playing an import-
ant role in the absorption of fats, and possibly in other ways. Bile is a con-
tinuous secretion, but in animals possessing a gall-bladder its ejection into the
duodenum is intermittent. For the details of the mechanism of its secretion,
its dependence on nerve- and blood-supply, etc., the reader is referred to the
section on Secretion. Bile is easily obtained from living animals by establishing
a fistula of the bile-duct or, as seems preferable, of the gall-bladder. The
latter operation has been performed a number of times on human beings. In
some cases the entire supply of bile has been diverted in this way to the ex-
terior, and it is an interesting physiological fact that such patients may con-
tinue to enjoy good health, showing that, whatever part the bile takes normally
in digestion and absorption, its passage into the intestine is not absolutely
necessary to the nutrition of the body. The quantity of bile secreted during
the day has been estimated for human beings of average weight (43 to 73 kilo-
grams) as varying between 600 and 850 cubic centimeters. This estimate is
based upon observations on cases of biliary fistula.' Chemical analyses of the
bile show that, in addition to the water and salts, it contains bile-pigments,
bile-acids, cholesterin, lecithin, neutral fats and soaps, sometimes a trace of urea,
and a mucilaginous nucleo-albumin formerly designated improperly as mucin.
The last-mentioned substance is not formed in the liver-cells, but is added
to the bile by the mucous membrane of the bile-ducts and gall-bladder. The
quantity of these substances present in the bile must vary greatly in different
animals and under different conditions. As an illustration of their relative
importance in human bile and of the limits of variation the two following
analyses by Hammarsten ^ may be quoted :

I. II.

Solids 2.520 2.840

Water 97.480 97.160

Mucin and pigment 0.529 0.910

Bile-salts 0-931 0.814

Taurocholate 0.3034 0.053

* Copeman and Winston : Journal of Physiology, 1889, vol. x. p. 213 ; and Kobson : Proceedings
of the Royal Society, London, 1890, vol. 47, p. 499.

■^ Reported in Centralblatt fur Physiologie, 1894, No. 8.

262 .l^V AMEIUVAN TEXT-BOOK OF PHYSIOLOGY.

I. ;i.

Glycocholate 0.6276 0.761

Fatty acids from soap 0.1230 0.024

Cliolesterin 0.003U 0.096

^^"'•""1 0.02-20 0.1286

Fat -•

Soluble salts 0.8070 0.8051

Insoluble salts 0.0250 0.041 1

The color of bile varies in different animals according to the preponderance
of one or the other of the main bile-pigments, bilirubin and biliverdin. The
bile of carnivorous animals has usually a bright golden color, owing to the pres-
ence of bilirubin, while that of the herbivora is a bright green from the
biliverdin. The color of human bile seems to vary : according to some author-
ities, it is yellow or brownish yellow, and this seems especially true of the bile
as found in the gall-bladder of the cadaver : according to others, it is of a
dark-olive color with the greenish tint predominating. Its reaction is feebly
alkaline and its specific gravity varies in human bile from 1050 or 1040 to
1010. Human bile does not give an absorption spectrum, but the bile of some
herbivora, after exposure to the air at least, gives a characteristic spectrum.
The individual constituents of the bile will now be described more in detail,
but with reference mainly to their origin, fate, and function in the body. For
a description of their strictly chemical properties and reactions reference must
be made to the Chemical section.

Bile-pigments. — Bile, according to the animal from which it is obtained,
contains one or the other, or a mixture, of the two pigments bilirubin and
biliverdin. Biliverdin is supposed to stand to bilirubin in the relation of an
oxidation product. Bilirubin is given the formula CjjHggN^Og, and biliverdin
CjjHgeN^Og, the latter being prepared readily from pure specimens of the
former by oxidation. These pigments give a characteristic reaction, known
as"Gmelin's reaction," with nitric acid containing some nitrous acid (nitric
acid with a yellow color). If a drop of bile and a drop of nitric acid are
brought into contact, the former undergoes a succession of color changes, the
order being green, blue, violet, red, and reddish yellow. The })lay of colors
is due to successive oxidations of the bile-pigments ; starting with bilirubin,
the first stage (green) is due to the formation of biliverdin. The pigments
formed in some of the other stages have been isolated and named. The
reaction is very delicate, and it is often used to detect the presence of bile-
pigments in other liquids — urine, for example. The bile-pigments originate
from haemoglobin. This origin was first indicated by the fact that in old
blood-dots or in extravasations there was found a crystalline product, the
so-called "hseraatoidin," which was undoubtedly derived from hfemoglobin,
and which upon more careful examination was proved to be identical with
bilirubin. This origin, which has since been made probable by other reac-
tions, is now universally accepted. It is supposed that when the blood-
corpuscles go to jiieccs in the circulation (p. 343) the hfcmoglobin is brought to
the liver, and then, under the influence of the liver-cells, is converted to an

CHEMISTRY OF DIGESTION AND NUTRITION. 263

iron-free compound, bilirubin or biliverdin. It is very signifirant to find that
the iron .separated by this means from the haemoglobin is for the most ])art
r('taine<l in the hver, a small portion only being secreted in the bile. It seems
probable that the iron held back in the liver is again used in some way to
make new ha3moglobin in the hieraatopoietic organs. The bile-pigments are
carried in the bile to the duodenum and are mixed with the food in its long
passage through the intestine. Under normal conditions neither bilirubin nor
biliverdin is found in the feces, but in their place is found a reduction pro-
duct, hydrobilirubin. Moreover, it is believed that some of the bile-pigment is
reabsorbed as it passes along the intestine, is carried to the liver in the portal
blood, and is again eliminated. That this action occurs, or may occur, has
been made probable by experiments of Wertheimer* on dogs. It happens that
sheep's bile contains a pigment (cholohsematin) which gives a characteristic
spectrum. If some of this pigment is injected into the mesenteric veins of a
dog, it is eliminated while passing through the liver, and can be recognized
unchanged in the bile. The value of this " circulation of the bile," so far as
the pigments are concerned, is not apparent.

Bile-acids. — " Bile-acids " is the name given to two organic acids, glyco-
cholic and taurochoUc, which are always present in bile, and, indeed, form
very important constituents of that secretion ; they occur in the form of their
respective sodium salts, and not as uncombined acids, as the term "bile-acids"
might lead one to believe. In human bile both acids are usually found, but
the proportion of taurocholate is variable, and in some cases this latter acnd
may be absent altogether. Among herbivora the glycocholate predominates
as a rule, although there are some exceptions ; among the carnivora, on the
other hand, taurocholate occurs usually in greater quantities, and in the dog's
bile it is present alone. Glycocholic acid has the formula CggH^jNOg, and
taurocholic acid has the formula CaeH^^NSO^. Each of them can be obtained
in the form of crystals. When boiled with acids or alkalies these acids take
up water and undergo hydrolytic cleavage, the reaction being represented by
the following equations :

025H,3NO« + H,0 = C^^H^oO, -f CH,(NH3)C00H.

Glycocholic acid. Cholic acid. GlycocoU (amido-acetic acid).

Taurocholic acid. Cholic acid. Taurin (amido-ethyl-

sulphonic acid).

These reactions are interesting not only in that they throw light on the structure
of the acids, but also because similar reactions doubtless take place in the intes-
tine, cholic acid having been detected in the intestinal contents. As the for-
mulas show, cholic acid is formed in the decomposition of each acid, and we
may regard the bile-acids as compounds produced by the synthetic union of
cholic acid with glycocoll in the one case and with taurin in the other.
Cholic acid or its compounds, the bile-acids, are usually detected in suspected
' Archives de Physiologie normale et pathologique, 1892, p. 577.

264 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

liquids by tlic well-known Pettenkofer reaction. As usually ]>crfornie(l, ti)e
test is made by adding to the liquid a few drops of a 10 per cent, solution of
canc-su<z;ar and then strong sulj)huric acid. The latter must be added carefully
and the temperature be kept below 70° C. If bile-acids are present, the liquid
assumes a beautiful red-violet color. It is now known that the reaction con-
sists in the formation of a substance (furfurol) by the action of the acid on
sugar, which then reacts with the bile-acids. The bile-acids are formed
directly in the liver-cells. This fact, which was for a long time the subject of
discussion, has been demonstrated in recent years by an im])ortant series of
researches made upon birds. It has been shown that if the bile-duct is ligated
in these animals, the bile formed is reabsorbed and bile-acids and pigments
may be detected in the urine and the blood. If, however, the liver is com-
pletely extirpated, then no trace of either bile-acids or bile-pigments c^n be
found in the blood or the urine, showing that these substances are not
formed elsewhere in the body than in the liver. It is more difficult to ascer-
tain from what substances they are formed. The fact that glycocoU and
taurin contain nitrogen, and that the latter contains sulphur, indicates that
some proteid or albuminoid constituent is broken down during their })ro-
duction.

A circumstance of considerable physiological significance is that these acids
or their decomposition products are absorbed in part from the intestine and
are again secreted by the liver: as in the case of the pigments, there is an
intestinal-hepatic circulation. The value of this reabsorption may lie in the
fact that the bile-acids constitute a very efficient stimulus to the bile-secreting
activity of the cells, being one of the best of cholagogues, or it may be that it
economizes material. From what we know of the history of the bile-acids
it is evident that they are not to be considered as excreta : they have some
important function to fulfil. The following suggestions as to their value have
been made: In the first place, they serve as a menstruum for dissolving the
cholesterin which is constantly present in the bile and which is an excretion
to be removed ; secondly, they facilitate the absorption of fats from the intes-
tine. The value of bile in fat-absorption will ]>resently be referred to more
in detail. It is an undoubted fact that when bile is shut off from the intes-
tine the absorption of fats is very much diminished, and it has been shown
that this action of the bile is owing to the presence of the bile-acids. In what
way they act is unknown.

Cholesterin. — Cliolcsterin is a non-nitrogenous substance of the fornmla
CjgH^^O. It is a constant constituent of the bile, although it occurs in variable
quantities. Cholesterin is very widely distributed in the body, being found
especially in the white matter (medullary substance) of nerve-fibres. It seems,
moreover, to be a constant constituent of all animal and plant cells. It is
assumed that cholesterin is not formed in the liver, but that it is eliminated
by the liver-cells from the blood, which collects it from the various tissues of
the body. That it is an excretion is indicated by the fact that it is eliminated
unchanged in the feces. Cholesterin is insoluble in water or in dilute saline

CHEMISTRY OF DIGESTION AND NUTRITION. 265

liquids, aiul is held in solution in the bile by means of the bile-acids. We
must regard it as a waste product of cell-life, formed probably in minute
quantities, and excreted mainly throu<^li the liver. It is partly eliminated
throu;4h the skin, in the sebaceous and sweat secretions, and in the milk.

Lecithin, Fats, and Nucleo-albumin. — Lecithin also seems to be present,
generally in small quantities, in the cells of the various tissues, but it occure
especially in the white matter of uerve-tibres. It is probable, therefore, that,
so far as it is found in the bile, it represents a waste product formed iu
difiPerent parts of the body and eliminated through the bile. The special
importance, if any, of the small proportion of fats and fatty acids in the bile
is unknown. The ropy, mucilaginous character of bile is due to the presence
of a body formed in the bile-ducts and gall-bladder. This substance was
formerly designated as mucin, but it is now known that in ox-bile at least
it is not a true mucin, but is a nucleo-albumin (see Chemical section). Hani-
raarsten reports that in human bile some true mucin is found. Outside the
fact that it makes the bile viscous, this constituent is not known to possess
any especial ])hysiological significance.

General Physiological Importance of Bile. — The physiological value
of bile has been referred to in speaking of its several constituents, but it will
be convenient here to restate these facts and to add a few remarks of general
interest. Bile is of importance as an excretion iu that it removes from the
body waste products of metabolism, such as cholesterin, lecithin, and bile-
pigments. With reference to the pigments, there is evidence to show that a
part at least may be reabsorbed while passing through the intestine, and be
used again in some way in the body. The bile-acids represent end-products
of metabolism involving the proteids of the liver-cells, but they are undoubt-
edly reabsorbed in part, and cannot be regarded merely as excreta. As a
digestive secretion the most important function attributed to the bile is the
part it takes in the digestion of fats. In the first place, it aids in the splitting
of a part of the neutral fats and the subsequent emulsification of the re-
mainder (p. 246). More than this, bile aids materially in the absorption of the
emulsified fats. A number of observers have shown that when a permanent
biliary fistula is made, and the bile is thus prevented from reaching the intes-
tinal canal, a large proportion of the fat of the food escapes absorption and
is found in the feces. This property of the bile is known to depend upon
the bile-acids it contains, but how they act is not clearly understood. It was
formerly believed, on the basis of some experiments by Von Westinghausen,
that the bile-acids dissolve or mix with the fats and at the same time moisten
the mucous membrane, and for these reasons aid in bringing the fat into
immediate contact with the epithelial cells. It was stated, for instance,
that oil rises higher in capillary tubes moistened with bile than in similar
tubes moistened with water, and that oil will filter more readily through
paper moistened with bile than through paper wet with water. Groper,^ who
repeated these experiments, finds that they are erroneous. AYe must fall back,
1 Archil' fur Anatomie u. Physiologle (" Physiol. Abtheilung"), 1889, p. 505.

2C,Ct AX A.VKRICAy TEXT-IUJOK OF I'JI YSIOLOd V.

therefore, iipmi the ireiienil statiiiiciit that the Idle-acids stimulate the epithe-
lial eells to a i^reater activity in the al>s«»rj)tioii of" fat, or possibly accomplish
the same end In st^me more indirect way as yet undis<-overed. It was formerly
believe<l that bile is also of great im[)ortaiice in restraining the processes of
putrefaction in the intestine. It was asserted that bile is an efficient antiseptic,
and that this pi'operty comes into use normally in preventing excessive ])ntre-
ftiction. liacteriological experiments made by a niunber of observers have
shown, however, that bile itself has very feeble antiseptic ]>rojjerties, as is
indi<-ated by the fact that it ]>utrefies readily. The free bile-acids and cholalic
acid do have a direct retarding effect ujiou putrefactions outside the bodv ;
but this action is not very pronounced, and has not been demonstrated satis-
factorily for bile itself. It seems to be generally true that in eases of biliary
fistula the feces have a very fetid odor when meat and fat are taken in the
food. But the increased putrefaction in these cases may possibly be due to
some indirect result of the withdrawal of bile. It has been suggested, for
instance, that the deficient absorption of fiit which follows upon the removal
of the bile results in the proteid and carbohydrate material becoming coated
with an insoluble layer of fat, so that the penetration of the digestive enzymes
is retarded and greater opjiortunity is given for the action of bacteria. We
may conclude, therefore, that while there does not .seem to be sufficient warrant
at present for believing that the bile exerts a direct antiseptic action upon the
intestinal contents, nevertheless its presence limits in some way the extent of
putrefaction. Lastly, bile takes a direct part in suspending or destroying
peptic digestion in the acid chyme forced from the stomach into the duodenum.
The chyme meeting with bile and pancreatic juice is neutralized or is made
alkaline, which alone would ])revent further peptonization. Moreover, when
chyme and bile are mixed a ])recipitate occurs, consisting j)artly of })roteids
(proteoses and syntonin) and partly of bile-acids. It is probable that pepsin,
according to its well-known property, is thrown «lown in this floccnlent pre-
cipitate and, as it were, prepared for its destruction.

Glycogen. — One of the most important functions of the liver is the for-
mation of fjli/cof/en. This substance was found in the liver in 1857 by Claude
Bernard, and is one of several brilliant discoveries made by him. Glycogen has
the formula (C6Hio05)„, which is also the general formula given to vegetable
starch; glycogen is therefore frequently spoken of as "animal starch." It
gives, however, a port-wine-red color with iodine solutions, instead of the
familiar deep blue of vegetable starch, and this reaction serves to detect glyco-
gen not only in its solutions, but also in the liver-cells. Glycogen is readily
soluble in water, and the solutions have a characteristic opalescent appearance.
Like starch, glycogen is acted upon by amylolytic enzymes, and the end-
products are apparently the same — namely, maltose, or maltose and .some dex-
trin. For a more complete account of the chemical reactions of glycogen, and
for the methods of obtaining it from the liver, reference must be made to the
Chemical section.

Occurrence of Glycogen in the Liver. — Glycogen can be detected in

CHEMISTRY OF DIGESTION AND NUTJilTION. 207

tlu' liver-c'L'lls microscopically. If the liver of a dog is removed twelve or
fourteen hours after a hearty meal, hardened in alcohol, and sectioned, the
liver-cells will be found to contain clumj)s of clear material which give the
iodine reaction for glycogen. P]vcn when distinct aggregations of the glycogen
cannot be made out, its presence in the cells is shown by the red reaction with
iodine. By this siin])le method one can demonstrate the im])ortant fact that
the amount of glycogen in the liver increases after meals and decreases again
during the fasting hours, and if the fast is sufficiently prohmged it may dis-
appear altogether. This fact is, however, shown more satisfactorily by quanti-
tative determinations, by chemical means, of the total glycogen present. The
amount of glycogen present in the liver is quite variable, being influenced by
such conditions as the character and amount of the food, muscular exercise,
body-temperature, drugs, etc. From determinations made upon various
animals it may be said that the average amount lies between 1.5 and 4 per
cent, of the weight of the liver. But this amount may be increased greatly
by feeding upon a diet largely made up of carbohydrates. It is said that in
the dog the total amount of liver-glycogen may be I'aised to 17 per cent., and
in the rabbit to 27 per cent., by this means, while it is estimated for man
(Neumeister) that the quantity may be increased to at least 10 per cent. It
is usually believed that glycogen exists as such in the liver-cells, being depos-
ited in the substance of the cytoplasm. Reasons have been brought forward
recently to show that possibly this is not strictly true, but that the glycogen is
held in some sort of weak chemical combination. It has been shown, for
instance, that although glycogen is easily soluble in cold water, it cannot be
extracted readily from the liver-cells by this agent. One must use hot water,
salts of the heavy metals, and other similar means that may be supposed to
break up the combination in which the glycogen exists. For practical purposes,
however, we may speak of the glycogen as lying free in the liver-cells, just as
we speak of hfemoglobin existing as such in the red corpuscles, although it is
probably held in some sort of combination.

Orig-in of Glycogen. — To understand clearly the views held as to the
origin of liver glycogen, it will be necessary to describe briefly the effect of
the different food-stuffs upon its formation.

Effect of Carbohydrates on the Amount of Glycogen. — The amount of
glycogen in the liver is affected very quickly by the quantity of carbohydrates
in the food. If the carbohydrates are given in excess, the supply of glycogen
may be increased largely beyond the average amount present, as has been stated
above. Investigation of the different sugars has shown that dextrose, levulose,
saccharose (cane-sugar), and maltose are unquestionably direct glycogen -formers,
that is, that glycogen is formed directly from them or from the products into
which they are converted during digestion. Now, our studies in digestion have
shown that the starches are converted into maltose, or maltose and dextrin,
during digestion, and, further, that these substances are changed or inverted to
the simpler sugar dextrose during absorption. Cane-sugar, which forms such
an important part of our diet, is inverted in the intestine into dextrose and

268 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

levulose, and is absorbed in this loim. Jt is evident, therefore, that the hulk
of our carbohydrate food reaches tlie liver as dextrose, or as dextrose and
levulose, and these forms of sugar must be converted into glycoiren in the
liver-cells by a process of dehydration such as may be represented in substance
by the fonnula C,;H,^,Og — H/) = Cgll,/).,. In the case of levulose there is
reason to believe that it is changed first to dextrose in the liver before being
converted into glycogen. However that may be, there is no doubt that both
dextrose and levulose increase markedly the amount of glycogen in the liver ;
and, since cane-sugar is inverted in the intestine before absorption, it also must
be a good glycogen-former — a fact which has been abundantly demonstrated
by direct experiment. Lusk ^ has shown, however, that if cane-sugar is in-
jected under the skin, it has a very feeble effect in the way of increasing the
amount of glycogen in the liver, since under these conditions it is probably
absorbed into the blood without undergoing inversion. Experiments with sub-
cutaneous injection of lactose gave similar results, and it is generally believed
that the liver-cells cannot convert the double sugars to glycogen, at least not
readily ; hence the value of the inversion of these sugars in the alimentary
canal before absorption. The relations of lactose to glycogen-formation have
not been determined satisfactorily. If it contributes at all to the direct forma-
tion of glycogen, it is certainly less efficient than dextrose, levulose, or cane-
sugar. When the proportion of lactose in the diet is much increased, it quickly
begins to appear in the urine, showing that the limit of its consumption in the
body is soon reached. This latter fact is somewhat singular, since in infancy
especially milk-sugar forms a constant and important item of our diet, and
one would suppose that it is especially adapted to the needs of the body.

Efcd, of Proteids on Glycogen-formation. — It was pointed out by Bernard,
in his first studies upon glycogen-formation, that the liver can produce glycogen
from proteid food. This conclusion has since been verified by more exact
investigations. When an animal is fed upon a diet of proteid alone, or on
proteid and gelatin, the carbohydrates being entirely excluded, glycogen is still
formed in the liver, although in smaller amounts than in the case of carbohy-
drate foods. This is an important fact to remember in studying the metabo-
lism of the proteids in the body, for, as glycogen is a carbohydrate and con-
tains no nitrogen, it implies that the proteid molecule is dissociated into a
nitrogenous and a non-nitrogenous part, the latter being converted to glycogen
by the liver-cells. The possibility of the ju'oduction of glycogen from proteids
accords with a well-known fact in medical practice with reference to the path-
ological condition known as diahetcx. In this disease sugar is excreted in the
urine, sometimes in large quantities. As the sugar of the blood is formed
from the carbohydrates in the food, it was thought that by excluding this
food-stuff from the diet the excretion of sugar might be prevented. It has
been found, however, that in some cases at least sugar continues to be present
in the urine even upon a pure proteid diet. If we suppose that some of the
proteid goes to form glycogen, the result observed is explained, for the gly-

^ Voit: Zeitschrift fur Biologic, 1891, xxviii. p. 285.

CHEMISTRY OF DIGESTION AND NUTRITION. 269

cogeri, as will be explaiucd presently, is finally converted to sugar and is given

off to the blood.

Kfi'd of Fats and other Substance.^ upon Gli/coc/cn-formation. — It has been
found that fats take no part in the formation of liver glycogen. Glycerin
increases the amount of glycogen in the liver, but the evidence goes to show
that it is not a direct or an indirect glycogen-former. Glycerin seems to
prevent the reconversion of glycogen to sugar by the liver-cells, and thus
leads to an increased percentage of this substance in the liver.

The Function of Glycogen : Glycogenic Theory.— The meaning of the
formation of glycogen in the liver has been, and still is, the subject of discussion.
The view advanced first by Bernard is perhaps most generally accepted. Ac-
cording to Bernard, glycogen forms a temporary reserve supply of carbohydrate
material which is laid up in the liver during digestion and which is gradually
made use of in the intervals between meals. During digestion the carbohy-
drate food is absorbed into the blood of the portal system as dextrose or as
dextrose and levulose. If these passed through the liver unchanged, the con-
tents of the systemic blood in sugar would be increased perceptibly. It is now
known that when the percentage of sugar in the blood rises above a certain
low limit, the excess will be excreted through the kidney and will be lost.
But as the blood from the digestive organs passes through the liver the ex-
cess of sugar is abstracted from the blood by the liver-cells, is dehydrated to
make glycogen, and is retained in the cells in this form for a short period.
From time to time the glycogen is reconverted into sugar (dextrose) and is
given off to the blood. By this means the percentage of sugar in the systemic
blood is kept nearly constant (0.1 to 0.2 per cent.) and within limits best
adapted for the use of the tissues. The great importance of the formation of
glycogen and the consequent conservation of the sugar-supply of the tissues will
be more evident when we come to consider the nutritive value of carbohydrate
food. Carbohydrates form the bulk of our usual diet, and the proper regula-
tion of the supply to the tissues is therefore of vital importance in the main-
tenance of a normal healthy condition. The second part of this theory, which
holds that the glycogen is reconverted to dextrose, is supported by observations
upon livers removed from the body. It has been found that shortly after the
removal of the liver the supply of glycogen begins to disappear and a corre-
sponding increase in dextrose occurs. Within a comparatively short time all
the glycogen is gone and only dextrose is found. It is for this reason that in
the estimation of glycogen in the liver it is necessary to mince the organ and to
throw it into boiling water as quickly as possible, since by this means the liver-
cells are killed and the conversion of the glycogen is stopped. How the
glycogen is changed to dextrose by the liver is a matter not fully explained.
According to some, the conversion is due to an enzyme produced in the liver.
Extracts of liver, as of many other organs, do contain a certain amount of an
amylolvtic enzvme, but this enzvme changes glycogen to maltose, whereas in the
liver tiie glycogen is normally changed to dextrose. It is probable, therefore,
that the conversion of glycogen to dextrose is dependent directly upon the

270 AN AMEUK'AX TEXT- HOOK OF PlI YSlOLOiJ Y.

metabolic activity of tlic livcr-cclIs, and so loiif^ as these cells are in a living
conditiou they can effect this chanj^e. In this description of" the origin and
nicanini>; of the liver glycogen reference has been made only to the glvcogen
derived directly from digested cari)ohydrates. The glycogen derived from proteid
foods, once it is formed in the liver, has, of course, the same functions to fulfil.
It is converted into sugar, and eventually is oxidized in the tissues. For the
sake of comj)Ieteness it may be well to add that some of tht; sugar of the blood
formed from the glycogen may under certain conditions be converted into fat in
the adipose tissues, instead of being burnt, and in this way it may be retained
in the body as a reserve supply of food of a more stable character than is the
glycogen.

Glycogen in the Muscles and other Tissues. — The history of glycogen is
not conn)lete without some reference to its occurrence in the muscles. Glycogen
is, in fact, found in various places in the body, and is widely distributed through-
out the animal kingdom. It occurs, for example, in leucocytes, in the placenta,
in the rapidly-growing tissues of the embryo, and in considerable abundance in
the oyster and other molluscs. But in our bodies and in those of the mam-
mals generally the most significant occurrence of glycogen, outside of the liver,
is in the voluntary muscles, of which glycogen forms a normal (constituent. It
has been estimated that the percentage of glycogen in resting muscle varies
from 0.5 to 0.9 per cent., and that in the nmsculature of the whole body there
may be contained an amount of glycogen equal to that in the liver itself.
A])parently muscular tissue, as well as liver-tissue, has a glycogenetic func-
tion— that is, it is capable of laying up a supply of glycogen from the sugar
brought to it by the blood. The glycogenetic function of muscle has been
demonstrated recently by Kulz,^ who has shown that an isolated muscle irrigated
with an artificial supply of blood to which dextrose had been added is capable
of changing the dextrose to glycogen, as shown by the increase in the latter sub-
stance in the muscle after irrigation. Muscle glycogen is to be looked upon,
probably, for reasons to be mentioned in the next paragraph, as a temjxirary
and local reserve supply of material, so that, while we have in the liver a large
general depot for the temporary storage of glycogen for the use of the body at
large, the muscidar tissue, which is the most active tissue of the body from
a chemical standpoint, is also capable of laying up in the form of glycogen
any excess of sugar brought to it. The fact that glycogen occurs so widely in
the rapidly-growing tissues of embryos indicates that this glycogenetic func-
tion may at times be exercised by any tissue.

Conditions Affecting the Supply of Glycogen in Muscle and Liver. —
In accordance with the view given above of the general value of glycogen —
namely, that it is a temporary reserve supply of carbohydrate material which
may be rapidly converted to sugar and oxidized with the liberation of energy —
it is found that the sup])ly of glycogen is grei\tly affected by conditions calling
for increased oxidations in the body. Muscular exercise will (piicklv exhaust the
supply of nmselc and liver glycogen, provided it is not renewed by new food.
' Zeltschri/t fiir Biologie, 1890, p. 2'M.

CHEMISTRY OF DIGESTION AND NUTRITION. 271

111 :i .stiirvini;- animal <;lycogen will finally disappear, except })erliaps in traces,
but tins disappearance will occur much sooner if the animal is made to use its
nuisc-les at the same time. It has been shown also by Morat and Dufourt that
if a muscle has been made to contract vigorously, it will take up much more
suo-ar from an artificial supi)ly <»f l>lood sent through it than a similar muscle
which has been resting; on the other hand, it has been found that if the nerve
of one leg is cut so as to paralyze the muscles of that side of the body, the amount
of glycogen will increase rapidly in these muscles as compared with those of
the other leg, that have been contracting meantime and using up their glycogen.
Formation of Urea in the Liver. — The nitrogen contained in the proteid
material of our food is finally eliminated, after the metabolism of the proteid
is completed, mainly in the form of urea. As will be explained in another
part of this section, it has been definitively proved that the urea is not formed in
the kidneys, the organs which eliminate it. It has long been considered a
matter of the greatest importance to ascertain in what organ or tissues urea is
formed. Investigations have now gone so far as to demonstrate that it arises
chiefly in the liver, hence the property of forming urea must be added to the
other important functions of the liver-cell. Schroder ^ performed a number of
experiments in which the liver was taken from a freshly-killed dog and irri-
gated through its blood-vessels by a supply of blood obtained from another
dog. If the supply of blood was taken from a fasting animal, then circulating
it through the isolated liver was not accompanied by any increase in the amount
of urea contained in it. If, on the contrary, the blood was obtained from a
well-fed dog, the amount of urea contained in it was distinctly increased by
jiassing it through the liver, thus indicating that the blood of an animal after
digestion contains something which the liver can convert to urea. It is to be
noted, moreover, that this power is not possessed by the organs generally, since
blood from the well-fed animals showed no increase in urea after being circu-
lated through an isolated kidney or muscle. As further proof of the urea-
forming power of the liver Schroder found that if ammonium carbonate was
added to the blood circulating through the liver — to that from the fasting as
well as from the well-nourished animal — a very decided increase in the urea
always followed. It follows from the last experiment that the liver-cells are
able to convert carbonate of ammonia into urea. The reaction may be ex-
pressed by the equation (NH4)2C03 — 211,0 = CON2H4. Schondorff ^ in some
recent work has shown that if the blood of a fasting dog is irrigated through
the hind legs of a well-nourished animal, no increase in urea in the blood can
be detected ; but if the blood, after irrigation through the hind legs, is subse-
quently passed through the liver, a marked increase in urea results. Obviously,
the blood in this experiment derives something from the tissues of the leg
which the tissues themselves cannot convert to urea, but which the liver-cells
can. Finally, in some remarkable experiments upon dogs made by four in-
vestigators (Hahn, Massen, Nencki, and Pawlow), which will be described

^ Archivfiir experimentelle Pathologie und Phai-makologie, vols. xv. and xix., 1882 and 1885.
^ PJlUger's Archivfiir die gesammte Phi/siologie, 1893, vol. liv. p. 420.

272 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

briefly in tlic uext section in connection with urea, it was shown that when
the liver is practiaiUy destroyed there is a marked diminution in the urea
of the urine, its place being taken by carbamic acid. In birds uric acid takes
the place of urea as the main nitrogenous excretion of the body, and Minkowski
has shown that in them removal of the liver is followed by an important
diminution in the amount of uric acid excreted. From experiments such as these
it is safe to conclude that urea is formed in the liver and is then given to the
blood and excreted by the kidney. When we come to describe the physiological
history of urea (p. 274), an account will be given of the views held with regard
to the antecedent substance or substances from which the liver produces urea.
Physiology of the Spleen. — Much has been said and written about the
spleen, but we are yet in the dark as to the distinctive function or functions of
this organ. The few facts that are known may be stated briefly without going
into the details of theories which have been offered at one time or another.
The older experimenters demonstrated that this organ may be removed from
the body without serious injury to the animal. An increase in the size
of the lymph-glands and of the bone-marrow has been stated to occur after
extirpation ; but this is denied by others, and, whether true or not, it gives
but little clue to the normal functions of the spleen. Laudenbach* finds that
one result of the removal of the spleen is a marked diminution in the number
of red corpuscles and the quantity of haemoglobin. He infers, therefore, that the
spleen is normally concerned in some way in the formation of red corpuscles.
These facts are significant, but they need, perhaps, further confirmation. The
most definite facts known about the spleen are in connection with its move-
ments. It has been shown that there is a slow expansion and contraction of
the organ synchronous with the digestion periods. After a meal the spleen
begins to increase in size, reaching a maximum at about the fifth hour, and
then slowly returns to its. previous size. This movement, the meaning of -which
is not known, is probably due to a slow vaso-dilatation, together, perhaps, with
a relaxation of the tonic contraction of the musculature of the trabecule. In
addition to this slow nKjvement, Roy^ has shown that there is a rhythmic
contraction and relaxation of the organ, occurring in cats and dogs at intervals
of about one minute. Roy supposes that these contractions are eflected through
the intrinsic musculature of the organ — that is, the plain muscle-tissue present
in the capsule and trabecule — and he believes that the contractions serve to
keep up a circulation through the spleen and to make its vascular supply more
or less independent of variations in general arterial pressure. These observa-
tions are valuable as indicating the importance of the spleen functions. The
fact that there is a special local arrangement for maintaining its circulation
makes the spleen unique among the organs of the body, but no light is thrown
upon the nature of the function fulfilled. The spleen is supplied richly with
nerve-fibres which when stimulated either directly or reflexly cause the organ
to diminish in volume. According to Schaefer,'' these fibres are contained in

1 Ckniralblatt fur Physiologic, 1895, Bd. ix. S. 1. » Journal of Physiology, 1881, vol. iii. p. 203.
^ Proceedings of the Royal Society, London, 1896, vol. lix., No. 355.

CHEMISTRY OF DIGESTION AND NUTRITION. 273

the splanchnic nerves, which carry also inhibitory fibres whose stimulation pro-
duces a dilatation of the spleen.

The chemical composition of the spleen is complicated but suggestive. Its
mineral constituents are characterized by a large percentage of iron, which
seems to be present as an organic compound of some kind. Analysis shows
also the presence of a number of fatty acids, fats, cholesterin, and, what is
perhaps more noteworthy, a number of nitrogenous extractives such as
xanthin, hypoxanthin, adenin, guanin, and uric acid. The presence of
these bodies seems to indicate that active metabolic changes of some kind occur
in the spleen. As to tbe theories of the splenic functions, the following may be
mentioned : (1) The spleen has been supposed to give rise to new red corpuscles.
This it undoubtedly does during fetal life and shortly after birth, and in some
animals throughout life, but there is no reliable evidence that the function is
retained in adult life in man or in most of the mammals. (2) It has been
supposed to be an organ for the destruction of red corpuscles. This view is
founded partly on very unsatisfactory microscopic evidence according to which
certain large amoeboid cells in the spleen ingest and destroy the old red corpus-
cles, and partly upon the fact that the spleen-tissue seems to be rich in an iron-
containing compound. This theory cannot be considered at present as anything
more than a suggestion. (3) It has been suggested that uric acid is produced
in the spleen. This substance is found in the spleen, as stated above, and it has
been shown recently by Horbacewsky that the spleen contains a substance
from which uric acid or xanthin may readily be formed ; but further investiga-
tion has shown that the same substance is found in lymphoid tissue generally.
If, therefore, uric acid is produced in the spleen, it is a function of the large
amount of lymphoid tissue contained in it, and a function which it shares with
similar tissues in the rest of the body. The lymphoid tissue of the spleen must
also possess the property of producing lymphocytes, since, according to the gen-
eral view, these corpuscles are formed in lymphoid tissue generally wherever
the so-called " germ-centres " occur. (4) Lastly, a theory has been supported
by Schiff and Herzen, according to which the spleen produces something (an
enzyme) which, when carried in the blood to the pancreas, acts upon the tryp-
sinogen contained in this gland, converting it into trypsin. The experimental
evidence upon which this view rests has not been confirmed by other observers.

G. The Kidney and the Skin as Excretory Organs.

The secretion of the kidneys is the urine. The means by which this secre-
tion is produced, its relations to the histological structure of the kidney, and
its connections with the blood- and nerve-supply of that organ will be found
described in the section on Secretion. In this section will be discussed only
the chemical composition of urine, and especially the physiological significance
of its different constituents. The urine of man is a yellowish liquid varying
greatly in depth of color. It has an average specific gravity of 1020^and an
acid reaction. The acid reaction is noLdue to a free acid, but to an ackl salt,
the_acid phosphateof sodium (NaHaPOJ. Under certain normal conditions

18

274 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

human urine may show a neutral or even a slightly alkaline reaction, especially
after meals. In fact, the reaction of the urine seems to depend directly on the
character of the food. Among carnivorous animals the urine is uniformly
acid, and among herbivorous animals it is uniforndy alkaline, so long as
they are using a vegetable diet, but when starving or when living upon the
mother's milk — that is, whenever they are existing upon a purely animal diet —
the urine becomes acid. The exphmation, as given by Drechsel, is tliat upon
an animal diet more acids are produced (from the sulphur and phosphorus)
than the bases present can neutrali/x', whereius upon a vegetable diet carbonates
are formed from the oxidation of the organic acids of the food in (piantities
sufficient to neutralize the mineral acids. The chemical composition of urine is
very complex. Among the constituents constantly present under the conditions
of normal life we have, in addition tq_water_and inorgainc salts, the folhnving
substances: Urea^ uric acid; xanthin ; creatinin ; hippuric acid; the urinary
pigments (urobilin); sulphocyanides in traces; acetone; oxalic acid, probably
as Ciilcium oxalate ; several ethereal sulphuric acids, such as phenol and cresol
sulphuric acids, indoxyl sulphuric acid (indican), and skatoxyl sulphuric acid;
aromatic oxy-acid ; some combinations of glycuronic acid ; some representa-
tives of the fatty acids; and dissolved gases (N and CO^,). This list would be
very nmch extended if it attempted to take in all those substances occasion-
ally found in the urine. The complexity of the composition and the fact that
so many diflTerent organic compounds occur or may occur in small quantities
is readily understood when we consider the nature of the secretion. Through
the kidneys there are eliminated not only what we might call the normal £nd-
]3roducts_of the metabolism of the tissues, excluding the COg, but also, in
large part, the prgducts of decomposition in the alimentary canal^ the end-
products of many organic substances occurring in our foods and not usually
classed as food-stuffs, foreign sul)stances introduced as drugs, etc., all of which
are eliminated either in the form in which they are taken or as derivative
products of some kind. We shall speak briefly of the most important of the
normal constituents, dwelling especially upon their origin in the body and their
physiological significance. For details of chemical ])ropcrties, reactions, meth-
ods of ])reiiaration, etc. reference must be made to the Ciiemical section.

Urea. — Urea, which is given the formula CH^NgO, is usually considered
as an amide of carbonic acid, having therefore the structural formula of

CO<xTTT-- It occurs in the urine in relatively large quantities (2 per cent. +).

As the total quantitv of urine secreted in twenty-four hours by an adidt male
may be placed at from 1500 to 1700 cubic centimeters, it follows that from 30
to 34 grams of urea are eliminated from the body during this period It is
the most important of the nitrogenous excreta of the body, the end-product
of the physiological oxidation of the proteids of the body, and also of the
albuminoids when they appear in the food. If we know how much urea is
secreted in a given period, we know approximately how much proteid has
been broken down in the body in the same time. In round numbers, 1 gram

CHEMISTRY OF DIGESTION AND NUTRITION. 275

of proteid M-ill yield \ ^I'uin of urea, as may be calculated easily from the
amount of uitrogcn contained in each. Since, however, some of the nitrogen
of proteid is eliminated in other forms — uric acid, creatinin, etc. — even aa
exact determination of all the urea would not be sufficient to determine with
accuracy the total amount of proteid broken down. This fact is arrived at
more perfectly, as we shall explain later, by a determination of the total
nitrogen of the urine and other excretions. In addition to the urine, urea is
found in slight quantities in other secretions, in milk (in traces), and in sweat.
In the latter liquid the quantity of urea in twenty-four hours may be quite
appreciable — as much, for instance, as 0.8 gram — although such a large amount
is found only after active exercise. It has been ascertained definitely that urea
is not formed by the kidneys : it is brought to the kidneys in the blood for
elimination, the cells of the convoluted tubules being especially adapted for
taking up this material and transmitting it through their substance to the
lumen of the tubules. That urea is not made in the kidneys is demonstrated
by such facts as these : If blood, on the one hand, is irrigated through an
isolated kidney, no urea is formed, even though substances (such as ammonium
carbonate) from which urea is readily produced are added to the blood; on the
other hand, urea is constantly present in the blood (0.0348 to 0.1529 per cent.),
and if the two kidneys are removed, it continues to accumulate steadily in the
blood as long as the animal survives. It has been ascertained that the urea is
produced mainly in the liv^er; an account of some of the experiments demon-
strating this fact is given on page 271. The most important questions that
remain to be decided are. Through what steps is the proteid molecule metab-
olized to the form of urea? and, AVhat is the antecedent substance brought
to the liver, from which it makes urea? It is impossible to answer these
questions perfectly, but recent investigations have thrown a great deal of light
on the whole process, and they give hope that before long the entire historv
of the derivation of urea from proteids and albuminoids will be known. The
results of this work may be stated briefly as follows :

1. Urea arises from proteids by a process of hydrolysis and oxidation, with
the formation eventually of ammonia compounds, most probably the ammo-
nium salt of carbamic acid, which are then conveyed to the liver and there
changed to urea. The latter part of this theory — that the liver may produce
urea from carbamate of ammonia — rests upon solid experimental evidence, as
follows : In the first place, Drechsel found carbamic acid in the blood of dogs,
and Drechsel and Abel have shown that it occurs normally in the urine of
horses as calcium carbamate; and Abel has recently shown that it maybe
found in the urine of dogs or infants after the use of lime-water. Drechsel
has shown, further, that ammonium carbamate may be converted into urea.
If one compares the formulas of ammonium carbamate and urea, it is seen that
the former may pass over into the latter by the loss of a molecule of water, as —

Ammonium carbamate. Urea.

270 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Drechsel siippusc.-?, however, that this tlehydratiou is? ellected in an indirect
manner; that there is first an oxidation removing two atoms of hydrogen,
and then a i-eduetion removing an atom of oxygen. lie sueceeded in showing
that when an aqueous sohition of ammonium carbamate is submitted to elec-
trolysis, and the direction of the current is changed repeatedly so as to get
alternately reduction and oxidation processes at each pole, some urea will be
produced. These facts show the existence of ammonium carbamate in the
body, and the possibility of its conversion to urea. Recent exjterinients made
by Ilahn, Pawlow, Massen, and Xcncki ' show that in dogs removal of the
liver is followed by the appearance of carbamates in the urine and a marked
decrease in the amount of urea. In these remarkable experiments a fistula was
made between the portal vein and the inferior vena cava, the result of which
was that the whole portal circulation of the liver was abolisiied, and the only
blood that the organ received was through the hepatic artery. If, now, this
artery was ligated or the liver was cut away, as was done in some of the ex-
periments, then the result was practically an extirpation of the entire organ — an
operation which has always been thought to be impossible with mammals. The
animals in these investigations survived this operation for some time, but they
died finally, showing a series of symptoms wliich indicated a deep disturbance
of the nervous system. It was found that the symptoms of poisoning in these
animals could be bn)ught on before they developed spontaneously by feeding
the dogs upon a rich meat diet, or with salts of ammonia or carbamic acid. Later
investigations^ showed that in normal animals the ammonia contents of the
blood in the portal vein are from three to four times what is found in the arte-
rial blood, but that after the operation described the ammonia in the arterial
blood increases and at the time of the development of the fatal symptoms
reaches about the percentage which is normal to the blood of the portal vein.
It would seem from these investigations that the liver stands between the
portal circulation and the general systemic circulation and protects the latter
from the comparatively large amount of ammonia compounds contained in the
portal blood by converting these compounds to urea. If the liver is thrown
out of function, ammonia (ammonium carbamate) accumulates in the blood and
causes death. The rich amount of ammonia in iha portal blood seems to
come chiefly from the decomposition of proteid material in the glands of the
stomach and pancreas during secretion. Similar ammonia salts are probably
formed in other active })roteid tissues, since the percentage of ammonia in the
tissues is considerably greater than in the blood, and these compounds also are
doubtless converted to urea in the liver, in part at least. As to the origin of
the ammonium carbamate there is little direct evidence. It comes in the long
run, of course, from the nitrogenous food-stuffs, ])roteids and albuminoids.
Drechsel's supposition is that the proteids first undergo hydrolytic cleavage,
with the formation of amido- bodies such as Icucin, tyrosin, aspartic acid,
glycocoll, etc. ; that these bodies undergo oxidation in the tissues, with the

* Archivfur experimentelle Pathnkigie unci Pharmakologie, 1893, Bd. xxxii. S. 161.
« Mencki, Pawlow, and Zaleski : Ibid., 1895, Bd. xxxvii. S. 26.

CHEMISTR Y OF DIGESTION AND NUTRITION. 277

foriiiatioii of" NH3, COg, iind H/) ; and that tlie NII3 and CO2 then unite syn-
thetically to form ammonium carbamate, vvhieh is carried to the liver aud
changed to urea. There is reason to believe that this formation of ammonium
carbamate may take place in the tissues generally. The carbamate theory i.s
at least in accord with the facts so far as known, and it is more complete and
satisfactory than others which have been offered.

2. Even after the removal of the liver some urea is still found in the urine.
This fact proves that other organs are capable of producing urea, but what the
other organs are and by what process they make urea are points yet undeter-
mined. It seems probable that some of the ammonia compounds which are
now known to be formed in the tissues generally and to be given off to the
blood may be converted into urea elsewhere than in the liver. Just as the
glycogenic function of the liver-cells is shared to a less extent by other tis-
sues— e. g. the muscle-fibres — it is possible that their power of converting
ammonia salts to urea may be possessed to a lesser degree by other cells, and
for this reason removal of the liver is not followed at once by a fatal result.
Concerning this point, however, we must wait for further investigation.
Drechsel has recently called attention to a method of obtaining urea directly
from proteid outside of the body. His method is interesting not only
because it is the first laboratory method discovered of producing urea from
proteid, but also because it is possible that substantially the same process may
occur inside the body. The method consists, in brief, in first boiling the pro-
teid with an acid ; HCl was used, together with some metallic zinc, so as to
keep up a constant evolution of hydrogen and to exclude atmospheric oxygen.
Among the products of decomposition of the proteid thus produced was a
substance termed lysaUnin (CgHuNgO), and when this body was isolated and
treated with boiling baryta-water (Ba(OH)2) some urea was obtained. It is to
be noted that in this case the urea was obtained not by the oxidation of the
proteid, but by a series of decompositions or cleavages of the proteid molecule.
Now, lysatinin occurs also in the body as one of the products of the con-
tinued action of trypsin on proteids (seep. 241). It is possible, therefore, that
by further hydrolysis this substance, when it occurs, is converted to urea, and
that normally a part of the urea arises from proteids by this process.

Uric Acid and Xanthin Bodies. — Uric acid, which has the formula
C5H4N4O3, is found constantly, but in relatively small quantities, in human
urine and in the urine of mammals generally. The total quantity in the urine of
man under normal conditions varies from 0.2 to 1 gram every twenty-four hours.
In the urine of birds and reptiles it forms the chief nitrogenous constituent. In
these animals it takes the place physiologically of urea in mammalia in that it
represents the main end-product of the metabolism of the proteids in the body.
It is evident that at some point in the process the katabolism of the proteids in
mammalia differs from that in birds and reptiles, since in the one urea, and in
the other uric acid, is the outcome. Uric acid occurs in such small quantities
in mammals that its place of origin has not been investigated successfully. It has
been shown by Horbacewsky that in the lymphoid tissue generally, including

278 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the adenoid tissue of the spleen, tlierc is containe<l a substance which may he
re<j:;ard('il as the motlier-suhstanci' of uric acid. Tie ventures the hvjiothesis
that uric acid represents an end-product in the nietabolisni of leucocytes, but
the view at present can be regarded only as an interesting suggestion. Among
birds and reptiles it has been shown that the liver is the chief producer of uric
acid, just as it is of urea in nianiinals. Extirpation of the kidneys in birds
leads to an accumulation of uric acid in the blood and tissues, showing that the
kidneys do not produce the uric acid. Extirpation of the liver, on the contrary,
leads to a marked diminution in the uric acid of the urine, and it is noteworthy
that its place is taken by anunoniuni salts, probably aniiuonium lactate. This
would indicate that in these animals proteid metabolism leads in some way to
the formation of ammonium lactate, which is then carried to the liver and com-
bined synthetically to make uric acid before being excreted by the kidneys. It
is stated that in man also, in certain pathological conditions of the liver — for
example, acute yellow atrophy and phosphorus-poisoning — lactates are found in
the urine. Reasoning from analogy, we should suppose that in mammalia too
uric acid is formed iu the liver, but there is at present no positive evidence in
favor of this view. Although the quantity of uric acid ])roduced, or at least
eliminated, during a day is so small in the mammalia, it is needless to say that
the history of its formation, when completely known, will be of great import-
ance, not only in that it will throw additional light upon the metabolism of
the proteids in the body, and indeed upon the structure of the ])roteid molecule,
but also because of its bearing upon the nature of certain pathological con-
ditions ; for it has been found that in fever, in leucaemia, and possibly iu other
diseases, there is an increased production of uric acid. Several other nitrogenous
substances — xanthin, hypoxanthiu, guaniu, and adeniu — formiug members of
what is known as the xauthiu group, are closely related in composition to uric
acid. Some or all of these substances may occur in the urine, especially xanthin
and hypoxanthiu, whose formulas are respectively CjH^X^Og and CjII^N^O.
They are found only in minute quantities. To the extent that they occur they
represent so much proteid broken down in the body ; but what peculiarity in
metabolism leads to their formation rather than to that of uric acid, or indeed
urea, has not been discovered. They are found in greatest quantity in muscle,
and are present, therefore, in meat extracts. It is interesting in this connection
to call attention to the fact that theobromin (dimethyl-xanthin) and caifcin
(trimethyl-xanthin) are closely related to the xanthin bodies.

Creatinin. — Creatinin (C4H7N.5O) is a crystalline nitrogenous substance
constantly found in urine. It is closely related to creatin (CJIgNgOo), the two
substances differing by a molecule of water; the creatin changes to creatinin
upon heating with mineral acids. Creatinin occurs in urine to the extent
of about 1.12 grams per day in man. In dogs it has been found that
the amount may vary between 0.5 and 4.9 grams per day according to
the diet, an increase in the amount of meat in the diet causing an increase
in the creatinin. This is readily explained by the fact that creatin is a
constant constituent of muscle, and when taken into the stomach it is

CHEMISTRY OF DIGESTION AND NUTRITION. 279

eliminated in tlic urine as creatinin. It is evident, therefore, that part
of the creatinin of the urine is derived from tlie meat eaten, and does
not represent a metabolism within the hody. A part, however, comes
undoubtedly from the destruction of jn'oteid within the body. In this con-
nection the following facts are suggestive and worthy of consideration, although
they cannot be explained satisfactorily : The mass of protcid tissue in the body
is found in the muscles, and the end-product of the destructive metabolism of
proteid is supposed to be chiefly urea. Nevertheless, urea is not found in the
muscles, while creatin occurs in considerable quantities, as raucii as 90 grams
being contained in the body-musculature at any one time. Only a small
quantity (1.12 grams) of creatin is eliminated in the urine as creatinin during
a day. What becomes of the relatively large quantity of creatin in the mus-
cles? It has been suggested that it is one of the precursors of urea — that it
represents an end-product of the protcid destroyed in muscle whiclj is subse-
quently converted to urea in the liver or elsewhere. This supposition is sup-
ported by the fact that creatin may be decomposed readily in the laboratory,
with the formation of urea among other products. But against this theory
we have the important fact that creatin introduced into the blood is not con-
verted to urea, but is eliminated as creatinin.

Hippuric Acid, — This substance has the formula C9II9NO3. Its molecular
structure is known, since upon decomposition it yields benzoic acid and gly-
cocoll, and, moreover, it may be produced synthetically by the union of these
two substances. Hippuric acid may be described, therefore, as a benzoyl-amido-
acetic acid. It is found in considerable quantities in the urine of herbivorous
animals (1.5 to 2.5 per cent.), and in much smaller amounts in the urine of
man and of the carnivora. In human urine, on an average diet, about 0.7
gram is excreted in twenty-four hours. If, however, the diet is largely
vegetable, this amount may be increased greatly. These last facts are readily
explained. It has been found that if benzoic acid or related substances con-
taining this group are fed to animals, they appear in the urine as hippuric
acid. Evidently, a synthesis has taken place within the body, and Bunge and
Schmiedeberg proved conclusively that in dogs, and probably, therefore, in
man, the union of the benzoic acid to glycocoll occurs mainly in the kidney
itself. AVe can understand, therefore, why vegetable foods which are known to
contain substances belonging to the aromatic series and yielding benzoic acid
should increase the output of hippuric acid in the urine. Since, however, in
starving animals or in animals fed entirely on meat hippuric acid is still pres-
ent, although reduced in amount, it follows that it arises in part as one of the
results of body-metabolism. Among the various products of the breaking-
down of the proteid molecule, it is probable that some benzoic acid occurs,
and, if so, it is excreted in combination with glycocoll as hippuric acid. It
should be added, finally, that some of the hippuric acid is supposed to be de-
rived from the process of proteid putrefaction which occurs to a greater or
less extent in the large intestine.

Conjugated Sulphates. — A good part of the sulphur eliminated in the

280 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

urine is in the form of etliereal salts with organic compounds of the aromatic
and indigo series. Quite a number of these compounds have been described ;
the most imi)ortant are the compounds with phenol (CgHsOSCXOlI), eresol
(C;H,0.S020H), indol (CglleXOSOpH), and skatol (CgllgNOSO.OII).
These four substances, phenol, cresol, indol, and skatol, are formed in the in-
testine during the process of j)utrefaetive decomposition of the ])roteids (p. 249).
They are produced iu small quantities, and they may be excreted in part in
the feces, but in part they are absorbed into the blood. They are in them-
selves injurious substances, but in passing through the liver — which must of
necessity happen before they get into the general circulation — they are syn-
thetically combined with sulphuric acid, making the so-called *' conjugated sul-
phates," which arc harmless, and which are eventually excreted by the kidneys.

"Water and Inorganic Salts. — Water is lost from the body through three
main channels — namely, the liuigs, the skin, and the kidney, the last of these
being the most important. The quantity of water lost through the lungs
probably varies within small limits only. The quantity lost through the
sweat varies, of course, w'ith the temperature, with exercise, etc., and it may
be said that the amounts of water secreted through kidney and skin stand iu
something of an inverse proportion to each other; that is, the greater the
quantity lost through the skin, the less will be secreted by the kidneys.
Through these three organs, but mainly through the kidneys, the blood is
being continually depleted of water, and the loss must be made up by the
ingestion of new water. AVhen water is swallowed in excess the superfluous
amount is rapidly eliminated through the kidneys. The amount of water
secreted may be increased by the action of diuretics, such as potassium nitrate
and caifein, wdiich probably act directly upon the secretory cells in the
glomeruli.

The inorganic salts of urine consist chiefly of the chlorides, phosphates,
and sulphates of the alkalies and the alkaline earths. It may be said in gen-
eral that they arise partly from the salts ingested with the food, which salts
are eliminated from the blood by the kidney in the water-secretion, and in part
they are formed in the destructive metabolism which takes ])lace in the body,
particularly that involving the proteids and related bodies. Sodium chloride
occurs in the largest quantities, averaging about 15 grams per day, of which
the larger part, doubtless, is derived directly from the salt taken in the food.
The phosphates occur in combination Avith Ca and Mg, but chiefly as the acid
phosphates of Na or K. The acid reaction of the urine is caused by these
latter substances. The phosphates come in part from the destruction of phos-
phorus-containing tissues in the body, but chiefly from the ])hosphates of the
food. The sulphates of urine are found partly conjugated with organic sub-
stances, as described above, and partly as simple sulphates. The total quantity
of sulphuric acid eliminated is estimated to average about 2.5 grams per day.
Sulphur constitutes a constant element of the proteid molecule, and the quan-
tity of it eliminated in the urine may be used, as iu the case of nitrogen, to
determine the total destruction of proteid within a given period.

CHEMISTRY OF DIGESTION AND NUTRITION. 281

Functions of the Skin. — The pliy.siolu^ical activities of" the skin are
varied. It forms, iu the first place, a sensory surface covering the body, and
interposed, its it were, between the external world and the inner mechanism.
Nerve-fibres of pressure, temperature, and pain are distributed over its sur-
face, and by means of these fibres reflexes of various kinds are effected which
keep the body adapted to changes in its environment. The physiology of the
skin from this standj)oint is discussed in the section on Cutaneous Sensations.
Again, the skin plays a part of immense value to the body in regulating the
body-temperature. This regulation, which is effected by variations in the
blood-supply or the sweat-secretion, is described at appropriate places in the
sections on Animal Heat, Circulation, and Secretion. In the female, during
the period of lactation, the mammary glands, which must be reckoned among
the organs of the skin, form an important secretion, the milk ; the physiology
of this gland is described iu the sections on Secretion and Reproduction. In this
section we are concerned with the physiology of the skin from a different stand-
point— namely, as an excretory organ. The excretions of the skin are formed
in the sweat-glands and the sebaceous glands. The sweat-glands are distrib-
uted more or less thickly over the entire surface of the body, with the excep-
tion of the prepuce and glans penis, w hile the sebaceous glands, usually in con-
nection with the hairs, are also found everywhere except upon the palms of
the liands and the soles of the feet.

Sweat. — Sweat, or perspiration, which is the secretion of the sweat-glands,
is a colorless liquid with a peculiar odor and a salty taste. Its specific gravity
is given at 1004, and in man it usually has an acid reaction. As can readily be
understood, the quantity secreted in twenty-four hours varies greatly, the secre-
tion being influenced by variations in temperature, by exercise, and by psychical
and pathological conditions ; an average estimate places the daily secretion at
from 700 to 900 grams. Chemically, the secretion consists of water and inor-
ganic salts, traces of fats, fatty acid, cholesterin, and urea. Of the inorganic
salts, NaCl is by far the most abundant : it occurs in quantities varying from
2 to 3.5 parts per thousand. The elements of the sweat which are of import-
ance from an excretory standpoint are water, inorganic salts, and urea or related
nitrogenous compounds. As was said above, sweat constitutes the second in
importance of the three main channels through which water is lost from the
body. The quantity eliminated in the sweat is to a certain extent inversely
proportional to that secreted by the kidneys ; but the physiological value of
the secretion of water by the sweat-glands seems to lie not so much in the fact
that it is necessary in maintaining the water-equilibrium of the blood and tis-
sues as in the important part it takes in controlling the heat-loss from the skin :
the greater the evaporation of sweat, the greater the loss of heat. The urea is
described as occurring in traces. As far as it occurs, it represents, of course, so
much proteid destroyed, but usually in calculating the proteid loss of the body
this element has been neglected. Argutinsky demonstrated, however, that in
special cases — namely, during periods of unusual muscular work or after vapor-
baths— the total weight of nitrogen eliminated by the skin may be of consider-

282 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

able importance, amounting to as much as 0.7 to 0.8 gram. Under ordinary
circ'uni.stanoes the excretion of" urea and related conijjouuds tlir(>u<i;h the skin
must be regarded as of very sul)sidiary importance, but the amount may be
increased marketlly under pathological conditions.

Sebaceous Secretion. — The sebaceous secretion is an oily, semi-liquid
material, the (juantity ot" which cannot be estimated even approximately.
Chemically, it consists of water and salts, albumin and epithelium, liits and
fatty acids. Its excretory importance in connection with the metabolism of
the body must be slight. Its chief physiological value nnist be sought in
its etJ'ect upon the hairs, which are kept oiled and pliant by the secretion.
Moreover, it forms a thin, oily layer over most of the surface of the
skin ; and we may suppose that this layer of oil is of value in two
ways — in preventing too great a loss of water through the skin, and in
offering an obstacle to the absorption of aqueous solutions brought into
contact Mith the skin.

Excretion of COg. — In some of the lower animals — the frog, lor ex-
ample— the skin takes an important part in the respiratory exchanges, elim-
inating COg and absorbing O. In man, and presumably in the mammalia
generally, it has been ascertained that changes of this kind are very slight.
Estimates of the amount of COj given off from the skin of man during
twenty-four hours vary greatly, but the amount is small, and is certainly less
than one one-hundredth part of the amount given off through the lungs.

H. Body-metabolism ; Nutritive Value of the Food-stuffs.

Determination of Total Metabolism. — ^^'e have so far studied the
changes that the food-stuffs undergo during digestion, the form in which they
are absorbed into the blood, their history in the tissues to some extent, and the
final condition in which, after being decomposed in the body, they are eliminated
in the excreta. To ascertain the true nutritional value of the food-stuffs it
is of the utmost importance that we should have some means of estimating
accurately the kind and the amount of body-metabolism during a given period
in relation to the character of the diet used. Fortunately, this end may be
reached by a careful study of the excreta. The methods employed can readily
be understood in principle from a brief description. It has been made suf-
ficiently clear before this, perhaps, that by determining the total amount of the
nitrogenous excreta we can reckon back to the amount of proteid (or albu-
minoid) destroyed in the body. In the case of proteids or albuminoids which
undergo physiological oxidation all the nitrogen appears in the forms of urea,
uric acid, creatinin, xanthin, etc., which are eliminated mainly through the urine,
and may therefore be collected and determined. The following practical facts
are, however, to be borne in mind in this connection : The nitrogenous excre-
tion of the urine is mainly in the form of urea which can be estimated as such,
but it is much more accurate to determine the total nitrogen in the urine during
a given period, using some one of the approved methods for nitrogen-deter-
mination, and to calculate back from the amount of nitrogen to the amount of

CHEMISTRY OF DIGESTION AND NUTRITION. 283

proteid. By this means all the nitrogenous excreta which may occur in the
urine are allowed for ; and since the various proteids differ but little in the
amount of nitrogen which they contain, the average being from 15.5 to 16 per
cent., it is only necessary to nuilti])ly the total (quantity of nitrogen found in the
excretions by 6.25 (proteid molecule : N :: 100 : 16) to ascertain the amount of
proteid destroyed. In accurate calculations it is necessary to determine the total
nitrogen in the feces as well as in the urine, and for two reasons: first, in ordi-
nary diets a certain proportion of vegetable and animal proteid escapes digestion,
and this amount must be determined and deducted from the total proteid eateu
in order to ascertain what nitrogenous material has actually been taken into the
body; second, the secretions of the alimentary canal contain a certain quan-
tity of nitrogenous material, which represents a genuine excretion, and should
be included in estimates of the total proteid-destruction. Practical experience
has shown that in man about 29 per cent, of the total nitrogen of the feces has
this latter origin. The nitrogen eliminated as urea, etc, in the sweat, milk,
and saliva is neglected under ordinary circumstances because the amount is
too small to affect materially any calculations made. To determine the total
amount of non-nitrogenous material destroyed in the body during a given
period, two data are required : first, the total nitrogen in the excreta of the
body ; second, the total amount of carbon given off from the lungs and in the
various excreta. From the total nitrogen one calculates how much proteid was
destroyed, and, deducting from the total carbon the amount corresponding to
this quantity of proteid, what remains represents the carbon derived from the
metabolism of the non-nitrogenous material — that is, from the fat or carbo-
hydrate. By methods of this kind it is possible to reckon back from the
excreta to the total amount of material, consisting of proteid, fat, and carbo-
hydrate, which has been consumed in the body within a certain period. If, now,
by analyzing the food or by making use of analyses already made (see p. 216), one
determines how great a quantity of proteid, fat, and carbohydrate has been taken
into the body in the same period, then, by comparison of the total ingesta and
egesta, it is jwssible to strike a balance and to determine whether all the proteid,
fat, and carbohydrate of the food have been destroyed, or whether some of the
food has been stored in the body, and in this case whether it is nitrogenous or
non-nitrogenous material, or, lastly, whether some of the reserve material of
the body, nitrogenous or non-nitrogenous, has been destroyed in addition to
the supply of food. It is needless to remark that " balance experiments " of
this character are very laborious, particularly as they must be made over long
intervals — one or more days. Nevertheless, a great deal of work of this
kind has been done upon man as well as upon lower animals, especially by
Voit' and Pettenkofer. In the experiments upon man the urine and feces
were collected carefully and the total nitrogen was determined ; at the same time
the total quantity of COg given off from the lungs was estimated for the entire
period. The determination of the CO2 was made possible by keeping the man
in a specially-constructed chamber through which air was drawn by means of a
' Hermann's Handbuch der Physiologie, 1881, vol. vi.

284 J.V AMEIilCAX TEXT-liOOK OF PII YSJOLOd Y.

pump; tlie total quantity of air drawn through was indicated hy a gasometer,
and a measured j)ortion of this air was drawn off through a separate gasometer
and was analyzed for its CO^, It was found that the method is j)raeti('al)le : that
by the means described a nearly perfect balance may be struck between the income
and the outgo of the body. Experiments of this general character have been
used to determine the fate of tlie food-stuffs in the body under different con-
ditions, the essential part that each food-stuff takes in general nutrition, and
so on. In this and the succeeding sections we shall have to consider some of
the main results obtained ; but first it will be convenient to define two terras
frequently used in this connection — namely, "nitrogen equilibrium" and
''carbon equilibrium."

Nitrogen Equilibrium. — By "nitrogen equilibrium" we mean that condition
of an animal in which, within a definite period, the nitrogen of the excreta is
equal in amount to the nitrogen of the food ; in other words, that condition
in which the proteid (and albuminoid) food eaten exactly covers the loss of
proteid (and albuminoid) in the body during the same time. If an animal
is giving off more nitrogen in its excreta than it receives in its food, then
the animal must be losing proteid from its body ; if, on the contrary, the food
that it eats contains more nitrogen than is found in the excreta, the animal nmst
be storing proteid in its body. The condition of nitrogen ecpiilibrium is the
normal state of a properly-nourished adult. It is important to remember that
nitrogen equilibrium may be maintained at different levels; that is, one may
begin with a starving animal and slowly increase the amount of nitrogenous food
until nitrogen equilibrium is just established. If now the amount of nitrog-
enous food is increased — say doubled — the excess does not, of course, continue
to be stored up in the animal's body ; on the contrary, in a short time the
amount of proteid destroyed in the body will be increased to such an extent
that nitrogen equilibrium will again be established at a higher level, the animal
in this case eating more and destroying more. The highest limit at which nitro-
gen equilibrium can be maintained is determined, apparently, by the power
of the stomach and the intestines to digest and absorb proteid food. Further
details upon this point will be given presently, in describing the nutritive
value of the food-stuffs.

Carbon Equilibrium. — The term " carbon equilibrium " is sometimes used
to describe the condition in which the total carbon of the excreta (occurring in
the CO,, urea, etc.) is exactly covered by the carbon of the food. As one can
readily understand, an animal might be in a condition of nitrogen equilibrium
and yet be losing or be gaining in weight, since, although the consumption of
proteids in the body might just be covered by the proteids of the food, the
consumption of nou-proteids, fats and glycogen, might be greater or less than
was covered by the supply of food. In addition, we might speak of ixn equi-
librium as regards the water, salts, etc., although these terms are not generally
used. An adult in good health usually so lives as to keep in both nitrogen
and general body equilibrium — that is, to maintain his normal weight — while
slight variations in w^eight from time to time are probably for the most part

CHE3IISTRY OF DIGESTION AND NUTRITION. 285

due to a loss or a gain in boily-lat — in otiier words, to changes in the carbon
equilibrium.

Nutritive Importance of the Proteids. — Tlie (Hgestion and absorp-
tion of proteids liave been considered in previous sections. We believe that
the digested proteid is absorbed into the blood in a slightly modified form, with
the exception of the variable quantity which suffers decomposition into the
simpler amido- compounds while in the intestine as a result of putrefaction or of
the prolonged action of trypsin. Subsequently this proteid material parses into
the lymph and is brought into contact with the tissues. Its main nutritive
importance lies in its relations to the tissues, and, speaking generally, we
may say that the final fate of the proteid molecule is that it undergoes a ])hys-
iological oxidation whereby the complex molecule is broken down to form
the simpler and more stable compounds COg, H/), and urea. This destruction
of the proteid molectde takes place in or under the influence of the living cells,
and it gives rise to a liberation of energy mainly in the form of heat. It is
impossible to follow the various ways in which this physiological oxidation
takes place. It is probable, however, that some of the proteid undergoes de-
struction without ever becoming a part, an organized part, of the living cells,
although its oxidation is effected through the agency of the cells. It has been
proposed by Voit ^ to designate the proteid which is oxidized in this way as
" the circulating albumin or proteid." According to Voit, a well-fed animal
has in its lymph and tissues always a certain excess of proteid which is to
undergo the fate of the circulating proteid, and this supposition is used to
explain the fact that for the first day or so a starving animal metabolizes
more proteid, as determined by the nitrogenous excreta, than in the subse-
quent days, after the supply of the circulating proteid has been destroyed.
A portion of the proteid food, however, before its final destruction is utilized
to replace the nitrogenous waste of the tissues; it is built up into living proto-
plasm to supply the place of organized tissue which has undergone disassimi-
lation or to furnish new tissue in growing animals. To the proteid which is
built up into tissue Voit gives the name of " organeiweiss," the best translation
of which, perhaps, is " tissue-proteid." It should be stated that this division
of the proteid into circulating proteid and tissue-proteid has been severely
criticised by some physiologists, but it has the merit at least of furnishing
a simple explanation of some curious facts with regard to the use of proteid
in the body. To avoid misunderstanding, it is well to say that the sepa-
ration into circulating proteids and tissue-proteids does not mean that the
proteid which is absorbed from the alimentary canal is of two varieties.
The terms refer to the final fate of the proteid in the body: a certain
portion is utilized to replace protoplasmic tissue, and it then becomes "tis-
sue-proteid," while the balance is metabolized in various ways and con-
stitutes the "circulating proteid." Any given molecule of proteid, as far
as is known, may fulfil either function. With regard to the general nutri-
tive value of proteids, it has been demonstrated clearly that they are abso-

* Hernmnn's Handbuch der Physiologic, 1881, vol. vi. p. 300,

286 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

lutely neces.-^arv for the fonimtion of protoplasmic tissue. An animal fed only
on non-nitrogenous food such as fats and carbohydrates will inevitably starve
to death in time : this has been shown by actual experiments, and, besides, it
follows from a priori considerations. Protoplasm contains nitrogen; fats and
carbohydrates are non-nitrogenous, and therefore cannot be used to make new
protoplasmic material. It is requisite, moreover, not only that the food shall
contain some nitrogen, but that this nitrogen shall be in the form of proteid.
If an animal is fed upon a diet containing fats and carbohydrates and nitrog-
enous material other than proteids, such as amido-acids or gelatin, nitrogenous
equilibrium cannot be maintained. There will be a steady loss of nitrogen in
the excreta, due to a breaking-down of proteid tissue within the body, and the
final result of maintaining such a diet would be the death of the animal. It
may be said, then, with certainty of animal metabolism that jiroteid food is ai)So-
lutely necessary for the formation of new protoplasm ; its place in this respect
cannot be taken by any other element of our food. But, in addition to this use,
proteid, as has been described above, may be oxidized in the body without being
first constructed into protoplasmic material. According to an older theory in
physiology, advanced by Liebig, food-stuffs were either plastic or respirator}' ;
by plastic foods he meant those which were built into tissue, and he sup-
posed that the proteids belonged to this class ; by respiratory foods he meant
those which were oxidized or burnt in the body to produce heat : the fats and
carbohydrates constituted this class. We now know that proteids are respi-
ratory as well as plastic in the terms of this theory ; they serve as sources of
energy as well as to replace tissue, and Liebig's classification has therefore
fallen into disuse. Our present ideas of the twofold use of proteid food may
be supported by many observations and experiments, but perhajis the most
striking proof of the correctness of these views is found in the flict that a car-
nivorous animal can be kept in both nitrogen and carbon equilibrium upon a
meat diet only, excluding for the time a consideration of the water and iiKirganic
salts. Pettenkofer and Voit kept a dog weighing 30 kilograms in nitrogen
and carbon equilibrium upon a diet of 1500 grams of lean meat per day, and
by increasing the diet to 2500 grams per day the animal even gained in weight,
owing to an increase in fat. Pfliiger states also that he was able to keep a dog
in body-equilibrium as long as eight months upon a meat diet. Facts like
these demonstrate that the animal organism may get all its necessary energy
from proteid food alone, although, as we shall see later, it is more econom-
ical and more beneficial to get a part of it at least from the oxidation of
fats and carbohydrates. Adopting the theory of "circulating proteids," we
may say that any excess of proteid al)ove that utilized for tissue-repair
or tissue-growth will be metabolized in the body, with the liberation of
energy. It makes no difference how much proteid material we consume :
the excess beyond that used to replace tissue is quickly destroyed in some
way, and its nitrogen appeal's in the urine as urea or one of the related
compounds. A good example of the power of the tissues to oxidize large
amounts of proteid is given in the following experiment, selected from a

CHEMISTRY OF DIGESTION AND NUTRITION. 287

paper by Pfliiger. Dog, weight 28.1 kilograms, fed at 11 A. m. with 2070.7
grams of meat :

2070.7 grams of meat contain 69.2 grams N.

Total nitrogen eliminated in urine and feces in twenty-four

hours (7 A. M. to 7 A. M.) 71.2 " "

Deficit of N 0.9(] grams.

The total nitrogen in the urine alone was 68.5 grams.

In urine from 7 A.M. to 11 A.M., the fasting period 6.9 grams.

In urine from 11 A. M. to 7 A. M., time after feeding 61.6 "

Therefore in the four liours of fasting the animal eliminated in his urine
1.7 grams N per hour, while in the twenty hours after eating he excreted
3.1 grams N per hour. This experiment shows not only the completeness
with which an exce.?sive proteid diet is handled by the tissues, but also the
rapidity with which the excess is destroyed. In so far as proteid food is burnt
in the body onlv as a source of energy and without being used to form new tis-
sue, its place can be supplied in part, but only in part, by non-nitrogenous food-
stuffs— carbohydrates and fats. The double use of proteid as a tissue-former and
an energy-producer would seem to imply that if, in any given case, sufficient pro-
teid were used in the diet to cover the tissue-waste, the balance of the diet might
be composed of fats and carbohydrates, and the animal thereby be kept in nitrog-
enous equilibrium. Apparently this is not the case, as is seen from experiments
of the following character : When an animal is allowed to starve, the nitrogen in
the urine, after the first few days, becomes practically constant, and represents
the amount of oxidation of proteid tissue taking place in the body. If, now, the
animal is given an amount of proteid just equal to that being destroyed in the
body, nitrogenous equilibrium is not established ; some of the body-proteid con-
tinues to be lost, and to get the animal into equilibrium a comparatively large
excess of proteid must be given in the food. The same result holds if carbo-
hydrates and fats are given along with the proteid, with the exception that upon
this diet nitrogen equilibrium is more readily established — that is, less proteid
is required in the food. Upon the theory of circulating proteids and tissue-
proteids, this fact may be accounted for by saying that of the proteid given as
food, a part always undergoes destruction as circulating proteid without going
to form tissue, so that to cover tissue-waste a larger amount of proteid must be
taken as food than would be necessary if it could all be used exclusively for the
repair of tissue. Carbohydrates and fats diminish the amount of proteid
destroyed as circulating proteid, and thereby enable us to keep in nitrogen
equilibrium on a smaller proteid diet. With albuminoid food (gelatin) the
facts seem to be different. If albuminoids be given in the food together with
proteids or with proteids and a non-nitrogenous food-stuff (fats or carbo-
hydrates), nitrogen equilibrium may be established upon a much smaller
amount of proteid than in the case of a diet consisting of proteid alone or of
proteid together with fats and carbohydrates. It seems probable that albu-
minoids can take the place entirely of circulating proteids, so that only enough

288 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

proteid need be given to cover actual tissue-waste. 'J'liis point will he referred
to again in speaking of the value of the albuminoids.

Luxua Consumption. — The fact that normally more proteid is eaten, even
in a mixed diet, than is necessary to cover the actual tissue-waste led some of
the older physiologists to speak of the excess as unnecessary, a luxus, and the
rapid destruction of the excess in the body was described as a " luxus con-
sumption." There can be no doubt about the fact that proteid may be, and
normally is, eaten in excess of what is necessary to repair tissue-waste, c^r in
excess of what is requisite to maintain nitrogenous equilibrium at a low
level. But it is altogether improbable that the excess is really a "luxus."
It has been stated, in speaking of nitrogenous equilibrium, that an animal
may be kept in this condition upon a certain minimal amount of pro-
teid, or upon various larger amounts up to the limit of the power of the
alimentary canal to digest and absorb ; but it has also been shown (Munk')
that if an animal is fed upon a diet containing quantities of proteid barely
sufficient to maintain N equilibrium, it will after a time show signs of mal-
nutrition. It seems to be necessary, as Pfliiger pointed out, that the tissues
should have a certain excess of proteid to destroy in order that their nutri-
tional or metabolic powers may be kept in a condition of normal activity.
Hence we find that well-nourished individuals habitually consume more j)roteid
than would theoretically suffice for N equilibrium. For example, the average
diet of an adult contains, or should contain, from 100 to 118 grams of })roteid
per day, but it has been shown that nitrogen and body equilibrium in man
may be maintained, for short periods at least, upon 40 grams of proteid a day,
provided large amounts of fats or carbohydrates are eaten. It is scarcely neces-
sary to add that this beneficial excess has a limit, and that too great an excess
of proteid food may cause troubles of digestion as well as of general nutrition.

Nutritive Value of Albuminoids. — The albuminoid most frequently oc-
curring in food is gelatin. It is derived from collagen of the connective
tissues. Collagen of bones or of connective tissue takes up water when boiled
and becomes converted into gelatin. We eat gelatin, therefore, in boiled meats,
soups, etc., and, besides, it is frequently employed directly as a food in the
form of table-gelatin. Collagen has the following percentage comj)osition :
C, 50.75 per cent. ; H, 6.47 ; N, 17.86 ; O, 24.32 ; S, 0.6. It resembles the
proteid molecule closely in chemical composition, and it would seem that the
tissues might use it as they do proteid, for the formation of new protoi)lasm.
Experiments, however, have demonstrated clearly that this is not the case.
Animals fed upon albuminoids together with fats and carbohydrates do not
maintain N equilibrium ; a certain proportion of tissue breaks down, giving
an excess of nitrogen in the urine. The final result of such a diet would be
continued loss of weight and, finally, malnutrition and death. Gelatin, how-
ever, is readily digested, gelatoses and gelatin ])eptones being formed ; these
are absorbed and oxidized in the body, with the formation of CO^, HjO, and
urea or some related nitrogenous product. Gelatin serves, then, as a source
* DuBois-Reymond's Archiv fur Physioloc/ie, 1891, p. 338.

Nourishment (grams)

Meat.

Gelatin. Fat.

400

— 200

400

— —

400

200 —

CHEMISTRY OF DIGESTION AND NUTRITION. 289

of energy to the body in the same sense as do carbohydrates and fats. When
any one of these three substances is used in a diet, the proportion of proteid
necessary for the maintenance of N equilibrium may be reduced greatly. Upon
the theory of circulating proteids, this is explained by saying that these sub-
stances are burnt in place of proteid, and that the proportion of this latter
material which undergoes the fate of circulating proteid is thereby diminished.
Actual experiments have shown that gelatin is more efficacious than either fats
or carbohydrates in protecting the proteid in the body, and it has been sug-
gested, therefore, that it may take the place, partly or completely, of the circu-
lating proteid, according to the amount fed. If this suggestion is true, we
may say that gelatin has a nutritive value the same as that of the proteids,
except that it cannot be constructed into living proteid. The relative value
of fats, carbt)liyd rates, and gelatin in protecting proteid from destruction in
the body is illustrated by tKe following experiment, reported by Voit. A dog
weighing 32 kilograms was fed alternately upon proteid and sugar, proteid
and fat, and proteid and gelatin :

Calculated destruction of flesh
Sugar. in body (grams).

— 450
250 439

— 356

Muuk ^ has attempted recently to determine how far the proteids of food mav
be replaced by gelatin. In these experiments a dog was brought into a condi-
tion of nitrogenous equilibrium upon a diet of flesh-meal, rice, and lard, con-
taining 9.73 grams of nitrogen. During the period this diet was continued the
animal, whose weight was 16.5 kilograms, was oxidizing in its body 3.7 grams
of proteid daily for each kilogram of weight. In a second period lasting four
days the quantities of rice and lard were the same as before, but the proteid in
its diet was reduced to 8.2 grams, which contained 1 gram of nitrogen ; the
balance of the nitrogen was supplied in the form of gelatin, so that in round
numbers only one-sixth of the required daily amount of nitrogen was given
as proteid. The result was that the animal maintained its nitrogen equilib-
rium for the short period stated. It was found that the experiments could
not be continued longer than four days, owing to the growing dislike of the
animal for the gelatin food. During the second period the animal was receiving
in its food and burning in its body only 0.5 gram of proteid daily for each
kilogram of weight, as against 3.7 grams upon a normal diet. It would not
be possible to substitute fats or carbohydrates for the proteids of the daily diet
to anything like the same extent without causing a consumption of some of the
store of proteid material within the body.

Nutritive Value of Fats. — The fats of food are absorbed into the lacteals
as neutral fats. They eventually reach the blood in tiiis condition, and are
afterward in some way consumed by the tissues. The final products of their
oxidation must be the same as when burnt outside the body — namely, COg

* Pfluger^s Archivfiir die gesammfe Physiologie, 1894, vol. Iviii. p. 309.
19

20O ^.V AMERICAX TEXT-BOOK' OF PHYSIOLOGY.

and HjO — and a corresjwnding amount of energy must be liberated. Speak-
ino; (yiMierally, then, the essential nutritive value of the fats is that they furnish
enerijy to tiie biHly, and, from a chemical standpoint, they must contain more
available energy, weight for weight, than the proteids or the carbohydrates
(st^e p. 303). In a well-nourished animal a large amount of fat is found
normally in the adipose tissues, particularly in the so-called " paimiculus
adiposus" beneath the skin. Physiologically, this body-fat is to be regarded
as a reserve suj^ply of nourishment. AMien food is eaten and absorbed in
excess of the actual metiibolic power of the body, the excess is stored in the
adipose tissue as fat, to be drawn upon in case of need — as, for instance,
during partial or complete starvation. A starving animal, afler its small
supply of glycogen is exhaustal, lives entirely upon iKxly-proteids and fats;
the larger the supply of fat, tiie more effectively will the proteid tissues be
protected from destruction. In accordance with this fact, it has been shown
that when subjected to complete starvation a fat animal will survive longer
than a lean one. Our supply of fat is called upon not only during complete
abstention from food, but also whenever the diet is insufficient to cover the
oxidations of the body, as in deficient food, sickness, etc.

Formation of Fat in the Body. — The origin of body-fat has always been
an interesting problem to physiologists. Naturally, the first supposition made
was that it comes directly from the fat of the food. According to this view,
a certain proportion of the fat of the food was su])posed to be deposited directly
in the cells of adipose tissue, and in this way all our supply of fat originated.
This theory was soon disproved. It was shown, especially upon cows and pigs,
that the amount of fat formed in the body within a given time, including the
fat of milk in the case of the cow, might be far in excess of the total amoiuit
of fat taken in the food during the same period, thus demonstrating that a cer-
tain proportion at least of the body-fat must have some other origin. More-
over, the genesis of the fat-droplets in fat-cells, as studied under the microscojie,
did not agree with the old view ; and there was the further fact that each animal
has its own peculiar kind of fat ; as Liebig says, " In hay or the other fodder
of oxen no beef-suet exists, and no hog's lard can be found in the potato refuse
given to swine." In fact, the evidence was so conclusive against this theory that
physiologists for a time were led to adopt the opposite view that no fat at all can
be obtained directly from the fot of the food. However, it has now been shown
that under certain conditions fat may be deposited directly in the tissues from
the fat of food. Lebedeff, and afterward Munk, proved that if a dog is first
starved until the reserve supply of fat in the body is practically used up, and
it is then fed richly upon foreign fats, such as rape-seed oil, linseed oil, or
mutton tallow, it will again lay on fat, and some of the foreign fat may be
detected in its body. The conditions necessary to be fulfilled in order to get
this result make it probable that under normal conditions none of the fat of
the body is derived directly from the fat of the food. On the contrary, tiie
fat of the foot] is completely oxidized, and our body-fat is normally con-
structed anew from either proteids or carbohydrates. As to its origin from

CHEMISTRY OF DIGESTION AND NUTRITION. 291

proteid, Voit has devoted Duinerou.s researches to tlie purpose of demon-
strating that this is the main source of body-fat. His belief is that in the
course of metabolism the proteid molecule undergoes a cleavage, with the for-
mation of a nitrogenous and a non-nitrogenous part. The former, after further
changes, is eliminated in the form of urea, etc. ; the latter may be converted
into fat, or possibly into glycogen. The theoretical maximum of fat which
can arise in this way is 51.5 per cent, of the entire amount of proteid. Voit
attempted to demonstrate this theory by actual experiments. He showed that
dogs fed upon large amounts of lean meat did not give off as much carbon in
the excreta as they received in the food. The excess of carbon must have been
retained in the body, and, in all probability, in the form of fat. As corrob-
orative evidence he cites the ajiparently direct conversion of proteid material
into fat in such cases as the formation of fat-droplets in the fat-cells or cells
of the mammary glands, and in muscle-fibres and liver-cells undergoing fatty
degeneration ; but evidence of this latter character is not conclusive, since we
have no immediate proof that the fat arises directly from the proteid material
in the cells. Voit's experimental evidence has been questioned recently by
Pfliiger, his criticisms being directed mainly toward the calculations involved
in Voit's experiments. The result of this criticism has been to make us more
cautious in attributing the origin of body-fat solely or mainly to ])roteids, but
as regards the possibility of some proteid being converted into fat in the body
there can be no reasonable doubt. It has been proved (p. 268) that glycogen
may be formed from proteid, and since it is now generally accepted that fats
are formed from carbohydrates, the possibility of an indirect production of fats
from proteids seems to follow necessarily.

The connection between the carbohydrates of the food and the fat of the
body has been a subject of discussion and investigation among physiologists
for a number of years. It was the original belief of Liebig that carbohydrates
are the source of body-fat. This view was afterward abandoned under the
influence of the work of Pettenkofer and Voit, but renewed investigations seem
to have re-established it upon solid experimental grounds. In some older
experiments of Lawes and Gilbert it was shown that the fat laid on by a young
pig during a certain period was greater than could be accounted for by the
total fat in the food during that period, plus the theoretical maximum obtain-
able from the proteid fed during the same time. Of more recent experiments
demonstrating the same point, a single example may be quoted from Rubner,*
as follows : A small dog, weighing 6.2 kilograms, was fed richly with meat for
two days and Avas then starved for two days ; its w^eight at the end of this time
was 5.89 kilograms. The animal was then given for two days a diet of cane-
sugar 100 grams, starch 85 grams, and fat 4.7 grams. It was kept in a respira-
tion apparatus and its total excretion of nitrogen and carbon was determined :

Total C excretion 87.10 grams C.

" C ingesta 176.fi " "

89.5 " " retained in the body.

1 Zeitschri/tfur Biologie, 1886, vol. 22, p. 272.

292 AN A^^ERICAN TEXT-BOOK OF PHYSIOLOOY.

The total nitrogen excreted ^ 2.55 grams. Tlie oarboii contained in the pro-
teid thus broken down plus that in the 4.7 grains of fat = 13 grams. If we
make the assumption tiiat all of the V from these two sources was retained
within the body, there would still be a balance of 76.5 grams C (89.5 — 13.0)
whicii must have been stored in the body either as glycogen or as fat. The
greatest possible storage of glycogen was estimated at 78 grams = 34.6 grams
C, so that 76.5 — 34.6 = 41.9 grams C as tiie minimal amount which must
have been retained as fat and must have arisen from the carbohydrates of the
food. Similar experiments have been made upon herl)ivorous animals, and
as the result of investigations of this character we are compelled to admit that
the carbohydrates form one source, and possibly the main source, from which
the body -fats are derived. This belief accords with the well-known fact that
in fattening stock tlic best diet is one containing a large amount of carbo-
hydrate together with a certain quantity of proteid. On the view that fats
were formed only from proteids, the efficacy of the carbohydrates in such a diet
was supposed to lie in the fact that they protected a part of the proteid from
oxidation, and thus permitted the forn)ation of fat from proteid ; but it is now
believed that the carbohydrates of a fattening diet are, in part, converted
directly to fat, although the chemistry of the transformation is not as yet
understood. Diets, such as the well-known Banting diet, intended to reduce
obesity are characterized, on the contrary, by a small proportion of carbo-
hydrates and a relative excess of proteid.

Nutritive Value of Carbohydrates. — The nutritive importance of the
carbohydrates is similar in general to that of the fats; they are oxidized and
furnish energy to the body. In addition, as has been described in the pre-
ceding paragraph, they may be converted into fat and stored in the body as
a reserve supply of nourishment. As a matter of fact, the carbohydrates form
the bulk of ordinary diets. They are easily digested, easily oxidized in the
body, and from a financial standpoint they form the cheapest food-stuff. The
final products in the physiological oxidation of carbohydrates must be COj and
H.,0. Inasmuch as the H and O in the molecide already exist in the proper
proportions to form Wf) (CgHjoOg, C^J^^fi^^), it follows that relatively less oxy-
gen will be needed in the coml)ustion < »f carbohydrates than in the case of proteids
or of fats. Whatever may be the actual process of oxidation, we may consider that
only as much O is needed as will suffice to oxidize the C of the sugar to COj.

Hence the ratio of O absorbed to CO^ eliminated, — — % a ratio which is known

as the respiratory quotient, will approach nearer to unity as the quantity of
carbohydrates in the diet is increased. From our study of the digestion of
carbohydrates (p. 257) we have found that most of the carbohydrates of our
food pass into the blood as dextrose (or levulose), and any excess above a cer-
tain percentage is converted temporarily to glycogen in the liver, the nuiscles,
etc., to be again changed to dextrose before being used. The sugar undergoes
final oxidation in the tissues to COg and HgO. AVhile it is possible that this
oxidation may be direct — that is, that the sugar may be burnt directly to COg and

CHEMISTRY OF DIOESTION AND NUTRITION. 293

H O-it is usually suppose.1 to be pveccM by a splitting of the sug-ar molocule.
The stops in the process arc not <lcfinitoly known ; a,«,nl,ng to one hypotb-
^te the n>oloe„lo H,.t nn.le,-goc« elcavagc, with the t onnat.on of la*c ad
^ i-T O - 2C 1I,0,), which is then oxidized. Accoi-dmg to another liypoth-
Sf the'sngar first breaks down, with the formation of aleohol an,l CO,, a.s n>
tbe'veast fermentation outside the body.

There have been diseovered recently in connecfon wul, the pancrea., a
number of facts that are interesting not only in thcn.selves, but doubly so
be".t thev pron.ise, when n.ore fully investigatetl, to throw son.ebght on
the nl er-o consn.nption of sugar by the tissues. It has been shown by
V Merin. and Minkowski' and othe,. that if the pancreas of a dog ,s e, m-
pktely removed, the tissues lose the power of eonsummg sugar, so that
am,„ ulates in the blood and finally escapes in the ur.ne, eausmg what
ir en llled "pancreatic diabetes." If a small part of the pancreas ,s
S i the body, even though it is not connected by its duct w,th the duo-
dtum dabetes does not i^eur. The inference usually made from these
e pe me r that the pancreas gives off something to the blood-an n.ternal
s^reton-whieh is necessary to the physiological consun.p .on of sugar.
rXt way the pancreas exerts this influence has yet to be d.scovered ;
™ Jb ; it is throuU the action of a sp.=ific enzyme wh.ch helps to break
Town the sugar; possibly it is by some other means. But the neces-sUy of
thTpancreas in ome wav for the normal consumption of sugar by tbe t.ssu^
generally seen, to be indisputably established. It is a d.scovery of the utmos
fZrtanee in its relations to the normal nutrition of the body, and also
l^CTf it, possible bearing on the pathological condition known as *«M..
^nZ In this latter disease the tissues, for some reason are unable to
Tx d ■ th sugar in normal amounts, and a good part of it, therefore, escapes
th outh the urine. The facts and theories bearing upon d.abetes are of
unu": 1-est in connection with the nutritive history of the carbohydrates,
toti^r a fuller description reference must be made to moi-e elabo.-a^e works.
' Anotler statement' in connection with the fate "^ -■^^ '» *;^^«'^„:
worthv of a brief reference: It has been asserted by Lepine and Banal that
There is normally present in blood an enzyme capable of destroy.ng sugar
Tlb-tlory rest' upon the undoubted fact that sugar adcW to blood outsue
I wTsoou disappear. They call the process " glycolys.s," and t e enzy^^.
to which they attr bute this disappearance the " glycolytic enzyme. Othe.s
how V (Afhus), have claimed that this enzyme is only a post-mortem resul
ofTedi it grain of the corpuscles of the btel, and that .t - - P-"'
in circulating blood. We must await further mvest.gafon upon th,s po.nt,
and be content here with a mere trference ^^^,^^^^
Nutritive Value of Water and Salts.— Watei is losi (uni.v i i

in WeCntities through the kidney, the skin, the lungs, and the fec^, and
• it is fepC by water teken in the food or separately, and partially also by
tl,:"l£ formed in the oxidations of the body. A certain percentage of

1 ATchi, fir eipermenUUe Pathologk u. PUrmAohgk, 1893, IJXI. p. 85.

294 AN AMERICAN TEXT-BOOK' OE PHYSIOLOaY.

water in tlie tissues and in the li([iii(ls <»i' tlie body is naturally al)solntely
essential to the normal play of metabolism; and eonditions, snch as muscular
exercise, which increase the water-loss brint^ about also an increjtsed water-
consumption, the regulation being effected through the nervous mechanism
whicli mediates the sensation of thirst. The water taken into the bodv does
not, however, serve directly as a source of energy, since it is finally eliminated
in the form in which it is taken in ; it serves only to replace water lost from
the tissues and licjuids of the body, and it furnishes also tlie menstruum for the
varied chemical reactions which take place. Continued deprivation of water
leads to intolerable thirst, the cause of which is usually referred to the altered
composition of the tissues generally, including the peripheral nervous system.
Inorganic Salts. — The essential value of the inorganic salts to the proper
nutrition of the body does not commonly force itself upon our attention, since,
as a rule, we get our proper supply unconsciously with our food, without the
necessity of making a deliberate selection, NaCl (common table-salt) forms
an exception, however, to this rule. Speaking generally, inorganic salts do
not serve as a source of energy to the body. Most of the salts found in
the urine and other excreta are eliminated in the same form in which they
were received into the body. Some of them, however, notably the phosphates
and the sulphates, are formed in the course of the metabolism of the tissues,
and without doubt reactions of various kinds occur affecting the composition
of many of the salts — for example, the decomposition of the chlorides to form
the HCl of gastric juice. But these reactions do not materially influence the
supply of energy in the body : the value of the salts lies in the general fact
that they are necessary to the maintenance of the normal ])hysical and chem-
ical properties of the tissues and the body-fluids. Experimental investigation '
has shown in a surprising way how immediately important the salts are in this
respect. Forster fed dogs and pigeons on a diet in which the saline constit-
uents had been much reduced, althougli not completely removed. The animals
were given proteids, fats, and carbohydrates, but they soon passed into a
moribund condition. It seemed, in fact, that the animals died more quickly
on a diet poor in salts than if they had been entirely deprived of food.
Similar experiments were made by Lunin upon mice, with corresponding
results. He showed, moreover, that while mice live very well upon cow's milk
alone, yet if given a diet almost free from inorganic salts, consisting of the
casein and fats of milk plus cane-sugar, they soon died. INIoreover, if all the
inorganic salts of milk were added to this diet in the exact proportion in which
they exist in the ash of milk, the mixture still failed to supjwrt life. It would
seem from this result that the inorganic salts cannot fulfil completely their
proper functions in the body unless they exist in some special combination
with the organic constituents of the food. In this coiniection it is well to bear
in mind that proteids as they occur in nature seem always to be combined
with inorganic salts, and the jiroperties of proteids, as we know them, are
undoubtedly dependent in part upon the presence of this inorganic constituent.
' Bunge: Physiological and Pathological Chemistry, translated by Wooldridge, 1890.

CHEMISTRY OF DIGESTION AND NUTRITION. 295

It has been shown, lor example, that if egg-albuiniu is completely deprived
of its ash, it is no longer soluble in water. We may assume that the original
synthesis of the organic and inorganic constituents is made in the plant king-
dom, and that, in its own way, the inorganic constituent of the molecule is as
necessary to the proper nutrition of the animal tissues as is the organic. One
salt (NaCl) is consumed by many animals, including man, in excess of the
amount unconsciously ingested with the food. Bunge points out that purely
carnivorous animals are not known to crave this salt, while the herbivora
with some exceptions — for example, the rabbit — take it at times largely in ex-
cess. The need of salt on the part of these animals is well illustrated among
the wild forms by the eagerness with which they visit salt-licks. Bunge
advances an ingenious theory to account for the difference in regard to the use
of salt between the herbivora and the carnivora. He points out that in plant
food there is a relatively large excess of potassium salts. When these salts
enter the liquids of the body they react with the NaCl present and a mutual
decomposition ensues, with the formation of KCl and the sodium salt of the
acid formerly combined with the potassium, and the new salts thus formed are
eliminated by the kidneys as soon as they accumulate beyond the normal limit.
In this way the normal proportion of NaCl in the tissues and the body-fluids
is lowered and a craving for the salt is produced. Bunge states that it has been
shown among men that vegetarians habitually consume more salt than those
who are accustomed to eat meats. The salts of calcium and of iron have also
a special importance which needs a word of reference. The particular import-
ance of the iron salts lies in their relation to hsemoglobin. The continual
formation of new red blood-corpuscles in the body requires a supply of iron
salts for the synthesis of the haemoglobin, and, although there is a probability
(see p. 263) that the iron compound of the disintegrating corpuscles is again
used in part for this purpose, we must suppose that the body requires addi-
tional iron in the food from time to time to take the place of that which is
undoubtedly lost in the excretions. It has been shown that iron is contained
in animal and vegetable foods in the form of an organic compound, and the
evidence at hand goes to show that only when it is so combined can the iron
be absorbed readily and utilized in the body, while the efficacy of the inor-
ganic salts of iron as furnishing directly a material for the production of hserao-
globin is, to say the least, open to doubt. Bunge isolated from the yolk of
eggs an iron-containing nuclein which he calls hcematogen, because in the
developing hen's egg it is the only source from which the iron required
for the production of haemoglobin can be obtained. It is possible that sim-
ilar compounds occur in other articles of food. Most of the iron taken with
food, however, including that present in the haemoglobin of meats, passes
out in the feces unabsorbed. It is probable that there is an actual excre-
tion of iron from the body, and, so far as known, this excretion is effected
in small part through the urine, but mainly through the walls of the intes-
tine, the iron being eliminated finally in the feces. The large proportion of
calcium salts found in the skeleton implies a special need of these salts in

296 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

the food, particularly in that of" the young. It has been shown that if" young
dogs are fed upon a diet poor in Ca salts, the bones f"ail to develop properly,
and a condition similar to rieUets in children becomes a})parent. In addition
to their relations to bonc-iormation and the fact that they form a normal con-
stituent of the tissues and liquids of the body, calcium salts are necessary to
the coagulation of blood (see p. 355), and, moreover, they seem to be connected
in some intimate way with the rhythmic contractility of heart-muscle, and,
indeed, with the normal activity of protoplasm in general, animal as well as
plant. Notwithstanding the special importance of calcium in the body, no
great amount of it seems to be normally absorbed or excreted. Voit has
shown that the calcium eliminated from the body is excreted mainly througli
the intestinal walls, but that most of the Ca in the feces is the unabsorbed Ca
of the food. It is possible that the Ca must be present in some special com-
bination in order to be absorbed and utilized in the body. A point of special
interest in connection with the nutritive value of the inorganic salts was brought
out by Bunge in some analyses of the body-ash of sucking animals in compar-
ison with analyses of the milk and the blood of the mother. In the case of the
dog he obtained the following results (mineral constituents in 100 parts of ash) :

Young Pup. Dog's Milk. Dog's Serum.

K,0 8.5 10.7 2.4

Na.,0 8.2 6.1 52.1

CaO 35.8 34.4 2.1

MgO 1.6 1.5 0.5

FA 0.34 0.14 0.12

P.,05 39.8 37.5 5.9

CI 7.3 12.4 47.6

The remarkable quantitative resemblance between the ash of milk and the
ash of the body of the young indicates that the inorganic constituents of milk
are especially adapted to the needs of the young; while the equally striking
difference between the ash of milk and the ash of the maternal blood seems to
show that the inorganic salts of milk are formed from the blood-serum not
simply by osmosis, but rather by some selective secretory act. These facts
come out most markedly in connection with the CaO and the P2O5. For
further details as to the history of calcium and iron in the body, consult the
section on Chemistry of the Body, under calcium and iron.

I. Accessory Articles of Diet ; Variations of Body-metabolism

UNDER Different Conditions ; Potential Energy of Food ;

Dietetics.

Accessory Articles of Diet. — By accessory articles of diet we mean those

substances which are taken with foml, not for the purpo.se of replacing ti.-^sue or

yielding energy, but to add to the enjoyment of eating, to stinmlate the appetite,

to aid in digestion and absorption, or for some other subsidiary purpose. They

include such things ils the condiments (mustard, pepper, etc.), the flavoi-s, and

the stimulants (alcohol, coffee, tea, chocolate, beef-extracts). They all possess,

undoubtedly, a positive nutritive or digestive value beyond contributing to the

CHEMISTRY OF DIGESTION AND NUTRITION 207

mere pleasures ol" tlie palate, but their iin})ortauce is of a subordinate character.
They may be omitted from the diet, as happens or may happen in the case of
animals, without affecting injuriously the nutrition of the Ixxly, although it is
probable that neither man nor the lower animals would voluntarily eat Ibod
entirely devoid of flavor.

Stiiimlants. — The well-known stimulating effect of alcohol, tea, coffee, etc.
is probablv due to a specific action on the nervous system whereby the irri-
tabilitv of the tissue is increased. The physiological effect of tea, coffee, and
chocolate is due to the alkaloids caffein (trimethyl-xanthin) and theobromin
(dimethyl-xanthin). In small doses these substances are oxidized in the
body and yield a corresponding amount of energy, but their value from this
standpoint is altogether unimj)ortant compared with their action as .stimulants.
Alcohol also, when not taken in too large quantities, may be oxidized in the
bodv and furnish a not inconsiderable amount of energy. It is, however, a
matter of controversy at present whether alcohol in small doses can be con-
sidered a true food-stuff, capable of serving as a direct source of energy and of
replacing a corresponding amount of fats or of carbohydrates in the daily diet.
The evidence is parti v for and partly against such a use of alcohol. For examj^le,
Reichert^ finds that moderate doses of alcohol given to a dog do not affect the
heat-production of the body as measured by a calorimeter. Since the alcohol
is completely or nearly completely oxidized in the body and gives off consider-
able heat in the process, the fact that the total heat-production remains unal-
tered indicates that the oxidation of the alcohol protects an isodynamic amount
of proteid or nou-proteid material in the body from consumption, thus actiiig
as a food-stuff capable of replacing other elements of the food. On the con-
trary, Miura^ has arrived at exactly opposite results in a series of experiments
made by another method. In these experiments Miura brought himself into
a condition of nitrogen equilibrium upon a mixed diet. Then for a certain
period a portion of the carbohydrates was omitted from the diet and its place
substituted by an isodynamic amount of alcohol. The result was a loss of
proteid from the body, showing that the alcohol had not protected the proteid
tissue as it should have done if it acts as a food. In a third period the old
diet was resumed, and after nitrogen equilil^rium had again been established the
same proportion of carbohydrate was omitted from the diet, but alcohol was
not substituted. When the diet was poor in proteid, it was found that less pro-
teid was lost from the body when the alcohol was omitted than when it was used,
indicating that, so far from protecting the tissues of the body by its oxidation,
the alcohol exercised a directly injurious effect upon proteid-consumption.
Numerous other researches might be quoted to show that the effect of moderate
quantities of alcohol upon body-metabolism is not yet satisfactorily understood.
Before making any positive statements as to the details of its action it is wise,
therefore, to wait until reliable experimental results have accumulated. The
specific action of alcohol on the heart, stomach, and other organs has been inves-
tigated more or less completely, but the literature is too great and the results are
1 Therapeutic Gazette, 1890. ^ ZeUschrifl f. Min. Medicin, 1892, vol. xx. p. 137.

298 .l.V AMEBIC AX TEXT-BOOK OF PHYSIOLOGY.

too uncertain to permit any rfeum6 to be given here. When alcohol is taken
in excess it produces the familiar svmptoms of intoxication, which may pass
subsequently into a condition of stupor or even death, ])rovided the quantity
taken is siitlicieurly great. So, also, the long-continued use of alcohol in large
quantities is known to produce serious lesions of the stomach, liver, nerves, blood-
vessels, and other organs. The effect of alcohol upon the Ixxlv evidently varies
greatly with the quantity used. It may perhaps be said with safety that in small
quantities it is beneficial, or at least not injurious, barring the danger of acquiring
an alcohol habit, while in large quantities it is directly injurious to various ti.ssues.

Condimotts and Flavors. — These substances probably have a directly bene-
ficial effect on the processes of digestion by promoting the secretion of saliva,
gastric juice, etc., in addition to the important fact that they increase the pal-
atableness of foo<l, and hence increase the desire for food. With reference to
the condiments, Brandl has shown, in the paper referred to on p. 252, that mus-
tard and pepjjer also markedly increase the absorption of soluble products from
the stomaeli.

Conditions Influencing- Body -metabolism. — In considering the influence
of the various food-stuffs upon body-metabolism we have for the most part
neglected to mention the effect of changes in the condition of the body. It
goes without saying that such things as muscular work, sleep, variations in
temperature, etc. have or might have an important effect upon the character
and amount of the chemical changes going on in the body, and in conse-
quence a great many elaborate investigations have been made to ascertain pre-
cisely the effect of conditions such as those mentioned upon the amount of
the excretions, the production of heat in the body, and other similar points
which throw light upon the nature of the metabolic processes.

Effect of Muscular Work. — It is a matter of common knowledge that mus-
cular work increases the amount of food consumed, and therefore the total
body-metabolism, but it has been a point in controversy whether the increased
oxidations affect the proteid or the non-proteid material. According to Liebig,
the source of the energy of muscular work lies in the metabolism of the proteid
constituents, and with increased muscular work there should be increased de-
struction of proteid and an increase in the nitrogenous excretions. That the
total energy of muscular work is not derived from the oxidation or metabolism
of proteid alone was clearly demonstrated by the famous experiment of Fick
and Wislicenus. These physiologists ascended the Faulhorn to a height of
1956 meters. Knowing the weight of his body, each could estimate how much
work was done in ascending such a height. Fick's weight, for example, was
66 kilograms, therefore in climbing the mountain he performetl 66 X 1956 =
129,096 kilogrammetei-s of work. In addition, the work of the heart and the
respiratory muscles, which could not be determined accurately, was estimated
at 30,000 kilogrammeters. There was, moreover, a certain amount of muscular
work performed in the movements of the arms and in walking upon level
ground that was omitted entirely from their calculations. For seventeen hours
before the ascent, during the climb of eight hours, and for six hours afterward

CHEMISTRY OF DIGESTION AND NUTRITION. 299

their food was entirely non-nitrogenous, so that the urea eliminated came
entirely from the proteid of the body. Nevertheless, when the urine was
collected and the urea estimated it was found that the potential energy c(jntained
in the proteid destroyed was entirely insufiicient to account for the work done.
Although later estimates would modify somewhat the actual figures of their
calcnlation, the margin was so great that the experiment has been accepted as
showing conclusively that the total energy of muscular work does not come
from the oxidation of proteid alone. Later experiments made by Voit upon
a dog working in a tread-wheel and upon a man performing work while in the
respiratory chamber (p. 283) gave the surprising result that not only may the
energy of nuiscular work be far greater than the potential energy of the proteid
simultaneously oxidized, but that the performance of muscular work within
certain limits does not affect at all the amount of proteid metabolized in the
body, since the output of urea is the same on working-days as during days of
rest. Careful experiments by an English physiologist, Parkes, made upon
soldiers while resting and after performing long marches showed also that
there is no distinct increase in tlie excretion of urea after muscular exercise.
It follows from these experiments that Liebig's theory as to the source of the
energy of muscular work is incorrect, and that the increase in the oxidations
in the body which inidoubtedly occurs during nmscular activity must atfect
only the non-proteid material, that is, the fats and carbohydrates. Quite
recently the question has been reopened by experiments made under Pfliiger
by Argutinsky.^ In these experiments the total nitrogen excreted was deter-
mined with especial care in the sweat as well as in the urine and the feces.
The muscular work done consisted in long walks and mountain-climbs.
Argutinsky found that w^ork caused a marked increase in the elimination of
nitrogen, the increase extending over a period of three days, and he estimated
that the additional proteid metabolized in consequence of the work was suf-
ficient to account for most of the energy expended in performing the walks
and climbs. A number of objections have been made to Argutinsky's work.
It has been asserted that during his experiment he kept himself upon a
diet deficient in non-proteid material ; that if the supply of this material had
been sufficient, none of the additional proteid would have been oxidized. It
must be admitted, however, that the experiments of Argutinsky compel us to
state the proposition above as to the relation between muscular work and
proteid metabolism in a more careful way. It is necessary to modify the
statement generally made to the extent of saying that muscular work causes
no increase in proteid metabolism, provided the supply of food is abundant.
If now we compare the amounts of CO2 eliminated during work and during
rest, it will be found that there is a very decided increase during work. In the
experiments made by Pettenkofer and Voit the CO2 given off by a man
during a day of muscular work was nearly double that eliminated during a
resting-day. Indeed, the same fact has been observed repeatedly upon isolated
muscles made to contract by artificial stimuli. Assuming, then, that muscular

' Pfliiger' s A rchiv fixr die gesammie Physiologie, 1890, vol. 46, p. 552.

300 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

work causes no increase in the nitrogen excreted, hut a marked increase in the
CO2 eliminated, we are justified in saying that the energy of muscuhn- work
under normal conditions comes mainly, if not exclusively, from tlie oxidation
of non-proteid material. The machine that does the work, tiie muscle, is
par excellence a proteid tissue, but the normal resting metabolism of its pro-
teid substance is not increased by the chemical changes of contraction. Or,
to j)ut it in another way, the chemical changes wdiich give rise to the energy
liberated in contraction involve only the non-proteid material. It is interest-
ing to remember in this connection that the consumption of glycogen, or of
the sugar derived from it, is intimately connected with muscular work. The
glycogen of the body in an animal deprived of food disappears much more
rapidly if the animal is made to work his muscles than if he remains at
rest. In an exi)eriment by Kiilz upon well-fed dogs it was found that the
glycogen was practically all used up in a single fasting-day during which the
animals did a great deal of work. Morat and Dufourt have shown also that
a muscle after prolonged contraction takes much more sugar from the blood than
it did previous to the contraction, and Ilarley ^ finds that power to perform
muscular work may be increased and susceptibility to fatigue be diminished
by eating sugar in quantities. It is, in fact, generally agreed that glycogen is
used up in muscle-contractions, but the way in w'hich the destruction of the
glycogen is effected is not definitely known. After the glycogen has been con-
sumed it is probable that the other constituents of the body, the fats and the
proteids, are called upon to furnish the necessary energy. For this reason
we should expect, in a person performing excessive muscular work, that there
would be an increased destruction of proteid when the supply of non-proteid
food is insufficient.

Metabolism during Sleep. — It has been shown that during sleep there is no
marked diminution of the nitrogen excreted, and therefore no distinct decrease
in the proteid metabolism; on the contrary, the COg eliminated and the
oxygen absorbed are unquestionably diminished. This latter fact finds its
simplest explanation in the supposition that the muscles are less active during
sleep. The muscles do less work in the way of contractions, and, in addition,
probably suffer a diminution in tonicity which also affects their total metab-
olism.

Effect of Variations in Temperature. — In w^arm-blooded animals variations
of outside temperature Within ordinary limits do not affect the body-tem-
perature. A full account of the means by which this regulation is effected
will be found in the section upon Animal Heat. So long as the temper-
ature of the body remains constant, it has been found that a fall of outside
temperature increases the oxidation of non-proteid material in the body, the
increase being in a general way proportional to the fall in temperature. That
the increased oxidation affects the non-proteid constituents is shown by the
fact that the urea remains unchanged in quantity, other conditions being the
same, while the oxygen-consumption and the COg-elimination are increased. A
* Journal of Physiology, 1894, vol. xvi. p. 97.

CHEMISTRY OF DIGESTION AND NUTRITION. 301

rise of outside temperature has naturally tlie opposite effect : oxygen-consump-
tion and COa-elimination are diminished. This effect of temperature upon
the body-metabolism is due mainly to a reflex stimulation of the motor nerv^es
to the musc^les. The temperature-nerves of the skin are affected by the rise
or fall in outside temperature, and bring about reflexly an increased or a dimin-
ished innervation of the muscles of the body. The fact that variations in
outside temperature affect only the consumption of non-proteid material falls
in, therefore, with the conception of the nature of the metabolism of muscle in
activity, given above. When the means of regulating the body-temperature
break down from too long an exposure to excessively low or excessively high
temperatures, the total body-metabolism, proteid as well as non-proteid, in-
creases with a rise in body-temperature and decreases with a fall in temperature.
In fevers arising from pathological causes it has been shown that there is also
an increased production of urea as well as of COg.

Effect of Starvation. — A starving animal must live upon the material pres-
ent in its body. This material consists of the fat stored up, the circulating
and tissue proteid, and the glycogen. The latter, which is present in compara-
tively small quantities, is quickly used, disappearing more or less rapidly
according to the extent of muscular movements made, although in any case it
practically vanishes in a few days. Thereafter the animal lives on its own
proteid and fat, and if the starvation is continued to a fatal termination the
body becomes correspondingly emaciated. Examination of the several tissues
in animals starved to death has brought out some interesting facts. Voit took
two cats of nearly equal weight, fed them equally for ten days, and then killed
one to serve as a standard of comparison and starved the other for thirteen
days: the latter animal lost 1017 grams in weight, and the loss was divided as
follows among the different organs :

Actual loss Loss to each 100 grams

(in fresh organ). (fresh organ).

Bone 55 grams. 14 grams.

Muscle 429 " 31 "

Liver 49 " 54 "

Kidney 7 " 26 "

Spleen 6 " . 67 "

Pancreas 1 " 17 "

Testis 1 " 40 "

Lung 3 " 18 "

Heart 0 " 3 "

Intestine 21 " 18 "

Brain and cord 1 " 3 "

Skin and hair 89 " 21 "

Fat 267 '• 97 "

Blood 37 " 27 "

According to these results, the greatest absolute loss was in the muscles (429
grams), while the greatest percentage loss was in the fat (97 per cent.), which
had practically disappeared from the body. It is very significant that the
central nervous system and the heart, organs which we may suppose were in
continual activity, suffered no loss of weight: they had lived at the expense of

302 A^" AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the other tis^sues. We must suppase that in a starving animal the fat and the
proteid material, particularly that of the voluntary muscles, pass into solution
in the blood, and are then used to nourish the tissues generally and to supply
the heat necessary to nuiintain the body-temperature. Examination of the
excreta in starving animals has shown that a greater quantity of pnjteid is
destroyed during the first day or two than in the subsequent days. This fact
is explained on the supposition that the body is at first richly supplied with
"circulating proteid" derived from its previous food, and that after this is
metabolized the animal lives entirely, so far as proteid-consiimption is concerned,
upon its '' tissue proteid." The general fact that the lo&s of proteid is great-
est during the first one or two days of starvation has been confirmed recently
upon men, in a number of interesting experiments made upon professional
fasters. For the numerous details as to loss of weight, variations of tempera-
ture, etc., carefully recorded in these latter experiments, reference must be made
to original sources.^ It may be added, in conclusion, that the fatter the body is
to begin with, the longer will starvation be endured, and that if water is con-
sumed freely the evil effects of starvation, as well as the disagreeable sensations
of hunger, are very much reduced.

Potential Energy of Food. — The chemical changes occurring in the body
are accompanied by a liberation of energy in different forms — for example, as
heat, electricity, and mechanical work. By far the most of this energy takes
the form, directly or indirectly, of heat. Even when the muscles are ajiparently
at rest we know that they are undergoing chemical changes which give rise to
heat. AVhen a muscle contracts, the greater part (four-fifths) of the energy
liberated by the chemical change takes the form of heat; a much smaller
part (about one-fifth as a maximum) may perform mechanical work, which
in turn, as in the case of the res})iratory muscles and the heart, may be con-
verted to heat within the body. Roughly speaking, an adult man gives off
from his body in the course of twenty-four hours about 2,400,000 calories of
heat (1 calorie = the heat necessary to raise 1 cubic centimeter of water 1° C).
This supply of heat is derived from the metabolism or physiological oxidation
of the j)roteids, the fats, and the carbohydrates which we take into the body in
our food. By means of the oxygen absorbed through the lungs these substances
are burnt, with the formation of COg, HjO, and urea or some similar nitrog-
enous waste product. In the long run, then, the source of body-energy is found
in the potential energy contained in our food. Our energy-yielding foods —
proteids, fats, and carbohydrates — are more or less complex botlies which are
built up originally by plant organisms with the consumption of solar energy ;
when they are burnt or otherwise destroyed, with the formation of simpler
bodies (such as COg or H^O), the contained potential energy is liberated in the
form of heat, and this is what occurs in the body. From the standpoint of the
law of conservation of energv it is easv to understand that the amount of
available energy in any food-stuff may be determined by burning it outside the
body and measuring the quantity of heat liberatetl. If a gram of sugar is
' Virchow's Archiv, vol. 131, supplement, 1893, and Luciani, Das Hungern, 1890.

CHEMISTRY OF DIGESTION AND NUTRITION. 303

burut, it is converted to COj and H2O and a certain quantity of heat is liber-
ated; if the same gram of sugar had been taken into the body, it would event-
ually have been reduced to the form of COj and HgO, and the total quantity
of heat liberated would have been the same as in the combustion outside the
body, although the destruction of the sugar in the body may not be a direct,
but an indirect, oxidation ; that is, the oxygen may first be combined with sugar
and other food-stuffs to form a complex molecule which afterward dissociates
into simpler compounds similar to those obtained by direct oxidation, or there
may be first a dissociation or cleavage followed by oxidation of the dissociation
products. In determining the total energy given to the body we need only
consider the form in which a substance enters the body and the form in which
it is finally eliminated. In the case of proteids the combustion in the body is
not so complete as it is outside ; the final products are CO2, HgO, and urea ;
the urea, however, still contains potential energy which may be liberated by
combustion, and in determining the energy of proteid available to the body,
that which is lost in the urea must be deducted. As a matter of fact, there is
some evidence (see origin of urea, p. 276) to show that proteid in the body is
completely oxidized to CO2, HgO, and NH3; but, since the NH3 in this case
recoml^ines with a part of the CO2 and the HgO to form ammonium carbamate,
and this in turn is converted into urea, the additional energy liberated in the
first combustion is balanced by that absorbed in the synthetic production of the
urea. The potential energy of the fats, carbohydrates, and proteids can be
determined by combustion outside the body ; the energy liberated is measured
in terms of heat by some form of calorimeter, and the quantity of heat so
obtained, expressed in calories, is known usually as the " combustion equiva-
lent." To be perfectly accurate, each particular form of fat, proteid, etc.
should be burnt and its energy be determined, but usually average figures are
employed, as the amount of heat given off by the different varieties of any one
food-stuff — proteids, for example — does not vary greatly. According to Stoh-
manu, 1 gram of beef deprived of fat = 5641 calories, while 1 gram of veal
gives 5663 calories. For muscle extracted with water, Rubner obtained the
following figures: 1 gram = 5778 calories. The combustion equivalent of urea
(Rubner) is 2523 calories. Since 1 gram of proteid yields about one-third of
a gram of urea, we must deduct 841 calories from the combustion equivalent
of one gram of proteid to get its available energy to the body : 5778 — 841 =
4937 calories. The combustion equivalents of fats and carbohydrates, as given
by Stohmann, are: 1 gram of fat =9312 calories; 1 gram of starch = 4116
calories. Weight for weight, fat contains the most energy, and, as we know,
in cold weather and in cold climates the proportion of fat in the food is
increased. In dietetics, however, the use of fat is limited by the difficulty
attending its digestion and absorption as compared with carbohydrates. Fats
and carbohydrates have the same general nutritive value to the body: they
serve to supply energy. Since the amount of potential energy contained in
each of these substances may be determined accurately by means of its com-
bustion equivalent, it would seem probable that they might be mutually

304 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

interchangeable in dietetics in the ratio of their eoniljiistion equivalents.
Such, in fact, is the case. The ratio of interchange is known as the " iso-
dynamic equivalent," and it is given usually as 1 : 2,4 or 2.2 ; that is, fats
may replace over twice their weight of carbohydrate in the diet. It Ibllows
from the general principles just stated that if we wished to know the amount
of heat ])r()duced in the body in a given time, say twenty-four hours, wc might
ascertain it in one of two ways : In the first place, the animal might be })laccd
in a calorimeter and the heat given oif in twenty-four hours be measured
directly. This method, which is that of direct calorimetry, is described more
completely in tiic section treating of Animal Heat. Secondly, one might
feed the animal upon a diet containing known quantities of proteid, fats, and
carbohydrates, and by collecting the total N and C excreta determine how much
of each of these had been destroyed in the body. Knowing the combustion
equivalent of each, the total quantity of heat liberated in the body could be
ascertained. This latter method is known as indirect calorimetry. The two
methods, if applied simultaneously to the same animal, should give identical
results. It is very interesting to know that an experiment of this character
has been successfully performed by Rubner;^ his experiments were made with
the greatest accuracy and with careful attention to all the possible sources of
error, and it was found that the quantities of heat as determined by the two
methods agreed to within less than 0.5 per cent. These experiments are note-
worthy because they furnish us with the first successful experimental demon-
stration of the accuracy of the general principles, stated above, upon which
the available energy of foods is calculated.

Dietetics. — The subject of the ])roper nourishment of individuals or col-
lections of individuals — armies, inmates of hospitals, asylums, prisons, etc. —
is treated usually in books upon hygiene, to which the reader is referred for
practical details. The general principles of dieting have been obtained, how-
ever, from experimental work upon the nutrition of animals. These princij)les
have been stated more or less completely in the foregoing pages, but some
additional facts of importance may be referred to conveniently at this point.
In a healthy adult who has attained his maximum weight and size the main
object of a diet is to furnish sufficient nitrogenous and non-nitrogenous food-
stuffs, together with salts and water, to maintain the body in equilibrium —
that is, to prevent loss of proteid tissue, fat, etc. In si)eaking of the nutritive
value of the food-stuffs it was shown that in carnivora (dogs) this condition
of equilibrium may be maintained upon proteid food alone, putting aside all
consideration of salts and water, or upon proteids and fats, or ui)on ])roteids and
carbohydrates, or upon proteids, fats, and ciirbohyd rates. AVhcn proteids alone
are used, the quantity must be increased far above that necessary in the case of
a mixed diet, and it is doubtful whether, in the case of man or the herbivora,
a healthy nutritive condition could be maintained long upon such a diet, owing
to the largely increased demand upon the power of the alimentary canal to
digest and absorb proteids, to the greater labor thrown on the kidneys, etc.
^ Zeitsckrift fur Biologic, 1893, vol. xxx. p. 73.

CHEMISTRY OF DIGESTION AND NUTRITION.

305

The experience of iiKiiikiiid, as well a.s the results of experimental investiga-
tion, shows that the healthy diet is one composed of proteids, fats, and carbo-
hydrates. The pr()])ortion in which the fats and the carbohydrates should be
taken — and, to a certain extent, this is true also of the proteids — may be
varied within comparatively wide limits, in accordance with the law of " iso-
dynamic equivalents." This is illustrated by the following "average diets"
calculated by diifevent physiologists to indicate the average amount of food-
stuffs required by an adult man under normal conditions of life :

Average Diets.

Moleschott.

Ranke.

Voit.

Forster.

Atwater.

Proteid 130 grams.

Fats 40 "

Carbohydrates .... 550 "

100 grams.
100 "
240 "

118 grams.
56 "
500 "

131 grams.
68 "
494 "

125 grams.
125 "
400 "

In Voit's diet, which is the one usually taken to represent the daily needs
of the body, it will be noticed that the ratio of the nitrogenous to the non-
nitrogenous food-stuffs is about as 1:5. It must be remembered, in regard to
these diets, that the amounts of food-stuffs given refer to the dry material : 118
grams of proteid do not mean 118 grams of lean meat, for example, since
lean meat (flesh) contains a large proportion of water. Tables of analyses of
food (one of which is given on page 216) enable us to determine for each par-
ticular article of food the proportion of dry food-stuffs contained in it, and in how
great quantities it must be taken to furnish the requisite amount of proteid,
fats, or carbohydrates. There is. however, still another practical consideration
which must be taken into account in estimating the nutritive value of articles
of food from the analyses of their composition, and that is the extent to which
each food-stuff in each article of food is capable of being digested and absorbed.
Practical experience has shown that proteids in certain articles of food can be
digested and absorbed nearly completely when not fed in excess, while in other
foods only a certain percentage of the proteid is absorbed under the most favor-
able conditions. This difference in usableness of the food-stuffs in various
foods is most marked in the case of proteids, but it occurs also with the fats
and the carbohydrates. Facts of this kind cannot be determined by mere
analysis of the foods; they must be obtained from actual feeding experiments
ujion man or the lower animals. In general, it may be said that in meats from
2 to 3 per cent., in milk from 6 to 12 per cent., and in vegetables from 10 to
40 per cent, of the proteid escapes absorption. The greater value of the meats,
then, as a source of proteid supply consists not only in the greater average per-
centage of proteid contained in them as compared with the vegetables, but also
in the fact that their proteid is more completely absorbed from the alimentary
canal, less being lost in the feces. Munk ^ gives an interesting table showing
how^ much of certain familiar articles of food would be necessary, if taken
alone, to supply the requisite daily amount of proteid or non-proteid food ; his
' Weyl's Handbuch der Hygiene, 1893, vol. iii., part i. p. 69.
20

306

AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

estimates are based upon the percentage composition of the foods and upon
experimental data showing tlie extent of absorption of the food-stiiflfs in each
food. In this table ho sup})oses that the (hiily diet should contain 110 grams
proteid = 17.5 grams of N, and non-proteids sufficient to contain 270 grams
of C:

For 110 prams proteid
(17..') grams N).

For 270 prams C.

Milk

2900 grams.

540 "
18 eggs.

800 grams.
1650 "
1900 "
1870 "

990 "

520 "
4500 "

3800 grams.
2000 "
37 eggs.

670 grams.
1000 "
1100 "

750 "

660

750 "
2550 "

Meat (lean)

Hen's eggs

Wlieat flour

AVlieat bread

Kve bread

Kice

Corn

Peas

Potatoes

As Munk points out, this table shows tliat any single food, if taken in quantities
sufficient to supply the nitrogen, would give too much or too little C, and the re-
verse; those animal foods which, in certain amounts, supply the nitrogen needed
furnish only from one-quarter to two-thirds of the necessary amount of C. To
live for a stated period upon a single article of food — a diet sometimes recom-
mended to reduce obesity — means, then, an insufficient quantity of cither N
or C and a consequent loss of body-weight. Such a method of dieting amounts
practically to a partial starvation. In practical dieting we are accustomed to
get our supply of })roteids, fats, and carbohydrates from both vegetable and
animal foods. To illustrate this fact by an actual case, in which the food was
carefully analyzed, an experimenter (Krummacher) weighing 67 kilograms
records that he kept himself in N equilibrium upon a diet in which the pro-
teid was distributed as follows :

300 grams meat
666.3 c.c. milk
100 grams rice
100 " bread
500 c.c. wine

63.08
18.74

grams

proteid

7.74

K

11.. 32

((

1.17
102.05

<(
((

9.78 grams N.
2.905 "
1.2 " "
1.7.55 "
0.182 "

15.868

For a person in health and leading an active normal life, appetite and experi-
ence seem to be .safe and sufficient guides by which to control the diet ; but in
conditions of di.sease, in regulating the diet of children and of collections of
individuals, scientific dieting, if one may use the phrase, has accomplished
much, and will be of greater service as our knowledge of the physiology of
nutrition increases.

V. MOVEMENTS OF THE ALIMENTARY CANAL,
BLADDER, AND URETER.

Plain Musclej-tissue.

The movements of the alimentary canal and the organs concerned in mic-
turition are effected for the most part through the agency of plain muscle-
tissue. The general properties of this tissue have been referred to in the
section upon the Physiology of Muscle and Nerve, but it seems appropriate in
this connection to again call attention to some points in its general physiology
and histology, inasmuch as the character of the movements to be described
depends so much upon the fundamental properties exhibited by this variety of
muscle-tissue. Plain muscle as it is found in the walls of the abdominal and
pelvic viscera is composed of masses of minute spindle-shaped cells whose size,
is said to vary from 22 to 560 fx in length and from 4 to 22 n in width, the
average size, according to Kolliker, being 100 to 200 jjl in length and 4 to 6 //
in width. Each cell has an elongated nucleus, and its cytoplasm shows a
longitudinal fibrillation. Cross striation, such as occurs in cardiac and striped
muscle, is absent. These cells are united into more or less distinct bundles or
fibres, which run in a definite direction corresponding to the long axes of the
cells. The bundles of cells are united to form flat sheets of muscle of varying
thicknesses, which constitute part of the walls of the viscera and are distin-
guished usually as longitudinal and circular muscle-coats according as the cells
and bundles of cells have a direction with or at right angles to the long axis
of the viscus. The constituent cells are united to one another by cement-
substance, and according to several observers^ there is a direct protoplasmic
continuity between neighboring cells — an anatomical fact of interest, since it
makes possible the conduction of a wave of contraction directly from one cell
to another. Plain muscle-tissue, in some organs at least, e. g. the stomach,
intestines, bladder, and arteries, is under the control of motor nerves. There
must be, therefore, some connection between the nerve-fibres and the muscle-
tissue. The nature of this connection is not definitely established ; according
to Miller 2 the nerve-fibres terminate eventually in fine nerve-fibrils which run
in the cement-substance between the cells and send off small branches which
end in a swelling applied directly to the muscle-cell. Berkley ^ finds a similar

1 See Bohenian : Anatomischer Anzeifier, 1894, Bd. 10, No. 10.
* Archiv fiir mikroskopische Anatoviie, 1892, Bd. 40.
' Anatomischer Anzeiger, 1893, Bd. 8.

307

308

.l.V AMERICAN TEXT- BOOK OF PHYSIOLOGY.

oiuling of the nerves, and in acUlitiun ckscribes in the
muscuhiris nuieosaj of the intestine a larj^e globuhir
end-organ which he considers as a motor phite.

Perhaps the most striking physiological ])eculiarity
of plain muscle, as compared with the more familiar
striated muscle, is the sluggishness of its contrac-
tions. Plain nmscle, like striated muscle, is inde-
j)endently irritable. Various forms of artificial
stimuli, such as electrical current^,, mechanical,
chemical, and thermal stimuli, may cause the tis-
sue to contract when directly applied to it, but the
contraction in all cases is characterized by the
slowness with which it develops. There is a long
latent period, a gradual shortening which may per-
sist for some time after the stimulus ceases to act,
and a slow relaxation. These features are repre-
sented in the curve shown in Figure 81, which it is
instructive to compare with the typical curve of a
striated muscle (Fig. 34). The slowness of the con-
traction of plain muscle seems to depend upon the
absence of cross striation. Striped muscle as found in
various animals or in different muscles of the same
animal — e. g. the pale and red muscles of the rabbit
— differs greatly in the rapidity of its contraction,
and it has been shown that the more perfect the cross
striation the more rapid is the contraction. The
cross striation, in other words, is the expression of a
mechanism or structure adapted to quick contractions
and relaxations, and the relatively great slowness of
movement in the plain muscle seems to result from
the absence of this particular structure. It should be
added, however, that plain muscle in different parts
of the body exhibits considerable variation in the
rapiditv with which it contracts under stimulation,
the ciliary muscle of the eyeball, for exami)le, being
able to react more rapidly than the muscles of the in-
testines. The gentle prolonged contraction of the plain
muscle is admirably adapted to its function in the
intestine of moving the food-contents along the canal
with sufficient slowness to permit normal digestion
and absorption. Like the striated muscle, and un-
like the cardiac muscle, plain muscle is capable of

Fig. 85.— Contraction of a strip of plain muscle from the stomach of a terrapin. The bottom line
gives the time-record in seconds ; the middle line shows the time of application of the stimulus, a tetan-
izing current from an induction coil ; the upper line is the curve recorded by the contracting muscle.

MOVEMI^TS OF Till-: ALTMENTARY CANAL, ETC. 309

giving subiiuiximal as well as inaxiinal contractions; with incroased strength
of stimulation the amount of the shortening increases until a raaxinmm is
reached. This fact may be observed not only upon isolated strips of muscle
from the stomach, but may be seen also in the ditfcreut degrees of contraction
exhibited by the intestinal musculature as a whole when acted upon by various
stimuli.

In his researches upon the movements of the ureter Engelmann ' showed
that a stimulus ajjplieil to the organ at any point caused a contraction which
starting from the [)oint stinnilated might spread for some distance in either
direction. Engelmann interprets this to mean that the contraction wave in
the case of the ureter is propagated directly from cell to cell, and this possi-
bility is suj>ported by the fact, before referred to, that there is direct proto-
plasmic continuity between adjoining cells. This passage of a contraction wave
from cell to cell has, in fact, often been quoted as a peculiarity of plain
muscle-tissue. In the case of the ureter the fact seems to be established, but
in the intestines, where there is a rich intrinsic supply of nerve-ganglia, it
is not possible to demonstrate clearly that the same property is exhibited.
The wave of contraction in the intestine following artificial stimulation is,
according to most observers, usually localized at the point stimulated or is
propagated in only one direction, and these facts are difficult to reconcile
with the hypothesis that each cell may transmit its condition of activity
directly to neighboring cells. Upon the plain muscle of the ureter Engel-
mann was able to show also an interesting resemblance to cardiac muscle,
in the fact that each contraction is followed by a temporary diminution in
irritability and conductivity ; but this important property, which in the case of
the heart has been so useful in explaining the rhythmic nature of its contrac-
tions, has not been demonstrated for all varieties of plain muscle occurring in
the body.

A general property of plain muscle which is of great significance in explain-
ing the functional activity of this tissue is exhibited in the phenomenon of
" tone." By tone or tonic activity as applied to muscle-tissue is meant a con-
dition of continuous contraction or shortening which persists for long periods
and may be slowly increased or decreased by various conditions affecting the
muscle. Both striated and cardiac muscle exhibit tone, and in the latter at
least the condition is independent of any inflow of nerve-impulses from the
extrinsic nerves. Plain muscle exhibits the property in a marked degree. The
muscular coats of the alimentary canal, the blood-vessels, the bladder, etc., are
usually found under normal circumstances in a condition of tone which varies
from time to time and differs from an ordinary visible contraction in the slow-
ness with ^vhich it develops and in its persistence for long jieriods. Such con-
ditions as the reaction of the blood, for example, are known to alter greatly
the tone of the blood-vessels, a less alkaline reaction than normal causing
relaxation, while an increase in alkalinity favors the development of tone.
Tone may also be increased or diminished by the action of motor or inhibitory

^ Pfluger's Archivfiir die gesammte Physiologie, 1869, Bd. 2, S. 243.

310 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

neivo-fibres, but the precise relationship between the changes underlying the
development of tone and those leading to the formation of an ordinary contrac-
tion has not been satisfactorily determined.

The mode of contraction of the plain muscle in the walls of some of the
viscera, especially the intestine and ureter, is so characteristic as to be given
the s})eeial name of pci'istjdsis. By peristalsis, or vermicular contra(;tion as it
is sometimes called, is meant a contraction which, beginning at any point in
the wall of a tubular viscus, is propagated along the length of the tube in the
form of a wave, each part of the tube as the wave reaches it passing slowly
into contraction until the maximum is reached, and then gradually relaxing.
In viscera like the intestine, in which two muscular coats are present, the
longitudinal and the circular, the })eristalsis may involve both layers, either
simultaneously or successively, but the striking feature observed when M'atching
the movement is the contraction of the circular coat. The contraction of this
coat causes a visible constriction of the tube, which may be followed by the
eye as it passes onward.

Mastication.

Mastication is an entirely voluntary act. The articulation of the mandi-
bles with the skull permits a variety of movements ; the jaw may be raised
and lowered, may be projected and retracted, or may be moved from side to
side, or various combinations of these diiferent directions of movement may be
effected. The muscles concerned in these movements and their innervation are
described as follows : The masseter, temporal and internal pterygoids raise the
jaw ; these muscles are innervated through the inferior maxillary division of
the trigeminal. The jaw is depressed mainly by the action of the digastric
muscle, assisted in some cases by the mylo-hyoid and the genio-hyoid. The
two former receive motor-fibres from the inferior maxillary division of the
fifth cranial, the last from a branch of the hypoglossal. The lateral movements
of the jaws are produced by the external pterygoids, when acting separately.
Simultaneous contraction of these muscles on both sides causes projection of
the lower jaw. In this latter case forcible retraction of the jaw is produced by
the contraction of a part of the temporal muscle. The external pterygoids
also receive their motor fibres from the fifth cranial nerve, through its inferior
maxillary division. The grinding movements commonly used in masticating
the fot)d between i\\Q molar teeth are produced by a combination of the action
of the external pterygoids, the elevators, and perhajxs the dci)ressors. At the
same time the movements of the tongue and of the muscles of the cheeks and
lips serve to keep the food properly placed for the action of the teeth, and to
gather it into position for the act of swallowing.

Deglutition.

The act of swallowing is a complicated reflex movement w'hich may be
initiated voluntarily, but is for the most part completed quite independently

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 311

of the will. The classical dccni.tiou of the act given by Magendie divides it
into three sb.ges, corresponding to the three anatomical regions, the mouth,
pharynx and oesophagus, through which the swallowed n.orsel pa&ses on its
w-w to the stonuwh. The Hrst stage consists i.. the passage ol the bolus ot
food tlu-ongh the istlnnus of the fauces-that is, the opening lymg between he
ridges formed by the palato-glossi mnseles, the so-c-allcd antermr p.llars of the
fauces This part of the act is usually ascribal to the movements ol the tongue
iiself ' The bolus of food lying "po" '^ "PI*-- S"''*'"'* '» ^'""^ ""™"' ^^
the elevation of the tongue against the soft i>alate from the fp toward the ba^
This portion of the movement n.ay be regarded as voluntary to the extc.it at
least of manipulating the food into its proper position on the dorsum of the
tongue, although it is open to doubt whether the entire movement is usually
effe^tei bv a voluntary act. Under normal conditions the P--->-f' "° »
food upon the tongue seems essential to tlie complete execiit.on of the act,
and an attempt to make the movement with very dry material upon he tongue
i ilr not successful or is performed with difficulty. The second act com-
prises thi pa.ssage of the bolus from the isthmus of the fauces to the oesophagus
Hat is, its transit through the pharynx. The pharynx being a common
palge f r the air and the tbod, it is important that this part o the act should
be consummated quickly. According to the usual description the -o tor po-r
driving the bolus downward through the pharynx ,s derived from the contl ac-
tion of the pharyngeal muscles, particularly the constrictors, which con ract from
Ibove downward and drive the food into the oesophagus, f'""!'--"^^'
however, a number of other muscles are brought into action the general effee
of which is to shut off the nasal and laryngeal openings and thus prevent the
entrance of food into the corresponding cavities. The whole reflex ,s therefore
an excellent example of a finely co-ordinated movement. _ „ , ..

The following events are oleseribed: The mouth cavity is .shut off by the
position of the tongue against the .soft palate and by the coiitraetion of the
mu cles of the anterior pillai-s of the fauces. The opening into the nasa cavity
"Toil by the elevation of the soft palate (action of the evator palati and
tlisor palad muscles) and the contraction of the posterior pdlai. of the fauces
pa a o-pharvngei muscles) and the elevation of the uvula (azygos uvnte mus-
Ik The soft palate, uvula, and posterior pillars thus form a sloping surface
tting Iff the Lisal d.ambe; and facilitating the passage of the fo<^ b-kwa^_
into the pharynx where the constrictor muscles may act upon it. The l«n.
to V opering into the larynx is closed by the adduction ot the vocal cords (lat-
en crico-arvtcnoids and constrictors of the glottis) and by the elevation of he
eiirWni and a depression, in part mechanical, of the ep-g *. over h
larynx (action of the thyro-hyoids, digastrics, genm-hyoiols, and mylo-hyo ds
ol the muscles in the Lytono-epiglottidean folds). The moyemen^ of *
epiglottis during this stage of swallowing liave been "'-';; 'J™:;t IK^of
usual view is that it is pressed down upon the '->•"•?- -f^;^'^;^'^™
a box and thus effectually protects the respiratory passage. It has b««° ^''°3'
however, that removal of the epiglottis does not prevent normal swallowing,

312 AN A3IERICAN TEXT-BOOK OF PHYSIOLOGY.

and recently Stuart and McCormick ' have reported the case of" a man in whom
part of the pharynx had been permanently removed by surgical o})eration and
in whom the epiglottis could be seen during the act of swallowing. In this
individual, according to their observations, the epiglottis was not folded back
during swallowing, but remained erect. Later observations by Kanthack and
Anderson,^ made partly upon themselves and partly upon the lower animals,
tend, on the contrary, to support the older view. They state that in norma!
individuals the movement of the epiglottis backward during swallowing ma\
be felt by simply passing the finger back into the pharynx until it comes into
contact with the epiglottis. At the beginning of the movement there is also a
contraction of the longitudinal muscles of the pharynx which tends to pull the
})harvngeal walls toward the bolus of food while, as has been said, the nearly
simultaneous contraction of the constrictors presses upon the food and forces
it downward. The food is thus brought quickly into the opening of the
oesophagus and the third stage commences.

The transit of the food through the oesophagus is eifected by the action
of its intrinsic musculature. The nniscular coat is arranged in two layers, an
external longitudinal and an internal circular. These are composed of plain
muscle-tissue in the lower third or two-thirds of tiie oesophagus, but in most
mammals tlie upper third or more contains striated muscular tissue. The
chief factor in the transportation of the bolus through the oesophagus has
been supposed to consist in the contraction of the circular muscle. This con-
traction begins at the pharyngeal opening of the oesophagus and passes down-
ward in the form of a wave, peristaltic contraction, which moves rapidly in the
upper segment where the musculature is striated, and more slowly in the lower
segments in accordance with the ])hysiological characteristics of plain muscle.
The result of this movement would naturally be to force the food onward to
the stomach. The longitudinal muscles of the oesophagus are without doubt
brought into action at the same time, but in this as in other cases of peristalsis
in tubular viscera it is not perfectly clear how they co-operate in producing
the onward movement. It may be that their contraction slightly ])recedes
that of the circular muscle, and thus tends to dilate the tube and to bring it
forward over the bolus. At the opening of the oesophagus into the stomach,
the cardiac orifice, the circular fibres of the oesophagus function as a sphincter
which is normally in a condition of tone, particularly when the stomach con-
tains food, and thus shuts off the cavity of the stomach from the oesophagus.
In swallowing, however, the advancing peristaltic Avave has sufficient force to
overcome the tonicity of the sphincter, and possibly there is at this moment a
partial inhibition of the sphincter. In cither case the result is that the food
is forced through the narrow opening into the stomach with sufficient energy
to give rise to a soinid which may be heard by auscultation over this region.^
According to measurements by Kronecker and Meltzer the entrance of the

' Joui-nal of Anatomy and Physiologi), 1892.

^Journal of Phymolocjy, 1893, vol. xiv. p. 154.

' See Meltzer: Centralblatt fur die med. Wisseiwchaften, 1881, Xo. 1.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 313

food into the stomach occurs iu man about six seconds after tlie beginning of
the act of swallowing.

Kronecker-Meltzer Theory of Deglutition.— The usual view of the
mechanism of swallowing has been seriously modified by Kronecker and
Meltzer.' The experiments of these observers seem to be so conclusive that
we must believe that in the main their explanation of the process is correct.
According to their view the chief factor in ibrcing soft or liquid food through
the pharynx and oesophagus is the sharp and strong contraction of the mylo-
liyoid muscles. The bolus of food lies upon the dorsum of the tongue and
by the pressure of the tip of the tongue against the palate it is shut off from
the front part of the mouth-cavity. The mylo-hyoids now contract, and tlie
bolus of food is put under high pressure and is shot in the direction of least
resistance — namely, through the pharynx and oesophagus. This effect is aided
by the simultaneous contractions of the hyoglossi muscles, which tend to still
further increase the pressure upon the food by moving the tongue backward
and downward. This same movement of the tongue suffices also to depress
the epiglottis over the larynx, and thus protect the respiratory opening. By
means of small rubber bags connected with recording tambours, which were
placed in the pharynx and at different levels iu the oesophagus, they were able
to demonstrate the rapid spirting of the food through the whole length of
pharynx and oesophagus, the time elapsing between the beginning of the swal-
lowing movement and the arrival of the food at the cardiac orifice of the
stomach being not more than 0.1 second. The contraction of the constrictors
of the pharynx and the peristaltic wave along the oesophagus, according to
this view, normally follow after the food has been swallowed, and may be
regarded as a movement in reserve which is useful in removing adherent frag-
ments along the deglutition passage, or possibly, in case of the failure of the
first swallowing act from any cause — as may result, for instance, in swallowing
food too dry or too solid — serves to actually push the bolus downward,
although at a much slower rate. From auscultation of the deglutition sound
which ensues when the food enters the stomach through the cardia, Kronecker
and Meltzer believe that usually the swallowed food after reaching the end of
the oesophagus is kept from entering the stomach by the tonic contraction of
the sphincter at that })oint, until the subsequent peristaltic wave of the oesoph-
agus, which reaches the same point in about six seconds after the beginning of
the act of swallowing, forces it through. There are, however, exceptions to
this rule. In some persons, apparently, the food is forced into the stomach by
the energy of the first contraction of the mylo-hyoid muscles. The difference
would seem to depend upon the condition of the sphincter at the cardiac
orifice. Moreover, these authors were able to determine by their method of
recording that the human oesophagus contracts apparently in three successive
segments. The first of these comjwises about six centimeters in the neck
region, and its contraction begins about 1 or 1.2 seconds after the beginning of
swallowing and is comparatively short, lasting 2 seconds, corresponding to the
* Du Bois-Reymond's Archiv fiir Physiologic, 1883, Suppl. Bd., S. 328.

314 AN AMERICAN TlLXT-JiOOK OF PHYSIOLOGY.

striated character of the imiscle. Tlie second segment covers about ten (.'enti-
raeters of the upper thoracic portion of the oesophagus; its contraction begins
about 1.8 seconds after tlie beginning of the contraction of the first segment,
and is longer, lasting (j to 7 seconds. Tlie third segment includes the
remainder of the oesophagus; its contraction begins about 3 seconds at'tci' the
contraction of the second segment, and lasts a much longer time, about i)-10
se<'onds. These figures apply, of course, to a single act of swallowing. It
will be seen that according to these authors the swallowing reflex consists
essentially in the successive contractions of five muscular segments or bands —
namely, the mylo-hyoids, the constrictors of the pharynx, and the three seg-
ments of the oesophagus described. The time elapsing between the contractions
of these successive parts was determined as follows :

From the beginning of the contraction of the niylo-hyoids to tliat of the

constrictors of the larynx 0.3 second.

From the beginning of the contraction of the constrictors to that of

the first (Tsophageal segment 0.9 "

Between the first and second oesophageal segments 1.8 seconds.

" " second and third " " 3.0 "

The total time before the wave of contraction reaches the stomach would
be therefore, as has been stated, about six seconds. When a second act of
swallowing is made within six seconds of the first swallow it causes an inhibi-
tion, apparently by a reflex effect upon the deglutition centre, of the })art of
the tract wliich has not yet entered into contraction, so that the peristaltic
wave does not reach the lower end of the oesophagus until six seconds after
the second act of swallowing.

Nervous Control of Deglutition. — The entire act of swallowing, as has
been said before, is essentially a reflex act. Even the comparatively simple
wave of contraction which sweeps over the oesophagus is apparently due to a
reflex nervous stimulation, and is not a simple conduction of contraction from
one portion of the tube to atiotlier. This fact was demonstrated by the
experiments of Mosso,^ who found that after removal of an entire segment
from the oesophagus the peristalti(! wave passed to the j>oi-tion of the oesoph-
agus left on the stomach side in spite of the anatomical break. The same
experiment was performed successfidly on rabbits by Kronecker and Meltzer.
Observation of the stomach end of the oesophagus in this animal showed tiiat
it w-ent into contraction two seconds after the beginning of a swallowing act
whether the oesophagus was intact or ligated or completely divided by a trans-
verse incision. The afferent nerves concerned in this reflex are the sensory
fibres to the mucous membrane of the pharynx and oesophagus, including
branches of the glossopharyngeal, trigeminal, vagus, and superior laryngeal
division of the vagus. Artificial stimulation of this last nerve in the lower
animals is known to produce swallowing movements. Wassilieff ^ records that
in rabbits he was able to produce the swallowing reflex by artificial stimula-
tion of the nuicous membrane of the soft palate over a definite area. The

1 MoleschoU's Uniersuchnngen, 1876, Bd. xi. * Zeitschrift fiir Biologie, 1888, Bd. 24, P. 29.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 315

sensory Hbres to this area arise from the trigeminal nerve. The same observer,
in experiments upon himself, was unable to locate any particular area of the
mucous nu'Mibrane of the mouth which seemed to be especially comieeted with
the swallowing reflex. The physiological centre of the reflex is supposed to lie
quite far forward in the medulla, but its anatomical boundaries have not been
satisfactorily defined. It seems probal)le that in this as in other cases the
physiological centre is not a circumscribed collection of nerve-cells, but com-
prises certain portions, more or less scattered, of the nuclei of origin of the
efferent fibres to the muscles of deglutition. These muscles are innervated by
fibres from the hypoglossal, facial, trigeminal, glossopharyngeal, and vagus.
The latter nerve supplies through some of its branches the entire oesophagus
as well as some of the pharyngeal muscles, the muscles closing the glottis, and
the aryteno-epiglottidean, M-hich is supposed to aid in depressing <the epiglottis.

Movements of the Stomach.

The musculature of the stomach is usually divided into three layers, a lon-
gitudinal, an oblique, and a circular coat. The longitudinal coat is continuous
at the cardia with the longitudinal fibres of the oesophagus ; it spreads out from
this point along the length of the stomach, forming a layer of varying thick-
ness ; along the curvatures the layer is stronger than on the front and posterior
surfaces, while at the pyloric end it increases considerably in thickness, and
passes over the pylorus to be continued directly into the longitudinal coat of
the duodenum. The layer of oblique fibres is quite incomplete ; it seems to be
continuous with the circular fibres of the oesophagus and spreads out from the
cardia for a certain distance over the front and posterior surfaces of the fundus
of the stomach, but toward the pyloric end disappears, seeming to pass into
the circular fibres. The circular coat, which is placed between the two pre-
ceding layers, is the thickest and most important part of the musculature of
the stomach. At the extreme left end of the fundus the circular bands are
thin and somewhat loosely placed, but toward the pyloric end they increase
much in thickness, forming a strong muscular mass, which, as we shall see,
plays the most important part in the movements of the stomach. At the pylo-
rus itself a special development of this layer functions as a sphincter pylori,
which with the aid of a circular fold of the mucous membrane makes it
possible to shut oif the duodenum completely or partially from the cavity
of the stomach. The portion of the stomach near the pylorus is fre-
quently designated simply as the *' pyloric part," but owing to its distinct
structure and functions the more specific name of "antrum pylori" seems
preferable. The line of separation between the antrum pylori and the body
or fundus of the stomach is made by a special thickening of the circular fibres
which forms a structure known as the " transverse band " by the older
writers,^ and described more recently^ as the "sphincter antri pylorici."
This so-called sphincter lies at a distance of seven to ten centimeters from the

' See Beaumont: Physiology of Digestion, 2d ed., 1847, p. 104.

^ Hofmeister und Schiitz : Archiv fiir exper. Pathologie und Pharmakologie, 1886, Bd. xx.

316 AN AMERICAN TEXT-BOOK OF I'llYSlOLOGY.

pylorus. Between it and the pylorus is the ''antrum j)ylori," of" which the
distinguishing; features are the comparative smoothness and paleness oC the
raucous membrane, the presence of the pyloric as distinguished from the finidic
glands, and the existence of a relatively very strong musculature.

The movements of the stomach during digestion have been the subject of
much study and experimentation, both in man and the lower animals, but it
cannot be said that the mechanism of the movements is as yet completely
understood. The fundamental facts to be borne in mind are that during a
period of several hours after ordinary food is received into the stomach the
musculatin-e of this organ contracts in such a way as t<j keej) the contents in
movement, while from time to time the thinner portions of the semi-digested
food are sent through the pylorus into the duodenimi. There is a certain
orderliness in the movement, and especially in the separation and ejection of
the more liquid from the solid parts, which indicates that the whole act is
well co-ordinated to a definite end. The older physiologists spoke of a selec-
tive power of the pylorus in reference to the recurring acts of ejection of the
more liquid portions into the intestine, but a phrase of this kind, as applied to
a muscular apparatus, is pertiiissible only as a figure of speech, and throws no
light whatever upon the nature of the process. It has been the object of
recent investigations to discover the mecihanical factors involved in these acts
and their relations to the musculature known to be present. It has been shown
satisfactorily that the movements of the stomach are not de|>endent Ufwu its
connection with the central nervous system. The stomach receives a rich sup-
ply of extrinsic nerve-fibres, some of which are distributed to its nniscles and
serve to regulate its movements, as will be described later ; but when these
extrinsic nerves are all severed, and indeed when the stomach is completely
removed from the body, its movements may still continue in apparently a
normal way so long as proper conditions of moisture and temperature are
maintained. We must believe, therefore, that the stomach is an automatic
organ, using the word automatic in a limited sense to imply essential independ-
ence of the central nervous system. The normal stomach at rest is usually
quiet, and the stimulus to its movements comes from the presence of the solid
or liipiid material received into it from the a-sophagus. Upon the reception
of this material the movements begin, at first feebly but gradually increasing in
extent, and continue until most or all of the material has been sent into the
duodentun, the length of time recpiired depending upon the nature and amount
of the food. The exact character of the movements has been variously de-
scribed by different observers. Upon man they were care fid ly studied by
Beaumont* in his famous observations upon Alexis St. Martin (see p. 225),
and the essential points in his description have of late years been confirmed by
experiments upon dogs,^ whose stomachs closely resemble that of man. These

^ The Physiology of Digestion, 1883.

^ Hofmeister und Sohiitz: Archiv filr exper. Pathologic und Phannakologie, 1880, ]?d. xx. ;
Moritz: Zeitschrift filr Biologic, 1895, Bd. xxxii. ; Rossbach : Deutsches Archiv fiir klinische
Medicin, 1890, Bd. xlvi.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 317

observations all tend to show that the main movements of the stomach are
effected by the musculature of the antrum pylori, whose contraction is not only
the chief factor in ejecting the material into the duodenum, but also aids in
keeping the contents of the stomach in motion. The extent to which contrac-
tions occur in the fundic end of the stomach does not seem to be so clearly de-
termined. According to some observers rhythmic movements are absent in the
fundus to the left of about the middle of the stomach, this portion simply re-
maining in a condition of tone; according to others the contractions begin near
the oesophageal opening and pass thence toward the pylorus. The very careful
experiments of ITofmcister and Schlitz upon the isolated stomach of the dog,
together with the reliable observations made by Beaumont under such favora-
ble conditions on the human stomach, give us a basis for a description of the
sequence and extent of the movements during digestion, which is probably cor-
rect in its main features at least, although some of the details still need investi-
gation.

According to these observers a normal movement begins near the cardia by
a flattening or constriction which is feeble and is apparent only on the side of
the great curvature. This constriction is due to a contraction of the circular
muscle-fibres, and the wave thus started passes toward the pylorus, increasing
in strength as it goes, while the parts behind previously in contraction slowly
relax. This peristaltic wave comes to a stop a short distance in front of the
antrum pylori by a constriction involving the whole circumference of the
stomach to which Hofraeister and Schutz gave the name of the " pre-antral "
constriction ; it seems to mark the climax of the peristaltic movement. The
obvious effect of this movement so far would be to push forward some of the
contents of the fundus into the antrum. Immediately upon the formation of
this constriction the strong " sphincter antri pylorici " or transverse band which
marks the beginning of the antrum, contracts strongly— so strongly, in fact, in
what may be considered normal movements, as to cut off entirely the antrum
pylori from the fundus. Following upon this the musculature of the antrum
contracts as a whole, squeezing upon its contents and sending them through the
narrow opening of the pylorus into the duodenum. If, however, the contents
of the antrum are not entirely liquid, but contain some solid particles too large
to escape through the narrow pylorus, their presence seems to stimulate an.
" antiperistaltic" wave in the musculature of the antrum pylori— that is, a rnus-
cular wave running in the reverse direction to that of a normal one, from right
to left, the effect of which is to throw back these solid particles into the fundus,
which is now in communication with the antrum, the sphincter antri pylorici
having relaxed. This reversed wave in the antrum seems to have been observed
repeatedly by Beaumont upon the human stomach, as well as by Hofraeister
and Schutz 'upon the dog's stomach, and enables us to understand how solid
particles thrown against the pylorus are again forced back into the fundus to
undergo further digestive and mechanical action. These movements, as a
whole, from fundus to pvlorus occur with a certain rapidity which varies with
the nature and amount of the contents of the stomach and the period of diges-

318 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tion. In Beaumont's observations the movements of the pylorus are recorded
as follownig each other at intervals of two to three minutes, while upon dogs
similar movements are recorded as occurring from three to six times in a
minute.

It will be seen tiiat according to this description the movements occur in
two phases : first, the feeble peristaltic movement running over the fundus
chiefly on the side of the great curvature and resulting in i)ushing some of the
fundic contents into the antrum ; second, the sharp contraction of the sphincter
autri pyloric! folloM'ed by a similar contraction of the entire musculature of the
antrum, both circular autl longitudinal, the effect of which is to squeeze some
of the contents into the duodenum. It is possible that either of tliese phases,
but especially the first, might occur at times without the other, and in the first
-phase it is probable that the longitudinal fibres of the stomach also contract,
shortening the organ in its long diameter and aiding in the propulsive move-
ment, but actual observation of this factor has not been successfully made. It
can well be understood that a series of these movements occurring at short
intervals would result in putting the entire semi-liquid contents of tlie stomach
into constant circulation. The precise direction of the current set up is not
agreed upon, but it is probable that the graphic description given by Beaumont
is substantially accurate. A portion of this description may be quoted, as fol-
lows: "The ordinary course and direction of the revolutions of the food are,
first, after passing the oesophageal ring, from right to left, along the small
arch ; thence, through the large curvature, from left to right. The bolus, as it
entei-s the cardia, turns to the left ; passes the aperture ; descends into the splenic
extremity, and follows the great curvature toward the pyloric end. It then
returns in the course of the small curvature."- The average time taken for one
of these complete revolutions, according to observations made by Beaumont,
seems to vary from one to three minutes.

It is possible, of course, that this typical circuit taken by the food may often
be varied more or less l)y different conditions, but the muscular movements
observed from the outside would seem to be adapted to keeping up a general
revolution of the kind described. The general result upon the food may easily
be imagined. It becomes thoroughly mixed with the gastric juice and any liquid
.which may have been swallowed, and is gradually disintegrated, dissolved, and
more or less completely digested so far as the proteid and albuminoid constitu-
ents are concerned. The mixing action is aided, moreover, by the movements
of the diaphragm in respiration, since at each descent it presses upon the stomach.
The powerful muscular contractions of the antrum serve also to triturate the
softened solid particles, and finally the whole mass is reduced to a liquid or
semi-liquid condition in which it is known as chyme, and in this condition the
rhythmic contractions of the muscles of the antrum eject it into the duodenum.
The rhythmic spirting of the contents of the stomach into the duodenum has
been noticed by a number of observers by means of duodenal fistulas in dogs,
established just beyond the pylorus. It has lieen shown also that when the
food taken is entirely liquid — water, for example — the stomach is emptied in a

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 319

surprisingly sliort time, witliiu twenty to tliirty minutes ; if, however, the
water is taken with solid food tlieii naturally the time it will remain in the
stomach may be much lengthened.

A very interesting part of the mechanism of the stomach the action of
which is not thoroughly understood is the sphincter of the pylorus. During
the act of digestion this sphincter remains in a condition of tone; whether
its tonic contraction is sufficient only to narrow the pylorus, or whether it
is sufficient to completely shut oflp the pylorus so that a partial relaxation
must occur with each contraction of the musculature of the antrum, is not
sufficiently well known. It has been shown, however, that this part of the
circular layer of muscle is distinctly under the control of the extrinsic
nerves, its tonicity being increased by impulses received through the vagi and
diminished or inhibited by impulses through the splanchnics. It will be seen
from the above brief description that the muscles of the antrum pylori do
most of the work of the stomach, while in the much larger fundus the food
is retained as in a reservoir to be digested and mechanically prepared for
expulsion into the intestine, the two parts of the stomach fulfilling therefore
somewhat different functions. Moritz ^ has called especial attention to this
fact, and points out the great advantage which accrues to the digestive pro-
cesses in the intestine in having the stomach to retain the bulk of the food
swallowed during a meal, while from time to time small portions only are
sent into the intestine for more complete digestion and absorption. In this
way the intestine is protected from becoming congested, and its digestive and
absorptive processes are more perfectly executed.

Extrinsic Nerves to the Muscles of the Stomach. — The stomach re-
ceives extrinsic nerve-fibres from two sources ; from the two va^i and from
the solar plexus. The fibres from the latter source arise ultimately in the
spinal cord, pass to some of the thoracic ganglia of the sympathetic system,
and thence by way of the splanchnics to the semilunar or solar plexus and
then to the stomach. These fibres probably reach the stomach as non-medul-
lated or sympathetic fibres. The vagi where they are distributed to the
stomach seem to consist almost entirely of non-medullated fibres also, and
probably the fibres distributed to the muscular coat are of this variety. The
results of numerous experiments seem to show quite conclusively that in general
the fibres received along the vagus path are motor, artificial stimulation of
them causing more or less well marked contractions of part or all of the
musculature of the stomach. It has been shown that the sphincter pylori as
well as the rest of the musculature is supplied by motor fibres from these
nerves. The fibres coming through the splanchnics, on the contrary, are
mainly inhibitory. When stimulated they cause a dilatation of the contracted
stomach and a relaxation of the sphincter pylori. Some observers have
reported expei'iments which seem to show that this anatomical separation of
the motor and inhibitory fibres is not complete ; that some inhibitory fibres
may be found in the vagi and some motor fibres in the splanchnics. The
* Zeitschrift fiir Biologic, 1895, Bd. xxxii.

320 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

anatomical courses of tliese fibres are insufficiently known, but there seems to
be no question as to the existence of the two physiological varieties. Through
their activity, without doubt, the movements of the stomach may be regu-
lated, favorably or unfavorably, by conditions directly or indirectly affect-
ing the central nervous system. AVertheimer ' has shown expcrimcntaliv that
stimulation of the central end of the sciatic or the vagus nerve mav cause
reflex inhibition of the tonus of the stomach, and Doyon ^ has confirmed this
result in cases wliere the movements and tonicity of the stomach were first
increased by the action of pilocarpin and strychnin. It must be borne in
mind, however, that the action of these extrinsic fibres under normal conditions
is probably only to regulate the movements of the stomach. As we have
seen, even the extirpated stomach under proper conditions seems to execute
movements of the normal type. N^ormally the movements are provoked bv a
stimulus of some kind, usually the presence of food material in the interior
of the stomach. How the stimulus acts in this case, Nvhether directly upon the
muscle-fibres or indirectly through the intrinsic ganglia of the stomach, has
not been determined, and the evidence for either view is so insufficient that a
discussion of the matter at this time would scarcely be profitable. We must
wait for more complete investigations upon the physiology as well as the his-
tology of the muscle- and nerve-tissue in this and in other visceral organs
constructed on the same type.

Movements of the Intestines.

The muscles of the small and the large intestine are arranged in two layers,
an outer longitudinal and an inner circular coat, while between these coats and
in the submucous coat there are present the nerve-plexuses of Auerbach and
Meissner. The general arrangement of muscles and nerves is similar, there-
fore, to that prevailing in the stomach, and in accordance with this we find that
the physiological activities exhibited are of much the same character, only, per-
haps, not quite so complex.

Forms of Movement. — Two main forms of intestinal movement have been
distinguished, the peristaltic and the pendular.

Peristalsis. — The peristaltic movement consists in a constriction of the walls
of the intestine which beginning at a certain point passes downward away from
the stomach, from segment to segment, while the parts behind the advancing
zone of constriction gradually relax. The evident effect of such a movement
would be to push onward the contents of the intestines in the direction of the
movement. It is obvious that the circular layer of muscles is chiefly involved in
peristalsis, since constriction can only be produced by contraction of this layer.
To what extent the longitudinal muscles enter into the movement is not definitely
determined. The term " anti-peri.stalsis " is used to describe the same form of
movement running in the opposite direction — that is, toward the stomach.
Anti-peristalsis is usually said not to occur under normal conditions ; it has
been observed sometimes in isolated pieces of intestine or in the exposed intes-

* Archives de Physiologic normale et pathologique. 1892, p. 379. * Ibid., 1895^ p. 374.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 321

tine of living animals when stimulated artificially, and Griitzner' reports a
number of curious experiments which seem to show that substances such as
hairs, animal charcoal, etc., introduced into the rectum may travel upward to the
stomach under certain conditions. The peristaltic wave normally passes down-
ward, and that this direction of movement is dependent upou some definite
arrangement in the intestinal walls is beautifully shown by the experiments of
Mall ^ and others upon reversal of the intestines. In these experiments a por-
tion of the small intestine was resected, turned round and sutured in place
again, so that in this piece what was the lower end became the up[)er end.
In those animals that made a good operative recovery the nutritive condition
gradually became very serious, and in the animals killed and examined the
autopsy showed accunudatiou of material at the upper end of the reversed
piece of intestine, and great dilatation.

The peristaltic movements of the intestines may be observed upon living
animals when the abdomen is opened. If the operation is made in the air
and the intestines are exposed to its influence, or if the conditions of tempera-
ture and circulation are otherwise disturbed, the movements observed are
often violent and irregular. The peristalsis runs rapidly along the intes-
tines and may pass over the whole length in about a minute; at the same time
the contraction of the longitudinal muscles gives the bowels a peculiar writhing
movement. Movements of this kind are evidently abnormal, and only occur
in the body under the strong stimulation of pathological conditions. Normal
peristalsis, the object of which is to move the food slowly along the alimentary
tract, is quite a different affair. Observers all agree that the wave of contraction
is gentle and progresses slowly. It has been studied very successfully, so far as
rate of movement is concerned, by experiments upon animals in which a loop
of the intestines was resected, to make a " Thiry-Vella " fistula (see p. 246).
Cash ^ finds that in such isolated loops foreign substances introduced are pro-
pelled at different rates according to the condition of the animal. In the fast-
ing animal it requires from one and a half to two and a half minutes for a
distance of one centimeter. During exercise the movement is more rapid,
while during the first few hours of digestion, that is the time during which
the stomach is emptying its contents into the intestine, the velocity of the
movement is greatly increased, requiring only from twenty to fifty seconds to
cover a distance of one centimeter. The force of the contraction as measured
by Cash in the dog's intestine is very small. A weight of five to eight grams
was sufficient to check the onward movement of the substance in the intestine
and to set up violent colicky contractions which caused the animal evident
uneasiness. We may suppose that under normal conditions each contraction
of the antrum pylori of the stomach, which ejects chyme into the duodenum,
is followed by a peristalsis that beginning at the duodenum passes slowly
downward for a part or all of the small intestine. According to most

^ Deutsche medicinische Wochenschrift, 1894, No. 48.
2 The Johns Hopkins Hospital ReporL% vol. i. p. 93.
^ Proceedinrjs of the Boyal Society, London, 1887, vol. 41.
21

322 AX AyfFJUrAX TEXT-BOOK OF PHYSIOLOGY.

observers the movement is blocked at the ileo-csecal valve, and the peristaltic
movements of the large intestine form an independent group similar in all
their general characters to those of the small intestine, but weaker and slower.
3Iechanism of the Pei'istallic Movement. — The means by which the peri-
staltic movement makes its orderly forward progression have not been satis-
factorily determined. The simplest explanation woidd be to assume that an
impulse is conveyed directly from cell to cell in the circular muscular coat, so
that a contraction started at any point would spread by direct conduction of
the contraction change. This theory, however, does not explain satisfiictorily
the normal conduction of the wave of contraction always in one direction, nor
the fact that a reversed piece of intestine continues to send its waves in what
was for it the normal direction. It is possible, therefore, that the co-ordination
of the movement may be effected through the local nerve-ganglia, but our
knowledge of the mechanism and physiology of these peripheral nerve-plexuses
is as yet too incomplete to be applied satisfactorily to the explanation of the
movements in question.

Pendular 3Iovements. — In addition to the peristaltic wave a second kind
of movement may lie observed in the exposed intestines of a living animal.
This movement is characterized by a gentle swinging to and fro of the different
loops, whence its name of pendular movement. The oscillations occur at
regular intervals, and are usuallv ascribed to rhvthmic contractions of the
longitudinal muscles. Mall,^ however, believes that the main feature of this
movement is a rhythmic contraction of the circular muscles, involving a part
or all of the intestines. He prefers to speak of the movements as rhythmic
instead of pendular contractions, and points out that owing to the arrangement
of the blood-vessels in the coats of the intestine the rhythmic contractions should
act as a pump to expel the blood from the submucous venous plexus into the
radicles of the superior mesenteric vein, and thus materially aid in keeping up
the circulation through the intestine and in maintaining a good pressure in the
portal vein, in much the same way as happens in the case of the spleen (see p.
272). How far these rhythmic or pendular contractions occur under perfectly
normal conditions has not been determined.

Extrinsic Nerves of the Intestines. — As in the case of the stomach, the
small intestine and the greater part of the large intestine receive viscero-motor
nerve-fibres from the vagi and the sympathetic chain. The former, according
to most observers, when artificially stimulated cause movements of the intestine,
and are therefore regarded as the motor fibres. It seems probable, however,
that the vajji carry or mav carry in some animals inhibitory fibres as well, and that
the motor effects usually obtained upon stimulation are due to the fact that in these
nerves the motor fibres predominate. The fibres received from the sympathetic
chain, on the other hand, give mainly an inhibitory effect when stimulated,
although some motor fibres apparently may take this path. Bechterew and
Mislawski^ state that the sympathetic fibres for the small intestine emerge from

* The Johns Hopkins Hospital Reports, vol. i. p. 37.

' Du Bois-Reymond's ArchivfUr Physiologic, 1889, Suppl. Bd.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 323

the spiual cord as niedullated fibres iu the >i.\th dor.^al to the first lumbar
spinal nerves, and pass to the sympathetic oliain in the splancimic nerves and
thence to the semilunar j)lexus, while the sympathetic fibres to the large intes-
tine and rectum arise in the four lower lumbar and the three upper sacral spinal
nerves. According to Langley and Anderson' the descending colon and rec-
tum receive a double norve-supj^ly — first from the lumbar spinal nerves (second
to fifth), the fibres })assing through the sympathetic ganglia and the inferior
mesenteric plexus and causing chiefly an inhibition ; second, through the sacral
nerves, the fibres ])assing through the norvus erigens and the hypogastric plexus
and causing chiefly contraction of the circular muscle.

These extrinsic fibres undoubtedly serve for the regulation of the move-
ments of the bowels from the central nervous system ; conditions which influ-
ence the central system, either directly or indirectly, may thus affect the intesti-
nal movements. The paths of these fibres through the central nervous system
are not known, but there are evidently connections extending to the higher
brain-centres, since psychical states are known to influence the movements of the
intestine, and according to some observers stimulation of portions of the cere-
bral cortex may produce movements or relaxation of the walls of the small and
large intestines. As in the case of the stomach, the extrinsic fibres seem to
have only a regulatory influence. When they are completely severed the
tonicity of the walls of the intestine is not altered, and peristaltic and rhythmic
movements may still occur. The same results may be obtained even upon
excised portions of the intestines (Salvioli, Mall). It seems probable, there-
fore, that normal peristalsis in the living animal may be effected independently
of the central nervous system, although its character and strength is subject
to regulation through the medium of the viscero-motor fibres, in much the
same May, and possibly to as great an extent, as the movements of the heart are
controlled through its extrinsic nerves.

Effect of Various Conditions upon the Intestinal Movements. — Experi-
ments have shown that the movements of the intestines may be evoked in many
ways beside direct stimulation of the extrinsic nerves. Chemical stimuli may
be applied directly to the intestinal wall. The most noteworthy reaction of
this kind is the curious effect of potassium and sodium salts as first described
by IS^othnagel.^ Potassium salts in proper concentration excite a strong local
contraction of the circular fibres, producing a deep constriction at the point of
application of the stimulus. Sodium salts, on the contrary, produce a contrac-
tion above the point of application which subsequently spreads for some dis-
tance, apparently in the direction of a normal persistalsis, since its effect is to force
the contents downward. Violent movements may be produced also by shutting
off the blood-supply, and again temporarily when the supply is re-established.
A condition of dyspnoea may also start movements in the intestines or in some
cases inhibit movements wdiich are already in progress, the stimulus in this case
seeming to act upon the central nervous system and to stimulate both the motor

1 Journal of Physiology, 1895, vol. xviii. p. 67.

^ Virchov/s Archil filr patfiologische Anatomie und Physiologic, 1882, Bd. 88, S. 1.

324 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and the inhibitory fibres. Oxygen gas within tlio howi-ls tends to suspend the
movements of the intestine, wliile COj, CH^, and H^S act as stimuli, increasing
the movements. Organic acids, such as acetic, propionic, formic, and capryhc,
which may be formed normally within the intestine as the result of bacterial
action, act also as strong stimulants.'

Defecation. — The undigested and indigestible parts of the food, together
with some of the debris anil secretions from the alimentary tract, are carried
slowly through the large intestine by its peristaltic movements and eventually
reach the sigmoid flexure and rectum. Here the nearly solid material stimu-
lates by its pressure the sensory nerves of the rectum and produces a distinct
sensation and desire to defecate. The fecal material is retained within the rectum
by the action of the two sphincter muscles which close the anal opening. One
of these muscles, the internal sphincter, is a strong band of the circular layer
of involuntary muscles which forms one of the coats of the rectum. AVhen
the rectum contains fecal material this muscle seems to be thrown into a
condition of tonic contraction until the act of defecation begins, when it is
relaxed. The sphincter is composed of involuntary muscle and is innervated
by fibres arising partly from the sympathetic system, and in part through
the nervus erigens, from the sacral spinal nerves. The external sphincter ani
is composed of striated muscle-tissue and is under the control of the will to
a certain extent ; when, however, the stimulus from the rectum is sufficiently
intense, voluntary control is overcome and this sphincter is also relaxed.
The act of defecation is in part voluntary and in part involuntary. The
involuntary factor is found in the contractions of the strongly developed mus-
culature of the rectum, especially the circular layer, which serves to force the
feces onward, and the relaxation of the internal sphincter. It seems that these
two acts are mainly caused by reflex stimulation from the lumbar spinal cord,
although it is probable that the rectum, like the rest of the alimentary tract,
is capable of automatic contractions. The rectal muscles receive a double
nervous supply, containing physiologically both motor and inhibitory fibres.
Some of these fibres come from the nervus erigens by way of the hypogastric
plexus, and some arise from the lumbar cord and pass through the correspond-
ing sympathetic ganglia, inferior mesenteric ganglion, and hypogastric nerve.
It has been asserted that stimulation of the nervus erigens causes contrac-
tion of the longitudinal muscles and inhibition of the circular muscles, while
stimulation of the hypogastric nerve causes contraction of the circular muscles
and inhibition of the longitudinal layer. This division of activity is not
confirmed by the recent experiments of Langley and Anderson.^

The voluntarv factor in defecation consists in the inhibition of the external
sphincter and the contraction of the abdominal muscles. When these latter
muscles are contracted and at the same time the diaphragm is prevented from
moving upward by the closure of the glottis, the increased abdominal jjressure
is brought to bear upon the abdominal and pelvic viscera, and aids strongly in
pres.sing the contents of the descending colon and sigmoid flexure into the

' Bokai: ArchivfUr ezper. Pathologic und Pharmakologie, 1888, Bd. 24, S. ]53. ' Op. cit.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 325

rectum. The pressure in the abdominal cavity is still further increased if
a deep inspiration is first made and then maintained dnrini^ the contraction
of the abdominal nmscles. Although the act of defecation is normally initiated
by voluntary effort, it may also be aroused by a purely involuntary reflex when
the sensory stinudus is sufficiently strong. Goltz ' has shown that in dogs
in which the spinal cord had been severed in the lower thoracic region defe-
cation was performed normally, the external sphincter being relaxed.

It would seem that the whole act of defecation is at bottom an involuntary
reflex. The })hysiological centre for the movement lies in the lumbar cord,
and has sensory and motor connections with the rectum and the muscles of
defecation, but this centre is in part at least provided with connections with
the centres of the cerebrum through which the act may be controlled by
voluntary impulses and by various psychical states, the effect of emotions
upon defecation being a matter of common knowledge. In infants the essen-
tially involuntary character of the act is well seen.

Vomiting. — The act of vomiting causes an ejection of the contents of the
stomach through the oesophagus and mouth to the exterior. It was long
debated whether the force producing this ejection comes from a strong contrac-
tion of the walls of the stomach itself or whether it is due mainly to the
action of the walls of the abdomen. A forcible spasmodic contraction of the
abdominal muscles takes place, as aiay easily be observed by any one upon
himself, and it is now believed that the contraction of these muscles is the
principal factor in vomiting. Magendie found that if the stomach was extir-
pated and a bladder containing water was substituted in its place and connected
with the oesophagus, injection of an emetic caused a typical vomiting movement
with ejection of the contents of the bladder. Gianuzzi showed, on the other
hand, that upon a curarized animal vomiting could not be produced by an emetic
— because, apparently, the muscles of the abdomen were paralyzed by the curare.
There are on record, however, a number of observations which tend to show that
the stomach is not entirely passive during the act. On the contrary, it may
exhibit contractions, more or less violent in character, which while insufficient
in themselves to eject its contents, probably aid in a normal act of vomiting.
The act of vomiting is in fact a complex reflex movement into wdiich many
muscles enter. The following events are described : The vomiting is usually
preceded by a sensation of nausea and a reflex flow of saliva into the mouth.
These phenomena are succeeded or accompanied by retching movements, which
consist essentially in deep spasmodic inspirations with a closed glottis. The
effect of these movements is to compress the stomach by the descent of the
diaphragm, and at the same time to increase decidedly the negative pressure in
the thorax, and therefore in the thoracic portion of the oesophagus. During
one of these retching movements the act of vomiting is effected by a convulsive
contraction of the abdominal wall which exerts a sudden additional strong
pressure upon the stomach. At the same time the cardiac orifice of the
stomach is dilated, possibly by an inhibition of the sphincter, aided it is sup-
' Archiv fur die gesammte Physiologic, 1874, Bd. viii. S. 460.

326 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

posed by tlie contraction of the longitudinal muscle-fibres of the (esophagus
and the oblique fibres of the niuxcular coat of the stomach. The stomach
contents are, therefore, forced violently out of the stomach through the u'soj)h-
agus, the negative pressure in the latter probably assisting in the act. The
passage through the (cso})hagus is effected mainly by the force of the contrac-
tion of the abdominal muscles; there is no evidence of antiperistaltic move-
ments on the part of the oesophagus itself. During the ejection of the contents
of the stomach the glottis is kept closed by the adductor muscles, and usually
the nasal chamber is likewise shut off from the pharynx by the contraction of
the posterior pillars of the fauces on the palate and uvula. In violent vomit-
ing, however, the vomited material may break through this latter barrier and
be ejected partially through the nose.

Nervous Mecluaiimii of Vomiting. — That vomiting is a reflex act is abun-
dantly shown by the frequency with which it is produced in consequence of
the stimulation of sensory nerves or as the result of injuries to various parts
of the central nervous system. After lesions or injuries of the brain vomiting
of\en results. Disagreeable emotions and disturbances of the sense of equi-
librium may produce the same result. Irritation of the mucous membrane
of various parts of the alimentary canal (as, for example, tickling the back
of the pharynx with the finger), disturbances of the urogenital apparatus,
artificial stimulation of the trunk of the vagus and of other sensory nerves,
may all cause vomiting. Under ordinary conditions, however, irritation of
the sensory nerves of the gastric nmcous membrane is the most common
cause of vomiting. This efifect may result from the products of fermentation
in the stomach in cases of indigestion, or may be produced intentionally by
local emetics, such as mustard, taken into the stomach. The afferent path
in this case is through the sensory fibres of the vagus. The efferent paths
of the reflex are found in the motor nerves innervating the muscles con-
cerned in the vomiting, namely, the vagus, the phrenics, and the spinal nerves
supplying the abdominal muscles. Whether or not there is a definite vomit-
ing centre in which the afferent impulses are received and through which
a co-ordinated series of efferent impulses is sent out to the various muscles,
has not been satisfactorily determined. It has been shown that the portion
of the nervous system through which the reflex is effected lies in the me-
dulla. But it has been pointed out that the muscles concerned in the act
are respiratory muscles. Vomiting in fact consists essentially in a simul-
taneous spasmodic contraction of expiratory (abdominal) muscles and inspi-
ratory muscles (diaphragm). It has therefore been suggested that the reflex
takes place through the respiratory centre, or some part of it. This view
seems to be opposed by the experiments of Thumas,^ who has shown that
when the medulla is divided down the mid-line respiratory movements con-
tinue as usual, but vomiting can no longer be produced by the use of emetics.
Thumas claims to have located a vomiting centre in the medulla in the imme-
diate neighborhood of the calamus scriptorius. Further evidence, however,
' Virckow's Archiv fur patholoyische Anatomie, etc., 1891, Bd. 123, S. 44.

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 327

is required upon this point. The act of vomiting may be produced not only
08 a reflex from various sensory nerves, but may also be caused by direct
action upou the medullary centres. The action of apomorphia is most easily
explained by supposing that it acts directly on the nerve-centres.

Micturition. — The urine is secreted continuously by the kidneys, is car-
ried to' the bladder through the ureters, and is then at intervals finally ejected
from the bladder through the urethra by the act of micturition.

Movements of the Ureters. — The ureters possess a muscular coat consisting of
an internal longitudinal and external circular layer. The contractions of this
muscular coat are the means by which the urine is driven from the pelvis of the
kidney into the bladder. The movements of the ureter have been carefully
studied by Engelmann.^ According to his description the musculature of the
ureter contracts spontaneously at intervals of ten to twenty seconds (rabbit), the
contraction beginning at the kidney and progressing toward the bladder in the
form of a peristaltic wave and with a velocity of about twenty to thirty milli-
meters per second. The result of this movement should be the forcing of the
urine into the bladder in a series of gentle rhythmic spirts, and this method of
filling the bladder has been observed in the human being. Suter and Mayer ^
report some observations upon a boy in wdiom there was ectopia of the bladder
with exposure of the orifices of the ureters. The flow into the bladder was
intermittent and was about equal upou the two sides for the time the child
was under observation (three and a half days).

The causation of the contractions of the ureter musculature is not easily
explained. Engelraann finds that artificial stimulation of the ureter or of a
piece of the ureter may start peristaltic contractions which mov'e in both direc-
tions from the point stimulated. He was not able to find ganglion-cells in the
upper two-thirds of the ureter, and was led to believe, therefore, that the con-
traction originates in the muscular tissue independently of extrinsic or intrinsic
nerves, and that the contraction wave propagates itself directly from muscle-
cell to muscle-cell, the entire musculature behaving as though it were a single,
colossal hollow muscle-fibre. The liberation of the stimulus which inaugurates
the normal peristalsis of the ureter seems to be connected with the accumulation
of urine in its upper or kidney portion. It may be supposed that the urine
that collects at this point as it flows from the kidney stimulates the muscular
tissue to contraction, either by its pressure or in some other way, and thus leads
to an orderly sequence of contraction waves. It is possible, however, that the
muscle of the ureter, like that of the heart, is spontaneously contractile under
normal conditions, and does not depend upon the stimulation of the urine.
Thus, according to Engelmann, section of the ureter near the kidney does not
materially affect the nature of the contractions of the stump attached to the
kidney, although in this case the pressure of the urine could scarcely act as a
stimulus. Moreover, in the case of the rat, in which the ureter is highly con-
tractile, the tube may be cut into several pieces and each piece will continue to

^ Pfliiger's Archivfiir die gesammte Physiologie, 1869, Bd. ii. S. 243; Bd. iv. S. 33,
* Archivfiir exper. Pathologic und Pharmakologie, 1893, Bd. 32, S. 241.

328 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

exhibit periodic peristaltic contractions. It docs not seem possible at present
to decide between these two views as to the cause of the contractions. The
nature of the contractions, their mode of proj^rcssion, and the way in which
they force the urine thruugh the ureter seem, however, to be clearly established.
Efforts to show a regulatory action upon tiiese movements through the central
nervous system have so far given only negative results.

Movements of the Bladder. — The bladder contains a muscular coat of plain
muscle-tissue, which, according to the usual description, is arranged so as to
make an external longitudinal coat and an internal circular or oblique coat.
A thin longitudinal layer of muscle-tissue lying to the interior of the circular
coat is also described. The separation between the longitudinal and circular
layers is not so definite as in the ease of the intestine ; they seem, in fact, to form
a continuous layer, one passing gradually into the other by a change in the
direction of the fibres. At the cervix the circular layer is strengthened, and
has been supposed to act as a sphincter with regard to the urethral orifice — the
so-called sphincter vesica iuternus. Round the urethra just outside the blad-
der is a circular layer of striated muscle which is frequently designated as the
external sphincter or sphincter urethrEe. The urine brought into the bladder
accimiulates within its cavity to a certain limit. It is prevented from escape
through the urethra at first by the mere elasticity of the parts at the urethral
orifice, aided perhaps by tonic contraction of the internal sphincter, although
this function of the circular layer at this point is disputed by some observers.
When the accumulation becomes greater the external sphincter is brought into
action. If the desire to urinate is strong the external sphincter seems undoubt-
edly to be controlled by voluntary effort, but whether or not, in moderate filling
of the bladder, it is brought into play by an involuntary reflex is not definitely
determined. Back-flow of urine from the bladder into the ureters is effectually
prevented bv the oblique course of the ureters through the wall of the
bladder. Owing to this circumstance pressure within the bladder serves to close
the mouths of the ureters, and indeed the more completely the higher the pres-
sure. At some point in the filling of the bladder the pressure is sufficient to
arouse a conscious sensation of fulness and a desire to micturate. Under nor-
mal conditions the act of micturition follows. It consists essentially in a strong
contraction of the bladder with a simultaneous relaxation of the external
sphincter, if this muscle is in action, the effect of which is to obliterate more or
less completely the cavity of the bladder and drive the urine out through the
urethra.

The force of this contraction is considerable, as is evidenced by the height
to which the urine may spirt from the end of the urethra. According to
Mosso the contraction may support, in the dog, a column of li(|uid two meters
high. The contractions of the bladder may be and usually are assisted by
contractions of the walls of the abdomen, especially toward the end of the act.
As in defecation and vomiting, the contraction of the abdominal muscles, when
the glottis is closed so as to keep the diaphragm fixed, serves to increase the
pressure in the abdominal and jielvic cavities, and is thus used to assist in or

MOVEMENTS OF THE ALIMENTARY CANAL, ETC. 329

complete the emptying ol'tlic l)la(l(l(M-. It is, however, ixtt an essential part of
the act of micturition. I'lie last portions of tli(,' nrine escaping into tlie urethra
are ejected, in the male, in spirts produced by the rhythmic contractions of the
l)ull)o-cavernosus nuiscie.

Considerable uncertainty and difference of opinion exists as to the physio-
logical mechanisiu by which this series of muscular contractions, and especiallv
the contractions of the bladder itself, is produced. According to the frequently
quoted description given by Goltz^ the series of events is as follows: The dis-
tention of the bladder by the urine causes finally a stimulation of the sensory
fibres of the organ and produces a reflex contraction of the bladder musculature
which squeezes some urine into the urethra. The first drops, however, that
enter the urethra stimulate the sensory nerves there and give rise to a coascious
desire to urinate. If no obstacle is presented the bladder then empties itself,
assisted perhaps by the contractions of the abdominal muscles. Tiie emptying
of the bladder may, however, be prevented, if desirable, by a voluntary con-
traction of the sphincter urethrse, which op])oses the eiFect of the contraction of
the bladder. If the bladder is not too full and the sphincter is kept in action
for some time, the contractions of the bladder may cease and the desire to
micturate pass oif. According to this view the voluntary control of the
process is limitetl to the action of the external sphincter and the abdominal
muscles ; the contraction of the bladder itself is purely an unconscious reflex
taking place through a lumbar centre.

The experiments of Goltz and others, upon dogs in which the spinal cord
was severed at the junction of the lumbar and the thoracic regions, prove
that micturition is essentially a reflex act with its centre in the lumbar cord,
but a number of physiologists have concluded that the contractions of the
bladder itself, in spite of its involuntary musculature, is also under control of
the will. Mosso and Pellacani " have made experiments upon women which
seem to show that this is the case. In these experiments a catheter was intro-
duced into the bladder and connected with a recording apparatus to measure
the volume of the bladder. It was found that, in some cases at least, the
woman could empty the bladder at will without using the abdominal muscles.
The same authors adduce experimental evidence to show that the sensation of
fulness and desire to micturate come from sensory stimulation in the bladder
itself caused by the pressure of the urine. They point out that the bladder is
very sensitive to reflex stimulation ; that every psychical act and every sensory
stimulus is apt to cause a contraction or increased tone of the bladder. The
bladder is, therefore, subject to continual changes in size from reflex stimula-
tion, and the pressure within it will depend not simply on the quantity of
urine but on the condition of tone of the bladder. At a certain pressure
the sensory nerves are stimulated and under normal conditions micturition
ensues. We may understand, from this point of view, how it happens that we
have sometimes a strong desire to micturate when the bladder contains but little

^ Pfliiger's Archivfiir die gesammte Physiologie, 1874, Bd. viii. S. 478.
^ Archives italienne de Biologic, 1882, tome i.

330 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

urine — for exaiupk', uikKt emotional excitement. In snch cases if the micturi-
tion is prevented, probably by the action of the external sphincter, the bladder
may subsequently relax and the .sensation of fulness and desire to micturate
pass away until the urine accumulates in sufficient (juantity or the pressure is
again raised by some circumstance which causes a reflex contraction of the
bladder.

Nervous Mechanism. — According to a recent paper by Langley and Anders(jn,'
the bladder in cats, dogs, and rabbits receives motor fibres from two sources: (1)
From the lumbar nerves, the fibres passing out iu the second to the fifth lumbar
nerves and reaching the bladder through the sympathetic chain and the infe-
rior mesenteric ganglion and hypogastric nerves. Stimulation of these nerves
causes comparatively feeble contraction of the bladder. (2) From the sacral
spinal nerves, the fibres originating in the second and third sacral spinal nerves,
or in the rabbit iu the third and fourth, and being contained in the so-called
nervus erigens. Stimulation of these nerves, or some of them, causes strong
contractions of the bladder, sufficient to empty its contents. Little evidence
was obtained of the presence of vaso-motor fibres. According to Xawrocki
and Skabitschewsky ^ the spinal sensory fibres to the bladder are found in part
in the posterior roots of the first, second, third, and fourth sacral spinal nerves,
particularly the second and third. When these fibres are stimulated they excite
reflexlv the motor fibres to the bladder found in the anterior roots of the second
and third sacral spinal nerves. Some sensory fibres to the bladder pass by way
of the hypogastric nerves. When these are stimulated they produce, according
to these authors^ a reflex effect upon the motor fibres in the other hypogastric
nerve, causing a contraction of the bladder, the reflex occurring through the
inferior mesenteric ganglion. This observation has been confirmed by several
authorities, and is the best example of a peripheral ganglion serving as a reflex
centre. Langley and Anderson,^ who also obtained this effect, give it a special
explanation, contending that it is not a true reflex.

The immediate spinal centre through which the contractions of the bladder
may be reflexly stimulated or inhibited lies, according to the experiments of
Goltz, in the lumbar portion of the cord, probably between the second and fifth
lumbar spinal nerves. In dogs in which this portion of the cord was isolatal
by a cro&s section at the junction of the thoracic and lumbar regions, micturi-
tion still ensued when the bladder was sufficiently full, and could be called
forth reflexly by sensory stimuli, especially by slight irritation of the anal
region.

' Jawmul of Physiology, 1895, vol. xix. p. 71.

* Pfliiger's Archivfiir die gesammte Physiologie, 1891, Bd. 49, S. 141.

^Journal of Physiology, 1894, vol. xvi. p. 410.

VI. BLOOD AND LYMPH.

BLOOD.

A. General. Properties: Physiology of the Corpuscles.

The blood of the body is contained in a practically closed system of tubes,
the blood-vessel^, within which it is kept circulating by the force of the heart-
beat. The blood is usually spoken of as the nutritive liquid of the body, but
its functions may be stated more explicitly, although still in quite general
terms, by saying that it carries to the tissues food-stuffs after they have been
properly prepared by the digestive organs; that it transports to the tissues
oxygen absorbed from the air in the lungs ; that it carries off" from the tissues
various waste products formed in the processes of disassimilation, such as
urea, uric acid, water, CO2, etc. ; and that in warm-blooded animals it aids in
equalizing the temperature of the body. It is quite obvious, from these
statements, that a complete consideration of the physiological relations of the
blood would involve substantially a treatment of the whole subject of physi-
ology. It is proposed, therefore, in this section to treat the blood in a re-
stricted way — to consider it, in fact, as a tissue in itself, and to study its com-
position and properties without especial reference to its nutritive relationship
to other parts of the body.

Histological Structure. — The blood is composed of a liquid part, the
plasma, in which float a vast number of microscopic bodies, the blood-corpius-
des. There are at least three different kinds of corpuscles, known respectively
as the red corpuscles; the white corpuscles or leucocytes, of which in turn
there are a number of different kinds ; and the hlood-plates. As the details
of structure, size, and number of these corpuscles belong properly to text-
books on histology, they will be mentioned only incidentally in this section
when treating of the physiological properties of the corpuscles. Blood-plasma,
when obtained free from corpuscles, is perfectly colorless in thin layers— for
example, in microscopic preparations ; when seen in large quantities it shows a
slightly yellowish tint, the depth of color varying with different animals. This
color is due to the presence in small quantities of a special pigment, the nature
of which is not definitely known. The red color of blood is not due, there-
fore, to coloration of the blood-plasma, but is caused by the mass of red cor-
puscles held in suspension in this liquid. The proportion by bulk of plasma
to corpuscles is usually given, roughly, as two to one.

Blood-serum and Befibrinated Blood.— In connection with the explanation
of the term " blood-plasma" just given, it will be convenient to define briefly

331

332 ^iV^ AMERICAN TEXT-BOOK O/' PHYSIOLOGY.

the terms " blood-serum " and " defibriuated blood." Blootl, after it escapes
from the vessels, usually clots or eoa<;ulates ; the nature of this j)roce&s is
discussed in detail on j). 352, The clot, as it forms, gradually shrinks and
squeezes out a clear liquid to which the name bfood-.scnDii is given, Serum
resembles the plasma of normal blood in general aj)pearance, but differs from
it in composition, as Avill be exj)laincd later. At ])resent we may say, by way
of a preliminary definition, that blood-serum is the licpiid part of blood after
coagulation has taken })lace, as blood-plasma is the liquid part of blood before
coagulation has taken place. If shed blood is whii)])e(l vigorously with a rod
or some similar object while it is clotting, the essential part of the clot —
namely, the fibrin — forms differently from what it does when the blood is
allowed to coagulate quietly ; it is deposited in shreds on the whipper. Blood
that has been treated in this way is known as defibr'mated blood. It consists
of blood-serum plus the red and white corpuscles, and as far as aj^pearances
go it resembles exactly normal blood ; it has lost, however, the power of clot-
ting. A more complete definition of these terms will be given after the sub-
ject of coagulation has been treated.

Reaction. — The reaction of blood is alkaline, owing mainly to the alka-
line salts, especially the carbonates of soda, dissolved in the plasma. The
degree of alkalinity varies with different animals: reckoned as NagCOg, the
alkalinity of dog's blood corresponds to 0,2 per cent, of this salt; of human
blood, 0.35 per cent. The alkaline reaction of blood is very easily demon-
strated upon clear plasma free from corpuscles, but with normal blood the red
color prevents the direct application of the litmus test. A number of simple
devices have been suggested to overcome this difficulty. For example, the
method employed by Zuntz is to soak a strip of litmus-paper in a concentrated
solution of NaCl, to place on this paj)er a drop of blood, and, after a few
seconds, to remove the drop with a stream of water or with a piece of filter-
paper. The alkaline reaction becomes rapidly less marked after the blood has
been shed; it varies also slightly under different conditions of normal life
and in certain pathological conditions. After meals, for instance, during the
act of digestion, it is said to be increased, while, on the contrary, exercise
causes a diminution. In no case, hoM'ever, does the reaction become acid.
For details of the methods used for quantitative determinations of the alka-
linity of human blood, reference must be made to original sources.'

Specific Gravity. — The specific gravity of human blood in the adult male

may vary from 1041 to 1067, the average being about 1055. Jones ^ made

a careful study of the variations in specific gravity of human blood under

different conditions of health and disease, making use of a simj)le method

which requires only a few drops of l)lood for each determination. He found

that the specific gravity varies with age and sex, that it is diminished after

eating and is increased by exercise, that it falls slowly during the day and

rises gradually during the night, and that it varies greatly in individuals, "so

' Peiper : Virchou^s Archiv, vol, cxvi,, 1889, p. 337,
* Journid of Phymdogy, vol. xii., 1891, p. 299.

BLOOD.

333

iniKh so that a speciHc gravity which is normal for oue may be a sigu ol dis-
ease in another." The siiecific gravity of the corpuscles is slightly greater
than that of the plasma. For this reason the corpuscles in shed blood, when
its coagulation is prevented or retarded, tend to settle to the bottom of the
containing utensil, leaving a more or less clear layer of supernatant pksma.
Among themselves, also, the corpuscles ditfer slightly in specific gravity, the
red corpuscles being heaviest and the blood-plates being lightest.

Red Corpuscles.— The red corpuscles in man and in all the mammalia,
with the exception of the camel and other members of the group Camelidie,
are biconcave circular disks without nuclei; in the Caraelid^ they have an
elliptical form. Their average diameter in man is given at 7.7// (l/i = 0.001
of a mm.); their number, which is usually reckoned as so many in a cubic
millimeter, varies greatly under diiferent conditions of health and disease.
The average number is given as 5,000,000 per cubic mm. for males and
4,500,000 for females. The red color of the corpuscles is due to the presence
in them of a pigment known as "hemoglobin." Owing to the minute size
of the corpuscles, their color when seen singly under the microscope is a
ftiint yellowish-red, but when seen in mass they exhibit the well-known
blood-red color, which varies from scarlet in arterial blood to purplish-red
in venous blood, this variation in color being dependent upon the amount of
oxygen contained in the blood in combination with the haemoglobin. Speaking
generally, the function of the red corpuscles is to carry oxygen from the lungs
to the tissues. This function is entirely dependent upon the presence^ of
hemoglobin, which has the power of combining easily with oxygen gas. The
physiology of the red corpuscles, therefore, is largely contained in a description
of the properties of hsemoglobiu.

Condition of the Haemoglobin in the Corpuscle.— The finer structure
of the red corpuscle is not completely known. It is commonly believed that
the corpuscle consists of two substances— a delicate, extensible, colorless pro-
toplasmic material, which gives to the corpuscle its shape and which is known
as the stroma, and the hemoglobin. The latter constitutes the bulk of the cor-
puscle, forming as much as 95 per cent, of the solid matter. It was formerly
thought that hemoglobin is disseminated as such in the interstices of the
porous spongy stroma, but there seem to be reasons now for believing that
it is present in the corpuscles in some combination the nature of which is
not fully known. This belief is based upon the fact that Hoppe-Seyler ^ has
shown that hemoglobin while in the corpuscles exhibits certain minor differ-
ences in properties as compared with hemoglobin outside the corpuscles. In
various ways the compound of hemoglobin in the corpuscles may be destroyed,
the hemoglobin being set free and passing into solution in the plasma. Blood
in which this change has occurred is altered in color and is known as " laky
blood." In thin layers it is transparent, whereas normal blood with the
hemo-lobin still in the corpuscles is quite opaque even in very thin strata.
Blood'may be made laky by the addition of ether, of chloroform, of bile or
1 Zeitschrijt fur physwlogiscke Chemie, vol. xiii., 1889, p. 477.

334 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the bile acids, of the .•^eniin of other animals, by an excess of water, by
alternately freezing and thawintr, and by a nnmber of other methods. In
connection with two of these methods of discharging haemoglobin from the
corpuscles theie have come into use in current medical and physiologicjd
literature two technical terms which it may be well to attempt to define.

GlohuUcidal Action of S€)'um. — It was shown first by Landois that the
serum of one animal may have the property of destroying the red corpuscles
in the blood of another animal, thus making the blood laky. This fact, which
has since been investigated more fully, is now designated under the term of
"globulicidal " action of the serum. It has been found that different kinds of
serum show different degrees of globulicidal activity, and that white as well as
red corj)uscles may be destroyed. Dog's serum or Inmian serum is strongly
globulicidal to rabbit's blood. It would seem that this lU'tion is not due to
mere variations in the amounts of inorganic salts in the different kinds of
serum, since the remarkable fact has been discovered that heating serum to
55° or 60° C. for a few minutes destroys its globulicidal action, although such
treatment causes no coagulation of the proteids nor any visible change in the
liquid. This globulicidal action seems to be associated with a similar destruc-
tive effect of serum on bacteria — its so-called " bactericidal action " — but a
satisfactory explanation of either phenomenon has not yet been given. The
subject is complicated by the fact that the serum of some animals fails to give
the globulicidal reaction ; horse's serum, for instance, does not destroy the red
corpuscles of rabbit's blood. A discussion of the theories and facts bearing
upon the matter would lead too far into pathological literature, to which the
reader is referred for further information.

Isotonic Solutions. — AVhen blood or defibrinated blood is diluted with
water, a point is soon reached at wliich haemoglobin begins to pass out of the
corjMiscles into the plasma or the serum, and the blood begins to become laky;
to obtain this effect different quantities of water may be required for the
blood of different animals, frog's blood, for example, requiring more water than
mammalian blood. It appears that the liquid surrounding the corjniscles must
have a certain concentration as regards salts or other soluble substances, such
as sugar, in order to prevent the entrance of water into the substance of the
corpuscle. There exists normally in the red corpuscle a certain quantity
of water, determined by the nature of its own substance and the attraction for
water exercised by the soluble substances in the liquid surrounding the corj)us-
cle. If the concentration of the outside liquid is diminished, this equilibrium
is destroyed and water passes into the corpuscle; if the dilution has been suf-
ficient, enough water pass&s into the corpuscle to make it swell and eventually
to force out the haemoglobin. Liquids containing inorganic salts, or other sol-
uble substances with an attraction for water, in quantities sufficient to prevent
the imbibition of water by the corpuscles are said to be " isotonic to the cor-
puscles." Red corpuscles suspended in such liquids do not change in shape nor
lose their haemoglobin. AVhen solutions of different substances are compared
from this standpoint, it is found that the concentration necessary varies with

BLOOD. 335

the substance used. Thus, a solution of NaCl of 0.64 per cent, is isotonic with a
sohition of sugar of 5.5 per cent, or a sohitiou of KNO3 of 1 .09 per cent. When
placed in any of these three solutions red corpuscles do not take uj) water — at
least not in quantities sufficient to discharge the haemoglobin. For a more
complete account of these relations the reader is referred to <jriginal sources
(Hamburger '). It may be said that the term was introduced first in connec-
tion with plant-cells. In the animal body it happens that the isotonic relations
of certain substances have been worked out for the red corpuscles, but similar
relations must exist with reference to tiie other cells. Speaking generally, it
may be said that tlie composition of normal blood and Iymj)li is isotonic to the
tissue-elements, and that it must be kept so to preserve the cells from injury.

Nature and Amount of Haemog-lobin. — Hsemoglobin is a vcrv com})lex
substance belonging to the group of combined proteids. (For the definition
and classification of proteids, as well as for the purely chemical properties of
hsemoglobin and its derivatives, reference must be made to the section on " The
Ciiemistry of the Body.") When decomposed in various ways haemoglobin
breaks up into a proteid (globulin, 96 per cent.) and a simpler pigment (haema-
tin, 4 per cent.). When the decomposition takes place in the absence of oxygen,
the products formed are globulin and haemochromogen, and the decomposition
seems to be of the nature of a simple dissociation. Haemochromogen in the
presence of oxygen quickly undergoes oxidation to the more stable haematin.
Ho}>pe-Seyler has shown that haemochromogen possesses the chemical group-
ing which gives to haemoglobin its power of combining readily with oxygen
and its distinctive absorption spectrum. On the basis of facts such as these,
haemoglobin may be defined as a compound of a proteid body with haemochro-
mogen. It seems, then, that although the haemochromogen portion is the
essential thing, giving to the molecule of haemoglobin its valuable physiological
properties as a respiratory pigment, yet in the blood-corpuscles this substance
is incorporated into a much larger and more unstable molecule, whose behavior
toward oxygen is different from that of the haemochromogen itself, the differ-
ence being mainly in the fact that the haemoglobin as it exists in the corpus-
cles forms w^ith oxygen a comparatively feeble combination which may be
broken up readily with liberation of the gas.

Haemoglobin is widely distributed throughout the animal kingdom, being
found in the blood-corpuscles of mammalia, birds, reptiles, amphibia, and
fishes, and in the blood or blood-corpuscles of many of the invertebrates.
The composition of its molecule is found to vary somewhat in different animals,
so that, strictly speaking, there are probably a number of different forms
of haemoglobin — all, however, closely related in chemical and physiological
properties. Elementary analysis of dog's haemoglobin shows the following
percentage composition (Jaquet) : C 53.91, H 6.62, N 15.98, S 0.542,
Fe 0.333, O 22.62. Its molecular formula is given as C^^^^^^^-^^YeO^^^,
which would make the molecular weight 16,669. Other estimates are given of
the molecular formula, but they agree at least in showing that the molecule
* Du Bois-Reymond's Archivfur Physiologic, 1886, p. 476; 1887, p. 31.

336 AN AMERICAN TEXT-BOOK OF PITYSIOLOGY.

is of enormous size. The molecular formula for hajmochroraogen is iiiiich
simpler; it is usually \i\\vn as C^JTjgN^FoOj. The exact amount of h;em()<i;lol)in
in iunuau blood varies naturally with the individual and with ditU'rent condi-
tions of life. According to Preyer,^ the average amount for the adult male is
14 grams of htemoglobin to each 100 grams of blood. It is estimated that in
the blood of a man weighing Q^ kilos, there are contained about 750 grams of
haemoglobin, which is distributed among some twenty-five trillions of corpuscles,
giving a total superficial area of about 3200 square meters. Practically all of
this large surface of haemoglobin is available lor the absorption of oxygen
from the air in the lungs, for, owing to the great number and the minute
size of the capillaries, the blood, in passing through a capillary area, becomes
subdivided to such an extent that the red corpuscles stream through the capil-
laries, one may say, in single file. In circulating through the linigs, therefore,
each corpuscle becomes exposed more or less completely to the action of the
air, and the utilization of the entire quantity of haemoglobin must be nearly
}>erfect. It may be worth while to call attention to the fact that the biconcave
form of the red corpuscle increases the superficies of the corpuscle and tends
to make the surface exposure of the haemoglobin more complete.

Compounds -with Oxygen and. other Gases. — Haemoglobin has the
property of uniting with oxygen gas in certain definite proportions, forming a
true chemical compound. This compound is known as oxi/hcemoglobin ;
it is formed whenever blood or haemoglobin solutions are exposed to air or
otherwise brought into contact with oxygen. Each molecule of luemoglobin
is supposed to combine with one molecule of oxygen, and it is usually estimated
that 1 gram of dried haemoglobin (dog) can take up 1.59 c.c. of oxygen
measured at 0° C. and 760 mm. of barometric pressure. Oxyhaemoglobin is
not a very firm compound. If placed in an atmosphere containing no oxy-
gen, it will be dissociated, giving off free oxygen and leaving behind luemo-
globin, or, as it is often called by way of distinction, " reduced hcemoglobin."
This power of combining with oxygen to form a loose chemical compound,
which in turn can be dissociated easily when the oxygen-pressure is lowered,
makes possible the function of haemoglobin in the blood as the carrier of
oxygen from the lungs to the tissues. The details of this process will be
described in the section on Respiration. Haemoglobin forms with carbon-
monoxide gas (CO) a compound, similar to oxyhaemoglobin, which is
known as carbon-monoxide hcemoglobin. In this compound also the union
takes place in the proportion of one molecule of haemoglobin to one
molecule of the gas. The compound formed differs, however, from oxy-
haemoglobin in being much more stable, and it is for this reason that the
breathing of carbon monoxide gas is liable to prove fatal. The CO unites
with the haemoglobin, forming a firm compound ; the tissues of the bo<ly are
thereby prevented from obtaining their necessary oxygen, and death results
from suffocation or asphyxia. Carbon monoxide forms one of the constituents
of coal-gas. The w-ell-known fatal eliect of breathing coal-gas for some time,

* Die Bluthrystalk, Jena, 1871.

BLOOD. 337

as in the case of individuals sleeping in a room where gas is escaping, is trace-
able directly to the carbon monoxide. Nitric oxide (NO) forms also with
haemoglobin a dofinite compound which is even more stable than the CO-
hiemoglobin ; if, therefore, this gas were brought into contact with the blood,
it would cause death in the same way as the CO.

Oxyhtemoglobin, carbon-monoxide hccmoglobin, and nitric-oxide haemoglo-
bin are similar compounds. Each is formed, appai'cntly, by a definite combina-
tion of the gas with the haeraochromogen portion of the hjemoglobin molecule,
and a given weight of hfcmoglobin unites presumably with an equal volume of
each gas. In marked contrast to these facts, Boiir ^ has shown that luemoglobin
forms a compound with carbon-dioxide gas, carbo-hcemoglobin, in which the
quantitative relationship of the gas to the haemoglobin differs from that shown
by oxygen. In a mixture of O and CO^ each gas is absorbed by hemoglobin
solutions independently of the other, so that a solution of haemoglobin nearly
saturated with oxygen can unite with as much CO2 as though it held no oxygen
in combination. Bohr suggests, therefore, that the O and the CO2 must unite
with different portions of the haemoglobin — the oxygen with the pigment portion,
the haemochromogen, and the COj possibly with the proteid portion. It seems
probable that haemoglobin plays a part in the transportion of the carbon
dioxide as well as the oxygen of the blood, but its exact value in this respect
as compared with the blood-plasma, which also acts as a carrier of CO2, has
not been definitely determined (see Respiration).

Presence of Iron in the Molecule. — It is probable that iron is quite
generally present in the animal tissues in connection with nuclein compounds,
but its existence in haemoglobin is noteworthy because it has long been known
and because the important property of combining with oxygen seems to be
connected with the presence of this element. According to the analyses
made, the proportion of iron in haemoglobin varies somewhat in different
animals : the figures given are from 0.335 to 0.47 per cent. The amount of
haemoglobin in blood may be determined, therefore, by making a quantitative
determination of the iron. The amount of oxygen with which haemoglobin
will combine may be expressed by saying that one molecule of oxygen will
be fixed for each atom of iron in the haemoglobin molecule. In the decom-
position of haemoglobin into globulin and haematin or globulin and haemo-
chromogen, Avhich has been spoken of above, the iron is retained in the
haematin.

Crystals. — Haemoglobin may be obtained readily in the form of ciystals

(Fig. 86). As usually prepared, these crystals are really oxyhaemoglobin, but

it has been shown that reduced haemoglobin also crystallizes, although with

more difficulty. Haemoglobin from the blood of diflferent animals varies to a

marked degree in respect to the power of crystallization. From the blood of

the rat, dog, cat, guinea-pig, and horse, crystals are readily obtained, while

haemoglobin from the blood of man and of most of the vertebrates crystallizes

much less easily. Methods for preparing and purifying these crystals will be

^ Skandivavisches Arckivfur Physiologie, 1892, Bd. 3, S. 47.
22

338

AX AMFJiTCAN TEXT-IIOOK OF PHYSTOLOGY.

found iu the .section on " The Chemistry of" tlie Body." To obtain si^eciniens
quickly for examination under the microscope, one of the most certain methods
is to take some blood from one of the animals whose luemoglobin crystallizes

easily, place it in a test-tube, add to it a few
drops of ether, shake the tube thorouji^hly
until the blood becomes laky — that is,
until the haemoglobin is discharged into
the plasma — and then place the tube
on ice until the crystals are deposited.
Small portions of the crystalline sedi-
ment may then be removed to a glass
slide for examination. Htemoglobin
from different animals varies not only
as to the ease with which it crystal-
lizes, but in some cases also as to the
form that the crystals take. In man
and in most of the mammalia haemoglo-
bin is deposited in the form of rhom-
bic prisms; in the guinea-pig it crys-
tallizes in tetrahedra {d, Fig. 86), and
in the squirrel in hexagonal plates. The
crystals are readily soluble in water, and
by repeated crystallizations the haemo-
globin may be obtained ])erfectly pure.
As in the case of other soluble proteid-
like bodies, solutions of haemoglobin are
guinea-pig; e, from the blood of a hamster;/, (decomposed bv alcohol, by mineral acids,

from the blood of a squirrel. ^ /. i i ' i i i •!•

bv salts of the heavy metals, by boihug,
etc. Notwithstauding the fact that haemoglobin crystallizes so readily, it is not
easily dialyzable, behaving in this respect like proteids and other colloidal
bodies. The compounds which hemoglobin forms with carbon monoxide
(CO) and nitric oxide (NO) are also crystallizable, the crystals being isomor-
phous with those of oxyhaemoglobin.

Absorption Spectra. — Solutions of haemoglobin and its derivative com-
pounds, when examined with a spectroscope, give distinctive absorption bands.
A brief account of the principle and arrangement of the spectroscoi)e, although
unnecessaiy for those familiar with the elements of Physics, is given by way
of introduction to the description of these absorption bands.

Light, when made to pass through a glass prism, is broken up into its constituent
rays, giving the play of rainbow colors known as the spectrum. A spectroscope is
an apparatus for producing and observing a spectrum. A simple form, which illus-
trates sufficiently well the construction of the apparatus, is shown in Figure 87, P
being the glass prism giving the spectrum. Light falls upon this prism through
the tube (a) to the left, known as the " collimator tube." A slit at the end of this
tube (s) admits a narrow slice of light— lamplight or sunlight— which then, by
means of a convex lens at the other end of the tube, is made to fall upon the prism

Fig. 86.-Cr}-stallized htemoglobin (after Frey) :
a, h, crystals from venous blood of man ; e, from
the blood of a cat; d, from the blood of a

BLOOD.

339

(p) with its rays parallel. In passing through the prism the rays are dispersed by
unequal refraction, giving a spectrum. The spectrum thus produced is examined by
the observer with the aid of the telescope («). When the telescope is properly focussed
for the rays entering it from the prism (p), a clear picture of the spectrum is seen. The
length of the spectrum will depend upon the nature and the number of prisms through
which the light is made to pass. For ordinary purposes a short spectrum is preferable
for haemoglobin bands, and a spectroscope with one prism is generally used. If the
source of light is a lamp-flame of some kind, the spectrum is continuous, the colors
gradually merging one into another from red to violet. If sunlight is used, the spectrum
will be crossed by a number of narrow dark lines known as the " Fraunhofer lines"

Fig. 87. —Spectroscope: p, the glass prism ; a, the collimator tube, showing the slit (s) through which the
light is admitted ; b, the telescope for observing the spectrum.

(see PI. I. , Fronthpiece, for an illustration in colors of the solar spectrum). The position of
these lines in the solar spectrum is fixed, and the more distinct ones are designated by letters
of the alphabet, A, b, c, d, e, etc., as shown in the charts below. If while using solar
light or an artificial light a solution of any substance which gives absorption bands is
so placed in front of the slit that the light is obliged to traverse it, the spectrum as
observed through the telescope will show one or more narrow or broad black bands,
which are characteristic of the substance used and which constitute its absorption spec-
trum. The positions of these bands may be designated by describing their relations to
the Fraunhofer lines, or more directly by stating the wave-lengths of the portions of the
spectrum between which absorption takes place. Some spectroscopes are provided with
a scale of wave-lengths superimposed on the spectrum, and when properly adjusted
this scale enables one to read off directly the wave-length of any part of the spectrum.

When very dilute solutions of oxyhsemoglobin are examined with the
spectroscope, two absorption bands a})pear, both occurring in the portion of
the spectrum included between the Fraunhofer lines d and E, The band
nearer the red end of the spectrum is known as the " a-band ;" it is narrower,
darker, and more clearly defined than the other, the "/9-band" (Fig. 88,and
also PI. I. spectrum 4). With a solution containing 0.09 per cent, of oxy-
hsemoglobin, and examined in layers one centimeter thick, the a-band extends
over the part of the spectrum included between the wave-lengths X 583

340

AN AMERICAN TEXT-BOOK OF PHYSIOLOCY.

(583 millionths of a millimeter) and I 571, and the ^-band between X 550 and
I 532 (Gamgee). The width and distinctness of the bands vary natnrally
with the concentration of the solution used (see PI. I. spectra 2, 3, 4, and 5),

70 65

55

50

4-5

B C

])

p: 6

G

FiG.88.— Diaprammatic representation of the absorption spectrum of oxyha-moglobin (after Rollett).
The numerals give the wave-lengths in hundred-thousandths of a millimeter; the letters show the
positions of the more prominent Fraunhofer lines of the solar spectrum. The red end of the spectrum
is to the left. The o-baud is to the right of d, the /3-band to the left of e.

or, if the concentration remains the same, with the width of the stratum of
liquid through which the light passes. With a certain minimal percentage of

oxyhaemoglobin (less than 0.01 per
cent.) the /3-band is lost and the a-
band is very faint in layers one cen-
timeter thick. With stronger solu-
tions the bands become darker and
wider and finally fuse, while some
of the extreme red end and a great
deal of the violet end of the spec-
trum is also absorbed. The varia-
tions in theabsorption spectrum with
differences in concentration are clear-
ly shown in the accompanying illus-
tration from Ptollett' (Fig. 89); the
thickness of the layer of licpiid is
supposed to be one centimeter. The
numbers on the right indicate the
percentage strength of the oxy-
haemoglobin solutions. It will be
noticed that the absorption which
takes place as the concentration of
the solution increases affects the red-
orange end of the spectrum last of all.
Solutions of reduced hemo-
globin examined with the spectro-
scope show only one absorption
band, known sometimes as the
''y-band." This band lies also in
the portion of the spectrum included
between the lines d and E; its relations to these lines and the bands of
oxyhaemoglobin are shown in Figure 90 and in PI. I. spectrum 6. The
' Hermann's Handbuch der Physiologic, vol. iv., 1880.

aBC

Fig. 89.— Diagram to show the variations in the ab-
sorption spectrum of oxyhajmoglobin with varying
concentrations of the solution (after Rollett). The
numbers to the right give the strength of the oxy-
hemoglobin solution in percentages ; the letters give
the positions of the Fraunhofer lines. To ascertain
the amount of absorption for any given concentration
up to 1 per cent., draw a horizontal line across the
diagram at the level corresponding to the concentra-
tion. Where this line passes through the shaded part
of the diagram absorption takes place, and the width
of the absorption bands is .seen at once. The diagram
shows clearly that the amount of absorption increases
as the solutions become more concentrated, especially
the absorption of the blue end of the spectrum. It
will be noticed that with concentrations between 0.6
and 0.7 per cent, the two bands between d and e fuse
into one.

BLOOD.

341

y-band is inucli more difTuso than the oxy haemoglobin bands, and its limits
theretbre, esjurially in weak solutions, are not well defined; in solutions
ot" blood diluted 100 times with water, whieh would give a h;enioglobin
solution of about 0.14 per cent., the absorption band lies in the part of the
spectrum included between the wave-lengths X 572 and X 542. The width

70 65

60

55

45

B C

D

E h

Fig. 90.— Diagrammatic representation of the absorption spectrum of haemoglobin (reduced hemoglo-
bin) (after Kollett). The inuiierals give the wave-lengths in hundred-thousandths of a millimeter ; tlie
letters show the positions of the more prominent Fraunhofer lines of the solar spectrum. The red end
of the spectrum is to the left. The single diffuse absorption band lies between D and e.

and distinctness of this band vary also with the concentration of the
solution. This variation is sufficiently well shown in the accompanying
illustration (Fig. 91), which is a companion figure to the one just given
for oxyhaemoglobin Fig. 89). It will be noticed that the last light to
be absorbed in this case is partly in the red end and partly in the blue,
thus explaining the purplish color
of hsemoo-lobin solutions and of
venous blood. Oxyhsemoglobiu so-
lutions can be converted to hiemo-
globin solutions, with a correspond-
ing change in the spectrum bands,
by placing the former in a vacuum
or, more conveniently, by adding
reducing solutions. The solutions
most commonly used for this pur-
pose are ammonium sulphide and
Stokes's reagent.^ If a solution of
reduced hemoglobin is shaken with
air, it quickly changes to oxyhsemo-
globin and gives two bands instead
of one when examined through the
spectroscope. Any given solution
may be changed in this way from
oxyhsemoglobin to hoemoglobin,
and the reverse, a great number
of times, thus demonstrating the
facility with which haemoglobin
takes up and surrenders oxygen.

^ Stokes's reagent is an ammoniacal solution of a ferrous salt. It is made by dissolving 2
parts (by weight) of ferrous sulphate, adding 3 parts of tartaric acid, and then ammonia to dis-
tinct alkaline reaction. A permanent precipitate should not be obtained.

aBC

Fig. 91.— Diagram to show the variations in the ab-
sorption spectrum of reduced hremoglobin with vary-
ing concentrations of the solution (after Rollett). The
numbers to the right give the strength of the hsemo-
globin solution in percentages ; the letters give the posi-
tions of the Fraunhofer lines. For further directions
as to the use of the diagram, see the description of
Figure 89.

342 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Solutions of* carbon-monoxide hnemoglobin also give a .spectrum willi two
absorption bands closely resembling in position and appearance those of oxy-
ha^nioglobin (see PI. I. spectrum 7). They are distinguislicd from tiie oxy-
ha?moglobin bauds by being slightly nearer the blue eud of the spectrum, as
may be demonstrated by observing the wave-lengths or, more conveniently,
by superimposing the two spectra. Moreover, solutions of carbou-mouoxide
haemoglobin are uot reduced to lueraoglobin by adding Stokes's licjuid, two
bands being still seen after such treatmeut. A solution of carbon-monoxide
haemoglobin suitable for spectroscopic examination may be prepared easily by
passing ordinary coal-gas through a dilute oxyhtemoglobin solution lor a few
minutes and then filtering.

Derivative Compounds of Haemoglobin. — A number of compounds
directly related to hiemoglobiu have been described, some of them being
found normally in the body. Brief mention is made of the best known of
these substances, but for the details of their preparation and chemical projier-
ties reference must be made to the section on " The Chemistry of the Body."

Methcmioc/lobin is a compound obtained by the action of oxidizing agents
on haemoglobin ; it is frequently found, therefore, in blood stains or patho-
logical liquids containing blood which have been exposed to the air for some
time. It is now supposed to be identical in composition with oxyhaemoglobin,
with the exception that the oxygen is held in more stable combination.
MetluBmoglobin crystallizes in the same form as oxyhjemoglobiu, and has a
characteristic spectrum (PI. I. spectrum 8).

Hccmochromogen (Ca^HggN^FcOs) is the substance obtained when haemo-
globin is decomposed by acids or by alkalies in the absence of oxygen. It
crystallizes and has a characteristic spectrum.

Hcemat'm (CagHgaN^FeOJ is obtained when oxyhaemoglobin is decomposed
by acids or by alkalies in the presence of oxygen. It is amorphous and has a
characteristic spectrum (PI. L spectra 9 and 10).

Hcemin (CgaHjoN^FeOgHCl) is a compound of htcmatin and HCl, and is
readily obtained in crystalline form. It is much used in the detection of
blood in medico-legal cases, as the crystals are very characteristic and are easily
obtained from blood-clots or blood-stains, no matter how old these may be.

H(cmatoporj)hyrin (CgjIIggN^Og) is a compound characterized by the absence
of iron. It is frequently spoken of as " iron-free hoematin." It is obtained
by the action of strong sulphuric acid on hiematin.

Hicmatoidin (CigHigNgOg) is the name given to a crystalline substance
found in old blood-clots, and formed undoubtedly from the haemoglobin of
the clotted blood. It has been shown to be identical with one of the bile-
pigments, bilirubin. Its occurrence is interesting in that it dcmon.strates the
relationship between haemoglobin and the bile-pigments.

Histohcrmatins are a group of pigments .said to be ])resent in many of the
tissues — for example, the muscles. They are supposed to be respiratory pig-
ments, and are related physiologically, and possibly chemically, to haemoglobin.
They have not been isolated, but their spectra have been described.

BLOOD. 343

Bile-pigments and Urinary Pigments — Haemoglobin is regarded as the
parent-substance of the bile-pigments and the urinary pigments.

Origin and Fate of the Red Corpuscles. — The mammalian rod corpuscle
is a cell that has lost its nucleus. It is not probable, therefore, that any given
corpuscle lives for a great while in the circulation. This is made more certain
by the fact that htemoglobin is the mother-substance from which the bile-
pigments are made, and, as these pigments are being excreted continually, it is
fair to suppose that red corpuscles are as steadily undergoing disintegration in
the blood-stream. Just how long is the average life of the corpuscles has not
been determined, nor is it certain where and how they go to pieces. It has
been suggested that their destruction takes place in the spleen, but the observa-
tions advanced in support of this hypothesis are not very numerous or con-
clusive. Among the reasons given for assuming that the spleen is especially
concerned in the destruction of red corpuscles, the most weighty is the histo-
logical fact that one can sometimes find in teased preparations of spleen-tissue
certain large cells which contain red corpuscles in their cell-substance in various
stages of disintegration. It has been supposed that the large cells actually
ingest the red corpuscles, selecting those, presumably, which are in a state of
physiological decline. Against this idea a number of objections may be
raised. Large leucocytes with red corpuscles in their interior are not found
so frequently nor so constantly in the spleen as we would expect should be
the case if the act of ingestion were constantly going on. There is some
reason for believing, indeed, that the whole act of ingestion may be a post-
mortem phenomenon ; that is, after the cessation of the blood-stream the
amoeboid movements of the large leucocytes continue, while the red corpuscles
lie at rest — conditions which are favorable to the act of ingestion. It may be
added also that the blood of the splenic vein contains no haemoglobin in solu-
tion, indicating that no considerable dissolution of red corpuscles is taking
place in the spleen. Moreover, complete extirpation of the spleen does not
seem to lessen materially the normal destruction of red corpuscles, if we may
measure the extent of that normal destruction by the quantity of bile-pigment
formed in the liver, remembering that haemoglobin is the mother-substance
from which the bile-pigments are derived. It is more probable that there is
no special organ or tissue charged with the function of destroying red corpus-
cles, and that they undergo disintegration and dissolution while in the blood-
stream and in any part of the circulation, the liberated haemoglobin being
carried to the liver and excreted in part as bile-pigment. The continual
destruction of red corpuscles implies, of course, a continual formation of new
ones. It has been shown satisfactorily that in the adult the organ for the
reproduction of red corpuscles is the red marrow of bones. In this tissue
hcematopoiesis, as the process of formation of red corpuscles is termed, goes on
continually, the process being much increased after hemorrhages and in certain
pathological conditions. The details of the histological changes will be found
in the text-books of histology. It is sufficient here to state simply that a
group of nucleated colorless cells, erj^throblasts, is found in the red marrow.

344 .l^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

These cells multiply bv karvokinesis, and the daughter-cells eventually pro-
duce haniioglobin in their cytoplasm, thus forming nucleated red corpuscles.
The nuclei are subsequently lost, either by disintegration or, more likely, by
extrusion, and the newly-formed non-nucleated red corpuscles are forced into
the blood-stream, owing to a gradual change in their position during develop-
ment caused by the growing htpmatopoietic tissue. AVhen the process has
been greatly accelerated, as after severe hemorrhages or in certain ])athologicaI
conditions, red corpuscles still retaining their nuclei may be found in the circu-
lating blood, having been forced out prematurely as it were. Such corpuscles
may subsequently lose their nuclei while in the blood-stream. In the em-
bryo, luBmatopoietic tissue is found in parts of the body other than the mar-
row, notably in the liver and spleen, which at that time serve as organs for
the production of new red corpuscles. In the blood of the young embryo
nucleated red corpuscles are at fii-st abundant, but they become less numerous
as the fetus grows older.^

Variations in the Number of Red Corpuscles. — The average number
of red corpuscles for the adult male, as has been stated already, is usually
given as 5,000,000 per cubic mm. The number is found to vary greatly,
however. Outside of pathological conditions, in which the diminution in
number may be extreme, differences have been observed in human beings
under such conditions as the following : The number is less in females
(4,500,000); it varies in individuals with the constitution, nutrition, and
manner of life ; it varies with age, being greatest in the fetus and in the new-
born child ; it varies with the time of the day, showing a distinct diminution
after meals ; in the female it varies somewhat in menstruation and in preg-
nancy, being slightly increased in the former and diminished in the latter
condition. Perhaps the most interesting example of variation in the number
of red corpuscles is that which occurs with changes in altitude. Residence in
high altitudes is quickly followed by a marked increase in the number of red
corpuscles. Viault^ has recently shown that living in the mountains two
weeks at an altitude of 4392 meters caused an increase in the corpuscles from
5,000,000 to over 7,000,000 per cubic mm., and in the third week the number
reached 8,000,000. From these and similar observations it would seem that a
diminished pressure of oxygen in the atmosphere stimulates the haematopoietic
organs to greater activity, and it is interesting to compare this result with the
effect of an actual loss of blood. In the latter case the production of red
corpuscles in the red marrow is increased, because, ap])arently, the ansemic
condition causes a diminution in the oxygen-supply to the haematopoietic tis-
sue, and thereby stimulates the erythroblastic cells to more rapid multiplication.
In the case of a sudden diminution in oxygen-pressure, as happens when the
altitude is markedly increased, we may suppose that one result is again a slight
diminution in the oxygen-supply to the tissues, including the red marrow, and

' For further details see Howell, " Life History of the Blood-corpuscles," etc., Journal of
Morphology, vol. iv., 1890.

* La Semaine medicale, 1890, p. 464.

BLOOD. 345

in couseqiience the eiythroblasts are again stimulated to greater activity. This
variation iu hiomoglobin with the altitude is an interesting adaptation which
ensures always a normal oxygen-capacity for the blood.

Physiology of the Blood-leucocytes. — The function of the blood-leuco-
cytes has been the subject of numerous investigations, particularly in connection
M'ith the pathology of blood diseases. Although many hypotheses have been
matle as the result of this work, it cannot be said that we possess any positive
information as to the normal function of these cells in the body. It must be
borne in mind in the first place that the blood-leucocytes are not all the same
histologically, and it may be that their functions are as diverse as is their mor-
phology. Various classifications have been made, based upon one or another
difference in microscopic structure and reaction. Thus, Ehrlich groups the leuco-
cytes according to the size and the staining of the granules contained in the cyto-
plasm, making in the latter respect three main groups : oxyphiles or eosinophiles,
those whose granules stain only with acid aniline dyes — that is, with dyes in
wdiich the acid part of the dye acts as the stain ; basophiles, those which stain
only with basic dyes ; and neutrophiles, those which stain only with neutral
dyes ^ (Fig. 92). This classification is frequently used, especially in patholog-

FiG. 92.— Blood stained with Ehrlich's "triple stain" of acid-fuehsin, methyl-green, and orange G.
(drawn with the camera lucida from normal blood) (after Osier): a, red corpuscles; b, lymphocytes; c,
large mononuclear leucocytes; d, transitional forms; e, nexitrophilic leucocytes with polymorphous
nuclei (polynuclear neutrophiles) ; /, eosinophilic leucocytes.

ical literature, but it is not altogether satisfactory, since no definite functional
relationship of the granules has been established ; and, moreover, it is unde-
cided whether or not the specific granules are permanent or temporary struc-
tures in the cells. A safer classification perhaps is the following: 1. Lympho-
cytes, which are small corpuscles with a round vesicular nucleus and very scanty
cytoplasm : they are not capable of amoeboid movements. These corpuscles are
so called because they resemble the leucocytes found in the lymph-gland, and

' For a recent discussion and modification of this classification see Kanthack and Hardy,
J(mmal of Physiology, vol. xvii., 1894, p. 81.

346 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

are supposed in fact to be brought into the blood through the lymph. 2. Mono-
nuclear leucocytes, which are large corpuscles with a vesicular nucleus and
abundant cytoplasm : thoy have the power of making anuel)oid movements.
3. Polymorphous or polynucleated leucocytes, which are large cori)Usck'.s with
the nucleus divided into lobes that are either entirely separated or are connected
by fine protoplasmic threads. This form shows active amoeboid movements.

It is impossible to say whether these varieties of blood-leucocytes are
distinct histological units which have independent origins and more or less
dissimilar functions, or whether, as seems more probable to the writer, they
represent different stages in the development of a single type of cell, the
lymphocytes forming the youngest and the polymorphic or polynucleated
leucocytes the oldest stage. Perhaps the most striking property of the leuco-
cytes as a class is their power of making amoeboid movements — a charac-
teristic which has gained for them the sobriquet of "wandering" cells. By
virtue of this property some of them are able to migrate through the walls
of blood-capillaries into the surrounding tissues. This process of migration
takes place normally, but is vastly accelerated under pathological conditions.
As to the function or functions fulfilled by the leucocytes, numerous sugges-
tions have been made, some of which may be stated in brief form as follows:
(1) They protect the body from pathogenic bacteria. In explanation of this
action it has been suggested that they may either ingest the bacteria, and thus
destroy them directly, or they may form certain substances, defensive proteids,
which destroy the bacteria. Leucocytes that act by ingesting the bacteria
are spoken of as "phagocytes" {(fdyetu, to eat; xotoc, cell). This theory of
their function is usually designated as the " phagocytosis theory of Metschni-
koff ;" it is founded upon the fact that the amoeboid leucocytes are known to
ingest foreign particles with which they come in contact. The theory of the
protective action of leucocytes has been used largely in pathology to explain
immunity from infectious diseases, and for details of experiments in support
of it reference must be made to pathological text-books. (2) They aid in
the absorption of fats from the intestine. (3) They aid in the absorption of
peptones from the intestine. These latter two theories will be spoken of
more in detail in describing the process of absorption. (See the section upon
Digestion.) It may be noticed here that these theories apply to the leucocytes
found so abundantly in the lymphoid tissue of the alimentary canal, rather
than to those contained in the blood itself. (4) They take part in the pro-
cess of blood-coagulation. A complete statement with reference to this
function must be reserved until the phenomenon of coagulation is de-
scribed, (o) They help to maintain the normal composition of the blood-
plasma as to proteids. It may be said for this view that there is considerable
evidence that the leucocytes normally undergo disintegration and dissolu-
tion in the circulating blowl, to some extent at least. The blood-proteids are
peculiar, and they are not obtained directly from the digested food. It is
possible that the leucocytes, which are the only typical cells in the blood, aid
in keeping up the normal supply of proteids. None of the theories mentioned

BLOOD. . 347

lias much positive evidence in its favor. It remains possible, on the one
hand, that all these as well as other functions may be performed by the
leucocytes, and, on the other hand, further discoveries may give an entirely
new explanation of the value of these cells to the body. As to the origin of
the leucocytes, it is known that they increase in number while in the circu-
lation, undergoing multipliaition by karyokiuesis ; but the greater number are
probably produced in the lymph-glands and in the lymphoid tissue of the
body, whence they get into the lymph-stream and eventually are brought into
the blood.

Physiology of the Blood-plates. — The blood-plates are small circular
or elliptical bodies, nearly homogeneous in structure and variable in size (0.5 to
5.5//), but they are always smaller than the red corpuscles (see Histology). Less
is known of their origin, fate, and functions than in the case of the leucocytes.
It is certain that they are not independent cells, and it is altogether probable,
therefore, that they soon disintegrate and dissolve in the plasma. When
removed from the circulating blood they are known to disintegrate very
rapidly. This peculiarity, in fact, prevented them from being discovered for
a long time after the blood had been studied microscopically. Recent work
has shown that they are formed elements, and not simply precipitates from the
plasma, as was suggested at one time. The theory of Hayem, their real
discoverer, that they develop into red corpuscles may also be considered as
erroneous. There is considerable evidence to show that in shed blood they
take part in the process of coagulation. The nature of this evidence will be
described later.

Lilienfeld ^ recently demonstrated that chemically the blood-plates contain
a nucleo-albumin (see section on Chemistry of the Body) to which he gives
the specific name of " nucleohiston." The same substance is contained in the
nuclei of leucocytes. This latter fact may be taken as additional evidence for
a view which has already been supported on morphological grounds — that the
blood-plates are derived from the nuclei of the leucocytes. According to this
theory, when the multinucleated leucocytes go to pieces in the blood the
fragments of nuclei contained in them persist for a longer or shorter time as
blood-plates, which in time eventually dissolve in the plasma. If this last
statement is correct, then it follows that the substance contained in the blood-
plates either goes to form one of the normal constituents of the plasma, useful
in nutrition or otherwise, or that it forms a waste product which is eliminated
from the body. The specific function, if any, of the blood-plates, beyond
that of aiding in coagulation, remains to be discovered.

B. Chemical Composition of the Blood ; Coagulation ; Total
Quantity of Blood ; Regeneration after Hemorrhage.

Composition of the Plasma and Corpuscles. — Blood (plasma and cor-
puscles) contains a great variety of substances, as may be inferred from its
double relations to the tissues as a source of food-supply and as a means of
^ Du Bois-Reymond!s Archiv fur Physiologie, 1893, p. 560.

348 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

removing the waste products of their fuuctioual activity. The constituents
existing in quantities sufficiently large for recognition by chemical means are
as follows: (1) Water; (2) proteids, of which three varieties at least are
known to exist in the plasma — namely, fibrinogen, paraglobulin (serum-
globulin), and serum-albumin ; (3) combined proteids (hajmoglobin, nudeo-
albumins) ; (4) extractives, including such substances as fats, sugar, urea,
lecithin, cholesterin, etc. ; and (5) inorganic salts. The proportions of these
substances found in the blood of various mammals differ somewhat, although
the qualitative composition is practically the same in all.

The following tables, taken from different sources, summarize the main
results of the quantitative analyses which have thus far been made :

Analysts of the Whole Blood, Human (C. Schmidt).

Water

Solids

Proteids and extractives

Fibrin (derived from the fibrinogen)

Ha^matin (and iron)

Salts

Man

Woman

(25 years).

(30 years.)

788.71

824.55

211.29

175.45

191.78

157.93

3.93

1.91

7.70

6.99

7.88

8.62

Inorganic Salts of Human Blood, 1000 parts {C. Schmidt).

Blood-corpuscles.

CI 1.75

KjO 3.091

Na,0 0.470

so: 0.061

PA 1-355

CaO

MgO

Blood-plasma.

CI 3.536

KjO 0.314

Na^O 3.410

SO3 0.129

P.A 0.145

Cad

MgO . .

These acids and bases exist, of course, in the plasma and the corpuscles as
salts. It is not possible to determine exactly how they are combined as salts,
but Schmidt suggests the following probable combinations :

Probable Salts in the Corpuscles.

Potassium sulphate 0.132

Potassium chloride 3.679

Potassium phosphate 2.343

Sodium phosphate 0.633

Sodium carbonate 0.341

Calcium phosphate 0.094

Magnesium phosphate .... 0.060

Probable Salts in the Plasma.

Potassium sulphate 0.281

Potassium chloride 0.359

Sodium chloride 5.546

Sodium phosphate 0.271

Sodium carbonate 1.532

Calcium phosphate 0.298

Magnesium phosphate .... 0.218

One interesting fact brought out in the above table is the peculiarity in
distribution of the potassium and sodium salts between the plasma and the
corpuscles. The plasma contains an excess of the total sodium salts, and the
corpuscles contain an excess of the potassium salts.

BLOOD.

349

Composition of Blood-plasma (1000 parts).'

Composition of Blood-serum (1000 parts).*

Water

Solids

Total proteids

Fibrin (derived from the fibrinogen

Paraglobiilin

Serum-albumin

Extractives and salts

Horse.

Horse.

917.6
82.4
69.5
6.5
38.4
24.6
12.9

85.97
72.57

45.65
26.92
13.40

Man.

92.07
76.20

31.04
45.16

15.88

Ox.

89.65
74.99

41.69
33.30
14.66

Red Corpuscles, Human Blood {Hoppe-Seyler).

I. II.

Oxyhaemoglobin 86.8 94.3 per cent.

Proteid (and nuclein ?) 12.2 5.1 "

Lecithin 0.7 0.4 "

Cbolesterin 0.3 0.3 "

Leucocytes, Thymus of Calf (Lilienfeld).
In the total dry substance of the corpuscles, which was equal to 11.49 per cent., there was contained—

Proteid 1.76 per cent.

Leuco-nuclein 68.78 "

Histon 8.67 "

Lecithin 7.51 "

Fat 4.02 "

Cbolesterin 4.40 "

Glycogen 0.80

The extractives present in the blood vary in amount under different conditions.

Average estimates of some of them, given in percentages of the entire blood,

have been reported as follows :

Dextrose (grape-sugar) 0.117 percent.

Urea 0.016 "

Lecithin 0.0844 "

Cbolesterin 0.041 "

Proteids of the Blood-plasma. — The properties and reactions of proteids
and the related compounds, as well as a classification of those occurring iu the
animal body, are described in the section on the Chemistry of the Body.
This description should be read before attempting to study the proteids of
the plasma and the part they take in coagulation. Three proteids are usually
described as existing in the plasma of circulating blood — namely, fibrinogen,
paraglobulin, or, as it is sometimes called, " serum-globulin," and serum-albu-
min. The first two of these proteids, fibrinogen and paraglobulin, belong to
the group of globulins, and hence have many properties in common. Serum-
albumin belongs to the group of so-called " native albumins " of which egg-
albumin constitutes another member.

Serum-albumin. — This substance is a typical proteid. Its elementary com-
position, according to Hammarsten, is as follows :

c H N s o

53.06 6.85 16.04 1.80 22.26

These figures can be regarded as approximate only. Serum-albumin shows the

' Hammarsten : A Text-book of Physiological Chemistry, 1893 (translated by Mandel).

350 AN AMERICAX TEXT-BOOK OF PHYSIOLOGY.

general reactions of the native albumins. One of its most useful reactions is
its behavior toward magnesium sulphate. Serum-all)umin usually occurs in
liquids together with the globulins, as is the case in blood. If such a liquid
is thoroughly saturated with solid MgSO^, the globulins are precipitated com-
pletely, wliile the albumin is not affected. So far as the blood and similar
liquids are concerned, a definition of serum-albumin might be given by saying
that it comprises all the proteids not precipitated by MgSO^. ^^'hen its
solutions have a neutral or an acid reaction, serum-albumin is precipitated in
an insoluble form by heating the solution above a certain degree. Precipi-
tates produced in this way by heating solutions of proteids are spoken of
as coagulations — heat coagulations — and the exact temperature at which
coagulation occurs is to a certain extent characteristic for each proteid. Tlu-
temperature of coagulation of serum-albumin is usually given at from 70°
to 75° C, but it varies greatly with the conditions. It has been asserted,
in fact, that careful heating under proper conditions gives separate coagula-
tions at three different temperatures — namely, 73°, 77°, and 84° C. — indi-
cating the possibility that what is called "serum-albumin " may be a mixture
of three or more proteids. Serum-albumin occurs in blood-plasma and blood-
serum, in lymph, and in the different normal and pathological exudations
found in the body, such as pericardial liquid, hydrocele fluid, etc. The amount
of serum-albumin in the blood varies in different animals, ranging among
the mammalia from 2.67 per cent, in the horse to 4.52 per cent, in man. In
some of the cold-blooded animals it occui-s in surprisingly small quantities —
0.36 to 0.69 per cent. As to the source or origin of serum-albumin, it is
generally believed that it comes from the digested proteids of the food. It
is known that proteid material in the food is not changed at once to serum-
albumin during the act of digestion ; indeed, it is known that the final product
of digestion is a proteid or group of proteids of an entirely different character —
namely, peptones and proteoses; but during the act of absorption into the
blood these latter bodies are supposed to undergo transformation into serum-
albumin. From a physiological standpoint serum-albumin is considered to be
the main source of proteid nourishment for the tissues generally. As will be
explained in the section on Nutrition, one of the most important requisites in
the nutrition of the cells of the body is an adequate supply of proteid material
to replace that used up in the chemical changes, the metabolism, of the tissues.
Serum-albumin is supposed to furnish a part, at least, of this supply. As long
as the serum- albumin is in the blood-vessels it is of course cut off" from the
tissues. The cells, however, are bathed directly in lymph, and this in turn is
formed from the plasma of the blood which is filtered — or, according to some
physiologists, secreted — through the vessel-walls. Serum-albumin may be
looked upon, then, as a supply of proteid nourishment which is replenished,
after every meal containing proteids, by absorption from the alimentary canaL
Paraglohulin, ^vhich belongs to the group of globulins, exhibits the gen-
eral reactions characteristic of the group. As stated above, it is completely
precipitated from its solutions by saturation with MgSO^. It is incompletely

BLOOD. 351

precipitated by saturation with common salt (NaCl). In neutral or feebly acid
solutions it coagulates upon heating to 75° C. Ilammareten gives its element-
ary composition as —

c H N s o

52.71 7.01 15.85 1.11 23.24

These figures must also be received as approximate, as it is not absolutely cer-
tain that the substance analyzed was chemically pure. Paraglobulin occurs in
blood, in lymph, and in the normal and pathologicid exudations. The amount
of })araglol)ulin present in blood varies in diiferent animals. Among the mam-
malia the amount ranges from 1.78 per cent, in rabbits to 4.56 j)er cent, in the
horse. In human blood it is given at 3.10 per cent., being less in amount,
therefore, than the serum-albumin. It will be seen, upon examining the
tables of composition of the blood-plasma and blood-serum of the hor.se
(p. 349), that more of this proteid is found in the serum than in the plasma.
This result, which is usually considered as being true, is explained by supposing
that during coagulation some of the leucocytes disintegrate and part of their
substance passes into solution as a globulin identical with or closely resembling
paraglol)ulin. The figures given above show that a considerable amount of
paraglobulin is normally present in blood. It is rea.sonable to suppose that,
like serum-albumin, this proteid is valuable as a source of nitrogenous food
to the tissues. It is uncertain, however, whether it is used by the tissues
directly as paraglobulin or is first converted into some other form of proteid.
It is entirely unknown, also, whether its value as a proteid supply is in any
way different from that of serum-albumin. The origin of paraglobulin
remains undetermined. It may arise from the digested proteids absorbed
from the alimentary canal, but there is no evidence to support such a view.
Another suggestion is that it comes from the disintegration of the leucocytes
(and oi\\Q.Y formed elements) of the blood. These bodies are known to contain
a small quantity of a globulin resembling paraglobulin, and it is passible that
this globulin may be liberated after the dissolution of the leucocytes in the
plasma, and thus go to make up the normal supply of paraglobulin. This
suggestion, however, is theoretical. The fact remains that at present the
origin and the special use of the paraglobulin are entirely unknown.

Fibrinogen is a proteid belonging to the globulin class and exhibiting all
the general reactions of this group. It is distinguished from paraglobulin by
a number of special reactions ; for example, its temperature of heat coagula-
tion is much lower (56° to 60° C), and it is completely thrown down from its
solutions by saturation with NaCl as well as with MgSO^. Its most import-
ant and distinctive reaction is, however, that under proper conditions it gives
rise to an insoluble proteid, fibrin, whose formation is the essential phenom-
enon in the coagulation of blood. Fibrinogen has an elementary composition,
according to Hammarsten, of —

c

H

N

s

0

52.93

6.90

16.66

1.25

22.26

Fibrinogen is found in blood-plasma, in lymph, and in some cases, though not

352 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

always, in the normal and pathological exudations. It is absent from blood-
serum, beini; used uj) during the process of clotting. It occui-s in ver>' small
quantities in blood, compared with the other proteids. There is no good
method of determining quantitatively the amount of fibrinogen, but estimates
of the amount of fibrin, which cannot differ very much from the fibrinogen,
show that in human blood it varies from 0.22 to 0.4 per cent. In horse's
blood it may be more abundant — 0.65 per cent. As to the origin and the
special physiological value of this proteid we are, if possible, more in the dark
than in the case of pnraglobulin, with the exception that fibrinogen is known to
be tiie source of the fil)riu of the blood. But clotting is an f)Ccasional phe-
nomenon only. AVhat nutritive function, if any, is possessed by fibrinogen
under normal conditions is unknown. Xo satisfactory account has been given
of its origin. It has been suggested by different investigators that it may
come from the nuclei of disintegrating leucocytes (and blood-plates) or from
the dissolution of the extruded nuclei of newly-made red corpuscles, but here
again we have only speculations, which cannot be accepted until some experi-
mental proof is advanced to support them.

Coagulation of Blood. — One of the most striking ])roperties of bloofl is
its power of clotting or coagulating shortly after it escapes from the blood-
ve&sels. The general changes in the bhxxl during this ])rocess are easily fol-
lowed. At first shed blood is perfectly fluid, but in a few minutes it becomes
viscous and then sets into a soft jelly which quickly becomes firmer, so that
the vessel containing it can be inverted without spilling the blood. The clot
continues to grow more compact and gradually shrinks in volume, pressing out
a smaller or larger quantity of a clear, faintly yellow liquid to which the name
blood-serum has been given. The essential part of the clot is the fibrin. Fibrin
is an insoluble proteid wdiich is absent from normal blood. In shed blood,
and under certain conditions in blood while still in the l)lood-vessels, this fibrin
is formed from the soluble fibrinogen. The deposition of the fibrin is peculiar.
It is precipitated, if the word may be used, in the form of an exceedingly fine
network of delicate threads which permeate the whole mass of the blood and
give the clot its jelly-like character. The shrinking of the threads causes
the subsequent contraction of the clot. If the blootl has not been shaken
during the act of clotting, almost all the red corpuscles are caught in the fine
fibrin meshwork, and as the clot shrinks these corpuscles are held more firmly,
only the clear liquid of the blooil being squeezed out, so that it is possible to
get specimens of serum containing few or no red corpuscles. The leucocytes,
on the contrary, although they are also caught at first in the forming mesh-
work of fibrin, may readily pass out into the serum in the later stages of clot-
ting, on account of their power of making amoeboid movements. If the blood
has been agitated during the process of clotting, the delicate network will be
broken in places and the serum will be more or less bloody — that is, it will
contain ninnerous re<l corpuscles. If during the time of clotting the blood is
vigorously whipped with a bundle of fine rods, all the fibrin will be deposited
as a stringy mass upon the whip, and the remaining liquid part will consist of

BLOOD. 353

serum plus tlie blootl-corpusdcs. Blood which has been whipped iu this way
is luiowu as " delibi-iuatcd blood." It resembles normal blood in appearance,
but is different in its composition : it cannot clot again. The way in which
the fibrin is normally deposited may be demonstrated most beautifully under
the microscope by placing a good-sized droi) of blood on a slide, covering it
with a cover-slip, and allowing it to stand ior several minutes until coagu-
lation is completed. If the drop is now examined, it is |)os,sible by careful
focussing to discover in the spaces between the masses of corpuscles many
exaini)]cs of the delicate librin network. The physiological value of clotting
is that it stops hemorrhages by closing the openings of the wounded blood-
vessels.

Time of Clotting. — The time neceasary for the clot to form varies slightly
in different individuals, or in the blood of the same individual varies with the
conditions. It may be said in general that under normal conditions the blood
passes into the jelly stage in from three to ten minutes. The separation of
clot and serum takes place gradually, but is usually completed in from ten to
forty-eight hours. The time of clotting shows marked variations in different
animals; the process is especially slow in the horse and the terrapin, so that
coagulation of shed blood is more easily prevented in these animals. In the
human being also the time of clotting may be much prolonged under certain
conditions — in fevers, for example. This fact was noticed in the days when
bloodletting was a common practice. The slow clotting of the blood permitted
the red corpuscles to sink somewhat, so that the upper part of the clot in such
cases was of a lighter color, forming what was called the "bufi'y coat." The
time of clotting may be shortened or be j)rolonged, or the clotting may be i)re-
vented altogether, in various Avays, and much use has been made of this fact
in studying the composition and the coagulation of blood as well as in con-
trolling hemorrhages. It will be advantageous to postpone an account of these
methods for hastening or retarding coagulation until the theories of coagulation
have been considered.

Theories of Coagulation. — The clotting of blood is such a prominent phe-
nomenon that it has attracted attention at all times, and as a result numerous
theories to account for it have been advanced. Most of these theories possess
simply an historical interest, and need not be discussed in a work of this charac-
ter, but some reference to older views is una\'oidable for a proper presentation
of the subject. To prevent misunderstanding it may be stated explicit! v in
the beginning that tliere is at present no perfectly satisfactory theory. Indeed,
the subject is a dilHcult one, as it is intimately connected witli the chemistrv
of the proteids of the blood, and it may be said that a complete understanding
of clotting waits upon a better knowledge of the nature of these proteids. It
happens that at the present time a great deal of attention is being paid to this
subject by experimenters, and it is possible that at any moment new facts may
be discovered which will alter present ideas of the nature of the process. In
considering the different theories that have been proposed tliere are two general
facts which should always be kept iu mind : first, that the main phenomenon

354 AN AMERICAN TENT- BOOK OF PIIYSIOLOCY,

which a tlieory of coaguhitiou has to explain is the formation of fibrin ; second,
that all theories nnite in the common belief that the fibrin is derived, in ])art at
least, from the fibrinogen of tlie plasma.

Schmidt's Older Theory of Coagulation. — The first theory which gained
general acceptance in recent times was that of Alexander Schmidt. It was
projK)scd in 1801, and it has served as the l)asi,s for all subseqnent theories.
Schmidt held that the fibrin of the clot is formed by a reaction between para-
globnlin (he called it " fibrinophistin ") and fibrinogen, and that this reaction is
brought about by a third body, to which he gave the name oi' fibrin ferment.
Fibrin ferment was believed to be absent from normal blood, but to be formed
after the blood was shed. Further reference will presently be made to the
nature of this substance. Schmidt was not able to determine its nature —
whether it was a proteid or not — but he discovered a method of preparing it
from blood-serum, and demonstrated that it cannot be obtained from blood
immediately after it leaves the blood-vessels, and that consequently it does not
exist in circulating blood, in any appreciable quantity at least. Finally,
Schmidt believed that a certain quantity of soluble salts is necessary as a
fourth " fibrin factor."

Hammarsten's Theory of Coar/ulation. — Ilammarsten, who repeated
Schmidt's experiments, demonstrated that paraglobulin is unnecessary for
the formation of fibrin. He showed that if a solution of pure fibrinogen is
prepared, and if there is added to it a solution of fibrin ferment entirely free
from paraglobulin, a typical clot is formed. This exi)eriment has since been
confirmed by others, so that at present it is generally accepted that paraglob-
ulin takes no direct part in the formation of fibrin. Hammarsten's theory
is that there are two fibrin factors, fibrin ferment and fibrinogen, and that
fibrin results from a reaction between these two bodies. The nature of this
reaction could not be determined, but Hammarsten showed that the entire
fibrinogen molecule is not changed to fibrin. A dissociation or splitting
occurs, so that in place of the fibrinogen there is present after clotting, on the
one hand, fibrin representing most of the weight of fibrinogen, and, on the
other hand, a newly-formed globulin-like proteid retained in solution in the
serum, to which proteid the name fibrin-globulin has been given. Ham-
marsten supposed that although paraglobulin took no direct part in the process,
it acted as a favoring condition, a greater quantity of fibrin being formed
when it was present. Some recent experiments ' show that this sup])ositiou
is incorrect, and that paraglobulin may be eliminated entirely from the theory.
The theory of Hammarsten, which is perhaps generally accepted at the present
time, is incomplete, however, in that it leaves undetermined the nature of the
ferment and of the reaction between it and the fibrinogen. The aim of the
newer theories has been to supply this deficiency.

Schmidt's Recent Theory of Coagidation. — In a recent book ^ containing
the results of a lifetime of work devoted to the study of blood-coagulation,

' Frederikse : Zeitschrlft fiir physiohgische Chemie, vol. 19, 1894, p. 143.
« Zur Blutlehre, Leipzig, 1893.

BLOOD. no 5

Sehmiclt has inodifiod liis well-known theory. His present ideas of the direct
and indirect connection of the proteids of the plasma with the formation of
fibrin are too complex to be stated clearly in brief compass. He classifies the
conditions necessary for coagulation as follows : (1) Certain soluble jji-otcids —
namely, the two globulins of the blood — as the material from which fibrin is
made. Schmidt does not believe, however, that paraglobuliu and fibrinogen
react to make fibrin, but believes that fibrinogen is formed from paraglobulin,
and that fibrinogen in turn is changed to fibrin. (2) A specific ferment, fibrin
ferment, to effect the changes in the proteids just stated. He pix3])oses for
fibrin ferment the distinctive name of thrombin. (3) A certain quantity of
neutral salts is necessary for the precipitation of the fibrin in an insoluble form.

T/ie Relation of Calcium Salts to Coagulation. — It has been shown by a
number of observers that calcium salts take an important part in the pro-
cess of clotting. This fact was most clearly demonstrated by Arthus and
Pages, who found that if oxalate of potash or soda is added to freshly-drawn
blood in quantities sufficient to precipitate the calcium salts, clotting will be
prevented. If, however, a soluble calcium salt is again added, clotting occurs
promptly. This fact has been demonstrated not only for the blood, but also
for pure solutions of fibrinogen, and we are justified in saying that without
the presence of calcium salts fibrin cannot be formed from fibrinogen. This
is one of the most significant facts recently brought out in connection with
coagulation. We know that fibrinogen when acted upon by fibrin ferment
produces fibrin, but we now know also that calcium salts must be present.
What is the relation of these salts to the so-called " ferment"? This question
has been differently answered in two recent theories of coagulation.

Pehelharing^ s Theory of Coagulation. — Pekelharing^ succeeded in sepa-
rating from blood-plasma a proteid body which has the properties of a nucleo-
albumin. He finds that if this substance is brought into solution together
with fibrinogen and calcium salts, a typical clot will form, while nucleo-
albumin alone, or calcium salts alone, added to fibrinogen solutions, cause
no clotting. His theory of coagulation is that what has been called " fibrin
ferment" is a compound of nucleo-albumin and calcium, and that when
this compound is brought into contact with fibrinogen a reaction occurs, the
calcium passing over to the fibrinogen and forming an insoluble calcium
compound, fibrin. According to this theory, fibrin is a calcium compound
with fibrinogen or with a part of the fibrinogen molecule. This idea is
strengthened by the unusually large percentage of calcium found in fibrin
ash. The theory supposes also that the fibrin ferment is not present in blood-
plasma — that is, in sufficient quantity to set up coagulation — but that it is formed
after the blood is shed. The nucleo-albumin part is derived from the cor-
puscles of the blood (leucocytes, blood-plates), Mhich break down and go into
solution. This nucleo-albumin then unites with the calcium salts present in
the blood to form fibrin ferment, an organic compound of calcium capable of
reacting with fibrinogen. The theory is a simple one ; it accounts for the

' Untersuckungen iiber das Fibrivfei-ment, Amsterdam, 1892.

35G AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

importance of calcium salts in coajjjulation, and reduces tiie iiiler<liaiiL!:e he-
tweeu fibrinotrt'H and fibrin ferment to the nature of an ordinai'v clieniical
reaction.

LUicnfeliVii T/icori/ of Coagnhiiion. — Lilienfeld ' has carried still further the
clieniical stiidv of the changes occurrinir in coatrulation. Like lY'Uelharing:
he finds that the three inipoi'tant sui)staiices to be considered in coa<^ulalioii
are tlbrinoj^en, nuclein compounds, and cal(;iuni salts. He differs from Pekel-
haring, however, in his description of liow these substances react with one
another in producing fibrin. Lilienfeld and others have shown that a com-
pound proteid to which the name " nucleohiston " is given may be extracted
from the nuclei of leucocytes and other cells, and that this ueucleohiston under
some circumstances favors the coagulation of liquids containing fibrinogen, but
under other circumstances prevents or retards coagulation. Nucleohiston is
readily decomposed into its two constituents — histon, a proteid body, and a
nueleo-proteid to which the specific name of" leuconuclein " is given. Histon
when injected into the blood of a living animal has a remarkable influence in
preventing coagulation : blood drawn shortly after the injection remains per-
fectly fluid, and its histological elements, red and white corpuscles and blood-
plates, retain perfectly their normal shapes. Leuconuclein, on the contrary,
although it is not able to produce fibrin from fibrinogen, does cause the fibrin-
ogen molecule to split, with the formation of a substance, " thrombosin,"
which comes down as a precipitate. If this thrombosin is dissolved in
dilute alkaline solution it clots readily when brought into contact with cal-
cium salts. Thrombosin may also be formed from fibrinogen by the action of
dilute acetic acid or nucleic acid (nuclein). Normal coagulation, according to
Lilienfeld, takes place as follows : After blood is shed there occurs a disinte-
gration of leucocytes (and blood-plates) resulting in the giving off of nuclein
compounds to the plasma. These nuclein substances, being dissolved in the
alkaline jilasnia, come in contact with the fibrinogen and decompose it, with
the formation of thrombosin. This latter substance then unites with the cal-
cium salts of the plasma to form fibrin, wiiieli, on this theory, might be defined
as a calcium compound of thrombosin. Lilienfeld's theory does not give a
satisfactory explanation of the nature of fibrin ferment, but is very valuable
in demonstrating that the essential act of clotting — that is, of the formation
of fibrin — is the union of calcium salts with a portion of the fibrinogen mole-
cule, and that this portion of the fibrinogen molecule may first be s])lit off by
the action of acetic acid or the acid nuclein coiiii)ounds. LTntil further inves-
tigations are made it is not possible to decide between the theories of Pekel-
haring and Lilienfeld. It is well, however, to emj)liasize the fact that there
is much in common between the two theories. E;ieh holds that the fibrin is a
compound of calcium salts with a jiortion of the fii)iinogeii molecule, the latter
undergoing splitting during the act of clotting. According to I^ilienfeld, this
splitting of the fibrinogen molecule is caused by nueleo-proteid, and the
thrombosin thus formed then comI)ii)es with the calcium. According to Pekel-

' Du Bois-Reymond's Arch ir fib- Phyxioloyie, 1893, p. 560.

BLOOD. 357

haring, the micleo-proteid first combines with the oalciiini, and tlien this cal-
cium compound reacts with the fibrinogen, transferring its calcium to a portion
of the molecule. We might say, therefore, that there are three fibrin fiictors
— fibrinogen, nucleo-proteid, and calcium salts; the first and last of" these exist
in the circulating blood, but the nucleo-proteid is formed usually only after
the blood is shed, and is derived from the disintegration of the formed ele-
ments, the leucocytes and blood-})l;ites. ilow these three factors interact to
form fibrin cannot be stated i)ositive!y, but it seems to be satisfactorily deter-
mined that the fibrin is a c()m|)ound of calcium with a ])ro(hict derived from
the splitting of the fibrinogen.

Nature and Orig-in of Fibrin Ferment (Thrombin). — Recent views as
to the nature of fibrin ferment have been referred to incidentally in the
description of the theories of coagulation just given. The relation of these
newer views to the older ideas can be presented most easily by giving a
brief description of the development of our knowledge concerning this bodv.
Schmidt' prepared solutions of fibrin ferment originally by adding a large
excess of alcohol to blood-serum and allowing the proteids thus precipitated
to stand under strong alcohol for a long time until they were thoroughly coagu-
lated and rendered nearly insoluble in water. At the end of the proper period
the coagulated proteids were extracted with water, and there was obtained a
solution Avhich contained only small quantities of proteid. It was found that
solutions prepared in this way had a marked effect in inducing coagulation
when added to liquids, such as hydrocele liquid, which contained fibrinogen,
but which did not clot spontaneously or else clotted very slowly. It was after-
ward shown that similar solutions of fibrin ferment are capable of setting up
coagulation very readily in so-called salted plasma — that is, in blood-plasraa
prevented from clotting by the addition of a certain quantity of neutral salts.
It was not possible to say whether the coagulating power of these solutions
was due to the small traces of proteid contained in them, or whether the ])ro-
teid was merely an impurity. The general belief for a time, however, was
that the proteids present were not the active agent, and that there was in solu-
tion something of an unknown chemical nature which acted upon the fibrinogen
after the manner of unorganized ferments. This belief was founded mainly
upon three facts : first, that the substance seemed to be able to act powerfully
upon fibrinogen, although present in such minute quantities that it could not be
isolated satisfactorily ; second, it was destroyed by heating its solutions for a few
minutes at 60° C. ; and, third, it did not seem to be destroyed in the reaction
of coagulation which it set up, since it was always present in the serum squeezed
out of the clot. Schmidt proved that fibrin ferment could not be obtained
from blood by the method described above if the blood was made to flow im-
mediately from the cut artery into the alcohol. On the other hand, if the shed
blood was allowed to stand, the quantity of fibrin ferment increased up to
the time of coagulation, and was present in quantity in the serum. Schmidt
believed that the ferment was formed in shed blood from the disintegration
of the leucocytes, and this belief was corroborated by subsequent histological

358 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

work. It was shown in microscopic preparations of coagulated blood that the
fibrin threads often radiated from broken-down leucocytes — an appearance
which seemed to indicate that the leucocytes served as p(Mnts of orij^in for the
deposition of tiic fibrin. When the blood-plates were discovered a great deal
of microscopic work was done tending to show that these bodies also are con-
nected with coagulation in the same way as the leucocytes, and serve probably
as sources of fibrin ferment. In microscopic preparations the fibrin threads
were found to radiate from masses of partially disintegrated plates ; and, more-
over, it was discovered that conditions which retard or prevent coagulation of •
blood often serve to preserve the delicate plates from disintegration. At the
present time it is generally believed that there is derived from the disintegra-
tion of the leucocytes and blood-plates something which is necessary to the
coao-ulation of blood, but there is some difierence of opinion as to the nature
of this substance and whether it is identical with Schmidt's fibrin ferment.
Pekelharing thinks that the substance set free from the corpuscles and plates
is a nuclco-])roteid, but that this uucleo-proteid is not capable of acting upon
fibrinoo-en until it has combined with the calcium salts of the blood. According
to his view, therefore, fibrin ferment, in Schmidt's sense, is a compound of cal-
cium and nucleo-proteid. Lilienfeld has shown by chemical reactions that
blood-plates and nuclei of leucocytes contain nucleo-proteid material which in
all probability is liberated in the blood-plasma by the disintegration of these
elements after the blood is shed. As he has shown also that this nucleo-
proteid material with the aid of calcium salts acts upon the fibrinogen to pro-
duce fibrin, it would seem clear that the so-called fibrin ferment is really a
nucleo-proteid compound. Lilienfeld contends, however, that solutions of
fibrin ferment prepared by Schmidt's method do not contain any nucleo-proteid
material, and that, although the liberation of the nucleo-proteid material is what
starts normal coagulation of blood, nevertheless so-called fibrin ferment is some-
thing entirely different from nucleo-proteid. In this point, however, his results
are contradicted by the experiments of Pekelharing and of Halliburton, who
both find that solutions of fibrin ferment prepared by Schmidt's method give
distinct evidence of containing nucleo-])roteid material. We may conclude,
therefore, that the essential element of Schmidt's fibrin ferment is a nucleo-
proteid compound. Whether or not this nucleo-proteid can act upon fibrinogen
directly, as Lilienfeld claims, or must first combine with calcium salts, as held
by Pekelharing, is a matter which must be left to future investigation.

Intravascular Clotting. — Clotting may be induced within the blood-
vessels by the introduction of foreign particles, either solid or gaseous — for
example, air — or by injuring the inner coat of the blood-vessels, as in ligat-
ing. In the latter case the area injured by the ligature acts as a foreign
surface and probably causes the disintegration of a number of corpuscles.
The clot in this case is confined at first to the injured area, and is known
as a "thrombus." Intravascular clotting more or less general in occurrence
may be produced by injecting into the circulation such substances as leucocytes
obtained by macerating lymph-glands, extracts of fibrin ferment, solutions of

BLOOD. ;J59

nucleo-albumius of different kiud.s, etc. According to tiic; tlu-ory of coagu-
lation adopted above, injections of these latter substances ought to cause coagu-
lation very readily, since the blood ahvady contains fibrinogen, and needs only
the presence of ferment to set up conguiation. As a matter of fact, however,
intravascular clotting is produced with some difficulty by these methods, show-
ing that the body can protect itself within certain limits from an excess of
ferment in the circulating blood. Just how this is done is not known, but
possibly it is due to some defensive activity of the living endothelial cells lining
the interior of the blood-vessels. Moreover, injection of leucocytes, nucleo-
albumins, etc. sometimes diminishes instead of increasing the coagulability of
blood, making the so-called "negative phase" of the injection. In the case
of leucocytes it is probable that this result is accounted for by the fact that
the nucleohiston liberated by their disintegration may undergo decomposition
in the blood with the formation of histon, which is known to prevent coagu-
lation (see p. 356).

Why Blood does not Clot within the Blood-vessels. — The reasons
why blood remains fluid while in the living blood-vessels, but clots quickly
after being shed or after being brought into contact with a foreign substance in
any way, have already been stated in describing the theories of coagulation,
but they will be restated here in more categorical form. Briefly, then, blood
does not clot within the blood-vessels because nucleo-proteids are not present
in sufficient quantities at any one time. Leucocytes and blood-plates probably
disintegrate here and there within the circulation, but the small amount of fer-
ment thus formed is insufficient to act upon the blood, and probably the ferment
is quickly destroyed or changed. When blood is shed, however, the formed
elements break down in mass, as it were, liberating a relatively large amount
of nucleo-proteids, which, in combination with the calcium salts, produce fibrin
from the fibrinogen. In shed blood the restraining action of the endothelial
cells of the blood-vessels, a more or less unknown factor, is also eliminated.

Means of Hastening or of Retarding Coagulation. — Blood coagulates
normally within a few minutes, but the process may be hastened by increasing
the extent of foreign surface with which it comes in contact. Thus, moving
the liquid when in quantity, or the application of a sponge or a handkerchief to
a wound, will hasten the onset of clotting. This is easily understood when it is
remembered that nucleo-proteids arise from the breaking down of leucocytes
and blood-plates, and that these corpuscles go to pieces more rapidly when in
contact with a dead surface. It has been proposed also to hasten clotting in
case of hemorrhage by the use of ferment solutions. Hot sponges or cloths
applied to a wound will hasten clotting, probably by accelerating the formation
of ferment and the chemical changes of clotting. Coagulation may be retarded
or be prevented altogether by a variety of means, of which the following are
the most important :

1. By Cooling. — This method succeeds well only in blood which clots
slowly — for example, the blood of the horse or the terrapin. Blood from
these animals received into narrow vessels surrounded by crushed ice may be

860 AN ami: in ('AN TKXr-BOOK OF PHYSIOLOGY.

kept fluid for an indefinite time. Tlie blo()d-cur])u.scles .s(Jon sink, so that this
method is an exeellent one for obtaining pure blood-plasma. The cooling
probably prevents clotting Jbv keeping the corpuscles intact.

2. By the Action of Neutral Salts. — Blood received at once from the blood-
vessels into a solution of such neutral salts as sodium sulphate or magnesium
sulphate, and well mixed, will not clot. In this case also the corpuscles settle
sluwiv, or thev may be centrifugalizcd, and specimens of plasma can be
obtained. For this purpose hoi-si-'s or cat's blood is to be preferred. Such
})lasma is known as ".salted plasma;" it is frequently used in experiments in
coagulation — for exam|)le, in testing the efficacy of a given ferment solution.
The best salt to use is MgSO^ in solutions of 27 i)er cent. : 1 part by volume
of this solution is usually mixed with 4 parts of blood ; if cat's blood is used a
smaller amount may be taken — 1 part of the solution to 9 of blood. Salted
plasma or salted blood again clots when diluted sufficiently with water or when
ferment solutions are added to it. How the salts prevent coagulation is not
definitely known — possibly by preventing the disintegration of corpuscles and
the formation of ferment, possibly by altering the chemical properties of the
proteids.

3. By the Action of Albnmose Solutions. — Certain of the products of
protcid digestion, pei)tones and albumoses, when injected into the circulation
retard clotting for a long time. For injection into dogs one uses 0.3 gi-am
to each kilogram of animal. If the blood is withdrawn shortly after the
injection, it will remain fluid for a long time. According to Pekelharing, the
albumoses act by combining with the calcium salts, or at least by preventing
them from reacting normally.

4. By the Use of Leech Extracts. — Extract of the heads of leeches, when
mixed with blood, will prevent coagulation. The extract contains some sub-
stance formed in the salivary glands of the leech. It is probable that this
substance acts normally to prevent the clotting of blood when sucked in by the
animal.

5. By the Action of Oxalate Solutions. — If blood as it flows from the
vessels is mixed with solutions of j^otassium or sodium oxalate in proportiim
sufficient to make a total strength of 0.1 per cent, or more of these salts,
coagulation will be prevented entirely. Addition of an excess of water will
not produce clotting in this case, but solutions of some soluble calcium salt
will quickly start the process. The explanation of the action of the oxalate
solutions is simple: they are supposed to precipitate the calcium as insoluble
calcium oxalate.

Total Quantity of Blood in the Body. — The total quantity of blood in
the body has been determined approximately for man and a number of the
lower animals. The method used in such determinations consists essentially
in first bleeding the animal as thoroughly as possible and weighing the quan-
tity of blood thus obtained, and afterward washing out the blood-vessels with
water and estimating the amount of luemoglobin in the washings. The results
are a.s follows: Man, 7.7 per cent, (^r^) of the body-weight ; that is, a man

BLOOD, 3G1

weigliin^- G8 kilos, has about 52-jG grams, or 49G.5 c.c, of blood in his body;
dog, 7.7 per cent.; rabbit and cat, 5 percent.; new-born human being, 5.26
per cent. ; and birds, 10 per cent. Moreover, tiie distribution of this blood
in the tissues of the body at any one time has been estimated by Kanke,' from
experiments on freshly-killed rabbits, as follows:

Spleen 0.'2.'> i)er cent.

Briiin anil cord 1.24 " "

Kidneys 1.63 " "

Skin 2.10 " "

Intestines 6.30 " "

Bones 8.24 " "

Heart, lungs, and great blood-vessels 22.76 " "

Kesting muscles 29.20 " "

Liver 29.30 " "

It will be seen from inspection of this table that in the rabbit the blood of
the body i.s distributed at any one time about as follows : one-fourth to the
heart, lungs, and great blood-vessels; one-fourth to the liver; one-fourth to
the resting muscles; and one-fourth to the remaining organs.

Regeneration of the Blood after Hemorrhage. — A large portion of the
entire quantity of blood in the body may be lost suddenly by hemorrhage
without producing a fatal result. The extent of hemorrhage Avhich can be
recovered from safely has been investigated upon a number of animals.
Although the results show more or less individual variation, it can be said
that in dogs a hemorrhage of from 2 to 3 per cent, of the body-weight ^ is
recovered from easily, while a loss of 4.5 per cent., more than half the entire
blood, will probably prove fatal. In cats a hemorrhage of from 2 to 3 ]>er
cent, of the body-weight is not usually followed by a fatal result. Just what
percentage of loss can be borne by the human being has not been deter-
mined, but it is probable that a healthy individual may recover without
serious difficulty from the loss of a quantity of blood amounting to as much
as 3 per cent, of the body-weight. It is known that if liquids which are iso-
tonic to the blood, such as a 0.9 per cent, .solution of NaCl, are injected into
the veins immediately after a severe hemorrhage, recovery will be more certain ;
in fact, it is possible by this means to restore persons after a hemorrhage which
would otherwise have been fatal. The phy.siological reason for this fact seems
to be that the large access of neutral liquid puts into circulation all the red
corpuscles. Ordinarily the number of red corpuscles is greater than that neces-
sary for a barely sufficient supply of oxygen, and increasing the bulk of liquid
in the vessels after a severe hemorrhage makes more effecti\e as oxygen-carriers
the remaining red corpuscles, inasmuch as it ensures a more rapid circulation.
If a hemorrhage has not been fatal, experiments on lower animals show that
the plasma of the blood is regenerated with astonishing rapidity, the blood
regaining its normal volume within a few hours in slight hemorrhages, and

1 Taken from Vierordt's Anatomische, physiologisehe und physikalische Daten und Tabellen, Jen&j
1893.

'^ Fredericq : Travaux du Laboratoire ( Univeii^ite de Liege), vo]. i., 1885, p. 189.

362 AN AMERICAN TEXT-BOOK OF PJIYSIOLOGY.

in from twenty-four to forty-eight hours if the loss of hh)ocl has been
severe ; but the number of red corpuscles and the hsenioglobin are regenerated
more slowly, getting back to normal only after a number of days or after
several weeks.

Blood-transfusion. — Shortly after the discovery of the circulation of the
blood (Harvey, 1628), the operation was introduced of transfusing blood from
one individual to another or from some of the lower animals to man. Ex-
travagant hopes were held as to the value of such transfusion not only as a
means of replacing the blood lost by hemorrhage, but also as a cure for various
infirmities and diseases. Then and subsequently, fatal as well as successful
results followed the operation. It is now known to be a dangerous under-
taking, mainly for two reasons: first, the strange blood, whether transfu.sed
directly or after defibrination, is liable to contain a quantity of fil)rin ferment
sufficient to cause intravascular clotting; secondly, the serum of one animal is
known to cause often a destruction of the blood-corpuscles of another. Owing
to this globulicidal action, which has previously been referred to (p. 334), the
injection of foreign blood is likely to be directly injurious instead of beneficial.
In cases of loss of blood from severe hemorrhage, therefore, it is far safer to
inject a neutral liquid, such as the so-called "physiological salt-solution" — a
solution of NaCl of such a strength (0.9 per cent.) as to be isotonic to the cor-
puscles. The bulk of the circulating liquid is thereby augmented, and all the
red corpuscles are made more efficient as oxygen-carriers, partly owing to the
fact that the velocity of the circulation is increased, and partly because the
corpuscles are kept from stagnation in the capillary areas.

LYMPH.

Lymph is a colorless liquid found in the lymph-vessels as well as in the
extravascular spaces of the body. All the tissue-elements, in fact, may be
regarded as being bathed in lymph. To understand its occurrence in the body
one has only to bear in mind its method of origin from the blood. Throughout
the entire body there is a rich supply of blood-vessels penetrating every tissue
with the exception of the epidermis and some epidermal structures, as the nails
and the hair. The plasma of the blood filters through, or is secreted through,
the thin walls of the capillaries, and is thus l)rought into immediate contact
with the tissues, to which it brings the nourishment and oxygen of the bloo<l
and from which it removes the waste products of metabolism. This extravas-
cular Ivmph is collected into small capillary spaces which in turn open into
definite lymphatic vessels. These vessels unite to larger and larger trunks,
forming eventually one main trunk, the thoracic or left lymphatic duct, and a
second smaller right lymphatic duct, which oi)en into the blood-vessels, each
on its own side, at the junction of the subclavian and internal jugular veins.
The lymph movement is from the tissues to the veins, and the flow is main-
tained chiefly by the difference in pressure between the lyrajih at its origin in

L YMPH. 363

the tissues and in the large lymphatic vessels. The continual formation of
lymph in the tissues leads to the development of a relatively high pressure in
the lymph capillaries, and as a result of this the lymph is forced toward the
point of lowest pressure— namely, the points of junction of the large lymph-
ducts with the venous system. A fuller discussion of the factors concerned in
the movement of lymph will be found in the section on Circulation. As would
be inferred from its origin, the composition of lymph is essentially the same as
that of blood-})lasma. Lymph contains the three blood-proteids, the extractives
(urea, fat, lecithin, cholesterin, sugar), and inorganic salts. The salts are found
in the same proportions as in the plasma ; the proteids are less in amount, espe-
cially the fibrinogen. Lymph coagulates, but does so more slowly and less
firmly than the blood. Histologically, lymph consists of a colorless liquid con-
taining a number of leucocytes, and after meals a number of minute fat-drop-
lets; red blood-corpuscles occur only accidentally, and blood-plates, according
to most accounts, are likewise normally absent.

Formation of Lymph. — The careful researches of Ludwig and his pupils
were formerly believed to prove that the lymph is derived directly from the
plasma of the blood by filtration through the capillary walls. Various condi-
tions which alter the pressure of the blood were shown to influence the amount
of lymph formed in accordance with the demands of a theory of filtration.
Moreover, the composition of lymph as usually given seems to support such a
theory, inasmuch as the inorganic salts contained in it are in the same concen-
tration, approximately, as in blood-plasma, while the proteids are in less con-
centration, following the well-known law that in the filtration of colloids
through animal membranes the filtrate is more dilute than the original solution.
This simple and apparently satisfactory theory has been subjected to critical
examination within recent years, and it has been shown that filtration alone
does not suffice to explain the composition of the lymph untl^r all circum-
stances. At present two divergent views are held upon the subject. Accord-
ing to some physiologists, all the facts known with regard to the composition
of lymph may be satisfactorily explained if we suppose that this liquid is
formed from blood-plasma by the combined action of the two physical pro-
cesses of filtration and diffusion. According to others, it is believed that, in
addition to filtration and diffusion, it is necessary to assume an active secretory
process on the part of the endothelial cells composing the capillary walls. A
discussion upon these points is in progress at present in current physiological
literature, and it is impossible to foresee definitely what the outcome will be,
since a final conclusion can be reached only by repeated experimental investi-
gations. The actual condition of our knowledge of the subject can be presented
most easily bv briefly stating the objections which have been raised by Heiden-
hain ^ to a pure filtration-and-diffusion theory, and indicating how these objec-
tions have been met.

L Heidenhain shows by simple calculations that an impossible formation
of lymph would be required, upon the filtration theory, to supply the chemical
"^ Arehiv fur die gesammte Physwlogie, 1891, Bd. xlix. S. 209.

;3(j4 AN AMERTCAN TEXT- HOOK OF PIl YSIOLOC Y.

needs of tlie organs in various organic and inorganic constituents. Thus, to
take an illustration which has Ihcu nuich discussed, one kilogram of cow's
milk contains 1.7 grams CaO, and the entire milk of twcntv-four iiours would
contain in round numbers 42.5 grams CaO. Since the lym})li contains nor-
mally al)out 0.18 parts of CaO per tiiousand, it would require 23(> liters of
lymph per day to supply the necessary CaO to the mammary glands. Heiden-
hain iiimself suggests that the difficulty in this case may he met by assuming
active diffusion processes in connection with liltration. If, for instance, in the
case cited, we suppose that the CaO of the lympii is quickly combined by the
tissues of the mammary gland, then the tension of calcium salts in the lymph
will be kept at zero, and an active ditl'usion of calcium into the lymph will occur
so long as the gland is secreting. In other wM)r(ls, the gland will receive its
calcium by mnch the same process as it receives its oxygen, and will get its
daily supply from a comparatively small bulk of lymph. Cohnstein ^ has
answered the problem in another way. He calls attention to the fact that
in the body the capillaries contain blood under a comparatively liigh pres-
sure, while on their exterior they are bathed with lymph, also under pres-
sure, although less than that of the blood. The pressure causing filtration
in this case is the difference in pressure between the inside and the outside
liquid. Moreover these liquids differ in comj)osition, so that diffusion must
also take place in such a manner that crystalloids will diffuse out into the
lymph, and an amount of water corresponding to the osmotic equivalent will
pass into the blood. The lymph that is actually formed will therefore be the
balance between these tw^o processes, and a liquid produced in this way he
designates specifically as a transudation. From laboratory experiments made
with ureters and veins he shows that the percentage composition of the transu-
dation in crystalloid substances will increase with the pressure of the outside
liquid. As this pressure is raised the filtration -stream is diminished, but the
diffusion is unaffected, hence the transudation will be more concentrated. It
is possible in this way, as he shows by experiment, to get a transudation much
more concentrated than the original liquid, and he assumes that in the body
the lymph formed in the tissues may be more concentrated than the blood, and
thus a small quantity of lymph may transport a large amount of crystalloid
substance. What seems to be a fatal objection to this reasoning, so far as it
applies to the difficulty first suggested with regard to the chemical needs of the
organs, is the time element. As Heidenhain points out, the more concentrated
the transudation the less its bulk, so that to get the required amount of CaO,
for example, would upon this hypothesis require nuich more than twenty-
four hours. Strictly speaking, however, the difficulty we are dealing with
here shows only the insufficiency of a pure filtration theory. It seems possible
that filtration and diffusion together woidd suffice to supply the organs, so far
at least as the diffusible substances are concerned.

2. Heidenhain found that occlusion of the inferior vena cava causes not
only an increase in the flow of lymph — as might be expected, on the filtration

' Archiv fur die gesamvite Plnjifiolofiie, 1894, Bd. lix. S. 350.

/. YMI'lI. 365

theory, from the cousequent rise of pressure in the capiUary regions — but also
an increased concentration in the percentage of proteiil in the lymph. This
latter fact has been satisfactorily explained by the experiments of Starling.'
Accordhig to this observer, the lymph Ibrmed in the liver is normally more
concentrated than that of the rest of the body. The occlusion of the vena
cava causes a marked rise in the capillary pressure in the liver, and most of
the increased lymph-flow under these circumstances comes from the liver,
hence the greater concentration. The results of this experiment, therefore, do
not antagonize the filtration-and-diflusion theory.

3. Heidenhein discovered that extracts of various substances which he
designated as " lymphagogues of the first class" cause a marked increase in the
flow of lymph from the thoracic duct, the lymph being more concentrated than
normal, and the increased flow continuing for a long ])eriod. Nevertheless,
these substances cause little, if any, increase in general arterial pressure; in
fact, if injected in sufficient quantity they produce usually a fall of arterial
pressure. The substances belonging to this class comprise such things as pep-
tone, egg-albumin, extracts of liver and intestine, and especially extracts of the
muscles of crabs, crayfish, mussels, and leeches. Heidenhain sn})poses that
these extracts contain an organic substance which acts as a specific stimulns to
the endothelial cells of the capillaries and increases their secretory action. The
results of the action of these substances has been differently explained by those
■who are unwilling to believe in the secretion theory. Starling^ finds experi-
mentally that the increased flow of lymph in this case, as after obstruction of
the vena cava, comes mainly from the liver. There is at the same time in the
portal area an increased pressure which may account in part for the greater flow
of lymph ; but, since this effect upon the portal pressure lasts but a short time,
while the greater flow of lymph may continue for one or two hours, it is
obvious that this factor alone does not suffice to explain the result of the injec-
tions. Starling suggests, therefore, that these extracts act pathologically
upon the blood-capillaries, particularly those of the liver, and render them
more permeable, so that a greater quantity of concentrated lymph filters
through them. No experimental proof is given to show that these extracts
do so affect the capillary walls. Starling's explanation is supported by
the experiments of Popoff*.^ According to this observer, if the lymyh is col-
lected simultaneously from the lower portions of the thoracic duct, which con-
veys the Ivmph from the abdominal organs, and from the upper part, which
contains the lymph from the head, neck, etc., it will be found that injection
of peptone increases the flow only from the abdominal organs. Popoff" finds
also that the peptone causes a dilatation in the intestinal circulation and a
marked rise in the portal pressure. At the same time there is some evidence
of injury to the walls of the blood-vessels from the occurrence of extravasa-
tion in the intestine. Cohnstein,^ from experiments made with peptone solu-

' Journal of Physiology, 1894, vol. xvi. p. 234. - Ibid., 1894, vol. xvii. p. 30.

* Centralhlatt fiir Physiologie, 1895, Bd. ix., No. 2.

* Archiv fiir die gesammte Physiologie, 1894, Bd. lix. S. 3G6.

'S{}(i AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tioDS, suggests a different explanatiou of tlie action of" tliesc lyniphagogues.
He believes that these substances diminish in some way tlie osmotic tension of
the blood. In consequence of this diminution the diffusion-stream of water
from lymph into the blood is lessened, and therefore the filtration-stream in
the opposite direction, if it remains unchanged, must cause an increased volume
of lymph. This, theory, although supported to some extent by exj)erimental
evidence, does not seem to explain the greater concentration of lymph obtained
in these cases. So far, however, as the action of the lyniphagogues of the first
class is concerned, it may be said that the advocates of the filtration-and-diffu-
sion theory have suggested a plausible explanation in accord with their theory.
The facts emphasized by Heidenliain with regard to this class of substances do
not compel us to assume a secretory function for the endothelial cells.

4. Inj(>ction of certain crystalline substances, such as sugar, NaCl, and
other neutral salts, causes a marked increase in the flow of lymph from the
thoracic duct. The lymph in these cases is more dilute than normal, and the
blood-plasma also becomes more watery, thus indicating that the increase in
water comes from the tissues themselves. Heidenliain designated these bodies
as " lymphagogues of the second class." His explanation of their action is
that the crystalloid materials introduced into the blood are eliminated by the
secretorv activity of the endothelial cells, and that they then attract water
from the tissue-elements, thus augmenting the flow of lymph. These sub-
stances cause but little change in arterial blood-pressure, hence Heidenhain
thought that the greater flow of lymph could not be explained by an increased
flltration. Starling^ has shown, however, that, although these bodies may not
seriously alter general arterial pressure, they may greatly augment intracapil-
lary pressure, particularly in the abdominal organs. His explanation of the
greater flow of lymph in these cases is as follows : '' On their injection into
the blood the osmotic pressure of the circulating fluid is largely increased. In
consequence of this increase water is attracted from lymph and tissues into the
blood by a process of osmosis, until the osmotic pressure of the circulating
fluid is restored to normal. A condition of hydrremic j)lethora is thereby pro-
duced, attended with a rise of pressure in the capillaries generally, especially
in those of the abdominal viscera. This rise of ]>ressure will be proportional
to the increase in the volume of the blood, and therefore to the osmotic pres-
sure of the solutions injected. The rise of ca])illary pressure causes great
increase in the transudation of fluid from the capillaries, and therefore in the
lymph-flow from the thoracic duct." This explanation is well supported by
experiments, and seems to obviate the necessity of assuming a secretory action
on the part of the capillary walls.

5. One of the most interesting facts developed by the experiments of Hei-
denhain and his pupils is that after the injection of sugar or neutral salts in
the blood the percentage of these substances in the lymph of the thoracic duct
may be greater than in the blood itself It is obviously difficult to explain
how this can occur by filtration or diffusion, since it seems to involve the pas-

' Op. ciL

LYMPH. 307

sage of crystalloid bodies from a less concentrated to a more concentrated solu-
tion. Cohnstein ^ has endeavored to sliow a fallacy in these results. He con-
tends that since it requires some time (several miiiiitcs) for the lymph to form
and pass into the thoracic ducrt, it is not justifialjle to compare the quantitative
composition of specimens of blood and lymph taken at the same time. If one
compares, in any given experiment, the maximal percentage in the blood of
the substance injected with its maximal percentage in tiie lymph, the latter
will be found to be lower. This, however, does not seem to be the case in all
the experiments reported. The work of Mendel ^ with sodium iodide seems to
establish the fact that when this salt is injected slowly its maximal percentage
in the lymph may exceed that in the blood ; and in the experiments made by
Cohnstein, as well as those by Mendel, it is shown that the percentage of the
substance in the lymph remains above that in the blood throughout most of
the experiment. In this point, therefore, there seems to be a real difficulty in
the direct application of the laws of filtration and difiTusion to the explanation
of the composition of lymph. It is possible, however, that a better under-
standing of the conditions prevailing in the capillaries with regard to osmosis
and filtration may clear up this difficulty.' Meanwhile it seems evident that
in spite of the very valuable work of Heidenhain, which has added so much
to our knowledge of the conditions influencing the formation of lymph, the
existence of a definite secretory activity of the pndothelial cells of the capil-
laries has not been proved.

^ Archivfiir die gesammte Physiologie, 1894-95, Bde. lix., Ix. und Ixii.

^ Journal of Physiology, 1896, vol. xix. p. 227.

^ See Hamberger: Du Bois-Reymnnd' s Archivfiir Physiologie, 1896, S. 36.

VII. CIRCULATION.

PART I.— THE MECHANICS OF THE CIRCULATION OF THE
BLOOD AND OF THE MOVEMENT OF THE LYMPH.

A. General Considerations.

The metaphorical phrase " circulation of the blood " means that every par-
ticle of blood, so long as it remains within the vessels, moves along a path
which, no matter how tortuous, finally returns into itself; that, therefore, the
particles wliich pass a given point of that patli may be the same which have
passed it many times already ; and that the blood moves in its path always in
a definite direction, and never in the reverse.

The discoverer of these weighty facts was " William Harvey, physician,
of London," as he styled himself. In the lecture notes of the year 1616,
mostly in Latin, which contain the earliest record of his discovery, he declares
that a "perpetual movement of the blood in a circle is caused by tiie beat of
the heart" ("perpetuum sanguinis motum in circulo fieri pulsu cordis").*
For a long time afterw^ard the name of the discoverer was coupled with the
expression which he himself had introduced, and the true movement of the
blood was known as the "Harveian circulation." -

Course of the Blood. — The metaphorical circle of the blood-path may
be shown l)y such a diagram as Figure 93.

If, in the body of a warm-blooded animal, we trace the course of a given
particle, beginning at the point where it leaves the right ventricle of the heart,
we find that course to be as follows : From the trunk of the pulmonary artery
(PA) through a succession of arterial branches derived therefrom into a capil-
lary of the lungs (PC) ; out of that, through a succession of pulmonary veins, to
one of the main pulmonary veins (PI'^ and the left auricle of the heart (LA) ;
thence to the left ventricle (LV); to the trunk of the aorta (.1); through a
succession of arterial branr-hes derived therefrom into any capillary (C) not
supplied by the pulmonary artery ; out of that, through a succession of veins
(T'') to one of the venre cavoe or to a vein of the heart itself; thence to the
right auricle (RA), to the right ventricle (RV), and to the trunk of the pul-
monary artery, where the tracing of the circuit began.

'William Harvev : Prcledlnnex Analrnnio' Univeranlix, edited, with an antotvpe reproduction
of the original, by a committee of tlie Royal College of Physicians of London, 1886, p. 80.

* Harvey's discovery of the circulation was first published in the modern sense in his work
ExercUalio nnatomicn de motu cordis et san(juinis in anim/tlibus, Francofurti, lfi'28. This great
classic c:in be read in English in the following : On the Motion of the Heart and Blood in Animals.
By William Harvey, M. D. ; Willis's translation, revised and edited by Alex. Bowie, 1889.
,S6S

CIRCULATION.

36U

It must be noted here that a particle of blood which traverses a capillary
of" the spleen, of the pancreas, of the stomach, or of the intestines, and enters
the portal vein, must next traverse a series of venous branches of diminishing
size, and a caj)illary of the liver, before entering the succession of veins which
will conduct the particle to the ascending vena cava (compare Figs. 93 and 94).

Most of the blood, therefore, whicli
leaves the liver has traversed two sets
of capillaries, connected with one
another by the portal vein, since quit-
tiusr the arterial svstem. This ar-

FiG. 93. — General diagram of the circulation :
the arrows indicate the course of the blood : PA,
pulmonary artery : P C, pulmonary capillaries ;
P y, pulmonar>' veins ; L A, left auricle ; L V, left
ventricle ; A, systemic arteries ; C, systemic capil-
laries ; T', systemic veins ; R A, right auricle , li V,
right ventricle.

Fig. 94.— Diagram of the portal system : the ar-
rows indicate the course of the blood: A, arterial
system ; V, venous system : C, capillaries of the
spleen, pancreas, and alimentary canal : P V, portal
vein ; C", capillaries of the liver ; C, the rest of the
systemic capillaries. The hepatic artery is not
represented.

rangement is of extreme importance for the physiology of nutrition. An
arrangement of the same order, though less conspicuous, exists in the
kidney.

Causes of the Blood-flew. — The force by which the blood is driven from
the right to the left side of the heart through the capillaries which are related
to the respiratory surface of the lungs, is nearly all derived, from the contrac-
tion of the muscular wall of the right ventricle, which narrows the cavity
thereof and ejects the blood contained in it; the force by Avhich the blood is
driven from the left to the right side of the heart through all the other capil-
laries of the body, often called the "systemic" capillaries, is derived nearly
all from the contraction of the muscular wall of the left ventricle, which nar-
rows its cavity and ejects its contents. The contractions of the two ventricles
are simultaneous. The force derived, from each contraction is generated by
the conversion of potential energy, present in the chemical constituents of the
muscular tissue, into energy of visible motion ; a part also of the potential
energy at the same time becoming manifest as heat. In the maintenance of
the circulation the force generated by the heart is to a very subordinate degree
supplemented by the forces which produce the aspiration of the chest and by

24

370 .4^y AMERICAN TEXT-BOOK OF PIIYSIOLOOY.

the force generated by the contractions of the skeletal muscles throughout the
body (sec p. ')87).

Mode of Working of the Pumping Mechanism. — During eacii contrac-
tion or ''systole" of the ventricles the blood is ejected into tiie arteries only,
because at that time the auricuio-vcntricular openings arc each closed by a valve.
During the innncdiatcly succeeding " diastole " of the ventricles, which con-
sists in the relaxation of their muscular walls and the dilatation of their
cavities, blood enters the ventricles by way of the auricles only, because at that
time the arterial openings are closed each by a valve which was open during
the ventricular systole ; and because the auriculo-ventricular valves which
were closed during the systole of the ventricles are open during their diastole.
During the first and longer part of the diastole of the ventricles the auricles,
too, are in diastole; the whole heart is in repose; and blood is not ()nly enter-
ing the auricles, but passing directly through them into the ventricles.
Near the end of the ventricular diastole a brief simultaneous systole of both
auricles takes place, during which they, too, narrow their cavities by the
muscular contraction of their walls, and eject into the ventricles blood which
had entered the auricles from the " systemic " and pulmonary veins respec-
tively. The systole of the auricles ends immediately before that of the ventri-
cles begins. The brief systole of the auricles is succeeded by their long dias-
tole, which corresponds in time with the whole of the ventricular systole and
with the greater part of the succeeding ventricular diastole. During the dias-
tole of the auricles blood is entering them out of the veins. Thus it is seen
that the direction in which the blood is forced is essentially determined by the
mechanism of the valves at the apertures of the ventricles; and that it is due
to these valves that the blood moves only in the definite direction before
alluded to. In the words, again, of Harvey's note-book, at this point written
in English, the blood is perpetually transferred through the lungs into the
aorta " as by two clacks of a water bellows to rayse water."'

Pulmonary Blood-path. — In the birds and mammals the entire breadth of
the blood-path, at one part of the physiological circle, consists in the capillaries
spread out beneath the respiratory surface of the lungs. The right side of the
heart exists only to force the blood into and past this portion of its circuit,
where, as in the systemic capillaries, the friction due to the fineness of the tubes
causes much resistance to the flow. This great comparative development of the
pulmonary portion of the blood-path in the warm-blooded vertel)rates is related
to the activity, in them, of the respiration of the tissues, which calls for a cor-
responding activity of function at the respiratory surface of the lungs, and for a
rapitl renewal in every systemic capillary of the internal respiratory medium, the
blood. This raj)id renewal implies a rapid circulation ; and that the speed is
great with M-hich the circuit of the heart and vessels is com))leted has been
proven by experiment, the method being too complicated for description here.^

^ PreledioTies, etc., p. 80.

* Karl Vierordt : Die Erscheinungen und Oesetze der Stromgeschwindigkeilen des Blutes. 2te
Ausgabe, 18S2.

CIRCULATION. 371

Rapidity of the Circulation. — By experiment the shortest time has been
measured whieh is taken by a particle of blootl in passing from a point in the
external jugular vein of a dog to and through the right cavities of the heart,
the pulmonary vessels, the left cavities of the heart, the commencement of
the aorta, and the arteries, capillaries, and veins of the head, to the starting-
point, or to the same ]X)int of the vein of the other side. This time has
been found to be from fifteen to eighteen seconds. Naturally, the time would
be different in different kiuds of animals and in the different circuits in the
same individual.

Order of Study of the Mechanics of the Circulation. — The significance
and the fundamental facts of the circulation have now been indicated. Its
phenomena must next be studied in detail.^ As the blood moves in a circle,
we may, in order to study the movement, strike into the circle at any point.
It will, however be found both logical and instructive to study first the move-
ment of the blood in the capillaries, whether systemic or pulmonary. It is
only in passing through these and the minute arteries and veins adjoining that
the blood fulfils its essential functions ; elsewhere it is in transit merely.
Moreover, it is only in the minute vessels that the blood and the nature of
its movement are actually visible.

After the capillary flow shall have become familiar, it will be found that
the other phenomena of the circulation will fall naturally into place as indi-
cating how that flow is caused, is varied, and is regulated.

B. The Movement of the Blood in the Capillaries and in the
Minute Arteries and Veins.

Characters of the Capillaries. — Each of the vessels which compose the
immensely multiplied capillary network of the body is a tube, commonly of
less than one millimeter in length, and of a few one-thousandths only of a
millimeter in calibre, the wall of which is so thin as to elude accurate measure-

FiG. 95.— A capillary from the mesentery of the frog (Ranvier).

meut. The calibre of each capillary may vary from time to time. These
facts indicate the minute subdivision of the blood-stream in the lungs, and
among the tissues — that is, at the two points of its course where the essential
functions of the blood are fulfilled. These facts also show the shortness of

^ The following is a very valuable book of reference : Robert Tigerstedt : Lehrbuch der
Physiologie des Kreislaufes, 1893.

372 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the distance to be traversed by tlie blood wliile f'ulfilliug these functions;
aud explain the importance of the comparatively slow rate at which it will be
found to move throuj!;h that short distance. The histological study of a typ-
ical capillary (see Fig. 95) shows that its thin wall is composed of a single
layer only of living flat endothelial cells feet edge to edge in close contact ; and
that the edges of the cells are united by a small quantity of the so-called
cement-substance. If the capillary be traced in either anatomical direction,
the wall of the vessel is seen to become less thin and more comj)lex, till it
merges into that of a typical arteriole or venule, the walls of which arci still
delicate, though less so than that of a capillary. That the (capillary walls are
so thin and soft, and are made of living cells, are very important facts as
regards the relations between blood aud tissue. It is of great importance
for the variation of the blood-supply to a part that they are also distensible,
elastic, aud possibly contractile.

Direct Observation of the Plow in the Small Vessels. — The capillary
flow is visible under the compound microscope, best by transmitted light, in
the transparent parts of both warm-blooded and cold-blooded animals. It is
important that the phenomena observed in the latter should be compared with
observations upon the higher animals; but the fundamental facts can be most
fruitfully studied in the frog, tadpole, or fish, inasmuch as no special arrange-
ments are needed to maintain the temperature of the exposed parts of these
animals. Moreover, their large oval and nucleated red blood-corpuscles are
well fitted to indicate the forces to which they are subjected. The capillary
movement, therefore, will be described as seen in the frog; it being nnder-
stood that tiie ])henomena are similar in the other vertebrates. In the
frog the movement may be studied in the lung, the mesentery, the urinary
bladder, the tongue, -or the web between the toes. During such study the
proper wall of the living capillary is hardly to be seen, but only the line on
each side which marks the profile of its cavity. Even the proper walls of
the transparent arterioles aud venules are but vaguely indicated. The plasma
of the blood, too, has so nearly the same index of refraction as the tissues,
that it remains invisible. It is only the red corpuscles and leucocytes that
are conspicuous ; and when one speaks of seeing the blood in motion, he means,
strictly speaking, that he sees the moving corpuscles, and can make out the
calibre of the vessels in which they move. The observer uses as low a power
of the microscope as will suffice, and takes first a general survey of the minute
arteries, veins, and capillaries of the part he is studying, noting their form,
size, and connections. In the arteries and veins he sees that the size of the
vessels is ample in comparison with that of the c()r])u.scles ; that, in the veins,
the movement of the blood is steady, but in the arteries accelerated and
retarded, with a rhythm corresponding to that of the heart's beat. In the
veins, moreover, the individual red corpuscles can be distinguished, while in
the arteries they cannot, as at all times they shoot past the eye too swiftly.
The fundamental. observation now is verified that the blood is incessantly
moving out of the arteries, through the capillaries, into the veiu.s.

CIRCULA TION.

37:3

Behavior of the Red Corpuscles. — Capillarit-s will readily be found iu
wliicli the red eorpuseles move two or three abreast, or only in single file.
They generally go with their long diameters parallel to, or moderately oblique
to, the current. Tn no ease will any blockade of corpuscles occur, so lono- as
the parts are normal. The numerous red corpuscles are seen to be well fitted
by their softness and elasticity, as well as by their form and size, for moving
through the narrow channels. They bend easily ui)()m themselves as they
turn sharp corners, but instantly regain their form when free to do so (see
Fig. 90). A very common occurrence is for a corpuscle to catch upon the
edge which parts two capillaries at a bifurcation of the network. For some
time the corpuscle may remain doubled over the projection like a sack thrown
across a horse's back ; but, after oscillating for a while, it will be disengaged,
at once return to its own shape, and disappear in one of the two branches

Fig. 96. — To illustrate the behavior of red eor-
puseles in the capillaries: the arrows mark the
course of the blood: a, a "saddle-bag" corpus-
cle ; h, a corpuscle bending upon itself as it
enters a side branch.

Fig. 97.— To illustrate the deformity pro-
duced in red corpuscles in passing through
a capillary of a less diameter than them-
selves.

(see Fig. 96). It is instructive to watch red corpuscles passing iu single file
through a capillary the calibre of which, at the time, is actually less than the
shorter diameter of the corpuscles. Through such a capillary each corpuscle
is squeezed, with lengthening and narrowing of its soft mass, but on emerging
into a larger ve.ssel its elasticity at once corrects even this deformity ; it regains
its form, and passes on (Fig. 97).

Evidences of Friction. — In the minute ves.sels, capillary and other, cer-
tain appearances should carefully be observed which are the direct ocular
evidence of that friction which M-e shall find to be one of the prime forces
concerned in the blood-movement, to which it constitutes a strong resistance.
If, in a channel which admits three red corpuscles beside one another, three
be observed when just abreast, it will be found that very soon the middle one
forges ahead, indicating that the stream is swiftest at its core. This is because
the friction within the vessel is least in the middle, and progressively greater
outward to the wall (Fig. 98). In the small veins the signs of friction are

374 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

strikiDgly seeu, as the outer layers among the mmierous corpuscles lag con-
spicuously, lu liie arterioles similar pheixjmena are seen if the normal swift-
ness of movement become sutiicieutly retarded for the individual corpuscles
to be visible.

Fig. 98— To illustrate the forging ahead of a Fig. 99.— The inert layer of plasma in the

corpuscle at the centre of the blood-stream. small vessels.

The arrow marks the direction of the blood.

An appearance which also tells of friction is that of the so-called " inert
layer" of plasma.^ In vessels, of whatever kind, which are wide enough for
several corpuscles to pass abreast, it is seeu that all the red corpuscles are always
separated from the profile of their channel by a narrow clear and colorless
interval — occupied, of course, by plasma. This is caused by the excess of the
friction in the layers nearest to the vascular wall (see Fig. 99). The friction
thus indicated, other things being equal, is less in a dilated than in a con-
tracted tube; and less in a sluggish than in a rapid stream. It probably
varies also with changes of an unknown kind in the condition of the cells of
the vascular wall.

Behavior of the Leucocytes. — If the behavior of the leucocytes be
watched, it will be seen to differ markedly from that of the red corpuscles, at
least when the blood-stream is somewhat retarded, as it so commonly is under
the microscope. Whereas the friction within the vessels causes tlie throng of
red corpuscles to occupy the core of the stream, the scantier leucocytes may
move mainly in contact with the wall, and thus be present freely in the inert
layer of plasma. Naturally their progression is then much slower and more
irregular than that of tiie red disks. Indeed, the leucocytes often adhere to
the wall for a while, in spite of shocks from the red cells which pass thorn.
Moreover, the spheroidal leucocyte rolls over and over as it moves along the
wall in a way very different from the progression of the red disk, which only
occasionally may revolve about one of its diametei-s. A leucocyte entangled
among the red cells near the middle of the stream is seen generally not only
to move onward but also to move outward toward the wall, and, before long,
to join the other leucocytes which are bathed by the inert layer of plasma.
It is due solely to the lighter specific gravity of the leucocytes that, under
the forces at work within the smaller vessels, they go to the wall, while the
denser disks go to the core of the current. This has been proved experimen-
tally by driving through artificial capillaries a fluid having in suspension par-
ticles of two kinds. Those of the lighter kind go to the wall, of the heavier

1 Poiseuille: "Recherches siir les causes du mouvement du sang dans les vaisseaux capil-
laires," Academie des Sciences — Savans itrangeis, 1835.

CIRCULATION. 375

kind to the core, even wlieii the luituie and form of the particles employed
are varied.'

Emigration of Leucocytes. — It lias been said that a leucocyte may often
adhere for a time to the wall of the capillary, or of the arteriole or venule,
in which it is. Sometimes the leucocyte not only adheres to the wall, but
passes throutjh it into the tissue without by a process which has received the
name of ''emigration."^ A minute projection from the protoplasm of the
leucocyte is thrust into the wall, usually where this consists of the soft cement-
substance between the endothelial cells. The delicate pseudopod is seen pres-
ently to have pierced the wall, to have grown at the expense of the main body
of the cell, and to have become knobbed at the free end which is in the tissue.
Later, the flowing of the protoplasm will have caused the leucocyte to assume
something of a dumb-bell form, with one end within the blood-vessel and the
other without. Then, by converse changes, the flowing protoplasm comes to
lie mainly within the lymph-space, with a small knob only within the vessel ;
and, lastly, this knob too flows out ; what had been the neck of the dumb-bell
shrinks and is withdrawn into the cell-body, and the leucocyte now lies wholly
without the blood-vessel, while the minute breach in the soft wall has closed
behind the retiring pseudopod. This phenomenon has been seen in capillaries,
venules, and arterioles, but mainly in the two former. It seems to be due to
the amoeboid properties of the leucocytes as well as to purely physical
causes. Emigration, although it may probably occur in normal vessels, is
strikingly seen in inflammation, in which there seems to be an increased
adhesiveness between the vascular wall and the various corpuscles of the

blood.

Speed of the Blood in the Mmute Vessels.— As a measure of the speed
of tlie blood in a vessel, we may fairly take the speed of the red corpuscles.
It must, however, be remembered that as the friction increases toward the wall,
the speed of the red corpuscles is least in the outer layers of blood, and in-
creases rapidly toward the long axis of the tube. At the core of the stream the
speed may be twice as great as near the wall. As we have seen, the stream of red
corpuscles in an arteriole is rapid and pulsating. In the corresponding venule,
which is commonly a wider vessel, the stream is less swift, and its pulse has dis-
appeared. In the capillary network between the two vessels the speed of the red
corpuscles is evidently slower than in either arteriole or venule ; and here, as in
the veins, no pulse is to be seen ; the pulse comes to an end with the artery
which exhibits it. In one capillary of the network under observation the
movement may be more active than in another ; and even in a given capillary
irregular variations of speed at different moments may be observed. Where
two^capillaries in which the pressure is nearly the same are connected by a
cross-branch, the red corpuscles in this last may sometimes even be seen to

' A. Schklarewsky : "Ueber das Bliit und die Suspensionsflussigkeiten," Pfliiger's Archivfur
die qe.fammie Physioloqie, 1868, Bd. i. p. 603. „ , , > ^ .i

■^ For the literature of emigration see R. Thoma : Text-book of General Pathology and Patho-
logical Anatomy, translated by A. Bruce, 1896, vol. i. p. 344.

'}7G .l.V AMERICAN TEXT-BOOK OF PJIY.SIOLOd Y.

oscillate, come to u staiKlstill, and then reverse the directiou of" their inove-
raent, and return to the capillary whence they had started. Naturally, no
such reversal will ever be seen in a capillary which springs directly from an
artery or which directly joins a vein. It will he remembered, however, that
any apparent speed of a corpuscle is much magnilied by the microscope, and
that therefore the variations referred to are comparatively uniniportant. \\'e
may, in fact, without material error, treat the speed of the blood in the Cnipii-
laries which intervene between the arteries and veins of a region as a})proxi-
mately uniform lor an ordinary period of observation, as the minute varia-
tions will tend to comj)ensate for one another. This speed is sluggish, as
already noted. In the capillaries of the web of the frog's foot it has been
found to be about 0.5 millimeter per second. The causes of this sluggishness
wmH be set forth later. That the very short distance between artery and vein
is traversed slowly, deserves to be insisted on, as thus time is atlfbrded for the
uses of the blood to be lulfilled.

Capillary Blood-pressure. — The pressure of the blood against the capil-
lary wall is low, though higher than that of the lymph without. This pres-
sure is subject to changes, and is readily yielded to by the elastic and deli-
cate wall. From these changes of pressure chauges of calibre result. The
microscope tells us less about tiie capillaiy blood-pressure than about the other
phenomena of the flow; but the microscope may sometimes show one striking
fact. In a capillary district under observation, a capillary not noted before
may suddenly start into view as if newly formed under tiie eye. This is
because its calibre has been too small for red corpuscles and leucocytes to enter,
until some slight increase of pressure has dilated the transparent tube, hitherto
filled with transparent plasma only. This dilatation has admitted corpuscles,
and has caused the vessel to appear.

That the caj)illary pressure is low is shown, moreover, by the fact that when
one's finger is pricked or slightly cut, the blood simply drips away ; that it
does not spring in a jet, as when an artery of any size has been divided. That
the capillary pressure is low may also be shown, and more accurately, by the
careful scientific application of a familiar fact: If one press with a blunt
lead-pencil upon the skin between the base of a finger-nail and the neigh-
boring joint, the ruddy surface becomes pale, because the blood is exj^elled
from the capillaries and they are flattened. If delicate weights be used,
instead of the pencil, the force can be measured which just suffices to whiten
the surface somewhat, that is, to counterbalance the pressure of the distend-
ing blood, which pressure thus can be measured approximately. It has been
found to be very much lower than the pressure in the large arteries, con-
siderably higher than that in the large veins, and thus intermediate between
the two ; whereas the blood-speed in the capillaries is less than the speed
in either the arteries or the veins. The pressure in the capillaries, meas-
ured by the method just described, has been found to be equal to that
required to sustain against gravity a column of mercury from 24 to 54 milli-

CIRCULA TION. 377

meters higli ; or, in the parlance of the laboratory, has been found equal to
from 24 to ') I inillinictcrs of nierciirv.'

Summary of the Capillary Flow. — Whether in the lungs or in the rest
of the body, the general characters of the capillary flow, as learned from direct
inspection and from experiment, may be summed up as follows: The blood
moves through the capillaries toward the veins with much friction, contin-
uously, slowly, without pulse, and under low pressure. To account for these
facts is to deal systematic^ally with the mechanics of the circulation ; and to
that task we must now address ourselves. •

0. The Pressure of the Blood in the Arteries, Capillaries, and

Veins.

"Why does the blood move continuously out of the arteries through the
capillaries into the veins? Because there is continuously a high pressure of
blood in the arteries and a low pressure in the veins, and from the seat of high
to that of low pressure the blood must continuously flow through the capillaries,
where pressure is intermediate, as already stated.

Method of Studying Arterial and Venous Pressure, and General
Results. — Before stating quantitatively the ditfereuces of pressure, we nuist
see how they are ascertained for the arteries and veins. The method of obtain-
ing the capillary pressure has been referred to already. If, in the neck of a
mammal, the left common carotid artery be clamped in two places, it can,
without loss of blood, be divided between the clamps, and a long straight glass
tube, open at both ends, and of small calibre, can be tied into that stump of
the artery which is still connected with the aorta, and which is called the
" proximal " stump. If now the glass tube be held upright, and the clamp
be taken oif which has hitherto closed the artery between the tube and the
aorta, the blood will mount in the tube, which is open at the top, to a consid-
erable height, and will remain there. The external jugular vein of the other
side should have been treated in the same way, but its tube should have been
inserted into tlie " distal " stump — that is, the stump connected with the veins
of the head, and not with the subclavian veins. If the clamp between the tube
and the head have been removed at nearly the same time with that upon the
artery, the blood may have mounted in the upright venous tube also, but only
to a small distance. To cite an actual case in illustration, in a small etherized
dog the arterial blood-column has been seen to stand at a height of about 1 55
centimeters above the level of the aorta, the height of the venous column
about 18 centimeters above the same level. The heights of the arterial and
venous columns of blood measure the pressures obtaining within the aorta and
the veins of the head respectively, while at the same time the circulation con-
tinues to be free through both the aorta and the venous network. Therefore,
in the dog above referred to, the aortic pressure was between eight and nine

' N. V. Kries : " Ueber den Druck^ii den Blntcapillaren der menschlichen Haut," Berichte
liber die Verhandlungender k.sdclusmhen Gesellachaft der Wissenschaf ten zu Leipzig, nvdih.-phys'ische
Classe, 1875, p. 149.

378 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

times as great a- that in the smaller veins of the head. As, during such an
experiment, the blood is free to pass from the aorta through one fxirotid and
botii vertebral arteries to the head, and to return through all the veins of
that part, except one external jugular, to the vena cava, it is demonstrated
that there must be a continuous flow from the aorta, through the capillaries
of the head, into the veins, because the pressure in the aorta is many times as
great as the pressure in the veins. Obviously, such an experiment, although
very instructive, gives only roughly qualitative results.

Two things will be noted, moreover, in such an experiment. One is that
the venous column is steady ; the other is that the arterial column is perpetu-
ally fluctuating in a rhythmic manner. The top of the arterial column shows
a regular rise and fall of perhaps a few centimeters, the rhythm of which is
the same as that of the breathing of the animal ; and, while the surface is thus
rising and falling, it is also the seat of frequent flickering fluctuations of
smaller extent, the rhythm of which is regular, and agrees with that of the
heart's beat. At no time, however, do the respiratory fluctuations of the arte-
rial column amount to more than a fraction of its mean height ; compared to
which last, again, the cardiac fluctuations are still smaller. It is clear, then,
that the aortic pressure changes with the movements of the chest, and with
the systoles and diastoles of the left ventricle. But stress is laid at present
upon the fact that the aortic pressure at its lowest is several times as high as
the pressure in the smaller veins of the head. Therefore, the occurrence of
incessant fluctuations in the aortic pressure cannot prevent the continuous
movement of the blood out of the arteries, through the capillaries, into the
veins.

The upright tubes employed in the foregoing experiment are called " man-
ometers." ^ They were first applied to the measurement of the arterial and
venous blood-pressures by a clergyman of the Church of England, Stephen
Hales, rector of Farriugdon in Hampshire, who experimented with them
upon the horse first, and afterward upon other mammals. He published his
method and residts in 1733.^ The height of the manometric column is a
true measure of the pressure which sustains it ; for the force derived from
gravity with which the blood in the tube presses downward at its lower open-
ing is exactly equal to the force with which the blood in the artery or vein is
pressed upward at the same opening. The downward force exerted bv the
column of blood varies directly with the height of the column, but, by the laws
of fluid pressure, does not vary with the calibre of the manometer, which cali-
bre may therefore be settled on other grounds. It follows also that the arterial
and venous manometers need not be of the same calibre. Were, however,
another fluid than the blood itself used in the manometer to measure a given
intravascular pressure, as is easily possible, the height of the column would
differ from that of the column of blood. For a given pressure the height

^ From /uavoc, rare. The name was given from such tjibes being used to measure the tension
of gases.

* Stephen Hales : Statical Essays: containing Haemaslaticks, etc., London, 1733, vol. ii. p. 1.

CIRCULATION,

379

of the column is invei'se to the
density of tiie manonietric fluid.
For example, a j^ivcu pressure will
sustain a far taller eoluiun i)f blood
than of niereurv.

The Mercurial Manometer. —
The method of Hales, in its orig-
inal simplicity, is valuable from
that very simplicity ibr demonstra-
tion, but not for research. The
elotting of the blood soon ends the
experiment, and, while it continues,
the tallness of the tube required for
the artery, and the height of the
column of blood, are very incon-
venient. It is essential to under-
stand next the principles of the
more exact instruments employed
in the modern laboratory.

In 1828 the French physician
and physiologist J. L. M. Poiseuille
devised means both of keeping the
blood from clotting in the tubes,
and of using as a measuring fluid
the heavy mercury instead of the
much lighter blood. He thereby
secured a long observation, a low
column, and a manageable man-
ometer.^ The " mercurial man-
ometer" of to-day is that of Poi-
seuille, though modified (see Fig.
100). In an improved form it con-
sists of a glass tube open at both
ends, and bent upon itself to the
shape of the letter U. This is held
upright by an iron frame. If mer-
cury be poured into one branch of
the U, it will fill both branches to
an equal height. If fluid be driven
down upon the mercury in one
branch or " limb " of the tube, it
will drive some of the mercury out
of that limb into the other, and the
rest at very unequal levels. The di
^ J. L. M. Poiseuille : Becherches

Fig. 100.— Diagram of the recording mercurial man-
ometer and the liymograph ; the mercury is indicated in
deep black : M, the manometer, connected by the leaden
pipe, L, with a glass cannula tied into the proximal
stump of the left common carotid artery of a dog ; A,
the aorta; C, the stop-cock, by opening which the man-
ometer may be made to communicate through JiT. the
rubber tube, with a pressure-bottle of solution of sodium
carbonate ; F, the float of ivory and hard rubber ; R, the
light steel rod, kept perpendicular by B, the steel bear-
ing ; P, the glass capillary pen charged with quickly dry-
ing ink ; T, a thread which is caused, by the weight of a
light ring of metal suspended from it, to press the pen
obliquely and gently against the paper with wliicli is
covered D, the brass "drum" of the kymograph, which
drum revolves in the direction of the arrow. The sup-
ports of the manometer and the body and clock-work
of the kymograph are omitted for the sake of simplicity.
The aorta and its branches are drawn disproportionately
large for the sake of clearness.

two surfaces of the mercury may come to
fference of level, expressed in millimeters,

sur la force du coeur aoriique, Paris, 1 828.

38U AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

measures the height of the manonietric column of mercury the downwaril pres-
sure of which in one limb of the tube is just equal to the downward pressure
of the fluid in the other. In order to adapt this " U-tube" to the study of the
blood-pressure, that limb of the tube which is to communicate with the artery
or vein is caj)pcd with a cock which can be closed. Into this same limb, a little
way below the cock, opens at right angles a short straight glass tube, which is
to communicate with the blood-vessel through a long flexible tube of lead, sup-
ported by the iron frame, and a short glass cannida tied into the blood-vessel
itself. Two short pieces of india-rubber tube join the lead tube to the manometer
and the cannula. Before the blood-vessel is connected with the manometer, the
latter is filled with fluid between the surface of the mercury next the blood-
vessel and the outer end of the lead tube, which fluid is such that when mixed
with blood it prevents or greatly retards coagulation. With this same fluid
the glass cannula in the blood-vessel is also filled, and then this cannula and
the lead tube are connected. The cock at the upper end of the " proximal
limb" of the manometer is to facilitate this filling, being connected l)y a rub-
ber tube with a " pressure bottle," and is closed when the filling has been
accomplished. The fluid introduced by Poiseuille and still generally used is
a strong watery solution of sodium carbonate. A solution of magnesium sul-
phate is also good. If, in injecting this fluid, the column of mercury in the
"distal limb" is brought to about the height which is expected to indicate the
blood-pressure, but little blood will escape from the blood-vessel when the
clamp is taken from it, and coagulation may not set in for a long time.

The Recording Mercurial Manometer and the Graphic Method. —
AVhen the arterial pressure is under observation, the combined respiratory
and cardiac fluctuations of tiie mercurial column are so complex and fre-
quent that it is very hard to read off their course accurately even with the
help of a millimeter-scale pUiced beside the tube. In 1847 this difliculty led
the German physiologist Carl Ludwig to convert the mercurial manometer
into a self-registering instrument. This invention marked an epoch not
merelv iu the investigation of the circulation, but in the whole science of
phvsiology, by beginning the present " graphic method " of physiological
work, which has led to an immense advance of knowledge in many depart-
ments. Ludwig devised the " recording manometer " by placing upon the
mercury in the distal air-containing limb of Poiseuille's instrument an ivory
float, bearing a light, stifl', vertical rod (see Fig. 100). Any fluctuation of the
mercurial column caused float and rod to rise and fall like a pistou. The rod
projected well above the manometer, at the month of which a delicate bear-
ing was provided to keep the motion of the rod vertical. A very delicate
pen placed horizontally was fastened at right angles to the upper end of the
rod. If a firm vertical surface, covered with ]iai)ei-, were now placed lightly
in contact with the pen, a rise of the mercury would cause a corresponding
vertical line to be marked upon tiie paj^er, and a succeeding fall would
cause the descending pen to inscribe a second line covering the first. If
now the vertical surface were made to move i)ast the pen at a uniform rate,

CIRCULATION. 381

the jjiiccessive up-aiul-down movciiuiiits of the mercury would uo lonj^er be
marked over aii<l over again iu the same place so as to produce a single ver-
tical line. The space and time taken up by each fluctuation would be graph-
ically recordetl in the form of a curve, itself a portion of a continuous trace
marked by the successive fluctuations; thus both the respiratory and cardiac
fluctuations could be registered throughout an observation by a single complex
curving line. Ludwig stretched his paper around a vertical hollow cylinder
of brass, made to revolve at a regular known rate by means of clock-woi'k,
and the conditions above indicated were satisfied ^ (see Fig. 100). Upon the
surface of such a cylinder vertical distance represents space, and a vertical line
of measurement is called, by an application of the language of mathematics,
an "ordinate;" horizontal distance represents time, and a horizontal line of
measurement is called an " abscissa." The curve marked by the events re-
corded is always a mixed record of space and time. The instrument itself,
the essential part of which is the regularly revolving cylinder, is called the
"kymograph."^ It has undergone many chatiges, and many varieties of it
are in use. Any motor may be used to drive the cylinder, provided that the
speed of the latter be uniform and suitable.

The curve written by the manometer or other recording instrument may
either be marked upon paper with ink, as iu Lud wig's earliest work ; or may
be marked with a needle or some other fine pointed thing upon paper black-

FiG. 101.— The trace of arterial blood-pressure from a dog anaesthetized with morphia aud ether. The
cannula -was in the proximal stump of the common carotid artery. The curve is to be read from left
to right.

P, the pressure-trace written by the recording mercurial manometer ;

B L, the base-line or abscissa, representing the pressure of the atmosphere. The distance between
the base-line and the pressure-curve varies, in the original trace, between 62 and 77 millimeters, there-
fore the pressure varies between 124 and 154 millimeters of mercury, less a small correction for the
weight of the sodium-carbonate solution ;

T, the time-trace, made up of intervals of two seconds each, and written by an electro-mag-
netic chronograph.

eued with soot over a flame. The trace written upon smoked pajjcr is the
more delicate. After the trace has been written, the smoked paper is removed
from the kymograph and passed through a pan of shellac varnish. This

' C. Lndwig: "Beitriige zur Kenntniss des Einflusses der Kespirationsbewegungen auf
den Blutlauf ini Aortensysteme," MulWs Archiv fiir Anatomie, Physioloc/ie, nnd inssenschaflliche
Medicin, etc., 1847, p. 242. ' From nvfia, a wave.

382 AX AMERICAN TEXT- BOOK OF PHYSIOLOGY.

ulicii dry fixfs tlic trace, which tlicreafter will not ix' spoiled by han<lling.
Ill Fij^iire 101 liu- uppermost line shows a trace which fairly represents the
successive fluctuations of the aortic pressure of the dog. The longer and
ampler fluctuations are respiratory, tiie briefer and slighter are cardiac. lu
each res])iratory curve the lowest jmint and the succeeding ascent coincide with
inspiration; the highest point and the succeeding descent with expiration.
The horizontal middle line is the base line, rej)resenting the pressure of the
atmosphere. The base-line has been shifted upward in the figure simply in
order to save room on the page. In the lowermost line the successive spaces
from left to right of the reader re])resent successive intervals of time of two
seconds each, written by an electro-magnetic chronograph. The pressure-trace
taken from a vein may in certain regions near the chest show respiratory fluc-
tuations, but nowhere cardiac ones, as the pulse is not transmitted to the veins.
The venous pressure is so small, that for the practical study of it a recording
manometer must be used in which some lighter fluid replaces the mercury,
M'hich would give a column of insuflicient height for working purposes. The
values obtained are then reduced by calculation to millimeters of mercury, for
comparison with the arterial pressure. The intravascular pressure at a given
moment can be measurer! by measuring a vertical line or " ordinate " drawn
from the curve written by the manometer to the horizontal base-line. The
latter represents the height of the manometric column when just disconnected
from the blood-vessel ; that is, when acted u])on only l)y the weight of the
atmosj)here and of the solution of sodium carbonate. To ascertain the blood-
pressure, the length of the line thus measured must be doubled ; because the
mercury in the proximal limb of the manometer sinks under the blood-pres-
sure exactly as much as the float rises in the distal limb. A small correction
must also be made for the weight of the solution of sodium carbonate.

The Mean Pressure. — The " mean pressure " is the average pressure dur-
ing whatever length of time the observer chooses. The mean pressure for the
given time is ascertained from the manometric trace by measurements too
complicated to be explained here. As the weight and consequent inertia of
the mercurv cause it to fluctuate accordincj to circumstances more or less than
the pressure, the mean pressure is much more accurately obtained from the
mercurial manometer than is the true height of each fluctuation, which is very
commonly written too small. Therefore, it is especially the mean pressure
that is studied by means of the mercurial manometer. The true extent and
finer characters of the single fluctuations caused by the heart's beat are better
studied with other instruments, as we shall see in dealing with the pulse.

It has been seen that the blood flows continuously through the capillaries
because the pressure is continually high in the arteries and low in the veins.
The reader is now in position to understand statements of the blood-pressure
expressed in millimeters of mercury. The mean aortic pressure in the dog is
far from being always the same even in the same animal. We have found it,
in the case referred to on page 377, to be equivalent to about 121 millimeters
of mercury. It will very commonly be found higher than this, and may range

CIRCULA TION. 383

up to, or above, 200 millimeter. In man it is pr<)l)al)ly higher than in the
(l()<r. i'lie pressure in tiie other arteries derived from the aorta which have
been studietl manometrically is not very greatly lower than in that vessel. In
the pulmouary arteries the pressure is probably much lower than in the aortic
system. The pressure in the small veins of the head of the dog, the cannula
being in the distal stump of the external jugular vein, we have found already
in one case to equal about 14 millimeters of mercury. In such a case the
presence of valves in the veins and other elements of difficulty make the
mean pressure hard to obtain as opposed to the maximum pressure during
the period of observation.

If a cannula be so inserted as to transmit the pressure obtaining within
the great veins of the neck just at the entrance of the chest, without interfer-
ing with the movement of the blood through them, and if a manometer be
connected with this cannula, the fluid wnll fall below the zero-point in the
distal limb, indicating a slight suction from within the vein, and thus a
slightly " negative " pressure.^ This negative pressure may sometimes become
more pronounced during inspiration and regain its former value during ex-
piration. Sometimes, again, the pressure during expiration may become posi-
tive. The continuous flow from the great arteries through the capillaries to
the veins, and through these to the auricle, is therefore shown by careful
quantitative methods, no less than by the tube of Hales, to be simply a
case of movement of a fluid from seats of lijgii to seats of lower pressure.

The Symptoms of Bleeding in Relation to Blood-pressure. — The dif-
ferences of pressure revealed scientifically by the manometer exhibit them-
selv^es in a very important practical way when blood-vessels are wounded and
bleeding occurs. If an artery be cleanly cut, the high pressure within drives
out the blood in a long jet, the length of which varies rhythmically ^vith the
cardiac pulse, but varies only to a moderate degree. From wounded capil-
laries, or from a wounded vein, owing to the low pressure, the blood does not
sjjring in a jet, but simply flows out over the surface and drips away without
pulsation. At the root of the neck, where the venous pressure may rhythmi-
cally fall below and rise above the atmospheric pressure, the bleeding from
a wounded vein may be intermittent.

D. The Causes of the Pressure in the Arteries, Capillaries,

AND Veins.

The causes of the continuous high pressure in the arteries must first engage
our attention.

Resistance. — The great ramification of the arterial sy.stem at a distance
from the heart culminates in the formation of the countless arterioles on the
confines of the capillary system. We have already seen direct evidence of the
friction in the minute vessels which results from this enormous subdivision of
the blood-path. The force resulting from this friction is propagated back-

' H. Jacobson: " Ueber die Blutbewegung in den Venen," Rcicherfs und du Bois-Bey-
moTuTs Archil- fur Anatomie, Physiologie, etc., 1867, p. 224.

384 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ward according to the laws of Huid pressure, and constitutes a strong resist-
ance to the onward movement of" the blood out of the iieart itself. Friction
is everywhere present in the vessels, but is greatest in the very small ones
collectively.

Power. — Where the aorta springs from tiie heart, the rhythmic contrac-
tions of the left ventricle force open the arterial valve, and force intermittent
charges of blood into the arterial system, overcoming thus the opposing force
derived from friction. The wall of the arterial system is very elastic every-
where. Thus the high pressure in the arteries results from the interaction of
the |)ower derived from the heart's beat and the resistance derived from fric-
tion. Tiiat the high pressure is continuous dei)ends upon the capacity for
distention possessed by the elastic arterial wall.

Balance of the Factors of the Arterial Pressure. — In order to
study the causation of the arterial pressure, let us imagine that it has for some
reason sunk very low ; but that, at the moment of observation, a normally
beating heart is injecting a normal blood-charge into the aorta. The first
injection would find the resistance of friction present, and the elastic arterial
wall but little distended. For this injection some room would be made by
the displacement of blood into the capillaries. But it would be easier for the
arterial wall to yield thau for the friction to be overcome, so the injected
blood would largely be stored within the arterial system and thus raise the
pressure. Succeeding injections would have similar results ; it would continue
to be easier for the injected blood to distend the arteries than to escape from
them ; and the arterial pressure would rise rapidly toward its normal height.
Presently, however, a limit would be reached ; a time would come when the
elastic wall, already well stretched, would have become tenser and stifier anil
would yield less readily before the entering blood ; and now a larger part
than before of each successive charge of blood would be accommodated
by the displacement of an equivalent quantity into the capillaries, and a smaller
part by the yielding of the arterial wall. Normal conditions of pressure
would be reached and maintained when the blood accommodated, during each
systole of the ventricle, by the yielding of the arterial wall should exactly
equal in amount the blood discharged from the arteries into the capillaries
during each ventricular diastole ; for then the quantity of blood parted with
by the arteries during both the systole and the diastole of the heart would
be exactly the same as that received during its systole alone.

We see that, at each cardiac systole, the cardiac muscle does work in main-
taining the capillary flow against friction, and also docs work upon the arte-
rial wall in expanding it. A portion of the manifest energy of the heart's
beat thus becomes potential in the stretched elastic fibres of the artery. The
moment that the work of ex})ansion ceases, the stretched elastic fibres recoil ;
their potential energy, just received from the heart, becomes manifest, and
work is done in maintaining the capillary flow against friction during the
repose of the cardiac muscle. At the beginning of this repose the arterial
valves have been closed by the arterial recoil. When, at each cardiac systole,

CIRCULATION. 385

the arterial wall expands before tlie entering blood, the pressure rises, for
more blood is entering the arterial system than is leaving it; when, at each
cardiac diastole, the arterial wall recoils, the pressure falls, for blood is leaving
the arterial system, and none is entering it. But before the fall has had time
to become pronounced, while the arterial pressure is still high, the cardiac sys-
tole recurs, and tlie prcs-ui-e rises again, as at the preceding fluctuation.

The Arterial Pulse. — The increased arterial pressure and amplitude at
the cardiac systole, followed by diminished pressure and amplitude at the
cardiac diastole, constitute the main phenomena of the arterial pulse. They
are marked in the maiiometric trace by those lesser rhythmic fluctuations of
the mercury which correspond with the heart-beats. The causes of the arte-
rial pul.se have just been indicated in dealing with the causes of the arterial
pressure. The pulse, in some of its details, Nvill be studied further for it.self
in a later chapter. For the sake of simplicity, the respiratory fluctuations of
the arterial pressure have not been dealt with in the discussion just con-
cluded. The causes of these important fluctuations are very complex and are
treated of under the head of. Respiration.

The arterial pressure, then, results from the volume and frequency of the
injections of blood made by the heart's contraction ; from the friction in the
vessels ; and from the elasticity of the arterial wall.

The Capillary Pressure and its Causes. — When we studied the move-
ment of the blood in the capillaries, we found the pressure in them to be low
and free from rhythmic fluctuations. In both of the.se qualities the capillary
pressure is in sharp contrast with the arterial. What is the reason of the differ-
ence ? The work of driving the blood through as well as into the capillaries is
done during the contraction of the heart's wall by its kinetic energy. During
the repose of the heart's wall and the arterial recoil this work is continued by
kinetic energy derived, as we have seen, from the preceding cardiac contraction.
The work of producing the capillary flow is done in overcoming the resistance
of friction. The capillary walls are elastic. The same three factors, then —
the power of the heart, the resistance of friction, the elasticity of the wall —
which produce the arterial pressure produce the capillary pressure also. Why
is the capillary pressure normally low and pulseless? The answer is not
difficult. The friction which must be overcome in order to propel the blood
out of the capillaries into the wider venous branches is only a part of the total
friction which oppo.ses the admission of the blood to the minuter vessels. The
resi.stance is therefore diminished which the blood has yet to encounter after
it has actually entered the capillaries. The force which propels the blood
through the capillaries, althougli amply sufficient, is greatly less than the
force which propels it into and through the larger arteries. In both
cases alike the force is that of the heart's beat. But, in overcoming the
friction which resists the entrance of the blood into the capillaries, a large
amount of the kinetic energy derived from the heart has become converted
into heat. The power is therefore diminished. As, in producing the high
arterial pres.sure, much power is met by much resistance, and the elastic wall

25

386 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

is, therefore, clisteiicleil with act'iiimihitcd blood ; so, in producing the low capil-
larv pressure, diminished power is met by diminished resistance, outflow is
relatively easy, accumulation is slight, and the elasticity of the delicate- wall
is but little called upon.

The Extinction of the Arterial Pulse. — Uiit why is the capillary pres-
sure pulseless, as the microscope shows? To explain this, no new factors need
<liscussion, but only the adjustment of the arterial elasticity to the intermittent
injections from the heart and to the total friction which opposes the admission
of blood to the ca))illaries. This adjustment is such that the recoil of the
arteries displaces blood into the capillaries during the ventricular diastole at
exactly the same rate as that })roduced by the ventricular contraction during
the ventricular systole. Thus, through the elasticity of the arteries, the car-
diac pulse undergoes extinction ; and this becomes complete at the confines
of the capillaries. The respiratory fluctuations become extinguished also, and
the movement of the blood in the capillaries exhibits no rhythmic changes.
This conversion of an intermittent flow into one not merely continuous but
approximately constant affords a constant blood-supply to the tissues, at the
same time that the cardiac muscle can have its diastolic repose, and the ven-
tricular cavities the necessary opportunities to receive from the veins the
blood which is to be transferred to the arteries.

A simple experiment will illustrate the foregoing. Let a long india-rubber
tube be taken, the wall of which is thin and very elastic. Tie into one end
of the tube a short bit of glass tubing ending in a fine nozzle, the friction at
which will cause great resistance to any outflow through it. Tie into the
other end of the rubber tube an ordinary syringe-bulb of india-rubber, with
valves. Expel the air, and inject water into the tube from the valved bulb
by alternately squeezing the latter and allowing it to expand and be filled
from a basin. The rubber tube will swell and pulsate, but if its elasticity
have the right relation to the size of the fine glass nozzle and to the amplitude
and frequency of the strokes of the syringe, a continuous and uniform jet will
be delivered from the nozzle, while the injections of water will, of course, be
intermittent.

The Venous Pressure and its Causes. — The pressure in the peripheral
veins is less than in the capillaries and declines as the blood reaches the larger
veins. Very close to the chest the pressure is below the pressure of the
atmosphere, and may sometimes vary from negative to positive, following the
rhythm of the breathing. These respiratory fluctuations will be considered later.
The low and declining pressures under which the blood moves through the
venules and the larger veins are due to the same causes as those which account
for the capillary pressure. It is still the force generated by the heart's con-
tractions, and made uniform by the elastic arteries, which drives the blood
into and through the veins back to the very heart itself. As the blood moves
through the veins, what resistance it encounters is still that of the friction
ahead. But the friction ahe^d is progressively less ; the conversion of kinetic
energy into heat is progressively greater. The venous wall possesses elas-

CIRCULA TION. 387

ticity, but this is even less called upon than that of the capillaries ; and, pres-
ently, in the larger veins, the niovinti; blood is found to press no harder from
within than the atniosphere fi'oni witiiout.

Subsidiary Forces which Assist the Flow in the Veins. — There are
certain forces \vhi(!h, occasionally or regularly, assist the heart to return the
venous blood into itself. Too much stress is often laid upon these ; for it is
easy to see by experiment that the heart can maintain the circulation wholly
without help. The origins of these subsidiary forces are, first, the contraction
of the skeletal muscles in general ; second, the continuous traction of the
lungs; third, the contraction of the muscles of inspiration.

The Skeletal Muscles and the Venous Valves. — A vein may lie in
such relation to a muscle that when the latter contracts the vein is pressed
upon, its feeble blood-pressure is overborne, the vein is narrowed, and blood
is squeezed out of it. The veins in many parts are rich in valves, competent
to prevent regurgitation of the blood while permitting its flow in the physio-
logical direction. The pressure of a contracting muscle, therefore, can only
squeeze blood out of a vein toward the heart, never in the reverse direction.
Muscular contraction, then, may, and often does, assist in the return of the
venous blood with a force not even indirectly derived from the heart. But
such assistance, although it may be vigorous and at times important, is tran-
sient and irregular. Indeed, were a given muscle to remain long in contrac-
tion, the continued squeezing of the vein would be an obstruction to the flow
through it.

The Continuous Pull of the Elastic Lungs. — The influence of thoracic
aspiration upon the movement of the blood in the veins deserves a fuller dis-
cussion. The root of the neck is the region where this influence shows itself
most clearly, but it may also be verified in the ascending vena cava of an
animal in which the abdomen has been opened. The physiology of respira-
tion shows that not only in inspiration, but also in expiration, the elastic fibres
of the lungs are upon the stretch, and are pulling upon the ribs and intercostal
spaces, upon the diaphragm, and upon the heart and the great vessels. This
dilating force at all times exerted upon the heart by the lungs is of assistance,
as we shall see, in the diastolic expansion of its ventricles. In the same way
the elastic pull of the lungs acts upon the venae cavae within the chest, and
generates within them, as well as within the right auricle, a force of suction.
The effects upon the venous flow of this continuous aspiration are best known
in the system of the ascending vena cava. This suction from within the
chest extends to the great veins just without it in the neck. In these, close to
the chest, as we have seen, manometric observation reveals a continuous slightly
negative pressure. A little farther from the chest, however, but still within
the lower portions of the neck, the intravenous pressure is slightly positive.
The elastic pull of the lung, therefore, continuously assists in unloading the
terminal part of the venous system, and thus differs markedly from the irreg-
ular contractions of the skeletal muscles.

The Contraction of the Muscles of Inspiration. — But some skeletal

388 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

muscles, those of inspiration, re<rularly add tlieir rhytluuie contractions to tlie
contiuuoiiri pull <)t" tlu' lun>;s, to reinforce the latter. P^ach time that the chest
expands there is an increased tendency for blood to be sucked into it through
the veins. At the beginninj^ of eaeii expiration this increase of suction
abruptly ceases.

The Respiratory Pulse in the Veins near the Chest, and its Limita-
tion.— In quiet breathinu- the niovenients of the eliest-wall j)ro(liic(; no very
conspicuous effect. If, however, deep and infrequent breaths be taken, the
pressure within the veins close to the chest becomes at each inspiration nnich
more negative than before ; and at each inspiration tiie area of negative
pressure mav extend to a greater distance from the chest along the veins of
the neck, and perhaps of the axilla. As the venous pressure in these parts
now falls as the chest rises, and rises as the chest falls, a visible venous pulse
presents itself, coinciding, not with the heart-beats, but with the breathing.
At each inspiration the veins diminish in size, as their contents are sucked
into the chest faster than they are renewed. At each expiration the veins may
be seen to swell under the pressure of the blood coming from the periphery.
If the movements of the air in the windpipe be mechanically imj)eded,
these changes in the veins reach their highest pitch ; for then the muscles of
expiration may actually compress the air within the lungs, and produce a
positive pressure within the vena cava and its branches, with resistance to the
return of venous blood during expiration, shown by the exaggerated swelling
of the veins. These phenomena are suddenly succeeded by suction, and by
collapse and disappearance of the veins from view, as inspiration suddenly re-
curs. The respiratory venous pulse, when it occurs, diminishes progressively
and rapidlv as the veins are observed ftirther and farther from the root of the
neck, — a fact which results from the Haceidity of the venous wall. Were the
walls of the veins rigid, like glass, the successive inspirations would produce
rhythmic accelerations of the flow throughout the whole venous system, and
the contractions of the muscles of inspiration would rank higher than they do
among the causes of the circulation. In flict, the walls of the veins are very
soft and thin. If, therefore, near the chest, the pressure of the blood within
the veins sink below that of the atmosphere without, the ])lace of the blood
sucked into the chest is filled only partly by a heightened flow of blood from
the periphery, but partly also by the soft venous wall, which promptly sinks
under the atmospheric pressure. This is shown by the visible flattening,
perhaps disappearance from view, of the vein. This process reduces the
venous pulse, where it occurs, to a local phenomenon ; for, at each inspira-
tion, the ]>romptly resulting shrinkage of all the affected veins together is just
equivalent to the loss of volume due to the sucking of blood into the chest.
Therefore the flow in the more peripheral veins remains unaffected, and the
pressure within them continues to be pulseless and positive. During expira-
tion the swelling of the veins near the chest, the return of positive pressure
within them, may be simply from the return of the ordinary balance of forces
after the effects of a deep inspiration have disappeared. But, if expiration be

CIBCULA riON. 389

violent and much inipoded, the positive pressure may rise much above the
normal. Here again, however, rej^ui-gitation will meet with opposition
from the venous valves, though the flow from the periphery may be much
impeded.

The " Dangerous Region," and the Entrance of Air into a Wounded
Vein. — Quite close to the chest, then, the normal venous pressure is always
slightly negative; and in deep inspiration it may become more so, and this
condition may extend farther from the chest along the neck and axilla, through-
out a region known to surgeons as "the dangerous region." It is important
to understand tlie reason for this expression. It has already been mentioned
that the wounding of a vein in this region may cause intermittent bleeding.
It now will easily be understood that such bleeding will occur only when the
pressure is positive — that is, during expiration. During deep and difficult
breathing, indeed, the venous blood may spring iu a jet during expiration
instead of merely flowing out, and may wholly cease to flow during inspira-
tion. The cessation is due, of course, to the blood being sucked into the
chest past the wound rather than pressed out of it.

It is not, however, the risks of hemorrhage that have earned the name of
"dangerous" for the region where intermittent bleeding may occur. The
danger referred to is of the entrance of air into the wounded vein and into the
heart, — an accident which is commonly followed by immediate death, for
reasons not here to be discussed. Very close to the chest, where the venous
pressure is continuously negative and the veins are so bound to the fasciae that
they may not collapse, this danger is always present. Throughout the rest
of the dangerous region, the entrance of air into a wounded vein will take
place only exceptionally. In quiet breathing the venous pressure is continu-
ously positive throughout most of this region; and then a wounded vein will
merely bleed. It is only in deep breathing that a venous pulse becomes vis-
ible here, and that the venous pressure becomes negative in inspiration. But
even in forced breathino- it is I'are for a wounded vein of the dauoerous reg-ion
to do more than bleed. The cause of this lies iu the flaccidity of the venous
wall. At each expiration the blood may jet from the wound ; but at the fol-
lowing deep inspiration the weight of the atmosphere flattens the vein so
promptly that the blood is followed down by the wounded wall and no air
enters at the opening. It is only when, during deep breathing, the wounded
wall for some reason cannot collapse, that the main part of the "dangerous
region " justifies its name. Should the tissues through which the vein runs
have been stiffened by disease, or should the wall of the vein adhere to a
tumor which a surgeon is lifting as he cuts beneath it, in either case the vein
will have become practically a rigid tube. Should it be wounded during a
deep inspiration, blood will be sucked past the wound, but the atmospheric
pressure will fail to make the wall collapse ; air will be drawn into the cut,
and blood and air will enter the heart together, probably with deadly effect.

Summary. — It appears from what has gone before that the elasticity of
the lungs and the contractions of the muscles of inspiration regularly assist Id

390 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

uuloading the veins in the immediate neighborhood of" the heart, and so remove
some part of the resistance to be overcome by the contractions of tiie cardiac
muscle. Wlion we come to the detaik'd study of the heart it will appear also
that a slight force of suction is generated i)y the heart itself, which force adds
its effects upon the flow of venous blood to those of the elasticity of the lungs
and of the contraction of the muscles of inspiration.

Tt must here be repeated, however, that the heart is quite competent to
maintain the circulation unaided. This is proven as follows : If in an anaes-
thetized mammal a cannula be placed in the windpipe, the chest be widely
opened, and artificial respiration be established, the circulation, though modi-
fied, continues to be etfective. By the opening of the chest its aspiration has
been ended, and can no longer assist in the venous return. If, further, the
animal be drugged in such a manner as completely to paralyze the skeletal
muscles throughout the body, their contractions can exert no influence upon
the venous return ; yet the circulation is still kept up by the heart, unaided
either by the elasticity of the lungs, by the contractions of the muscles which
produce inspiration, or by those of any other skeletal muscles.

E. The Speed of the Blood in the Arteries, Capillaries,

AND Veins.

If we keep as our text, in discussing the circulation, the character of the
capillary flow, it will be seen that we have now accounted for the facts that
the capillary flow is toward the veins ; that it shows much friction ; that it is
continuous, pulseless, and under low pressure. We have not yet accounted
for the fact that it is slow. We must now do so, but must first state and
account for the speed of the blood in tiie arteries and veins.

The Measurement of the Blood-speed in Large Vessels ; the " Strom-
uhr." — The speed of the blood in the larger veins and arteries must be meas-
ured indirectly. We can picture to ourselves the volume of blood which moves
past a given point in a given blood-vessel in one second, as a cylinder of
blood havina: the same diameter as the interior of the blood-vessel. The
length of this cylinder will then be expressed by the same number which will
express the velocity with which a particle of the blood would pass the given
point in one second, provided that this velocity be uniform and be the same
for all the particles. In order, then, to learn the average speed of the blood
at a given point of an artery or vein during a certain number of seconds, we
have only to measure the calibre of the blood-vessel and the quantity of
blood which passes the selected point during the period of observation.
From these two measurements the speed can be obtained by calculation. But
these two measurements are not quite easy. The physical properties of the
blood-vessels, especially of the veins, make their calibres variable and hard
to estimate justly as affected by the conditions present during an experiment.
The means adopted for measuring the quantity of blood passing a point in a
given time necessarily alters the resistance encountered by the flow, and so of
itself affects both the rate of flow and the blood-pressure; and, with the

CIRCULA TION.

391

Fig. 102.— Diagram of longitudinal sec-
tion of Ludwig's "Stroniuhr." The ar-
rows mark the direction of the blood-
stream. For further description see the
text.

latter, the calibre of the vessel. For tiie.se reasons any measuretneut of
the average speed of tiie blood l)y tlie above method is only a])proxiniately
correct. The be.st instrunu'nt for nieasurinu;
the quantity of blood driven past a point
during an experiment is the so-called "stroni-
uhr" or "rheouR'ter" of Ludwig, a longitu-
dinal section of wiiich is given diagrammati-
cally in Figure 102.' This is essentially a
curved tube shaped like the Greek capital
letter S2. Each end of the tube is tied into
one of the two stumps (a and b) of the divided
vessel. These ends of the tube are as nearly
as possible of the same calibre as the vessel
selected. Each limb of the tube is dilated
into a bulb, and the upper part of the tube,
including the two bulbs, is of glass; the lower
part of each limb is of metal. At the top,
between the bulbs, is an opening for filling
the tubes, which can easily be closed when not
in use. Each end of the tube is filled with
defibrinated blood before being tied into the
blood-vessel. In the limb of the tube {B,
Fig. 102) which is the farther from the heart if an artery be used, or the
nearer to the heart if a vein, the defibrinated blood is made to fill the cavity
up to the top of the bulb. In the other limb (.4, Fig. 102) the blood fills the
tube only up to a mark (e. Fig. 102) near the bottom of the bulb. Through
the opening between the bulbs the still vacant space, which includes the whole
of the bulb A, is filled with oil, all air being excluded. The opening is then
closed. If now the clamps be removed from the blood-vessel, the blood of the
animal will enter the tube at a and drive before it the contents of the tube.
Thus defibrinated blood from B will be driven into the distal stump of the
vessel at 6, and will enter the circulation of the animal. Oil will at the same
time be driven over from A to B. The bulb A has upon it two marks, d and
e, one near the top of it, the other near the bottom. The instant when the
line between the oil and the advancing blood reaches the mark near the top
of A is the instant when a volume of blood equal to that of the displaced oil
has entered A, past the mark near the bottom of it. The capacity of the tube
between the two marks is accurately known. The time required for this
space to be filled with the entering blood is measured by the observer. The
calibre of the metal tube at a is accurately known, and is assumed to be equal
to the calibre of the blood-vessel. From these measurements the average
speed of the blood-stream at a is calculated.

^ .J. Dogiel : "Die Aiismessung der stromenden Bliitvolumina," Berichle Uber die Verhand-
lungen der k. sdchsischen Gesellschaft der Wissenschaften zu Leipzig, Math.-physische Classe, 1867,
p. 200.

392 AN AMERICAN TEXT- HOOK OE PHYSIOLOGY.

Tlie metallic lower part of tlie instrument, wliicii includes both limbs of
the tube, is com|)letely divided li()rizt)ntally at c. The two parts are so built,
however, as to be maintained in water-tight apposition. This arrangement
permits the whole upper part of tlie instrument, induding the glass bulbs, to
be rotated suddenly upon the lower, so that the bulb B may corresjioiid with
the entrance for the blood at a, antl the bulb A with the exit for the l)lood at
h. If this rotation be effected at the instant when the space between the two
marks on .1 has been filled with blood, the bulb B, now charged with oil,
will be filled bv the blood which eutei's next, and the first charge of the ani-
mal's own blood will make its exit at b. Oil will now pass over from B to
A; when the line between it and the blood whieh is leaving A has just
reached the lower mark on yl,the bulbs are turned back to their original
position. Thus, by repeated rotations, each of which can be made to record
upon the kymograpii the instant of its occurrence, a number of charges of
blood can be received and transmitted in succession ; it is always the same
space, between the marks on A, which is used for measuring the charge ; and
the time of the experiment can be much prolonged. By this procedure the
errors due to a single brief observation can be greatly reduced. Indeed, the
time of entrance of a single charge of blood would be quite too short to give
a satisfactory result.

The use of the stromuhr not only affords necessary data for the calcu-
lation of tlie average speed of the blood, but seeks directly to measure the
volume of blood delivered in a given time by an artery to its capillary dis-
trict. It is evident that this volume is a quantity of fundamental importance
in the physiology of the circulation. Could we ascertain it, by direct meas-
urement or by calculation, for the aorta or pulmonary artery, we should know
at once the volume of blood delivered to the" capillaries in one second, and
thus the time taken for the entire blood to enter either those of the lungs or
of the system at large. By this knowledge, many important problems would
be advanced toward solution.

The Measurement of Rapid Fluctuations of Speed. — The stromidir
can give only the average speed of the blood during the experiment. To
study rapid fluctuations of speed, another method is needed. If, in a large
animal, a vessel, best an artery, be laid bare, a needle may be thrust into it at
right angles. If the needle be left to itself, the end which projects from the
artery will be deflected toward the heart, because the point will have been
deflected toward the capillaries by the blood-stream. The angle of deflection
might be read off, could a graduated semicircle be adjusted to the needle. If
the stream be arrested, the needle returns to its position at right angles to the
artery. The greater the velocity of the stream, the greater is the deflectiou of
the needle. If, later, the same needle be thrust into a tube of rubber through
which water flows at known rates of speed, the speed corresponding to each
angle of deflection of the needle may be determined. If the needle were
made to mark upon a kymograph, variations of the speed would be recorded
as a curve.

CinCULA TION. 393

An instrument based on (lie principles just described is valuable for the
Study of rapid clianjrcs of velocitv.' In an artery, its needle oscillates rlivth-
niically, showing tliat there tiie speed of the blood varies during each beat of
the heart, being greatly accelerated by the systole of the ventricle, and retarded
by the cessation of the systole. It will be remembered that the microscope
directly shows faint rhythmic accelerations in the minute arteries of the frog.
lu the veins rhythmic changes of speed do not occur except near the heart
from respiratory causes.

The Speed of the Blood in the Arteries. — The stromuhr shows that the
speed of the blood is liable to great variations. This flict, and the range of
speed in the arteries, are fairly exhibited by the results obtained by Dogiel
from the common carotid artery of a dog, the experiment upon which lasted
127 seconds. During this time six observations were made which varied in
length from 14 to 30 seconds each. For one of these periods the average
speed was 243 millimeters in one second ; for another ])eriod, 520 millimeters.
These were the extremes of speed noted in tliis case.'^ The speed in the
arteries diminishes toward the capillaries.

The Speed of the Blood in the Veins. — The speed in a vein tends to be
slower than that in an artery of about the same importance, but is not neces-
sarily so.^ It increases from the capillaries toward the heart.

The Speed of the Blood in the Capillaries. — The rate of the capillary
flow may be measured directly under the microscope. Certain physiologists
have also observed the movement of the blood in the retinal capillaries of
their own eyes, and have measured. its rate there.* Both methods show that
in the capillaries the speed is very much less than in the large arteries or large
veins. In the capillaries of the web of the frog's foot it is only about 0.5
millimeter in one second. In those of the mesentery of a young dog it has
been found to be 0.8 millimeter; in those of the human retina, from 0.6 to
0.9 millimeter.

Speed and Pressure of the Blood Compared. — If now we compare the
speed with the pressure of the blood in the arteries, in the capillaries, and in
the veins, we shall be struck by both similarities and differences. In the
arteries both pressure and speed rhythmically rise and fall together; and both
the mean pressure and the mean speed decline from the heart to the capillaries.
In the ca])illaries both pressure and speed are pulseless and low, — very low
compared with the great arteries. In the veins, however, the pressure is
everywhere lower than in the capillaries and falls from the capillaries to the
heart ; the speed is everywhere higher than in the capillaries and rises from

* M. L. Lortet : Recherche-s^ sur la vitesse du cours du sang dans les art^res du cheval au moyen
d^un nouvel hemodromographe, Paris, 1867.

■■^ J. Dogiel : loc. cit.

^ E. Cyon und F. Steinmann : " Die Geschwindigkeit des Blutstroms in den Venen," Bulletin
de V Academie Imperiale des Sciences de St. Petershourg, 1871 ; also in E. Cyon : Gesammelte physio-
log^ie Arbeiten, 1888, p. 110.

* K. Vierordt : Die Erscheinungen und Gesetze der Stromgeschwindigkeiten des Blutes, etc., 1862,

pp. 4i,iri.

394 AN AMEEICAX TEXT-BOOK OF PHYSIOLOGY.

the capillaries to the heart. It is apparent, therefore, that there is no direct
couueetiou between the pressure and the speed of the blood at a given jwint;
inasmuch as they change together along tlie arteries and change inversely
along the veins. How varied the combinations may be of pressure and speed
will be seen in studying the regulation of the circulation.

In the great veins, as in the arteries, the speed is very high compared with
the capillaries. In the capillaries the speed of the blood is least, while in
the tubes which supply and which drain them the speed is great. The physi-
ological value of these facts is clear. It has already been pointed out that the
blood moves slowly through the short and narrow tubes, where its exchanges
with tissue and with air are effected, and swiftly through the long tubes of
communication. What are the physical conditions wiiicii underlie these
physiological facts ?

The speed of the blood varies inversely as the collective sectional
area of its path. If the circulation in an animal continue uniform for a time
— during several breaths and heart-beats — it is evident that the forces con-
cerned must be so balanced that, during that time, equal quantities of blood
will have entered and left the heart, the arteries, the capillaries, and the veins,
respectively. If the arteries, for instance, lose more blood than the heart
transmits to them, this blood must accumulate in the veins till the arteries
become drained and the supply to the capillaries fails. The very maintenance
of a circulation, then, implies that equal quantities of blood must pass any
two points of the collective blood-path in equal times, except when a general
readjustment of the rate of flow may lead to a temporary disturbance of it.
It will be seen at once that this principle is consistent with the widest differ-
ences of rate between individual arteries of the same importance, or between
individual veins or capillaries. If in one artery the flow be increased by one-
half, and in another be diminished by one-half, the total flow in the two
arteries collectively will be the same as before.

If the principle just stated be considered in connection with tlie anatomy
of the blood-path, the differences of speed in the arterial, capillary, and venous
systems will at once be understood. The wider arteries and veins are few.
Dissection shows that when an artery or vein divides, the calibre, and, with
the calibre, the "sectional area" of the branches taken together, is commonly
larger than that of the parent trunk. In general it is a law of the arterial
and venous anatomy that the collective sectional area of the vessels of either
system increases from the heart to the capillaries. The smaller the individual
vessels are, the wider is the blood-path which they make up collectively.
Widest of all is the blood-path where the individual vessels are smallest — that
is, in the capillary system. The collective sectional area of the capillaries is
several hundred times that of the root of the aorta. The collective sectional
area of the veins which enter the right auricle is greater, perhaps twice as
great, as that of the root of the aorta. The venous system, regarded as a
single tube, is of much greater calibre than the arterial. It is perhaps better
to make these general statements than to compare the different figures given

CIRCULATION. 395

by different observers. The arterial and venous systems, treated as eacli a
single tube, may be compared roughly to two funnels, each having its nar-
row end at the heart. The very wiile and very short single tube of" the ca})il-
lary system may be imagined to connect the wide ends of the two funnels.
Equal quantities of blood pass in equal times any two points of the collec-
tive blood-path between the left ventricle and the right auricle. Therefore
where the blood-path is wide, these quantities must move slowly, and swiftly
where the blood-path is narrow. It is owing, then, to the rapid widening of
the arterial path that the speed declines, like the pressure, toward the capilla-
ries. It is owing to the huge relative calibre of the path at the capillaries
that in them the speed is by far the least while the same volume is passing
that passes a point in the narrow aorta in the same time ; it is owing to the
steady narrowing of the venous path toward the heart that the venous blood
is constantly quickening its speed while its pressure is falling. As the calibre
of the venous system is greater than that of the arterial, the average speed in
the veins is probably less than in the arteries. As the collective calibre of
the veins which enter the right auricle is greater than that of the aorta, the
blood probably moves into the heart less swiftly than out of it ; though of
course equal quantities enter and leave it in equal times provided those times
are not mere fractions of a beat. In connection with this it is significant
that the entrance of blood into the heart takes place during the long auric-
ular diastole, while its exit is limited to the shorter ventricular systole.

Time Spent by the Blood in a Systemic Capillary. — The width of the
path, then, determines the slow movement of the blood in the areas where it is
fidfilling its functions ; the narrowness of the path, the swiftness of move-
ment of the blood in leaving and returning to the heart. We have seen (p.
371) that a particle of blood may make the entire round of a dog's circulation
in from fifteen to eighteen seconds. If we assume the systemic capillary flow
to be at the rate of 0.8 millimeter in one second, the blood would remain about
0.6 of a second in a systemic capillary half a millimeter long. Slow as is the
capillary flow, it thus appears that it is none too slow to give time for the usos
of the blood to be fulfilled.

P. The Flow op Blood through the Lungs.
The blood moves from the right ventricle to the left auricle under the
same general laws as from the left ventricle to the right auricle. Certain dif-
ferences, however, are apparent, and must be noted. One difference is that
the collective friction is less in the pulmonary than in the systemic vessels,
and that therefore the resistance to be overcome by each contraction of the
right ventricle is less than that opposed to the left ventricle. Accordingly it
appears from dissection that the muscular wall of the right ventricle is much
thinner than that of the left. No accurate measurements can be made of the
normal pressure and speed of the blood in the arteries, capillaries, and veins
of the lungs, because they can be reached only by opening the chest and
destroying the mechanism of respiration, and thereby disturbing the normal

396 .l.V AMERICAN TEXT-BOOK OF PHYHIOLOdY.

conditions of the pulmonary hlood-stiram. In the opened chest these cannot
be entirely restored by artificial respiration. The thinness of the wall of the
pnlinonarv artery, however, indicates that it has much less pressure to support
than that of the aorta, whicli tact als<j is indicated by such roughly approxi-
mate results as have been obtained witli the manometer after opening the
chest.

As the pulmonary artery and veins lie wholly within the chest, but outside
tiie lungs, their trunks and larger branches all tend to be dilated continuously
by the elastic pull of the lungs — a pull which increases at each inspiration.
On the other hand, the pulmonary capillaries lie so close to the surface of each
lung that they are exposed to the same pressure, practically, as that surface,
and the full weight of the atmosphere may act upon them. These conditions
all tend to unload the capillaries and the pulmonary veins, but to weaken the
unloading of the pulmonary artery. The two effects can hardly balance one
another, however. The wall of the pulmonary artery is so much stiffer than
that of ihe vein, that the actual results should be favorable to the flow. The
elastieitv of the lungs and the contractions of the muscles of inspiration thus
lighten, probably, the work of the right ventricle as well as of the left. The
right ventricle, however, like the left, can accomplish its work without assist-
ance ; for the entire circulation, including, of course, the flow through the
lungs, continues after the chest has been opened, if artificial respiration be
maintained.

G. The Pulse-volume and the Work done by the Ventricles

OF the Heart.

The Cardiac Cycle. — It is assumed that the anatomy of the heart is known
to the reader.

The general nature and effects of the heart's beat have been sketched
already. Each beat has been seen to comprise a number of ])lienomena, which
occur in regular order, and which recur in the same order during each of the
succeeding beats. Each beat is therefore a cycle; and the phrase " cardiac
cvcle" has become a technical expression for " beat," as it conveys, in a word,
the idea of a regular order of events. As each of the four chambers of the
heart has its own systole and diastole, there are eight events to be studied in
connection with each cycle. The systoles of the two auricles, however, are
exactly simultaneous, as are their diastoles; and the same is true of the sys-
toles and of the diastoles of the two ventricles. We may, therefore, without
confusion, speak of the auricular systole and diastole, and of the ventric-
ular systole and diastole, as of four events, each involving the narrowing or
widening of two chambers, a right and a left. The heart of the mammal
or bird consists essentially of a pair of pumps, the ventricles, each of which
acts alternatelv as ^ ]>owerful force-pump and as a very feeble suction-
pump. To each ventricle is superadded a contractile apjiendage, the auricle,
through which, and to some extent by the agency of which, blood enters the
ventricle.

CIRCULA TION. 397

The Pulse-volume. — The central fact of the circulation of the blood is the
injoctioii, at intervals, by each ventricle, against a strong resistance, of a charge
of blood into its artery, which charge the ventricle has just received out of its
veins through its auricle. This (juantity nuist be exactly the same for the
two ventricles under normal conditions, or the circulation would soon come to
an end by the accumidation of the blood in either the j)ulmonary or the sys-
temic vessels. The blood ejected from each ventricle during the systole
nuist also be equal in volume to tiie blood which enters each set of capillaries,
the pulmonary or systemic, during that systole and the succeeding diastole of
the ventricles, provided the circulation be proceeding uniformly. The quantity
just referred to is called the "contraction volume" or "pulse-volume" of the
heart. Were it always the same, and could we measure it, we should possess
the key to the quantitative study of the circulation.

The pulse-volume may vary in the same heart at different times, as is easily
shown by opening the chest, causing the conditions of the circulation to change,
and noting that under certain conditions the heart during each beat varies
in size more than before. This variation of volume is easily possible because
the walls of the heart are of muscle, soft and distensible when relaxed. It is
probable that at no systole is the ventricle quite emptied ; that most of its
cavity may become obliterated by the coming together of its walls, but that a
spa(!e remains, just below the valves and above the papillary muscles, which is
not cleared of blood. It is also probable that not only the blood which is
ejected at the systole may vary in amount, but also the residual blood which
remains in the ventricle at the end of the systole.^ It is therefore clear that
it is useless to attempt the measurement of the pulse-volume by measuring
the fluid needed to fill the ventricle, even if the heart be freshly excised from
the living body and injected under the normal blood-pressure. Rough approx-
imations to this measurement may, however, be attempted in at least two
ways :

In the first place, a modification of the stromuhr has been applied suc-
cessfully to the aorta of the rabbit, between the origins of the corondry arteries
and of the innominate. This operation requires that the auricles be clamped
temporarily so as to stop the flow of blood into the venti'icles, and to permit
the aorta in its turn to be clamped and divided between the clamp and the
ventricle, without serious bleeding. After the circulation has been re-estab-
lished, the volume of the blood which passes through the instrument during
the ex])eriment, divided by the number of the heart-beats during the same
period, gives the pulse-volume. The average result obtained, for the rabbit,

1 F. Hesse: " Beitrage zur Mechanik der Herzbewegung," Arckw/iir Anatomie und Physiolo-
gie (anatomische Abtheilung), 1880, p. 328. C. Sandborg und W. Miiller : "Studien uberden
jMeclianismus des Herzens," Pflih/er's Archiv fur die gesammte Physioloc/ie, 1880, xxii. p. 408. C. S.
Roy and .1. G. Adami: "Contributions to the Physiology and Pathology of the Mammalian
Heart," Proceedings of the Boyal Society of London, 1891-92, i. p. 435. J. E. Johansson und R.
Tigerstedt : " Ueber die gegenseitigen Beziehungen des Herzens und der Geftisse ;" " Ueber die
Herzthiitigkeit bei verschieden grossem Wiederstand in den Gefiissen," Skandinamsches Archiv
fiir Physioloyie, 1891, ii. p. 409.

398 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

is a volume of blood the weight of which is 0.00027 of the weight of the
animal.'

A second way of attempting to ascertain the pulse-volume is to measure the
swelling and thesiirinkageof the heart. This is called the"plethysmographic" ^
method. One application of it is as follows : The chest and pericardium of an
animal are opened, and the heart is inserted into a brass case full of oil. The
opening through which the great vessels pass is made water-tight by mechanical
means which do not impede the movement of the blood into and out of the
heart. The top of the brass case is prolonged into a tube, the oil in which
rises as the heart swells and falls as it shrinks. Upon the oil a light piston
moves up and down, and records its movements upon the kymograph. The
instrument is called a " cardiometer," ^

The average pulse-volume of the human ventricle has been very variously
estimated upon the basis of observations of various kinds made upon mam-
mals of various species. The figures offered range, in round numbers, from
50 to 190 cubic centimeters. If we assume the human pulse- volume to
weigh 100 grams, and the blood of a man who weighs 69 kilograms to weigh
5.308 kilograms, or ^ of his body-weight, the pulse-volume will be about -^
of the entire blood, and the entire blood will pass through the heart, from
the veins to the arteries, in only fifty-three beats — that is, in less than one
minute. The speed with which a man may bleed to death if a great artery-
be severed is therefore not surprising.

The "Work done by the Contracting Ventricles. — Uncertain as is this
important quantity of the pulse-volume, the estimation of the work done by the
heart in maintaining the circulation must be based upon it, and upon the force
with which each ventricle ejects the pulse-volume. A small fraction of this
force is expended in im})arting a certain velocity to the ejected blood ; all the
rest serves to overcome a number of opposing forces. The force exerted by
the muscular contraction is opposed by the weight of the volume ejected, and
by the strong arterial pressure, which resists the opening of the semilunar
valve and the ejection of the pulse-volume. Moreover, the elasticity of the
lungs tends at all times to dilate the ventricles, with a force which is increased
at each recurring contraction of the muscles of inspiration. Probably there is
also in the wall of the ventricle itself a slight elasticity which must be over-
come by the ventricle's own contraction in order that its cavity may be effaced.
The strong arterial pressure, with which the reader is already familiar, is by
far the greatest of these resisting forces — in fact, is the only one of them
which is not of small importance in the present connection.

Are we obliged to measure the force of the systole indirectly ? Cau we not
ascertain it by direct experiment? Manometers of various kinds have been
placed in direct communication with the cavities of the ventricles. The fol-

* R. Tigerstedt: " Studien iiber die Blutvertheilung im Korper." Erste Abhandlung.
"Bestimmuug der von dem linken Herzen herausgetriebenen Blutmenge," Skandinavisches
Archiv fiir Physiologic, 1891, iii. p. 145.

■• From Tvl^vofidc, enlargement. ' C S. Roy and J. G. Adarai, op. cit.

CIRCULATION. 399

lowiug method, anioug others, has been employed : A tube open at both ends
is introduced througli tlie external jugular vein of an animal into the right
ventricle, or, with greater difficulty, through the carotid artery into the left
ventricle. In neither case is the valve, whether tricuspid or aortic, rendered
incompetent duriug this proceeding, nor need the general mechanism of the
heart and vessels be gravely disturbed. If the outer end of the tube be
connected with a recording mercurial manometer, a tracing of the pressure
within the right or left ventricle may be written upon the kymograph. It
is found, however, that the pressure within the heart varies so much and so
rapidly that the inert mercurial column will not follow the fluctuations, and
that the attempt to learn the mean pressure by this method fails. A valve,
however, may be intercalated in the tube between the ventricle and the man-
ometer— a valve so made as to admit fluid freely to the manometer, but to let
none out. The manometer will then record, and record not too incorrectly, the
maximum pressure within the right or left ventricle during the experiment ; in
other words, it will record the greatest force exerted during that time by the ven-
tricle in order to do its work.^ In this way the maximum pressure within
the left ventricle of the dog has been found to present such values as 176 and
234 millimeters of mercury, the corresponding maximum pressure in the aorta
being 158 and 21 2 millimeters respectively.^ The maximum pressures obtained
from simultaneous observations upon the right and left ventricle of a dog are
variously reported. It M'ould perhaps be not far wrong to say that in this
animal the pressure in the right ventricle is to that in the left as 1 to 2.6.^

The work done by each ventricle during its systole is found by multiplying
the weight of the pulse-volume ejected into the force put forth in ejecting it.
That force is equal to the pressure under which the pulse volume is expelled.
If we use as a basis of calculation the pressures observed in the dog's heart with
the maximum manometer, we may assume as the measure of a given pressure
within the contracting human left ventricle 200 millimeters of mercury, and for
the human right ventricle 77 millimeters. If for each column of mercury there
be substituted the corresponding column of blood, the heights will be 2.567
meters and 0.988 meter respectively. The force exerted by the right or left
ventricle upon the pulse-volume might therefore just equal that put forth in
lifting it to a height of 0.988 or 2.567 meters. If we assume 100 grams as
the weight of a possible pulse-volume ejected by a human ventricle, the work
done at each systole of the left ventricle would be 100 X 2.567 = 256.7 gram-
meters, and at each systole of the right ventricle 100X0.988 = 98.8 gram-
meters; a grammeter being the work done in raising one gram to the height
of one meter. The work of both ventricles together would be 256.7 -f- 98.8
= 355.5 grammeters. The foregoing estimates are offered not as statements
of what does occur, but as very rough indications of what may occur. Even

' F. Goltz und J. Gaule: "Ueber die Druckverhaltnisse im Innern des Herzens," Archiv
fiir die gesammte Physiologie, 1878, xvii. p. 100.

* S. de Jager: "Ueber die Saugkraft des Herzens," Pfliiger's Archiv fiir die gesammte Physi-
ologic, 1883, pp. 504, 505. ^ Goltz und Gaule, op. ciL, p. 106.

400 -.l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

thus, liovvever, they are of inoiiu'iit. When we think of the vast miinber of
beats executed by the heart every (hiy, the j^reat aiuoiint of energy rendered
manifest in maintainini; the ('ircukitit)n beeomes apparent, and our interest is
heigiitened in tiie faet tiiat all of this laro;e sum of energy is liberated in the
muscular tissue of the heart itself. Thus, too, the physiological significance
of the diastole is accentuated as a time of rest for the cardiac muscle, as well
as a necessary pause for the admission of blood into the ventricle. To disre-
gard minor considerations, the work done at a systole will evidently dej)end
u]ion the amount of the pulse-volume, of tlie arterial jiressure overcome, and
of the velocity imparted to the ejected blood. All these are variable. The
work of the ventricles therefore is eminently variable.

The Heart's Contraction as a Source of Heat. — In dealing with the
movement of the blood in the vessels we have seen that the energy of visible
motion liberated by the cardiac contractions is progressively changed into heat
by the friction encountered by the blood ; and that this change is nearly com-
plete by the time the blood has returned to the heart, the kinetic energy of
each systole sufficing to drive the blood from the heart back to the heart again,
but probably not being much more than is required for this purpose. Practi-
cidlv, therefore, all the energy of the heart's contraction becomes heat within
the body itself, and leaves the body under this form. As the heart liberates
during every day an amount of energy which is always large but very variable,
its contractions evidently make no mean contribution to the heat produced in
the body and parted with at its surface.

H. The Mechanism of the Valves of the Heart.
■ Use and Importance of the Valves. — The discussion just concluded
shows the work of the heart to be the forcible pumping of a variable pulse-
volume out of veins where the pressure is low into arteries where the pressure
is high. It is owing to the valves that this is possible, and so dependent is
the normal movement of the blood upon the valves at the four ventricular
apertures that the crippling of a single valve by disease may suffice to destroy
life after a longer or shorter period of imjiaired circulation.

The Auriculo-ventricular Valves. — The working of the aurieulo- ven-
tricular valves (see Fig. 103) is not hard to grasp. When the pressure within
the ventricle in its diastole is low, the curtains hang free in the ventricle,
although probably never in close contact with its wall. As the blood pours
into the ventricle, the pressure within it rises, currents flow into the space be-
tween the wall and th.e valve, and probably bring near together the edges of
the curtains and also their surfaces for some distance from the edges. Thus,
upon the cessation of the auricular systole, the sujiervening of a superior pres-
sure within the ventricle probably applies the already approximated edges
and surfaces of the curtains to one another so ])romi)tly that the commencing
contraction of the ventricle is not attended by regurgitation into the auricle.
The principle of closure is the same for the tricuspid valve as for the mi-
tral. As the forces are exactly equal and <»p[)osite which press together the

(Jl UVULA TION.

401

opposed parts of tlie surfaces of the curtains, those parts undergo no strain,
and hence are enabled to be excpiisitely delicate and flexible and therefore
easily fitted to one another. On the other hand, the parts of the valve which
intervene between ti>e surfaces of coutact and the auriculo-ventricular ring are
tough and nuich thicker, as they have to bear the brunt of the pressure within
the contracting ventricle. As the systole of the ventricle increases, the aiiric-
lUo-ventricular ring probably becomes smaller, and the curtains of the valve
probably become somewhat fluted from base to apex, so that their line of con-
tact is a zig-zag. At the same time their surfaces of contact may increase in
extent.

Tendinous Cords and their Uses. — The structure so far described is
wonderfully elfective because it is combined with an arrangement to prevent a
reversal of the valve into the auricle, which otherwise would occur at once.
This arrangement consists in the disposition of the tendinous cords, which act

Fig. 103.— The left ventricle and aorta laid open, to show the mitral and aortic semilunar valves (Henle).

as guy-ropes stretched between the mu.scular wall of the ventricle and the
valve, whether mitral or tricuspid. These cords are tough and inela.stic, and,
like the valve, are coated with the slippery lining of the heart. They are
stout where they spring from the muscle, but divide and subdivide into
branches, strong but sometimes very fine, which proceed fan-wise from their

2G

402 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

stem to their insertions (.see Fig. lO-'j). Tiiese insertions are both into the free
margin of the valve and into the whole extent of that sni-faee of it whieh
looks toAvard the wall of the veutriele, quite up to the ring. J^y means of this
arrangement of the eords each curtain is held taut from base to apex thiough-
out the systole of the ventricles, the opposed surfaces being kept in apj)osition,
and the parts of the curtains between these surfaces and the ring In-ing kept
from bellying unduly toward the auricle. Each curtain is held sufficiently
taut from side to side as well, because the tendinous cords inserted into one
lateral half of the curtain spring from a widely different part of the wall of
the heart from those of the other lateral half of it (see Fig. 103). At all times,
therefore, even when the walls of the ventricle are most closely approximated
during systole, the cords may pull in slightly divergent directions upon the
two lateral halves of each curtain. This arrangement of the cords may also
cause them, when taut, to pull in slightly convergent directions upon the
contiguous lateral halves of two neighboring curtains and thus to favor the
pressing of them together (see Fig. 103).

Papillary Muscles and. their Uses. — In the left ventricle the tendinous
cords arise in two groups, like bouquets, from two teat-like muscular projec-
tions which s])ring from opposite points of the wall of the heart, and which
are called the " papillary muscles " (.see Fig. 103). One of these gives origin
to the cords for the right half of the anterior and for the right half of the
posterior curtain ; the other papillary muscle gives rise to the cords for the
left halves of the two curtains. Each papillary muscle is commonly more or
less subdivided (see Fig. 103). The same principles are carried out, but less
regularly, for the origins of the tendinous cords of the more complex tricuspid
valve. Various opinions have been held as to the use of the papillary mu.scles.
It seems probable that during the change of size and form wrought in the
ventricle by its systole, the origins of the tendinous cords and the auriculo-
ventricular ring tend to be approximated and the cords to be slackened in
consequence. Perhaps this is checked by a compensatory shortening of the
papillary muscles, due to their sharing in the systolic contraction of the mus-
cular ma.ss of which they form a part. Observations have recently been made
which have been interpreted to mean that the papillary nui.'^cles begin their
contraction slightly later and end it slightly earlier than the mass of the
ventricle.^

Semilunar Valves. — The anatomy and the working of the semilunar
valves are the same in the aorta as in the pulmonary artery, and one account
will answer for both valves. Each valve is composed of three entirely sepa-
rate segments, set end to end within and around the artery just at its origin
from the ventricle. The attachments of the segments occupy the entire cir-
cumference of the vessel (Fig. 103). Like the tricu.«pid and mitral valves,
each semilunar segment is composed of a sheet of tis-sue which is tough, thin,
supple, and slippery ; but the semilunar valves differ from the tricuspid and

^C. S. Roy and J. G. Adami : "Heart-beat and Pulse-wave," The Practitioner, 1890, i.
p. 88.

CIRCULA TION. 403

mitral, not only in the complete distinctness of their segments, but also in
their mechanism. The tendinous cords are wholly luckinus and each segment
depends upon its direct connection with the arterial wall to prevent reversal
into the ventricle during the diastole of the latter. If the artery he carefully
laid open by cutting exactly between two of the segments, each of the three is
seen to have the form of a pocket with its opening turned away from the heart
(see Fig. 103). Behind each segment, the artery is dilated into one of the hol-
lows or ''sinuses" of Valsalva.^ As the valve lies immediately above the
base of the ventricle the segments rest upon the top of the thick muscular
wall of the latter, which atfords them a powerful support (see Fig. 104).
Each segment is attached by the whole length of its longer edge to the artery,
while the free margin is formed by the shorter edge. It is this arrangement
which renders reversal of a segment impossible (see Fig. 103).

Fig 104 -Diagram to illustrate the mechanism of Fig. 105.-Diagram to illustrate the mechanism of

■ ■ the semilunar valve. the semilunar valve and corpora Arantn.

While the blood is streaming from the ventricle into the artery, the three
segments are pressed away by the stream from the centre of the vessel, but
never nearly so far as to touch its wall. At all times, therefore, a pouch ex-
ists behind each segment, which pouch freely communicates with the general
cavity of the artery. As the ventricular systole nears its end, the ventricular
cavity doubtless becomes narrowed just below the root of the artery, and with
it the arterial aperture itself, while currents enter the sinuses of Valsalva.
Thus for a double reason the three segments of the valve are approximated,
and probably the last blood pressed out of the ventricle issues through a nar-
row chink between them. The instant that the pressure in the ventricle falls
below the arterial pressure, the three segments must be brought together by
the superior pressure within the artery, and tightly closed by its forcible recoil,
without regurgitation having occurred in the process (see Figs. 104, lOS)."

Lunuli and their Uses.— Each segment of a semilunar valve, when
closed, is in firm contact with its fellows not only at its free margin but also
over a considerable surface, marked in the anatomy of the segment by the
two "lunula" or little crescents, each of which occupies the surface of the
seo-ment from one of its ends to the middle of its free margin, the shorter edge

1 Named from the Italian physician and anatomist Valsalva of Bologna, born in 1666

^L Krehl- " Beitra-e zur Kenntniss der Fullung und Entleerung des Herzens, Abhand-

lungen'der matk.-physisehln Classe der k. sdchsischen Gesellsehaft der Wissemchaflm, 1891, Bd. xvu.

No. 5, p. 360.

404 AiX AMERICAX TEXT-BOOK OF PHYSIOLOGY.

of tlie lunula being one-half of the free margin of the segment (see Fig. 103).
Over the surface of each hiniilu each segment is in contact with a different
one of its two fellows (see Fig. 105). The firmness of closure tlius secured is
shown by Figure 104, wiiich represents a longitudinal section of the artery,
passing through two of the closed segments. The forces which press together
the opposed surfaces are equal and opj)osite, and the j)arts of the segments
■which correspond to these surfaces undergo no strain. The lunulae, therefore,
like the mutually opposed portions of the mitral or tricuspid valve, are very
delicate and flexible, while the rest of each semilunar segment is strongly
made, to resist of itself the arterial pressure.

Corpora Arantii and their Uses. — At the centre of the free margin of
each semilunar segment, just between the ends of the two lunuhe, there is a
small thickening, more pronounced in the aorta than in the pulmonary artery,
called the " body of Aranzi " ^ (corpus Arantii). This thickening both rises
above the edge and projects from the surface between tlie lunulas. When the
valve is closed, the three corpora Arantii come together and exactly fill a small
triangular chink, which otherwise might be left open just in the centre of the
cross section of the artery (see Figs. 103, 105).

The foregoing shows that the meclianism of the semilunar valves is no less
effective, though far simpler, than that of the mitral and tricuspid. That the
latter two should be more complex is natural ; for each of them must give
free entrance to and prevent regurgitation from a chamber which nearly
empties itself, and hence undergoes a very great relative change of volume;
while the arterial system is at all times distended and undergoes a change of
capacity which is relatively small while receiving a pulse-volume and trans-
mitting it to the capillaries.

I. The Changes in Form and Position of the Beating Heart, and

THE Cardiac Impulse.

General Changes in the Heart and Arteries. — During the brief systole
of the auricles these diminish in size while the swelling of the ventricles is
completed. During the more protracted systole of the v^entricles, which imme-
diately follows, these diminish in size while the auricles are swelling and the
injected arteries expand and lengthen. During the greater part of the suc-
ceeding diastole of the ventricles both these and the auricles are swelling, and
all the muscular fibres of the heart are flaccid, up to the moment when a new
auricular systole completes the diastolic distention of the ventricles, as above
stated. During the ventricular diastole, as the great arteries recoil they
shrink and shorten. The changes of size in the beating heart depend entirely
upon the changes in the volume of blood contained in it, and not upon changes
in the volume of the muscular walls. Tiie muscular fibres of the heart agree
with those found elsewhere in not changing their volume appreciably during
contraction, but their form only. The cardiac cycle thus runs its course with

' Named from Julius Caesar Aranzi of Bologna, an Italian physician and anatomist, born
in 1530. *

CIRCULA TION. 405

regularly recurring changes of .size in the auricles, the ventricles, and the
arteries. These changes of size are accompanied by corresponding changes
in the form a"d ])ositiou of tlie iieart, which are l)oth interesting iu them-
selves and important in relation to the diagnosis of disease. The basis
of their study consists in opening the chest and pericardium of an animal,
and seeing, touching, and otherwise investigating the beating heart. The
changes in the beating heart, moreover, underlie the production of the
so-called cardiac impulse, or apex-beat, which is of interest iu physical
diagnosis.

Observation of the Heart and Vessels in the Open Chest. — The beat-
ing heart may be exposed for observation in a mammal by laying it upon its
back, performing tracheotomy, and completely dividing the sternum in the
median line, beginning at the ensiform cartilage. Artificial respiration is next
established, a tube having been tied into the trachea before the chest was
opened. The two sides of the chest are now drawn asunder and the pericar-
dium is laid open to expose the heart.

If, in any mammal, the ventricles be lightly taken between the thumb and
forefinger, the moment of their systole is revealed by the sudden hardening of
the heart produced by it, as the muscular fibres contract and press with force
upon the liquid within. On the other hand, the ventricular diastole is marked
by such flaccidity of the muscular fibres that very light pressure indents the
surface, and causes the finger to sink into it, in spite of care being taken to
prevent this. Commonly, therefore, at the systole the thumb and finger are
palpably and visibly forced apart, no matter where applied, in spite of the fact
that the volume of the ventricles is diminishing. This sinking of the finger
or of an instrument into the relaxed wall of the heart has given rise to many
errors of observation regarding changes during the beat. The time when the
ventricles are hardened beneath the finger coincides with the up-stroke of the
arterial pulse near the heart, and, as shown by Harvey,^ with the time when
an intermittent jet of blood springs from a wound of either ventricle. The
hardening is proven thus to mark the systole of the ventricles. Those changes
of size, form, and position of the exposed heart which accompany the harden-
ing of the ventricles beneath the finger are therefore the chnnges of the ven-
tricular systole ; and the converse changes are those of the ventricular diastole.
To interpret all the changes correctly by the eye alone, without the aid of the
finger or of the jet of blood, is a task of surpassing difficulty in a rapidly beat-
ing heart, as was eloquently set forth by Harvey.^

Changes of Size and Form in the Beating Ventricles. — In a mam-
mal, lying upon its back, with the heart exposed, the ventricles evidently
become smaller during their systole. Their girth is everywhere diminished
and their length also, the latter much less than the former ; indeed the dimi-
nution in length is a disputed point. Not merely a change of size, but a

' Ezerciiaiio Anatomiea de Motu Cordis et Sanguinis in. Animnlibus, 1628, p. 23; Willis' trans-
lation, Bowie's edition, 1889, p. 23.

' Op. ciL, 1628, p. 20; Willis' translation, Bowie's edition, p. 20.

406 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

change of form is thus produced ; the heart becomes a smaller and shorter,
but a more pointed, cone. The systolic narrowing from side to side is very
conspicuous. In a mammal lying on its back, this narrowing is accompanied
by some increase in the diameter of the heart from breast to back so that the
surface of the ventricles toward the observer becomes more convex. Tims the
base of the ventricles, which tendeil to be roughly elliptical during their
relaxation, tends to become circular during their contraction ; and tiie diameter
of the circle is greater than the shortest diameter of the ellipse, which latter
diameter extends from breast to back. At the same time, the area of the base
when circular and contracted is much less thau when elliptical and relaxed.*
Naturally, none of these comparisons to mathematical figures makes any pre-
tence to exactness. At the same time that the contracting heart undergoes
these changes, the direction of its long axis becomes altered. In animals in
which the heart is oblique within the chest, the line from the centre of the
base to the apex, that is, the long axis, while it points in general from head
to tail, points also toward the breast and to the left. In an animal lying ou
its back, the ventricles when relaxed in diastole tend to form an oblique cone,
the apex having subsided obliquely to the left and toward the tail. As the
ventricles harden in their systole, they tend to change from an oblique cone to
a right cone ; the long axis tends to lie more nearly at right angles to the base ;
and consequently the apex, unfettered by pericardium or chest-wall, makes a
slight sweep obliquely toward the head and to the right, and thus rises up
bodily for a little way toward the observer. This movement was graphicallv
called by Harvey the erection of the heart.^ It is accompanied by a slight
twisting of the ventricles about their long axis, in such fashion that the left
ventricle turns a little toward the breast, the right ventricle toward the back.
This twisting movement is probably due simply to the course of the cardiac
muscular fibres.

Chang-es of Position in the Beating Ventricles. — The changes in form
imply changes in position. The oblique movement of the long axis inq)lies
that in systole the mass of the ventricles sweeps over a little toward the
median line and also a little toward the head. The shortening of the long
axis implies that either the apex recedes from the breast, or the base of the
ventricles recedes from the back, or both. Of these last three possible cases,
the second is the one that occurs. The oblique movement of the apex is
accompanied by no recession of it; but the auriculo-ventricular furrow and
the roots of the aorta and pulmonary artery move away from the s})inal
column as the injected arteries lengthen and expand, and, as the auricles swell,
during the contraction of the ventricles. During their diastole the ventricles
are soft; they swell; and changes of form and position occur which need not
be detailed now, as they are simply converse to those of the systole and have
been indicated already in dealing with the latter.

^ C. Ludwjg: " Ueber den Bau und die Bewegiingen der Herzventrikel," Zeitachrifl fiir
rationeUe Medizin, 1849, vii. p. 1S9.

^ Op. cit., 1628, p. 22. Translation, 1889, p. 22.

CTRCT^LA TTOX. 407

Changes in the Beating Auricles. — Kxccjit in small uiiiinals, the walls
of both the ventricles are so thiek that the eolor of the two is the same and
is unchanging, namely, that of their muscular mass; but the walls of the
auricles are so thin that their color is ail'ected In- that of the blood within, so
that the right auricle looks bluish and dark and the left auricle red and
bright. During the brief systole of the auricles they are seen to become
smaller and paler as blood is expelled from them, wdiile their serrated edges
and auricular appendages shrink raj)idly away from the observer. The
changes of the auricular systole are seen to ])re(;ede immediately the changes
of the systole of the ventricles and to succeed the repose of the whole heart.
During the relatively long diastole of the auricles these are seen to swell,
whether the ventricles are shrinking in systole or are swelling during the
first and greater part of their diastole.

Changes in the Great Veins. — In the vense cavse and pulmonary veins a
pulse is visible, more plainly in the former than in the latter, which pulse has
the same rhythm as that of the heart's beat. The causes of this pulse are
complex and imperfectly understood. It depends in part upon the rhythmic
contraction of muscular fibres iu the w^alls of the veins near the auricles, which
must heighten the flow^ into the latter, and which contraction the auricular
systole immediately follows.^ This venous pulse w^ill be mentioned again in
discussing the details of the events of the cycle (see p. 430).

Changes in the Great Arteries, — It is interesting to note that even in
so large an animal as the calf the pulse of the aorta or of the pulmonary
artery can hardly be appreciated by the eye, so far as the increase in girth of
either vessel is concerned. The expansion of the artery affects equally all
points iu its circumference, and being thus distributed, is so slight in propor-
tion to the girth of the vessel that the profile of the latter scarcely seems to
change its place. The lengthening of the expanding artery can be more
readily seen.

Effects of Opening the Chest. — Such are the changes observed in the
heart and vessels when exposed in the opened chest of a mammal lying on
its back. The question at once arises. Can these changes be accepted as iden-
tical with those which occur in the unopened chest of a quadruped standing
upon its feet, or of a man standing erect ? It will be most profitable to deal
at once with the case of the hunian subject. What are the possible, indeed
probable, diiFereuces between the changes in the heart in the unopened upright
chest and in the same when opened and supine ?

When air is freely admitted to both pleural sacs, all those complex efiPects
upon the circulation are at once abolished which we have seen to be caused
by the elasticity of the lungs and the movements of respiration. The arti-
ficial respiration will have an effect upon the pulmonary transit of the blood
and so upon the circulation ; but the details of this effect are not the same as
those of natural respiration, and, for our present purpose, may be disregarded.

^ T. Lauder Brunton and F. Fayrer : "Note on Independent Pulsation of the Pulmonary
Veins and Vena Cava," Proceedincjs of the Royal Society, 1876, vol. xxv. p. 174.

408 AN AMERICAN TEXT- HOOK OF lUFYSIOLOGY.

"What has been abolished i.s tin- coiitimial suction, riiythniically increased in
inspiration, exerted by the hings njion the heait and all the vessels within the
chest, which snction at all times favors the expansion and resists the con-
traction of the cavities of the heart and of the vessels. On the opening of
both pleural sacs the heart and vessels are exposed to the undiminished and
unvarying pressure of the atmosphere. Moreover, the heart has ceased to be
packed, as it were, between the j)leura! and lungs to right and left, the spine,
the front of the chest-wall, and the tliaphragni. From these considerations it
follows that the heart must be freer to (;hange its form and position in the
opened than in the unopened chest ; and that these changes must be more
modified by simple gravity in the former case than in the latter. Even in
the open chest we have studied these changes only in an animal lying on its
back. But if we turn the creature to either side, or place it upright in imi-
tation of the natural human posture, the ventricles of the exj)()sed heart in
any case tend to assume, in systole, the same form, which has been com-
pared roughly to a right cone with a circular base. This is the form proper
to the hardened structure of branching and connected fibres of which the
contracting ventricles consist. But if the exposed ventricles be noted in dias-
tole, it will appear that their form depends very largely upon the effects of
gravity upon the exceedingly soft and yielding mass formed by their relaxed
fibres. We have seen them, in diastole, to flatten from breast to back, to
spread out from side to side, to gravitate toward the tail and to the left. If
the animal is laid on its side, they flatten from side to side, they spread
out from breast to back, and gravitate to the right or left, as the case
may be.^

Probable Changes in the Heart's Form and Position in the Unopened
Chest. — It is fair to conjecture that the increase of the relaxed ventricles in
girth and in length which is seen in the open chest would not be greatly differ-
ent in the closed chest of a man in the upright posture. But it is ])robable
that the flattening of the exposed heart from breast to back, which is seen in
diastole, would not occur if the chest were closed. It is precisely in this direc-
tion that the flaccid heart exposed in the supine chest would be flattened un-
duly by its own weight, when deprived of many of its anatomical supports
and of the dilating influence of the lungs. The flattening from breast to back
must cause an exaggerated spreading out from side to side and hence an unduly
elliptical form of the base, inasmuch as, at the same time, the girth of the ven-
tricles is increasing as they enlarge in their diastole. Conversely, it is prob-
able, both a priori and from experimental evidence, that in the chest, when
closed and upright, the diminution in size of the contracting ventricles pro-
ceeds more symmetrically ; that their girth everywhere diminishes through a
diminution of the diameter from breast to back as well as of that from side to

' J. B. Haycraft: "Tlie Movements of the Heart within tlie Chest-cavity, and the Cardio-
gram," The Joumnl nf I'liyxinl<u/ij, vol. xii., Nos. 5 and 6, December, 1891, p. 44S ; ,J. B. Hay-
craft and T). R. Patcrson : ''The Changes in Shape and in Position of the Heart during the
Cardiac Cycle," The Journal of Physiology, vol. xix., Nos. 5 and (!, May, 1896. p. 496.

CIRCULA TION. 409

side, and not through an exaggerated lessening of the latter and an actual
increase of the former. In this case, too, the base would tend to become
more circular during the systole by means of a less marked change from the
diastolic form.^

It has been said that in systole the ventricles are somewhat shortened
in the exposed heart, and probably also in the unopened human chest. In
the open chest the apex does not recede at all in virtue of this shorten-
ing ; on the contrary, the base of the ventricles is seen to move toward
the apex, and away, therefore, from the spine. Experiment has proven that
the foregoing is true also of the unopened chest.^ It has been noted already
that this movement of the base, which in the upright chest would be a descent,
is accompanied by a lengthening of the aorta and pulmonary artery as their
distention takes place. Very probably it is the thrust of the lengthened arte-
ries which largely causes the descent of the base of the contracting ventricles,
which descent compensates for the shortening of the ventricles and retains the
apex in contact Avith the chest- wall.

The Impulse or Apex-beat. — It must always have been a matter of com-
mon knowledge that, in man, a portion of the heart lies so close to the chest-
wall that, at each beat, the soft parts of that wall may be seen and felt to pul-
sate over a limited area. This is commonly in the fourth or fifth intercostal
space, midway between the left margin of the sternum and a vertical line let
fall from the left nipple. A similar pulsation may be observed in other mam-
mals. The protrusion of the chest-wall at the site of this " impulse " or " apex-
beat " occurs when the arteries expand, and the up-stroke of their pulse is felt ;
and the recession of the chest coincides with the shrinking of the arteries away
from the finger. The impulse proper, that is the protrusion of the chest-wall,
occurs, therefore, at the time of the systole of the ventricles. By far the most
important factor of the apex-beat is probably the effort of the hardening ven-
tricles to change the direction of their long axis against the resistance of the
chest-wall. A heart severed from the body and bloodless, if laid upon a
table, lifts its apex as it hardens in systole and assumes its proper form. If a
finger be placed near enough to the rising apex to be struck by it, the same
sensation is received as from the impulse.

It is interesting to note that around the point where the soft parts of the
chest are protruded by the impulse, they are found to be very slightly drawn
in at the time of its occurrence. This drawing-in is called the ''negative
impulse," and must be caused by the diminution in size of the contracting
ventricles. These are air-tig-ht within the chest, and so their forciblv lessened
surface must be followed down, in varying degrees, under the pressure of
the atmosphere, by the elastic and yielding lungs and by the far less yield-
ing soft parts of the chest-wall.

The apex-beat can be brought to bear in various ways upon a recording
lever, and thus be made to inscribe upon the kymograph a rhythmically fluc-
tuating trace, which is called a cardiogram. Considerable attention has been

* J. B. Haycraft : loc. cit. " Haycraft : loc. cit.

410 Ay AMERICAN TEXT-BOOK OF PHYSIOLOGY.

given to the oliu'idation of the curve thus recorded; but, so far, too little
agreement has been reached for the subject to be entered u])on here.'

J. The Sounds of the Heart.

If the ear be applied to the human chest, at or near the [)la('e of the apex-
beat, the heart's pulsation will be heard as well as felt. This lact was known
to Harvey.^ About two hundred years later than Harvey, iu 1819, the
French physician Laennec, the inventor of auscultation, made known the fact
that each beat of the heart is accompanied not by one but by two separate
sounds. He also called attention to their great importance in the diagnosis of
the diseases of the heart.*

Relations of the Sounds — The first sound is heard during the time when
the apex-beat is felt ; it theretbre coincides with the systole of the ventricles.
The second sound is nuieh shorter, and follows the first immediately, or, to
speak more strictly, after a scarcely appreciable interval. The second sound,
therefore, coincides with the earlier part of the diastole of the ventricles.
The second sound is followed in its turn by a period of silence, commonly
longer considerably than the second sound, which silence lasts till the begin-
ning of the first sound of the next ventricular beat. The period of silence,
therefore, coincides with the later, and usually longer, portion of the diastole
of the ventricles, and with the systole of the auricles. It is interesting that
the great auscultator, Laennec, offered no explanation of the cause of either
sound, while he made and reiterated the incorrect and misleading statement
that the second sound coincides with the systole of the auricles. When the
heart beats oftener than usual, each beat must be accomplished in a shorter
time ; and it is found that, during a briefer beat, the period of silence is
shortened much more than the period during which the two sounds are audi-
ble ; which latter period may not be altered appreciably.

Characters of the Sounds. — The first sound is not only comparatively
long, but is low-pitched and muffled. The second sound is comj)aratively
short, and is high and clear. The two sounds, therefore, are sharply con-
trasted in duration, pitch, and quality. A rough notion of the contrasted
characters of the sounds may be obtained by pronouncing the meaningless
syllables "lubb dup." In other mammals the sounds have substantially the
same characters as in man.

Cause of the Second Sound. — Since Laennec's time, the cause of the
second sound has been demonstrated by experiment. The second sound is due
to the vibrations caused by the sinniltancous closure of the semilunar valves
of the pidmonary artery and of the aorta, when the diastole of the ventricles
has just begun. This cause was first suggested by the French physician

1 M. von Frey: Die Untermchung des. Pulses, etc., 1892, p. lOli; K. Tigerstedt: Lchrbuch der
Physiologie des Kreislaufes, Leipzig, 1893, p. 112.

^ ExercUniio Anntomica dc Main Cordis et Sanguinis in Animalibus, 1628, p. 30 ; Willis's trans-
lation, Bowie's edition, 1889, p. 34.

* R. T. II. Laennec: iJe rauscullalion mediak; etc., Paris, 1819.

CIRCULA riON. 411

Rouauet in 1832 ;' not long afterward it was conclusively proven by experi-
ment l)y the Enolisli physician C. J. B. Williams.^

Dr. \\'illianis'.s experiment was as follows: In a yonn^ ass the chest was
opened and the heart was exposed. It was ascertained tliat the second sound
was audible throuirh a stethoscope applied to the heart itself. A sharp hook
was then passed throui^h the wall of the pulmonary artery, and was so directed
as to make the semilunar valve incompetent temporarily. By means of a
second hook, the aortic semilunar valve \vas likewise made incompetent.
When both hooks were in position, the heart was auscultated afresh, and tha
second sound was found to have disappeared, and to be replaced by a hissing
murmur. The hooks were withdrawn during auscultation, and at the moment
of withdrawal the murmur disappeared and the normal second sound recurred.
Subsequent clinical and post-mortem observations have shown that the second
sound may be altered by disease which cripples the aortic valves.

Causes of the First Sound. — The causes of the first sound have not
been proven so clearly by the available evidence, which is partly experimental
and partly derived from physical diagnosis followed by post-mortem verifica-
tion. The first sound, like the second, was ascribed by Rouauet^ to vibrations
depending upon valvular closure, — the simultaneous closure of the tricuspid
and mitral valves ; but the persistence of the sound throughout the whole
ventricular systole made this cause less probable than in the case of the second
sound. Williams,^ on the other hand, ascribed the first sound to the con-
traction of the muscular tissue of the ventricles, — an explanation consistent
with the muffled quality of the first sound, and with its persistence through-
out the systole of the ventricles. It is now believed by many that both of
the foregoing explanations are correct, and that the first sound is composite in
its origin, and due both to closure of the valves and to muscular contraction.
The evidence in favor of these causes is, briefly, as follows :

In favor of a valvular element in the first sound, it may be urged : That
if the ventricles of a dead heart be suddenly distended with liquid, the mitral
and tricuspid valves produce a sound in closing ; and that clinical and post-
mortem observations show that the first sound may be altered by disease
which cripples the auriculo-ventricular valves.

In favor of an element in the first sound caused by muscular contraction
it may be urged : That in a still living but excised heart, the first sound con-
tinues to be heard under circumstances which preclude the closure and vibra-
tion of the valves, and leave in operation no conceivable cause for the first
sound except muscular contraction. Experiments upon the first sound of
the excised heart were reported in 1868 by Ludwig and Dogiel,^ and were

^ J. Eouanet : Analyse des bruits du cceur, Paris, 1832.

^ C. J. B. Williams : Die. Pathologie und Diagnose der Krankheiten der Brust, etc. Nach der
dritten, sehr vermchrten Aiiflage aiis dem Englischen iibersetzt, Bonn, 1838. (The writer has
not seen an English edition.) * Loc. cit. * Loc. cit.

= J. Dogiel and C. Liidwig: " Ein neiier Versuch iiber den ersten Herzton," Berichte iiber
die Verhandlungen der k. sdchsischen Gesellsckaft der Wissenschaften zu Leipzig, math.-physische
Classe, 1868, p. 89.

412 ^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

performed upon the dog as follows: The heart was exi)osed during arti-
ficial respiration, and loose ligatures were placed upon the venae cavse, the
pulmonary artery, the pulmonary veins, and the aorta. Next, the loose
ligatures were tightened in the order above written, during which process
the beating heart necessarily pumped itself as free as possible of blood.
The vessels were then divided distally to the ligatures, and the heart was
excised and suspended in a conical glass vessel containing freshly drawn defi-
brinated blood, in which the heart was fully immersed without touching the
glass at any point. Under these conditions the excised heart might execute
as many as thirty beats. The conical glass vessel was supported in a " ring-
stand." The narrow bottom of the vessel consisted of a thin sheet of india-
rubber, with which last was connected the flexible tube and ear-piece of a
stethoscope. By means of the latter any sound produced by the beating
heart could be heard through the blood and the sheet of rubber. The second
sound was not heard ; but at each contraction of the ventricles the first sound
was heard, not of the same length or loudness as normally, but otherwise unal-
tered. The conditions of experiment precluded error resulting from adventi-
tious sounds ; moreover, the heart before excision had pumped itself free of
all but a fraction of the amount of blood required to close the valves, and
had been so treated that no more could enter. It was therefore practically
impossible that the sound heard could have its origin at the valves ; and no
origin remained conceivable other than in the muscular contraction of the ven-
tricular systole. Later experiments, in which the auriculo-ventricular valves
have been rendered incompetent by mechanical means, have seemed to confirm
the importance of muscular contraction as a cause of the first sound.^

Acoustic Analysis of the First Sound. — By the use of a stethoscope
coml)ine(l with a jwculiar resonatoi-, the German physician Wintrich of Erlan-
gen^ satisfied himself that he could analyze the first sound uj)()n auscultation,
so as to detect in it two com])onents, one higher pitched, which he attributed
to the vibration of the auriculo-ventricular valves, and a component of lower
pitch, attributed to the muscular contraction of the heart. The other experi-
ments above referred to, however, which sustain muscular contraction as a cause
of the first sound, did not reveal a change of pitch following incompetence
of the valves, but only a diminution in loudness and duration.

K. The Frequency of the Cardiac Cycles.^

In a healthy full-grown man, resting quietly in the sitting posture, the
heart beats on the average about 72 times a minute. In the full-grown

' L. Krehl : '' Ueber den Plerzmuskelton," Archiv fur Anntnmie und Physiologic, Physiolo-
gische Abtheilung, 1889, p. 253 ; A. Kasem-Bek : " Ueber die Entstehung des ersten Herztones,"
Pflilger's Archiv fiir die gesammte Physiologic, 1890, Bd. xlvii. p. 53.

* Wintrich : " Experimentalstudien iiber Resonanzbewegungen der Membranen," <SVr2?m7.s-
berichle der phys.-med. ^ocieldt zu Eriangen, 1873; Wintrich: "Ueber Causation und Analyse
der Herztone," Ibid., 1875.

■' Tigerstedt : Lehrbuch der Physiologic des Kreislaufes, Leipzig, 1893, pp. 25-35; Vierordt:
Daten und TabeUen zum Oebrauchefiir Mediciner, 1888, pp. 105-109, 259.

CIRCULA TION. 413

woman the average is slightly higher, perimps 80 to the minute. The heart
beats less frequently iu tall people than in short ones. The difference between
men and women largely depeuds upon this, but careful observation shows that
in the case of men and women of the same stature the heart-beats are slightlv
more frequent in the women. There is, therefore, a real difference as to the
pulse between the sexes. Shortly before and after birth the heart-beats are
very frequent, from 120 to 140 to the minute. During childhood and youth,
the frequency diminishes gradually, the average falling below 100 to the min-
ute at about the sixth year, and below 80 to the minute at about the eighteenth
year. In extreme old age the pulse becomes slightly increased in frequency.
It must, however, be borne in mind that there are very wide differences
between individuals as to the average frequency of the heart-beats. Pulses
of 40 and even fewer strokes to the minute, or, on the other hand, of more
than 100 to the minute, are natural to some healthy people.

In every individual the frequency of the pulse varies decidedly, and may
vary very greatly, during each twenty-four hours. It is least during sleep,
and less in the lying than in the sitting posture. Standing makes the heart
beat oftener, the difference being greater between standing and sitting than
between sitting and lying. During muscular exercise the pulse-rate is much
increased, violent exercise carrying it possibly to 150 or even more. Thermal
influences have a marked effect, a hot bath, for instance, heightening the fre-
quency of the pulse and a cold bath diminishing it. The taking of a meal
also commonly puts up the frequency. The influence of emotion upon the
heart's contractions is well known. It may act either to heighten the rate or
to lower it. Finally, the practising physician soon learns that the heart's
rate is more easily affected by comparatively slight causes, emotional or other-
wise, in women, and especially in children, than in men — a fact of some
importance in diagnosis.

The causes of the differences referred to in this section are partly unkuoM-n,
and partly belong to the subject of the regulation of the circulation.

L. The Relations in Time op the Main Events of the Cardiac

Cycle.

We have now considered the effects produced by the cardiac pump ; its
general mode of working ; and the actual frequency of its strokes. We must
next study certain important details relating to the individual strokes or beats
of the ventricles and of the auricles. For this study the basis has already
been laid in the sections headed " Causes of the Blood-flow " (p. 369), " Mode
of Working of the Pumping Mechanism" (p. 370), ''The Cardiac Cycle"
(p. 396), and "Use and Importance of the Valves" (p. 400). These sections
should now be read again in the order just given. Details can best be dealt
with if we use, instead of the more familiar word " beat," the more technical
one " cycle."

The Auricular Cycle ; the Ventricular Cycle ; the Cardiac Cycle. —
Each systole and succeeding diastole of the auricles constitute a regularly

414 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

recurring pair of events wliicli may truly be sjiokcn of as an ''auricular
cycle;" and so also it is exaet to say that the ventricles have theii- evele, eon-
sisting of systole and sneeeeding diastole. As soon, however, as we strive for
clearness, we iind that the useful j)hrase "cardiac cycle" is necessarilv arl)i-
trary and imperfect. A perusal of the account given on p. 370 of the " INIode
of Working of the Pumping INIeehanism " shows at once that each auricular
cycle, consisting of systole followed by diastole, must begin shortly before
the corresponding ventricular cycle begins, and must end shortly before the
corresponding ventricular cycle ends. The pumping mechanism is such that
the auricular systole is completed just before the ventricular systole begins.
The phrase " cardiac cycle " implies a reference to both auricular and ven-
tricular events ; if now we assume that the beginning of the auricular sys-
tole marks the beginning of the cardiac cycle, this must end either with the
end of the auricular diastole or with the end of the ventricular diastole. In
the former case the cardiac cycle would coincide with the auricular cycle, but
would begin before the end of one ventricular diastole and would end before
the end of another, thus containing no one complete ventricular diastole. In
the second case, the cardiac cycle would contain one complete ventricular dias-
tole and a fraction of another, and would also contain two auricular sys-
toles. The second case is clearly even more objectionable than the first. The
cardiac cycle had best be defined as consisting of all the events both auricular
and ventricular which occur during one complete auricular cycle. The above
discussion deals with a phrase which is a constant stumbling-block to stu-
dents ; and the question may well be asked. Why should the expression
"cardiac cycle" not be abolished? The answer is, that this phrase is indis-
pensable in order to accentuate certain important relations of the auricular
cycle to the ventricular. During a heart-beat there is a period when the
auricles and ventricles are in diastole at the same time. During this period,
as we have seen, blood is passing from the veins directly through the auricles
into the ventricles, and all the muscular fibres of the heart are resting. This
period is therefore called that of " the repose of the whole heart," or the
" pause." Whenever the heart is not wholly at rest, either auricles or ven-
tricles must be in systole. We see, therefore, that each cardiac cycle must
coincide with an auricular systole, the instantly succeeding ventricular systole,
and a period of repose of the whole heart ; and it is precisely these two
systoles and the succeeding universal rest which most engage the attention
when the beating heart is looked at in the opened chest. These three
phenomena, it will be noted, exactly coincide with one complete auricular
cycle, and so do not confuse the definition of the cardiac cycle which has been
given already. We see, therefore, that the phrase which seemed at first so
misleading has a real value, and will cease to confuse if its limitations be care-
fully noted.

The Brevity and Variability of Each Cycle. — From the frequency with
which the cycles recur, it follows at once that each one, with its complex
changes in the walls, chambers, and valves, is very rapidly performed. If, for

CIRCULATIOX. 415

instance, the heart beat 72 times in one niniute, each cycle occupies only a
little more than 0.83 of a second. The brevity of each cycle is both an im-
portant physiological fact and a cause of difficulty in studying details, P^ach
cycle, however, necessarily is capable of completion in much less time if the
pulse-rate rise; for instance, during exercise. If repeated 144 times a minute
instead of 72 times, each cycle would occupy only one-half of its previous
time of completion. With a pulse of les? than 60, again, each cycle would
occuj)y over one second.

Relative Lengths of the Ventricular Systole and Diastole, — An im-
portant question is whether or no there is any fixed relation between the time
required for a systole of the ventricles and the time required for a diastole.
When the length of the cycle changes from one second to one-half a second,
will the length of the systole be diminished by one-half, and that of the dias-
tole also by one-half? Or is a nearly invariable time required for the ventri-
cles to do their work of ejection, while the period of rest and of receiving blood
can be greatly shortened, for a while at least? The answer is that, while both
systole and diastole may vary in length, the length of the systole is nnich the
less variable, while the diastole is greatly shortened or lengthened according as
the heart beats often or seldom.

These facts have been ascertained as follows: A trained observer^ auscul-
tated the sounds of the human heart during a number of cycles, and, at the
instant when he heard the beginning either of the first or of the second sound,
made a mark upon the revolving drum of a kymograph by means of a sig-
nalling apparatus. Of course, careful account was taken of the time lost
between the occurrence of a sound and the recording of it. It was found
that the time between the beginning of the first and that of the second
sound did not vary to the same degree as the frequency of the beats.
Although the interval in question may not be an exact measure of the
period of ventricular systole, it is sufficiently near it for the purposes of this
observation.

A second method ^ depended upon the interpretation of the curve inscribed
by a lever pressed upon the skin over a pulsating human artery. Such a curve
exhibits two sudden changes of direction, which were taken to indicate approxi-
mately the beginning and end of the injection of blood by the ventricle, and,
therefore, to affi3rd a rough measure of the duration of its systole. While the
interpretation of the curve in question is not wholly settled, it seems, neverthe-
less, to give a fair basis for conclusions as to the present question. The figures
resulting from the second method are especially instructive. It was found that,
with a pulse of 47 to the minute, the approximate length of the ventricular
systole was 0.347 of a second ; of the diastole, 0.930 of a second. With a
pulse of 128 to the minute, while the systole was only moderately diminished,

* F. C. Bonders : " De Rhytlimus der Hartstoonen," Nederlandsch Archief roor Getiees- en
Naiuurkunde, 1865, p. 141.

2 E. Thurston : " The Length of the Systole of the Heart as Estimated from Sphygmographic
Tracings," Journal of Anatomy and Physiology, 1876, vol. x. p. 494.

416 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

viz. to 0.256 of a second, the diastole was reduced to 0.213 of a second — an
enormous decline.

These results upon the human subject have been confirmed upon animals
by experiments in which were registered the movements of a lever laid across
the exposed heart; ' or the fluctuations of the pressures within the ventricles.*

By whatever means investigated, the ventricular systole is found to be
shortened with the cycle, and to be lengthened with it; the diastole is short-
ened or lengthened much more, however. In fact, if the pulse become very
frequent, the diastole may be so shortened that the "pause" nearly disap-
pears, and the systole of the auricles follows speedily after the opening of
the cuspid valves. This signifies that, for a time, the cardiac muscle can do
with very little rest, and that effective means exist for a very rapid "charg-
ing " of the ventricular cavity when necessary. For the working period of
the ventricle, however, a more uniform time is required. For the average
human pulse-rate this time of work is decidedly shorter than the time of
rest — viz. about 0.3 of a second for the former as against about 0.5 for the
latter.

Lengths of Auricular Events and of the Pause. — The systole of the
auricles is very brief, being commonly reckoned at about 0.1 of a second, as
the result of various observations.^ At the average pulse-rate, therefore, the
auricular systole is only about one-third as long as the ventricular, and the
length of the auricular diastole is to that of the ventricular as seven to five.
Consequently, a cardiac cycle of 0.8 of a second would comprise an auricular
systole of 0.1 of a second ; a ventricular systole of 0.3 of a second ; and a
pause, or repose of the whole heart, of 0.4 of a second — one-half of the cycle.

Practical Application. — The observations above described upon the inter-
val between the beginnings of the sounds have a practical bearing upon physical
diagnosis ; for they show how faulty are the statements often made which
assign regular proportions to the lengths of the sounds and the silences of the
heart. The length of the " second silence " must be very fluctuating, as it
comprises the longer part of the fluctuating ventricular diastole. The length
of the first sound and of the very brief first silence together nmst be very con-
stant, as they nearly coincide with the ventricular systole.

M. The Pressures within the Ventricles.^

We nmst now approach the study of further details of the working of the
ventricular pumps, which details depend for their elucidation upon the measur-
ing and recording of the pressures within the ventricles.

^ N. Baxt: "Die Verkiirzung der Systolenzeit durch den Nervns accelerans cordis," Archiv
fur Anntomie und Phijs^iolof/ie, Physiologisclie Abtlieilung, 1878, p. 122.

* M. von Frey und L. Krelil: " Untersuchungen iiber den Puis," ^4)t/i!'i' fiir Anatomie und
Physwlogie, Physiologisclie Abtheilung, 1890, p. 31. W. T. Porter: " Researches on the Filling
of the Heart," Journal of Physiology, 1892, vol. xiii. p. 531.

^ H. Vierordt : Daten und Tabellen zum Gebranche fiir Mediciner, 1888, p. 10.5.

* The matters connected with the ventricular pressure-curve may best be studied in the fol-
lowing writings, in which citations of other papers may be found : K. Hiirthle, in Pfliiger'a

CIRCULA TION. 4 1 7

Absolute Range of Pressure within the Ventricles and its Signifi-
cance.— In dealing; with tlic work done by the t'ontractiiii^ ventricles (p. 398)
we have .seen that tlie mereiuial inanonietcr, as used fur studying the pressure
within the arteries, is quite unable to follow the changes of tlie intra-ventric-
ular pressure; but that, by the intercalation of a valve, this instrununt can be
converted into a useful " niaxinuini luanoineter" for tlie nieasurino- and record-
ing of the hi^•llcst pressure occurring witiiin the ventricle during a given time
— that is, during a certain number of cycles. It must now be added that by a
simple change of valves this same instrument can at any moment be changed
into a '* minimum manometer."' We can thus, by means of the modified mer-
curial manometer, learn with fair correctness tlie extreme range of jircssure
within the ventricles. As instances of the extent of this range, two observa-
tions may be cited upon the left ventricle of the dog, the chest not having been
opened. In one animal the maximum was found to be 234 millimeters of mer-
cury, the maximum pressure in the aorta being 212 millimeters; and the min-
imum in the left ventricle was —38 millimeters — that is to say, 38 millimeters
less than the pressure of the atmosphere, the minimum pressure in the aorta
being 120 millimeters. In a second doo; the fiofures were 176 and —30 milli-
meters for the ventricle, the aortic range being from 158 to 112 millimeters.^
In the right ventricle of the dog such ranges as from 26 to —8 millimeters,
from 72 to —25, and various intermediate values, have been noted, both in
the unopened and the opened cbest.^ For reasons already stated (p. 395) no
trustworthy figures can be given for the pressures in the pulmonary artery ;
but they can never fail to be less than the highest pressures Avithin the right
ventricle.

The range of pressure, therefore, within either ventricle is in sharp contrast

Archiv fur die gesammte Physiologic, as follows : " Zur Technik der Untersuchung des Blut-
druckes," 1888, vol. 43, p. 399. "Technische Miuheilungen," 1890, vol. 47, p. 1. '^Ueber
den Ursprungsort der sekundiiren Wellen der Pulscnrve," vol. 47, p. 17. " Technische Mit-
theilungen," 1891, vol. 49, p. 29. " Ueber den Zusammenhang zwischen Herzthutigkeit und
Pulsforni," vol. 49, p. 51. " Kritik des Lufttransmissionsverfahrens," 1892, vol. 53, p. 281.
" Vergleichende Prufiing der Tonographen von Frey's und Hiirthle's," 1893, vol. 55, p. 319.
K. Hiirthle: "Orientirungsversuche iiber die Wirkung des Oxyspartein auf das Herz," Archiv
fib- experimentelle Palholngie unci Phannakologie, 1892, vol. xxx. p. 141. W. T. Porter : " Researches
on the Filling of the Heart," The Journal of Physiology, 1892, vol. xiii. p. 513. " A Kew Method
for the Study of the Intracardiac Pressure Curve," Journal of Experimental Medicine, vol. i.,
No. 2, 1896. M. von Frey und L. Krehl : " Untersuchungen iiber den Puis," Archiv fUr
Anatomic und Physiologic, Physiologisehe Abtheilung, 1890, p. 31. M. von Frey: "Die Unter-
suchung des Pulses," Berlin, 1892. "Das Plateau des Kammerpulses," ^Irc^iV /«»• Jnatornie
und Physiologic, Physiologisehe Abtheilung, 1893, p. 1. " Die Ermittlung absoluter Werthe fiir
die Leistung von Piilsschreibern," Archiv filr Anaiomie und Physiologie, Physiologisehe Abtheil-
ung, 1893, p. 17. "Zur Theorie der Lufttonographen," Archiv fiir Anatomic und Physiologie,
Physiologisehe Abtheilung, 1893, p. 204. "Die Erwarmung der Luft in Tonographen," Uen-
tralblatt fiir Physiologie vom 30 Juni 1894, Heft 7.

1 F. Goltz und J. Gaule : "Ueber die Druckverhiiltnisse im Innern des Herzens," Pjliigei-'s
Archiv fiir die gesammte Physiologie, 1878, xvii. p. 100.

■^ S. de Jager : " Ueber die Saugkraft des Herzens," Pfliiger's Archiv fiir die gesammte Physi-
ologie, 1883, Bd. xxxi. p. 491.

' S. de Jager: Loc. cit., pp. 506, 507 ; Goltz und Gaule: Loc. cit., p. 106.
27

418

AN AMERICAN TEXT- BOOK OE PHYSIOLOGY.

to that within tlie artery which it .suj)plios witli blood ; for the arterial ])rossiire,
although it fluctuates, is at all times far above tiiat of the atmosphere, and is
able, as we have seen, to maintain the circulation while tlie semilunar valve is
closed and the ventricular muscle is at rest. On the otlier hand, the pressure
within the ventricle, when at its highest, rises decidedly above the highest
arterial pressure, and thus the ventricle can overcome this and other opposing
forces, open the valve, and expel the blood. These facts have been stated
already. In falling, however, the pressure within the ventricle not only sinks
below that in the artery, and so permits the semilunar valve to close, but
sweeps downward to a point, it may be, below the pressure of the atmos})here,
and, in so doing, falls below the pressure in the auricle, and permits the open-
ing of the auriculo-ventricular valve and the entrance of blood out of the
auricle and the veins. As such a great range of pressure occurs in either
ventricle of a heart which is repeating its cycles with entire regularity, it is
presumable that at every cycle the pressure not only rises above that in the
arteries but may sink below that of the atmosphere.

Methods of Recording' the Course of the Ventricular Pressure. — It
now becomes of interest to ascertain, if possible, not only the range, but the
exact course, of these swift variations of pressure ; the causes of them, and the
effects which accompany them. It is hard to obtain, by the graphic method, a
correct curve of the pressure within either ventricle. We have seen that the
mercurial manometer is useless for this purpose; and it is very difficult to
devise any self-registering manometer which shall truly keep pace with fluctu-
ations at once so great and so rapid. The true form of this pressure-curve,

Fir.. 106.— Diapram of the elastic manometer: A, auricle; V, ventricle ; D, drum of the kjTnograph,
revolving in the direction of the arrow, and covered with smoked paper; L, recording lever in contact
with the revolving drum. (The working details of the instrument are suppressed for the sake of clear-
ness.)

therefore, still is partially in doubt, and is the subject of controversies which
largely resolve themselves into contests between rival instruments. We may
pass by without mention methods which are either antiquated or little used.
The following characters are common to the manometers with which the most
serious attempts have lately been made to obtain a true and minute record of
the fluctuations of pressure, even if great and rapid, within the heart or the
vessels (see Fig. 106). As in the case of the mercurial manometer, a cannula,

CIBCULA TION. 419

open at the end and charged with a Hiiid which checks the coagulatiou of the
hlood, is tied into a vessel, or, if the heart is under observation, is passed down
into it through an opening in a jugular vein or a carotid artery. If the chest
have been opened, the cannula may also be passed into the heart through a small
wound in an auricle or even through the walls of the ventricle itself The end
of the cannula which remains without the animal's body is connected, air-tight,
with a rigid tube of small, carefully chosen calibre, and as short as the condi-
tions of the experiment permit. The other end of this tube is not, as in the
mercurial manometer, left as an open mouth, but is connected, air-tight, with
a very small metallic chamber, which constitutes, practically, a dilated blind
extremity of the system formed by the tube and the cannula together. The
roof of this small metallic chamber is a highly elastic disk either of thin metal
or of india-rubber. Except for this small disk, all parts of the chamber, tube,
and cannula are rigid. In the instruments of some observers, the entire cavity
of the system formed by the chamber, tube, and cannula is filled with liquid,
viz. the solution which checks coagulation. Other observers introduce this
liquid only into the portion of the system nearest the blood ; the. terminal
chamber, and most of the rest of the system, containing only air. In every
case the blood in the vessel or in the heart is in free communication, through
the mouth of the tied-in cannula, with the cavity common to the tubes and
to the terminal chamber. At every rise of blood-pressure a little blood enters
this cavity, room being made for it by a displacement of liquid or of air,
which in turn causes a slight bulging of tlie elastic disk. At every fall of
blood-pressure a little blood mixed with liquid leaves the tubes as the elastic
disk recoils. If the disk is of the right elasticity, its rise and fall are directly
proportional to the rise and fall of the blood-pressure, and can be used to
measure it. Upon the centre of the disk rests a delicate lever of the " third
order," which rises and falls with the disk. The point of this lever traces
upon the revolving drum of the kymograph a curve which records the fluctua-
tions of the disk and therefore those of the blood-pressure. The elastic disk
and the contents, together, of such an apparatus possess less inertia than mer-
cury, and therefore follow far more closely rapid fluctuations of pressure.
Such instruments may be called " elastic manometers," and are often called
" tonographs," i. e. " tension-writers." They are of several forms.

It lias been indicated already that the pressure of the blood may be
communicated to the disk of an elastic manometer either by means ^ of
liquid or of air. A given series of fluctuations of blood-pressure may yield
decidedly different curves according to the method of " transmission " emploj^ed
to obtain them ; and the controversies as to the true form of the endocardiac
pressure-trace turn upon the question whether such " transmission by air " or
" transmission by liquid " yield the truer curve. The objections to the former
method depend upon the readier compressibility of air ; the objections to trans-
mission by liquid depend upon its greater inertia.

The General Characters of the Ventricular Pressure-curve.— What-
ever kind of elastic manometer and of transmission be used, the curve

420 AN AMERICAN TEXT-IiOOK OF I'll YSJOIJJIJ V.

obtiiined shows certain characters which arc rccoirnizetl by all as properly
belonging to the changes of pressure within the ventricle, whether right or
left. These general characters, moreover, pei-sist after the opening of the
chest. They are as follows (see Figs. 107, 108, 109): The muscular con-

Millimeters of
mercury.

Line of atmoHpheric
pressure.

Seconds.

Fig. 107 — Matriiifii-d curve of the course of pressure within the linht ventricle of the dog, the chest
being open ; to be read from left to right. Recorded by the elastic manometer, with transmission by air
(von Frey).

traction of the systole begins quite suddenly, and produces a swift and ex-
tensive rise of pressure, marked in the curve by a line but slightly inclined
from the vertical. In the same way the fall of pressure is nearly as sudden
and as swift as the rise, and perhaps even more extensive. The systolic ri.se
begins at a pressure a little above that of the atmosphere ; the diastolic fall
continues, toward its end, perhaps, with diminishing rapidity, till a point is
reached often below the pressure of the atmo.'^phere. The pressure then
rises, perhaps continuing negative for a longer or shorter time, but presently
becoming equal to that of the atmosphere. Near this it continues, perhaps
with a gentle upward tendency, until, near the end of the ventricular diastole,
the rise becomes more rai)id to the point at which the succeeding ventricular
systole is to begin.

It is the course of the pressure between its rapid ri.se and its rapid fall which
has been the most disputed. The ob-servers who employ manometers with liquid

lAne of atmonpheric
pressure.

Fig. 108.— Magnified curve of the course of pressure within the left ventricle and the aorta of the
dog, the chest being open ; to be read from left to right. Recorded simultaneously by two elastic man-
ometers with transmission by liquid. In both curves the ordinates having the same numbers have the
following meaning: 1, the instant preceding the closing of the mitral valve ; 2, the opening of the semi-
lunar valve; 3, the beginning of the "dicrotic wave," regarded as marking the instant of closure of the
semilunar valve ; 4, the instant preceding the opening of the mitral valve (Porter).

transmiasion, have so far found that the high swift rise at the outset of the
systole is soon succeeded by a sudden change. According to them the pressure
within the manometer now exhibits fluctuations of greater or less extent which

CIRCULA TION.

421

arc due, partly at least, to tlie inertia of the trau.smitting liquid ; but, with due
allowaiife made tor the.se, the cardiac pressure is seeu to niaiutain itself at a
high point iliri»tigliont most of the systole until the rapid fall Ix'gius. During
this period of high preasure, the height about which the fiuctuatious occur may
remain nearly the same ; or this height may gradually increase, or gradually
decrease, up to the beginning of the rapid fall. As is shown by Figure 108,
this course of the systolic pressure causes its curve to bend alternately down-
ward and upward between the end of its greatest rise and the beginning of its
greatest fall ; but between these two points the general direction of the curve
approaches the horizontal, and therefore entitles this portion of it to the name
of the "systolic plateau." The best of the manometers with air-transmis-
sion yields a curve of the pressure within the ventricle which presents a
ditfereut picture (Figs. 107 and 109). The steeply rising line may diminish

Millimeters of
mercury.

ine of atmospheric
pressure.

Tenthn of a second.

Fig. 109.— Magnified curve of the course of pressure -within the left ventricle of the dog, the chest
being open : to be read from left to right. Recorded by the elastic manometer with transmission by air.
The ordinates have the following meaning: 1, the closure of the mitral valve ; 2, the opening of the semi-
lunar valve ; 3, the closure of the semilunar valve ; 4, the opening of the mitral valve (von Frey).

its steepness somewhat as it aiscends, but its rapid turn at the highest point of
the curve is succeeded by no plateau. The line simply describes a single peak,
and begins the descent which marks the rapid fall of pressure recognized by
all observers. In these peaked curves this descent is often steepest in its
middle part. Such a peaked curve would indicate, of coui-se, that there is no
such thing as the maintenance, during any large part of the systole of the
ventricles, of a varying but high pressure. The experienced observer who is
the chief defender of the peaked curve holds the plateau to be a product either
of too much friction within the manometer tubes, or of a faulty position of the
cannula within the heart, whereby communication with the manometer is, for
a time, cut off. The able and more numerous adherents of the plateau, on the
other hand, attribute the failure to obtain it to the sluggishness of the instru-
ment employed. Recent comparative tests of elastic manometers, and other
studies, would seem to .show that the curves obtained by liquid transmission,
and which exhibit the plateau, afford a truer picture of the general course of the
pressure within the ventricles than the peaked curves written by means of air.

422

^.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

The Ventricular Pressure-curve and the Auricular Systole. — It is
striking tcstimouy to the siiu)othiie.<s of working of tiio cardiac mechanism,
that the curve of intra-ventricular pressure rarely gives any clear indication of
the beginning or end of the auricular systole. This event may be expected to
increase the pressure within the ventricles; and, in the curve, the verv gentle
rise which coincides with the latter and longer part of the ventricular diastole
passes into the .steep ascent of the commencing ventricidar systole bv a
rounded sweep, which indicates a more rai)idl\- heightened pressure within
the ventricle during the auricular systole. ^Vs a rule, no angle reveals an
instantaneous change of rate to show the beginning or end of the injection of
blood by the contracting auricle (see Figs. 107, 108, 109). Occasionallv, how-
ever, a slight " presystolic " fluctuation of the curve may seem to n)ark the
auricular systole.'

The Ventricular Pressure-curve and the Valve-play. — It is also
exceedingly striking that no curve, whether it be pointed or show the sys-
tolic plateau, gives a clear indication of tlie instant of the closing or open-
ing of either valve, auriculo-ventricular or arterial (see Figs. 107, 108, 109).
These instants, so important for the significance of the curve, can, however,
be marked upon it after they have been ascertained indirectly. A method
of general application would be as follows : Two elastic manometers are
"absolutely graduated " by causing each of them to record a series of pressures
already measured by a mercurial manometer. The two elastic manometers can
then be made to mark upon the same revolving drum the simultaneous changes
of pressure in a ventricle and in its auricle, or in a ventricle and its artery.

Fig. no.— Diagram of the differential manometer: A, artery: T', ventricle; /), drum of kymopraph,
revolving in the direction of the arrow, and covered with smoked paper; /., recording lever in contact
with the revolving drum ; S, a spring by which the movement of the lever worked by the disks is trans-
mitted to the recording lever. (The working details of the instrument are suppressed or altered for the
sake of clearness.)

The pressure indicated by any point of either curve can then be calculated
in terms of millimeters of mercury. That point upon the intra-ventricular
curve which marks a rising pressure just higher than the simultaneons pre.'^sure
in the auricle or artery, may be taken to mark the closing of the cuspid valve
^ von Frey and Krelil : Op. cit., p. 61.

CIRCULA TION. 42;]

or the opening of the seniihmar valve, as the case may be. By a converse
proce&s, the moment of opening of the cuspid valve, or of closing of the semi-
lunar, may also be ascertained. The practical difficulties in the way of
applying this method to the ventricle and auricle are much greater than to the
ventricle and artery. By another application of the principle just described, a
"differential manometer" has been devised for the })urpose of registering as a
single curve the successive differences, from moment to moment, between the
ventricular and auricular pressures, or the ventricular and arterial pressures
(see Fig. 110). To this end, two elastic manometers are fastened immovably
together, and their two elastic disks, instead of bearing upon separate levers,
are made to bear upon a single one, which has its fulcrum between the disks,
and is a lever not of the third order, but of the first, like a common balance.
As the lever or beam of the balance turns from the horizontal as soon as the
scales are pressed upon by unequal weights, so the lever of the differential
manometer turns as soon as the disks are unequally affected by the pressures
within the ventricle and the auricle, or the ventricle and the artery. As, how-
ever, the pressures upon the scales are from above, while those upon the disks
are from below, the disk which tends to " kick the beam " is the one acted
upon by the greater pressure, instead of by the less, as in the case of the scales.
The manometric lever marks its oscillations as a curve upon the kymograph
by the help of a second or " writing lever " connected with it. The persistence
of exactly equal pressures, no matter what their absolute value, in the two
manometers would cause a horizontal line to be drawn by the writing lever.
This would serve as a base-line. The differential manometer is a valuable
instrument, although it is evident that where such minute differences of space
and time are recorded as a curve by such complicated mechanisms, the sources
of error must be numerous and difficult to avoid.^

The methods which proceed by the measurement of differences of pressure
may sometimes be controlled, or even replaced, by an easier method, as follows:
If two manometers simultaneously record on the same kymograph the pressure-
curves of the ventricle and the auricle, or of the ventricle and the artery, any
very sudden change of pressure, produced in auricle or artery at the opening or
shutting of a cardiac valve, wnll produce a peak or angle in the curve of pres-
sure of the auricle or artery. By the rules of the graphic method the point in
the pressure-curve of the ventricle can easily be found which was written at
the same instant with the peak or angle in the auricular or arterial curve.
That point upon the ventricular curve, when marked, will indicate the instant
of opening or shutting of the valve in question. In the pressure-curve ob-
tained from the aorta close to the heart, there is a sudden angle which clearly
marks the instant when the opening of the semilunar valve leads to the sudden
rise of pressure which causes the up-stroke of the pulse (see Fig. 108). Again,
the fluctuation of aortic pressure which we shall learn to know as the "dicrotic
wave" begins at a moment which many believe to follow closely upon the clos-
ure of the semilunar valve. That moment may be indicated by a notch in the

' K. Hiirthle: Pfluger's Archivfiir die gesammte PhysioJofjie, 1891, vol. 49, p. 45.

424 A^'^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

aortic curve. So, too, the rise ot" pressure witiiin the auricle produced by its
systole may suddenly be succetded by a fall, the beginning ot" which must mark
the closure of the cuspid valve, which closure thus may correspond with the
apex of the auricular curve.

In Figure 108, ordinate 1 indicates the closing, and ordinate 4 the o])cn-
iug, of the mitral valve. These two points were found by help of the dif-
ferential manometer. Ordinate 2 indicates the opening, and ordinate 3 the
closing, of the aortic valve. These two points were marked with the help
of the curve of aortic pressure, also shown in Figure 108, each ordinate of
wOiich has the same number as the corresponding ordinate of the ventricular
curve. In the arterial curve, 2 marks the beginning of the systolic rise,
and 3 the beginning oi' the dicrotic wave, which latter point is treated by
the observer as closely corresponding to the closure of the aortic valve. In
Figure 109 each ordinate has the same number, and, as regards the valve-
play, the same significance, as in Figure 108. Ordinate 1 corresponds to the
apex of a peak in the auricular curve (not here given) which represents the
end of the auricular systole. Ordinate 2 corresponds to the beginning of the
systolic ascent in the aortic curve (not here given). Ordinate 3 was found
by comj)aring, by means of two elastic manometers, the simultaneous pressures
in the ventricle and the aorta. Ordinate 4 corresponds, on the auricular
pressure-curve, to a j)oint which marks the beginning of a decline of pres-
sure believed by the observer to succeed the opening of the cuspid valve.
In both the figures given of the ventricular curve, and in such curves
in general, the ]K)ints which mark the valve-play occur as follows: The
closure of the cuspid valve corresponds to a point, not far above the line
of atmospheric jiressure, where the moderate upward sweep of the ventric-
ular curve takes on the steepness of the systolic ascent. The systole of the
auricle is of little force, and the blood injected by it into the distensible ven-
tricle raises the pressure there but little; that little, however, is more than
the relaxing auricle presents, and the cuspid valve is closed. Somewhere on
the steep systolic ascent occurs the point corresponding to the rise of the ven-
tricular above the arterial pressure, and therefore to the opening of the semi-
lunar valve. But other forces beside the arterial ])ressure must be overcome
by the contracting muscle ; and the ventricular pressure mounts higher yet,
and either stays high for a while, producing the plateau, or, in a peaked curve,
at once descends. In either case, not long after the beginning of the sharp
descent, the point occurs at which the ventricular pressure falls below the arte-
rial, and the semilunar valve is closed. Beyond this point the curve continues
steeply downward, but it is not till a point is reached not far above, or possibly
even below, the atmospheric pressure that the pressure in the ventricle falls
below that in the auricle, and the cuspid valve is o])ened.

The Period of Reception, the Period of Ejection, and the Two Periods
of Complete Closure of the Ventricle. — During the whole of the jwriod
when the cuspid valve is open, the pressure is lower in the ventricle than in
the artery; the arterial valve is shut; and blood is entering the ventricle.

CTRCULA TION. 425

This may be o^iUed the ''period of reeeption of blood." Diiiiiij; the greater
part of tiie ])eri<)d when tlie cuspid valve is sliiit, tlie arterial valve is open ;
the pressure is hii>:lier in the ventricle than in tlie artery; and the ejection
of blood iVoin the Ibrnier is takint^ j)lace. This may be called the "period
of ejection," and lies in Fi<^ures 108 and 109 between the ordinates 2 and
3. The careful work which jjas enabled us to mark the valve-play upon
the ventricular curve has demonstrated the interesting fact that there occur
two brief j)eriods during each of which both valves are shut, and the ven-
tricle is a closed cavity. Of these two periods, one immediately precedes the
period of ejection, and the other immediately follows it. The first lies, in
Figures 108 and 109, between the ordinates 1 and 2 ; the second, between 3
and 4. The ex})lanation of these two periods is simple. It takes a brief but
measurable time for the cardiac muscle, forcibly contracting upon the impris-
oned liquid contents of the closed ventricle, to raise the pressure to the high
point required to overcome the opposing pressure within the artery and to open
the semilunar valve. Again, it takes a measurable time, probably seldom
quite so brief as the period just discussed, for the cardiac muscle to relax suffi-
ciently to permit the pressure in the closed ventricle to fall to the low point
required for the opening of the cuspid valve. The ventricular cycle, thus
studied, falls into four periods: the first is a brief period of complete closure
with swiftly rising pressure; the second is the period of ejection, relatively
long, and but little variable ; the third is a period of complete closure, with
swiftly falling pressure; the fourth is the period when the pressure is low and
blood is entering the ventricle. This last period is very variable in length,
but at the average pulse-rate it is the longest period of all.

Phenomena of the Period of Reception of Blood. — We have already
followed the course of the pressure within the ventricle from the moment of
oj)ening of the auriculo-ventricular valve to that of its closing (p. 416).
During this time the ventricle is receiving its charge of blood, the flaccidity of
the wall rendering expansion easy and keeping the pressure low. The blood
which enters first has been accumulating in the auricle since the closing of the
cuspid valve, and now, upon the opening of this, it both flows and is to some
slight degree drawn into the ventricle. This blood is followed by that which,
during the remainder of the " repose of the whole heart," moves through the veins
and the aiu'icle into the ventricle under the influence of the arterial recoil and
the other forces which cause the venous flow (p. 397) ; and the charge of the
ventricle is completed by the blood wdiich is injected at the auricular systole.

The Neg-ative Pressure within the Ventricles. — That the heart, in its
diastole, draws something from without into itself is a very ancient belief, and
this mode of its working played a great part in the doctrines of Galen and of
the Middle Ages. In 1543, Vesalius, who, on anatomical grounds, questioned
some of Galen's views as to the cardiac physiology, fully accepted this one.'

* AndreoR Vesalii Bruxellensis, Scholce medicorum Patavince professoris, de Humani corporis
fabrica Libri steptem. Basilese, ex officina loannis Oporini, Anno Salutis reparatae MDXLIII.
Page 587.

426 AiY AMERICAN TEXT-BOOK OF PHYSIOLOGY.

On tlie other hand, in 1628, Harvey rejected it. "It is manifest," he says,
" that the blood enters the ventricles not by any attraction or dilatation of the
heart, but by being thrown into thcni by the pulses of the auricles." ' In this
particular, modern research in some degree confirms the opinion of the ancients,
while denying to suction within the ventricles any such great effect as was
once believed in. As a rule, the cuspid valve is not opened till the pressure in
the ventricle has fallen to a point not far from the pressure of the atmcjsphere ;
it may be even below it. In any case the ventricular pressure usually becomes
negative very soon after the o|)ening of the cuspid valve. This negative pres-
sure is of variable extent and continues for a variable time. It is always
small as compared with the positive pressure of the systole. Under
some circumstances negative pressure may be absent, but it is so very com-
monly present as certainly to be a normal phenomenon (see Figs. 107,
108, and 109). This negative pressure is revealed by the elastic as well
as by the minimum mercurial manometer; it is present in both ventri-
cles ; and it is present, to a less degree, even after the chest has been
opened, and its aspiration destroyed. It is in virtue of the forces which
produce the negative pressure in the manometer that blood is drawn into
the heart.

Passing by disproven or improbable theories as to the causes of this suction,
we shall find the following statements justified : As the heart lies between the
lungs and the chest-wall (including in this term the diaphragm), it is subject,
like the chest-wall and the great vessels, to the continuous aspiration produced
by the stretched fibres of the elastic lungs. At every inspiration this aspiration
is increased by the contraction of the inspiratory muscles. We see, therefore,
that the ventricle must overcome this aspiration as part of the resistance to its
contraction ; and that, as soon as that contraction has ceased, the walls of the
ventricle must tend to be drawn asunder by those same forces of elastic recoil
in the pulmonary fibres, and of contraction of the muscles of inspiration, which
we have seen (p. 387) to produce a slight suction within the great veins in and
very near the chest. These same forces produce a slight suction within the
ventricles, relaxed in their diastole. But a very slight suction occurs at each
ventricular diastole even after the chest has been opened. The causes of this
are still obscure ; but it is to be borne in mind that the relaxing wall of the
ventricle, flabby as it is, possesses some little elasticity, especially at the am-iculo-
ventricular ring, and therefore may tend to resume a somewhat different form
from that due to its contraction. As the result of this slight elastic recoil, a
feeble suction may occur.

N. The Functions of the Auricles.

Connections of the Auricle. — Into the right and left auricles open the
systemic and pulmonary veins respectively, and each auricle may justly be re-
garded as the enlarged termination of that venous system with which it is con-
nected. Until modern times the terms of anatomy reflected this view, and
' Op. ciL, 1628, p. 26: Willis's translation, Bowie's edition, 1889, p. 28.

CIRCULATION. 427

from the ancient Greeks to a time later tlian Harvey, the word " heart " com-
monly meant the ventricles only, as it still does in the language of the
slaughter-house. This termination of the venous system, the auricle, com-
municates directly with the ventricle, at the auriculo-ventricular ring, by an
aperture so wide that, when the cuspid valve is freely open, auricle and ven-
tricle together seem to form but a single chamber.

The Auricle a Feeble Force-pump ; the Pressure of its Systole. — The
wall of the auricle is thin and distensible; it is also muscular and contractile.
But the slightest inspection of the dead heart shows how little force can be
exerted by the contraction of so thin a sheet of muscle. In the wall of the
appendix, however, the muscular structure is more vigorously developed than
over the rest of the auricle. The auricle, then, should be a very feeble force-
pump ; and such in fact, it is ; for the highest pressure scarcely rises above 20
millimeters of mercury in the right auricle of the dog,' and an auricular sys-
tole often produces a pressure of only 5 or 10 millimeters.^ This would be
but a small fraction of the maximum ventricular pressure of the same heart.
The auricle, however, is equal to its work of completing the filling of the
ventricle; and the feebleness of the auricle will not surprise us when we
consider that, at the beginning of its systole, the pressure exerted by the
contents of the relaxed ventricle is but little above that of the atmosphere,
and offers small resistance to the injection of an additional quantitv of
blood.

The systole of the auricles is so conspicuous a part of the cardiac cycle when
the beating heart is looked at, that its necessity is easily overrated. Even Har-
vey, in attacking the errors of his day, was led by imperfect methods to estimate
too highly the work of the auricular systole (see p. 426). The error, although
a gross one, is not rare, of considering the systole of the auricles to be as im-
portant for the charging of the ventricles as the systole of the ventricles is for
the charging of the arteries. On page 390 the proof has already been given
that the work of the heart may entirely suffice to maintain the circulation with-
out aid from any subsidiary source of energy. It must now be added that the
ventricles can, for a time, maintain the circulation without the aid of the auric-
ular systole — a clear proof that this systole is not a sine qua non for the
working of the cardiac pump.

If in an animal, not only anaesthetized but so drugged that all its skeletal
muscles are paralyzed, artificial respiration be established and the chest be
opened, the circulation continues. If the artificial respiration be suspended
for a time, the lungs collapse, asphyxia begins, and the blood accumulates
conspicuously in the veins and in the heart. Presently the muscular walls
of the auricles may become paralyzed by overdistention, and their systoles
may cease, while the ventricles continue at work and may maintain a circu-
lation, although of course an abnormal one. After the renewal of artificial
respiration, it may not be till several beats of the ventricles have succeeded,

^ Goltz und Gaule : op. cif., p. 106.

* W. T. Porter : op. cit., p. 533. S. de Jager : op. cit., p. 506.

428 AN AMERICAX TEXT-BOOK OF PTTYSIOLOGY.

without help iroin the auricles, in iinlctadiiijjj the latter and the \-eiiis, that the
auricles recouHueiice their beats.'

On the other hand, it is clear that the auricle is not without importance as
a t()rce-j)ump for conipletini; the tilling- of the ventricle, even if it can be dis-
pensetl with for a time. In curves of the blood-pressure during as])hy.\ia taken
sinndtaneously from the auricle and the ventricle, there may be noted the influ-
ence exerted upon the ventricular curve by ineffectiveness of the auricular sys-
tole. It is found that, in this case, that slight but accelerated rise of pressure
may fail which normally just precedes, and merges itself in, the large swift rise
of the ventricular systole. It is found, too, that, under these circumstances,
the total height of this systolic rise may be diminished.^ We shall see pres-
ently how, when the pulse becomes very frequent, the importance of the auric-
ular systole may be increased. We have seen already (p. 424) that normally it
may probably effect the closure of the cuspid valves.

Time-relations of the Auricular Systole and Diastole. — The auricular
systole is not only weak, but brief, being commonly reckoned at about U.l of a
second (see p. 416). If this be correct for man, at the average pulse-rate of
72 the auricular systole would comprise only about one-eighth of the cycle;
would be only one-seventh as long as the auricular diastole ; and only about
one-third as long as the ventricular systole which immediately follows that of
the auricle.

The Auricle a Mechanism for Facilitating the Venous Flow and
for the " Quick-charging " of the Ventricle. — Further points in regard to
the systole of the auricles can best be treated of incidentally to the general
question, AVhat is the princi])al use of this portion of the heart? The answer
is not so obvious as in the ease of the ventricles. It may, however, be stated
as follows : The auricle is a reservoir, lying at the very door of the ventricle.
That door, the cuspid valve, remains shut during the relatively long and un-
varying period of the ventricular systole and the brief succeeding period of fall-
ing pressure within the ventricle. These periods coincide with the earlier part
of the auricular diastole. During all this time the forces which cause the
venous flow are delivering blood into the flaccid and distensible reservoir of
the auricle, and can thus maintain a continuous flow. But the blood of which
the veins are thus relieved during the period of closure of the cuspid valve,
accumulates just above that valve to await its opening. When it is opened
by the superior auricular pressure, the stored-up blood both flows and is drawn
into the ventricle promptly from the adjoining reservoir. From this time
on, auricle and ventricle together are converted into a common storehouse for
the returning blood during the remainder of the repose of the whole heart,
which coincides with the later portion of the long auricular diastole. The
next auricular systole completes the charging of the ventricle ; and a second
use of this systole now becomes apparent, for the sudden transfer by it of
blood from auricle to ventricle not only completes the filling of the latter, but

' von Frey iind Krehl : op. cit., pp. 49, 59. G. Colin: Traile de physiologie comparee den ani-
maux, Paris. 1S88, vol. ii. p. 424. * von Frey und Krehl : op. ci(., p. 59.

CIRCULA TION. 429

lessens the contents of the anriele, jukI so jjicpjires it to act as a storehouse
duriii«:^ tlie coniinir systole of the ventricle. The auricle, then, is an apparatus
for the niuinteiiance of as even a flow as possible in the veins and for the ra})id
and thorough charging of the ventricle. It is clear that, for both uses, the
auricle's fiuiction as a reservoir is certainly no less important than its function
as a force-pump.

The value of a mechanism for the rapid filling of the ventricle increases
with the pulse-rate, and with a very frequent pulse must be of great imj)ort-
ance, because now time must be saved at the exj)ense of the pause, with its
quiet flow of blood through the auricle into the ventricle ; and the auricular
systole nmst follow more promptly than before upon the opening of the cus-
pid valve. If the pulse double in frequency, each cardiac cycle must be com-
pleted in one-half the former time; but we have seen that the ventricle
requires for its systole a time which cannot be shortened with the cycle to the
same degree as can its diastole. Of heightened value now to the ventricle
will be the adjoining reservoir, which is filling while the cuspid valve remains
closed, and from which, as soon as that valve is opened, the necessary supply
not only flows, but is sucked and pumped into the ventricle, for, when increased
demands are made upon the heart, the usefulness of an increased frequency of
beat disappears if the volume transferred at each beat from veins to arteries
diminish in the same proportion as the frequency increases. No increase of
the capillary stream can then follow the more frequent strokes of the pump.^

Negative Pressure •within the Auricle ; its Probable Usefulness. — The
course of the pressure-curve of the auricle, as shown by the elastic manome-
ter, is too complex and variable, and its details are too much disputed, for it
to be given here. But certain facts regarding the auricular pressure are of
much interest in connection with the use of the auricle which has just been
discussed. Once, and perhaps oftener, in each cycle, the pressure in the auricle
may become negative, perhaps to the degree of from —2 to —10 millimeters of
mercury even in the open chest,^ and of course becomes still more so when
the latter is intact, sinking in this case to perhaps— 11.2 millimeters.^ What
is striking in connection with the " quick-charging " of the ventricle is that
the greatest and longest negative pressure in the aiu-icle coincides, as we should
expect, with the earlier part of its diastole, and therefore with the systole of
the ventricle, when the auricle is cut off from it by the shut valve.* By
this suction within the auricle the flow from the veins into it probably is
heightened, and the store of blood increased which accumulates in the reservoir
to await the opening of the valve. The quick-charging mechanism itself' is
quickly charged. Nor should it be forgotten that the work of the ventricle
contributes in some degree to this suction within the auricle. The heart is
air-tight in the chest, which is a more or less rigid case. At each ventricular

* von Frey un<l Krehl : op. cit., p. 61.

^ de Jager : op. cit., p. 507. W. T. Porter : op. cit., p. 533.

* Goltz und Gaiile: op. cit., p. 109.

* von Frey und Krehl, op. cit., p. 53. Porter, op. cit., p. 523.

430 ^liV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

systole the heart pumps some blood out of tiiis case, and shrinks as it does so,
thus tending to produce a vacuum; in other words, to increase tiie amount of
negative pressure within the chest, and thus help to expand the swelling auri-
cles. Therefore for the suction which helps to charge the auricles during the
systole of the ventricles, that systole itself is partly resj)ousible.'

Is the Auricle Emptied by its Systole ? — Authorities differ still as to the
extent to which the auricle is emptied by its systole; some holding the scarcely
probable view that, during this time, its contents are all, or nearly all, trans-
ferred to the ventricle ; ^ and others taking tlie widely different view that the
auricle actually continues to receive blood during its systole, which latter simply
increases the discharge into the ventricle. According to this latter opinion the
flow from the great veins into the auricle is absolutely unbroken.^ All are
agreed however, that the auricular appendix is the raost completely emptied
portion of the chamber.

Are the Venous Openings into the Auricle closed during its Systole ?
If not, does Blood then regurgitate, or enter ? — As to these questions dif-
ferences of opinion are possible, because at the openings of the veins into the
auricle no valves exist which are effective in the adult, except at the mouth of
the coronary sinus. It Ls therefore a question, what happens at the mouths of
the veins during the auricular systole. These mouths are surrounded by rings
composed of the muscular fibres of the auricular wall ; and for some distance
from the heart the walls of some of the great veins are rich in circular fibres
of muscle. We have seen already (p. 407) that a rhythmic contraction of the
vense cavae and pulmonary veins occurs just before the systole of the auricles
and must accelerate the flow into the latter. Their swiftly following systole is
known to begin at the mouths of the great veins and from these to spread over
the rest of each auricle. It is evident at once that the circular fibres must
either narrow or obliterate, like sphincters, the mouths of the veins at the out-
set of the systole, and that these fibres thus take the place of valves. If the
closure be complete, all the blood ejected by the systole must enter the ventricle,
and a momentary standstill of blood and rise of pressure in the veins just with-
out the auricle must accompany its brief systole. A recent observer believes
the flow into the auricle to be interrupte<l even more than once during its cycle.*
If the venous openings be not closed but only narrowed during the systole
of the auricles, the transfer of all or most of the ejected blood to the ventricle
must depend upon the pressure being lower therein than at the venous openings.
A slight regurgitation into the veins would, like the complete closing of their
mouths, cause a momentary checking of their blood-flow just without the auri-
cle, and a slight rise of pressure. Such a checking of the flow has in some

' A. Mosso: Die Diar/nostik des Pulses, etc. Zweiter Theil : Ueber den negativen Puis,
p. 42.

"^ M. Foster: A Text-book of PhysloJorpj, New York, 1895, p. 182.

' Skoda : " Ueber die Function der Vorkammern des Herzens," Sitzungsben'chte der mnthem.-
natw-w. Classe der kais. Akademie der Wissenschaften in Wien, 1852, vol. ix. p. 788. L. Her-
mann : Lehrbuch der Physiologic, 1892, p. 66. * W. T. Porter: Op. cit., p. 534.

CIRCULATION. 431

cases been observed and ascribed to regurgitation.' A systolic narrowing with-
out closure of the venous mouths would leave room also for the view already
given, that so far is regurgitation from taking place, that even during the sys-
tole of the auricles blood enters them incessantly, and the venous flow is never
checked. In this case the systole of the auricle would still empty it partially
into the ventricle, owing to the lowness of the pressure there.

The time has not arrived for a decision as to all these questions, which are
surrounded by practical difficulties ; but fortunately they do not throw doubt
upon the functions of the auricle as a reservoir and pump which may be
swiftly filled, and may swiftly complete the filling of the ventricle which it
adjoins.

O. The Arterial Pulse.

Nature and Importance. — The expression " arterial pulse " is restricted
commonly to those incessant fluctuations of the arterial pressure which corre-
spond with the incessant beatings of the ventricles of the heart. These rhyth-
mic fluctuations of the arterial pressure have been explained already (p. 385)
to depend upon the rhythmic intermittent injections of blood from the ven-
tricles ; upon the resistance to these injections produced by the friction within
the blood-vessels ; and upon the elasticity of the arterial walls. It has also
been explained that the interaction of these three factors is such that the blood,
in traversing the capillaries, comes to exert a continuous pressure, free from
rhythmic fluctuations ; in other words, that the pulse undergoes extinction at
the confines of the arterial system. It is at once a])parent that the pulse may
be affected by an abnormal change, either in the heart's beat, in the elas-
ticity of the arteries, or in the peripheral resistance, or by a combination
of such changes ; and that, therefore, the characters of the pulse possess
an importance in medical diagnosis which justifies a brief further discus-
sion of them.

A pulsating- artery not only expands, but is lengthened. The sudden
increase in the contents of an artery which causes the pulse therein, is accom-
modated not merely by the increase of calibre which produces the " up-stroke "
of the arterial wall against the finger, but also by an increase in the length
of the elastic vessel. If the artery be sinuous in its course, this increase in
length suddenly exaggerates the curves of the vessel, and thus produces a
slight wriggling movement. This is sometimes very clearly visible in the
temporal arteries of emaciated persons. On the other hand, the increase in
the calibre of the artery is relatively so slight that it is invisible at the profile
even of a large artery, dissected clean for a short distance for the purpose of
tying it. Such a vessel appears pulseless to the eye, although its pulse is
easily felt by the finger, which slightly flattens the artery and thus gains a
larger surface of contact.

Transmission of the Pulse. — If an observer feel his own pulse, placing

' Franfois-Franck : " Variations de la vitesse du sang dans les veines sous I'influence
de la systole de I'oreillette droite," Archives de physiologie normale et pathologique, 1890, p. 347.

432 AN AMERICAN TEXT- BOOK' OF PIIYSIOLOaV.

the Hnger ot" one hand iijxni the (•(Uiiiiiuii carotid aftci'v, and that oi" the other
upon tlie dorsal artery of'tlie ibot at \\\v instep, he will pei-ccivc that the pulse
corresponding to a given heart-heat ocrurs later in the loot than in the neck.
This phenomenon is readily comprehended by considering that room for the
" pidse-vohime " injected by the heart is made in the root of the arterial system
both by local expansion and by a more rapid displacement of blood into the
Dext arterial segment. This next segment, in turn, acc(.)mmo(lates its increased
charge by local ex})ansion and by a more rapid disj)lacement ; and this same
process involves segment after segment in succession, onward toward the
capillaries. The expansion of the arterial system, then, is a progressive one,
and, as the phrase is, spreads as a wave from the aorta onward to the arteri-
oles. The rate of transmission of the " pulse- wave " from a point near the
heart to one remote from it, may be calculated. This is done by comparing
the time which elapses between the occurrence of the up-stroke of the pulse
in the Dearer and in the farther artery with the distance along the arterial
system which separates the two points of observation. In one case, for exam-
ple, that of an adult, the absolute amount (if the postponement of the pulse —
that is, the time required for the transmission of the pulse-wave from the
heart itself to the arteria dorsalis pedis, w^as 0.193 second.^ The time of
transmission of the pulse-wave from the heart to the dorsa/is pedis is often
longer than in this case, amounting to 0.2 second or a little more. If we
reckon the duration of the ventricular systole at about 0.3 second, it is evi-
dent that the fact of the postponement of the pulse in the arteries distant from
the heart does not invalidate the general statement that the arterial pulse is
synchronous with the systole of the ventricles.

The general estimates of the rate, as opposed to the absolute time, of trans-
mission of the pulse-wave vary, in different cases, from more than 3 meters
to more than 9 meters per second. As the blood in the arteries does not pass
onward at a swifter rate than about 0.5 meter per second, it is clear that the
wave of expansion moves along the artery many times faster than- the l)h>od
does ; and that to confound the travelling of the wave with the travelling of
the blood would be a very serious error, easily avoided by bearing in mind
the causes of the pulse-wave as already given.

Investigation by the Finger. — The feeling of tiie pulse has been a valu-
able and constantly used means of diagnosis since ancient times. Indeed, the
ancient medicine attached to it more importance than does the practice of
to-day. But it is still advisable to warn the beginner that he may not look
to the pulse for "pathognomonic" information ; that is to say, he may not
expect to diagnosticate a disease solely by touching an artery of the patient
under examination. The ])ulse is most commonly felt in the radial artery,
which is convenient, superficial, and well supported against an examining
finger by the underlying bone. Many other arteries, however, may be util-
ized.

Frequency and. Regularity. — The most conspicuous qualities of the pulse
' J. X. Czermak : Gesammelte Schriften, 1879, Bd. i. Abth. 2, p. 711.

CIRCULA TION. 433

are frequency and rea;ularity. Usually these can he appreciated not merely hy
a physician hut hy any intellii^ent person. 'J'he j)liysi()logical variations in
tiie frequency of the heart's heats liave heeu referred to already (p. 412). In
an intermittent pulse the rhythm is usually ret^ular, hut, at longer or shorter
intervals, the ventricle omits a systole, and therefore, the pulse omits an up-
stroke. Either intermittence or irregularity of the cartliac IJeats may he
caused hy transient disorder as well as hy serious disease.

Tension. — When unusual force is required in order to extinguish the ])ulse
hy compressing the artery against the hone, the arterial Avail, and hence the
pulse, is said to possess high tension, or the pulse is called incompressible, or
hard. Conversely, the pulse is said to he of low tension, compressible, or soft,
when its obliteration is unusually easy. A very hard pulse is sometimes called
"wiry;" a very soft one, "gaseous." High tension, hardness, incompressibil-
ity, obviously are directly indicative of a high blood-pressure in the artery ;
and the converse qualities of a low pressure. It follows from what has gone
before that the causes of changes in the arterial pressure, and hence in the
tension, may be found in changes either in the heart's action, or in the periph-
eral resistance, or, as is very common, in both. An instrument called the
sphygmomanometer^ is sometimes ap])lied to the skin over an artery, in order
to obtain a better measurement of its hardness or softness than the finger can
make. This instrument is not free from sources of error.

Size. — When the artery is unusually increased in calibre at each up-stroke
of the pulse, the pulse is said to be large. When, at the up-stroke, the calibre
changes but little, the pulse is said to be small. A very large pulse is some-
times called "bounding;" a very small one, " thready." Largeness of the
pulse must be distinguished carefully from largeness of the artery. The for-
mer phrase means that the fluctuating part of the arterial pressure is large
in pro])ortion to the mean pressure. But if the mean pressure be great
while the fluctuating part of the pressure is relatively small, the artery, even
at the end of the down-stroke, will be of large calibre, while the pulse will
be small.

It has been seen that the increased charge of blood which an artery receives
at the ventricular systole is accommodated partly by increased displacement of
blood toward the capillaries, and partly by that increase in the capacity of the
artery which is accompanied by the up-stroke of the pulse. The less the con-
tents of the artery the less is the arterial pressure, the less the tension of the
wall, and the more yielding is that wall. The more yielding the wall, the more
of the increased charge of blood does the artery accommodate by an increase of
capacity and the less by an increase of displacement. Therefore, a large pulse
often accompanies a low mean pressure in the arteries, and hence may appear
as a symptom after large losses of blood. In former days, when bloodletting
was practised as a remedial measure, imperfect knowledge of the mechanics
of the circulation sometimes caused life to be endangered ; for a "throbbing"
pulse in a patient who had been bled already was liable to be taken as an " in-

' From (7(pvy/u6c, pulse.
28

434 AX AMERICAN TEXT-BOOK OE PHYSIOLOGY.

dicatioii " lor the letting of more blood, i'i this were done, an eflot-t was
combated l>y repeatiniT its cause.'

Celerity of Stroke. — When each iip-stroke of the pulse appears to be
slowly accomplished, requiring a relatively long interval of tinif, the pulse
is called slow, or long. When each up-stroke ap|)ears to be (piickly accom-
plished, requiring a relatively short time, the pulse is called (juiek or short.
These contrasted qualities are among the mo.st obscure of those which the
skilled touch is called upon to appreciate.

The Pulse-trace. — The rise and fall of a j)ulsating human artery, if near
enough to the skin, may be made to raise and lower the recording lever of a
somewhat complicated instrument called a sphygmograph.- Of this instru-
ment a number of varieties are in use. If the fine point of the lever be kept
in contact with a piece of smoked paper which is in uniform motion, a "pulse-
trace " or " i)ulse-curve " is inscribed, which shows successive fluctuations,
larger and smaller, which tend to be rhythmically repeated, and Nvhich depend
upon tlie movements of the arterial wall produced by the fluctuations of blood-
pressure. In an animal, a manometer may be connected with the interi(jr of
an artery, and thus the fluctuations of the blood-pressure may be observed
more directly. It has been explained (p. 382) that the mercurial manometer
is of no value for the study of the finer characters of the pulse, owing to
the inertia of the mercury. On the other hand, the best forms of elastic
manometer give pulse-traces which are more reliable than those of the sphyg-
mograph. This is because the sphygmographic trace is subject to unavoid-
able errors dependent upon the physical (jualities of the skin and other
parts which intervene between the instrument and the cavity of the artery.
Nevertheless, the sphygmographic pulse-trace, or " sphygmogram," is the
only pulse-trace which can be obtained from the human subject; and, when
obtained from an animal, it has so much in common with the trace recorded
by the elastic manometer, that the sphygmograph has been much used for the
study of the human pulse, in health and disease, both by physiologists and by
medical practitioners. As a means of diagnosis, however, the sphygmogram
still leaves much to be desired. The same instrument, applied in immediate
succession to different arteries of the same person, gives, as might be expected,
pulse-traces of somewhat different forms. The same artery of the same per-
son yields to the same instrument at different times different forms of trace,
depending upon different physiological states of the circulation. But the same
artery yields traces of different form to sphygmographs of different varieties
applied to it in immediate succession ; and even moderate changes in adjust-
ment cause differences in the form of the successive traces which the same
instrument obtains from the same artery. It is no wonder, therefore, that
great care must be exercised in comparing sphygmogra)>hic observations, and
in drawing general conclusions from the information which they impart.

The Details of the Sphygmo^am. — Figure 111 is a fair example of

' Marshall Hall : Researches principally relative to the Morbid and Curative EffecU^ of Loss of
Blood, London, 1830. * From afvjfidr, pulse, and ypa<p£tv, to record.

CIRCLLA TION. 435

the sphygniograms commonly obtained from the healtliy human radial pulse.
"When this traee was taken, the sul.jc-t's heart was iKatin;^- from 58 to GU times

Fig. 111.— Sphygmograiii frmn a normal huiuau radial pulse beatiii),' from 5» to CO liines a minute. To be
read from left to right (Burdon-Sanderson).

a minute. The trace records the effects upou the lever of five successive com-
plete pulsations of the artery, which all agree in the general character of their
details, while differing in minor respects. By the tracing of each pulsation
the up-stroke is shown to be sudden, brief, and steady, wdiile the down-stroke
is gradual, protracted, and oscillating. The commencing recoil of the arterial
wall succeeds its expansion with some suddenness. In many sphygniograms
this is exaggerated by the inertia of the instrument. As shown by the trace rep-
resented in the figure, and by most such traces, the recoil soon changes from
rapid to gradual, and, in the trace, its protracted line becomes wavy, indicating
that the slow diminution of calibre varies its rate, or even is interrupted by one
or more slight expansions, before it reaches its lowest, and is succeeded by the
up-stroke of the next pulsation. In each of the five successive pulsations the
traces of which are shown in Figure 111, the line which represents the more
gradual portion of the down-stroke of the pulse is made up of three waves,
of which the first is the shortest, the last the longest and lowest, and the mid-
dle one intermediate in length, but by far the highest. This middle wave is,
in fact, the only one of the three to produce which an actual rise of pressure
occurs ; in each of the other two, no rise, but only a diminished rate of decline,
is exhibited. The changes of pressure which produce the first and third of
the waves just spoken of, in the pulse-trace under consideratioH, are very
obscure in their origin, and are inconstant in their occurrence, sometimes being
more numerous than in the trace shown in Figure 111, and sometimes failing
altogether to appear.

The Dicrotic Wave. — The oscillation of pressure, however, which i)ro-
duces the middle wave of each of the pulsations of Figure 111, is so constant
in its occurrence that it is undoubtedly a normal and important phenomenon,
although, in different sphygniograms, the height, and position in the trace, of
the wave inscribed by this oscillation may vary. Occasionally this oscillation
is morbidly exaggerated, so that it may be not only recorded by the sphygmo-
graph, but even felt by the finger, as a second usually smaller up-stroke of
the pulse. In such a case the artery is felt to beat twice at each single beat
of the ventricle, and is said, technically, to show a " dicrotic " ^ pulse. Where
a dicrotic pul.se can be detected by the finger, it is apt to accompany a mark-
edly low mean tension of the arterial wall. The dicrotic pulse was known,
and named, long before the sphygmograph revealed the fact that the pulse is
always dicrotic, although to a degree normally too slight for the finger to

^ From ^(KpoTOf, double-beating.

430 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

appreciate, Tlie yphygmograplii(! wave wliieli records the slight "diorotisin"
of the normal pulse is called the "dicrotic wave." Wliere dicrotism can be
felt by the finger, the sphygniograin naturally exhii)its a very conspicuous
dicrotic wave.

The origin of the dicrotic oscillation has been much discussed, and is not
yet thoroughly settled, important as a complete settlement of it would be to
the true interpretation and clinical usefulness of the sphygmogram. It is
believed by some that this fluctuation of pressure is produced at the smaller
arterial bi-aiiehes, as a reflection of the main pulse-wave, and that the dicrotic
wave, tiius reflected, travels toward the heart, and, naturally, reaches a given
artery after the main wave of the pulse has passed over it, travelling in the
opposite direction. The weight of opinion and of probability, however, is in
favor of the view that the dicrotic wave essentially depends upon a slight rise of
the arterial pressure, or slackening of its decline, due to the closing of the semi-
lunar valve ; and that, therefore, this wave follows the main wave of arterial
expansion outward from the heart, instead of being reflected inward from the
periphery. If the dicrotic wave be caused solely by reflection from the
periphery, it ought, in a sphygmogram from a peripheral arteiy, to begin at
a point nearer to the highest point of each pulsation than in the case of an
artery near the heart, in which latter vessel, naturally, a reflected wave would
undergo postponement. On the other hand, if the dicrotic wave be trans-
mitted toward the periphery, and caused solely by the closure of the aortic
valve, it ought, in a sphygmogram from a peripheral artery, to occupy very
nearly the same relative position as in a sphygmogram taken from an artery
near the heart. But a wave running toward the perijihery may be modified
by a reflected wave in the same vessel, and a reflected wave may undergo a
second reflection at the closed aortic valve, or even elsewhere, and thus give
rise to an oscillation which will be transmitted toward the periphery. These
statements show with what technical diflfieulties the subject is beset, whether
the sphygmograph be employed, or, in the case of animals, the elastic man-
ometer, the traces recorded by which also exhibit the dicrotic wave. As
already stated, however, the probabilities are in favor of the valvular origin
of the dicrotic wave.

If it be true that the closure of the aortic valve causes the dicrotic wave,
the instant marked by the commencement of this wave, in the manometric
trace inscribed by the pressure within the first part of tiie arch of the aorta
itself, practically marks the instant of closure of the aortic valve. We have
seen (p. 422) that this doctrine has been made use of in the elucidation of the
curve of the ])ressnrc within the ventricle.

The Diagnostic Limitations of the Sphygmogram. — The feeling of
the pulse, imperfect as is the most skilled touch, cannot be replaced by the
use of the sphygmograph. The presence, between the cavity of the artery
and the surface of the body, of a quantity of tissue the amount and elasticity
of which differ in different people, and even differ over neighboring points of
the same artery, renders it impossible so to adjust the spring of the sphygrao-

CIRCULATION. 437

graph as to be able to obtain a reliable base-line corresponding to the abscissa,
or line of atmospheric pressure, in the case of the inanonietric curve of blood-
pressuro. The effects produced by slight differences in the placing of the
instrument tend to the same result. \\y the absence of such a base-line the
sphygmographic curve is shorn of quantitative value as a curve of blood-
pressure, and cannot give information as to whether, in clinical language, the
pulse be hard or soft, large or small. Nor can a long or short pulse be iden-
tified from the appearance of the sphygmogram.' The pulse-trace still
requires much elucidation ; but when further study shall have rendered
clearer the true extent, the normal variations, and the causes of the complex
and incessant oscillations of the walls of the arteries, it may well be believed
that both physiology and ])ractical medicine will have gained an important
insight into the laws of the circulation of the blood.

P. The Movement of the Lymph.

The Lymphatic System. — The lymph is contained within the so-called
lymphatic system, the nature of which may be summarized as follows :

The lym])h appears first in innumerable minute irregular ga])s in the tis-
sues, which gaps con>municate in various ways with one another, and with
minute lymphatic vessels, which latter, when traced onward from their begin-
nings, presently assume a structure comparable to that of narrow veins with
very delicate walls and extremely numerous valves. These valves open away
from the gaps of the tissues, as the valves of the veins open away from the
capillaries. The lymphatic vessels unite to form somewhat larger ones, each
of which, however, is of small calibre as 'compared with a vein of medium
size, until at length the entire system of vessels ends, by numerous openings,
in two main trunks of very unequal importance, the thoracic duct and the
right lymphatic duct. The latter is exceedingly short, and receives the ter-
minations of the lymphatics of a very limited portion of the body ; the termi-
nations of all the rest, including the lymphatics of the alimentary canal, are
received by the thoracic duct, which runs the whole length of the chest.
Both of the main ducts have walls which, relatively, are very thin; and, like
the smaller lymphatics, the ducts are abundantly provided with valves so
disposed as to prevent any regurgitation of lymph from either duct into its
branches. Each duct terminates on one side of the root of the neck, where,
in man, the cavity of the duct joins by an open mouth the confluence of the
internal jugular and subclavian veins where they form the innominate vein.
At the opening of each duct into the vein a valve exists, which permits the
free entrance of lymph into the vein, but forbids the entrance of blood into
the duct.

It is a peculiarity of the lymphatic system that some of its vessels end and
begin by open mouths in the so-called serous cavities of the body — those vast
irregular interstices between organs the membranous walls of which interstices
are known as the peritoneum, the pleurae, and the like. For present purposes,

' M. von Frey : Die ZJntersncJmng dea PuJsrf, l.'^92, p. So.

438 AX AMERICAN TEX2-B00K OF PHYSIOLOGY.

therefore, these serou.s cavities may be regarded as vast local exj)ausioiis of
portions of the lyinph-])ath. Another j)eeuliarity of the lyinpiiatie system de-
pends upon the presence of the lym])hatic glands or ganglia, which also are
intercalated here and there between the mouths of lymj)hatic vessels which
enter and leave them. The nature and importance of these bodies have been
dealt with in dealing with the origin of the leucocytes and the nature of the
lymph (p. 345). For the present purposes the ganglia are of interest in this,
that the lymph which traverses their texture meets, in so doing, with much
resistance from friction. Physiologically, therefore, the lymph-path as a whole,
extending from the tissue-gaps to the veins at the root of the neck, both differs
from, and in some respects resembles, the blood-path from the capillaries to the
same point.

The origin of the lymph has been discussed already (p. 362), and has been
found to be partly from the i:)lood in the capillaries, and partly from the tis-
sues, to say nothing of the products directly absorbed from the alimentary
canal during digestion. The quantity of material which leaves the lymph-jiath
and enters the blood during twenty-four hours is undoubtedly large, amount-
ing, in the dog, to about sixty cubic centimeters for each kilogram of body-
weight. The movement of the lymph is, therefore, of physiological import-
ance ; and the causes of this movement must now be considered.

Absence of Lymph-hearts. — It is a striking fact that, in man and the
other mammals, there exist no "lymph-hearts" for the maintenance of the
lymphatic flow. Unstriped muscular fibres, indeed, exist in the walls of the
lymphatics; and rhythmical variations in the calibre of some of these hav^e
been described. It remains doubtful, however, whether these variations, when
present, are produced by muscular contractions in the walls of the lymphatics,
or whether the muscular fibres exist in these, as in the blood-vessels, rather
for the regulation of their calibre than for the propulsion of their contents.
It is not improbable that the muscular fibres of the walls of the lymphatics
further resemble those of the blood-vessels in being under the control of the
nervous system; and it has been shown that, in the splanchnic nerve of the
dog, there exist centrifugal fibres, stimulation of which produces dilatation of
the receptaculum chi/li?

Differences of Pressure. — The fundamental causes of the movement of the
lymph are, that at the beginning of its path in the gaps of the tissues it is
under considerable pressure ; that at the end of its path at the veins of the
neck it is under very low pressure, which often, if not usually, is negative;
and that, throughout the lymph-path, the valves are so numerous as to work
effectively against regurgitation. The pressure of the lymph in the gaps of
the tissues has been estimated at one half, or more, of the capillary blood-
pressure,* which latter has been stated (p. 376) to be from 24 to 54 millimeters

' L. Camus et E. (ilev: " Recherches .exp^rimentales sur les nerfs des vaisseaux lymph-
atiques," Archives de physiologie normale et pathologique, 1894, p. 454.

' A. Landerer : Die Gewebsspannung in ihrem Einfluss auj die ortliche Blui- und Lymphbeuegung,
Leipzig, 1884, p. 103.

VIRVVLATION. 439

of niercurv. Tlic {lifrerenee between one half of either of these pressures and
the prcssni-e in the veins of the neck, which pressure is not far from zero, is
quite enough to produce a How from the one point to the other. To this flow
a resistance is caused by tiie friction ah)ug the lymph-path, which resistance
causes the lymph to accumulate in the gaps of the tissues, and the pressure
there to rise, until the tension of the tissues resists further accumulatiou more
forcibly than friction resists the onward movement of the lymph. The little-
known forces which continually produce fresh lymph, and ])our it into the
tissue-gaps against resistance, cannot be discussed here further than has been
done in treating of the origin of the lymph (p. 362).

Thoracic Aspiration. — The causes have already been stated fully of that
low, perhaps negative, pressure in the veins at the root of the neck which ren-
ders possible the continuous discharge of the lymph into the blood (p. 387).
It need only be noted here that when inspiration rhythmically produces, or
heightens, the suction of blood into the chest, it must also produce, or heighten,
the suction of lymph out of the mouths of the thoracic and right lymphatic
ducts. Moreover, as the thoracic duct lies with most of its length within the
chest, each expansion of the chest must tend to expand the main part of the
duct, and thus to suck into it lymph from the numerous lymphatics which
join the duct from without the chest ; while the numerous valves in the duct
must promptly check any tendency to regurgitation from the neck.

The Bodily Movements and the Valves. — Like the flow of the blood in
the veins, the flow of the lymph in its vessels is powerfully assisted by the
pressure exerted upon the thin-walled lymphatics by the contractions of the
skeletal muscles ; for the very numerous valves of the lymphatics render it
impossible for the lymph to be pressed along them by this means in any other
than the physiological direction toward the venous system. Experiment shows
that even passive bending and straightening of a limb in which the mus-
cles remain relaxed, increases to a very great extent the discharge of lymph
from a divided lymphatic vessel of that limb. It is probable, therefore,
that movement in any external or internal part of the body, however pro-
duced, tends to relieve the tension in the tissues by pressing the lymph along
its path.

Conclusion. — The movement of the lymph produced in these various ways
is doubtless irregular ; but a substance in solution, injected into the blood, can
be identified in the lymph collected from an opening in the thoracic duct at
the neck in from four to seven minutes after the injection.^ The physiological
importance of the lymph-movement is shown not only by the large amount
of matter which daily leaves the lymphatic system to join the blood, but also
by the evil effects which result from an undue accumulation of lymph, more
or less changed in character, in the gaps of the tissues. Such an accumulation
constitutes dropsy. It may occur in a serous cavity or in the subcutaneous
tissue; in the latter case giving rise to a peculiar swelling which "pits on

* S. Tschirwinsky : " Zur Frage uber die Schnelligkeit des Lymphstromes und der Lymph-
filtration," Centrcdblatt fiir Physiologic, 1895, Band ix. p. 49.

440 .i.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

pressure." Auy tissue the meshes of which are thus engorged with lymph is
said to be " a'dematous." '

PART II.— THE INNERVATION OF THE HEART.

It has long been known that tlie frog^s heart can be kept beating for many
hours after it;? removal from the body. In 1881, Martin^ succeeded in main-
taining the beat of the dog's iieart after its complete isolation from the central
nervous system and the systemic blood-vessels. Ludwig and his pupils^ have
attained the same result in a different way. In 1895, Langendorff^ was able
by circulating warmed oxygenated, defibriuated blood through the coronary
vessels to maintain the hearts of rabbits, cats, and dogs in activity after their
total extirpation from the body. It is evident, thr-refore, that the cause of the
riiythmic beat of the heart lies within the heart itself, and not within the cen-
tral nervous system.

Cause of Rhythmic Beat. — It has been nmch disjjuted whether the car-
diac muscle possesses the power of rhythmical contraction or whether the
rhythmic beat is due to the periodic stimulation of the muscle by the discharge
of nerve-impulses from the ganglion-cells of the heart. The arrangement of
the ganglion-cells and nerves suggests the latter view.

The Intracardiac GangUon-cells and Nerves. — In the frog the cardiac nerves
arise by a single branch from each vagus trunk and run along the great veins
through the wall of the sinus venosus, wiiere many ganglion-cells are found,^
to the auricular septum. Here they unite in a strong plexus richly provided
with ganglion-cells.® Two nerves of unequal length and thickness leave this
plexus and pass along the borders of the septum to the auriculo-ventricular
junction, where each enters a conspicuous mass of cells known as Bidder's
ganglion.^ Ventricular nerves spring from these ganglia and can be followed
with the unaided eye some distance on the ventricle. With the chloride-of-
gold method, the methylene-blue stain, and especially the nitrate-of-silver im-
pregnation, the ventricular nerves can be traced to their termination. Some
difference of opinion exists regarding the manner of their distribution and the
precise nature of their terminal organs. The following fiicts, however, may be
considered established both for the batrachian and the mammalian heart.^

The ventricular nerves form a rich plexus beneath the pericardium and
endocardium. Branches from these plexuses form a third plexus in the myo-
cardium or heart nuiscle, from which arise a vast number of non-medullated

' From ohiijiia, a swelling. * Martin, 1S81, p. 119.

» Stolnikow, 18S6, p. 2; Pawlow, 1887, p. 452.

* Langendortt; 1895, p. 293: also >rartin and Applegarth, 1890, p. 275; Aniaiid, 1S91, p.
396; H^on and Gilis, 1892, p. 760; Porter, 1896, p. 39. * Remak, 1844, p. 463.

6 Ludwig, 1848, p. 140. ' Bidder, 1852, p. 169.

* The literature of this subject has been collected by Jacques (1894, p. 622; and 1896,
p. 517) and by Heymans and Demoor (1895, p. 619). For the development of the cardiac
nervous system in different classes of vertebrates, see His, Jr., 1891, pp. 1-64 ; compare His
and Romberg, 1890, pp. 374 and 416.

CIRCULATION. 441

terminal nerves, enveloping the muscle-fibres and ending in small enlargements
or nodosities of various forms. Similar " varicose" enlargements are observed
along the course of the nerves. The nerve-endings are in contact with the
naked muscle-substance, the mode of termination resembling in general that
observed in non-striated muscle. Ganglion-cells are found chiefly in the
auricular septum and the auriculo-vcntricular furrow, but are present also
beneath the pericardium of the upper half of the ventricle. Xo ganglia have
as yet been satisfactorily demonstrated within the apical hall" of the ventricle,
and most observers do not admit their presence within the ventricular nmscle
itself.* The nerve-cells are unipolar, bipolar, or multipolar.

Certain unipolar cells in the frog are distinguished by a spherical form, a
pericellular network, and two processes — namely, the axis-cylinder or straight
process, and the spiral {)rocess. The latter is wound in sj)iral fashion ab(jut
the axis-cylinder, ending in the pericellular net. According to Retzius and
others, the spiral is not really a process of the cell, but arises in a distant extra-
cardiac cell and carries to the heart-cell a nervous impulse which is transmitted
from the spiral })rocess to the cell by means of the contact between the peri-
cellular net and the cell-body. Section of the cardiac fibres of the vagus
causes the spiral " process " and pericellular net to degenerate, the cell-body
and axis-cylinder process remaining untouched, showing that the spiral process
is the terminal of a nerve-fibre running in the vagus trunk.^

Xerve-theory of Heart-beat. — The theory of the nervous origin of the
heart-beat rests in part on the correspondence between the degree of contrac-
tility of the various parts of the heart and the number of nerve-cells present
in them. Thus the power of rhythmical contraction is greater in the auricle,
in which there are many cells, than in the ventricle, in which there are fewer.
The properties of the apical half, or " apex," of the ventricle are considered
to be of especial importance in the study of this problem, because the apex, as
has been said, is believed to contain no ganglion-cells. This part of the ven-
tricle stops beating when separated from the heart, while the auricles and the
ventricular stump continue to beat. The apex need not be cut away in order
to isolate it. By ligating^ or squeezing the frog's ventricle across the middle
with a pair of forceps the tissues at the junction of the upper and the lower
half of the ventricle can be crushed to the point at which physiological con-
nection is destroyed but physical continuity still preserved.* Such frogs have
been kept alive as long as six weeks. The apex does not as a rule beat again.^
The exceptions can be exj)lained as the consequence of accidental stimulation.
The conclusion draw'n is that the apex, in which ganglion-cells have not been
satisfactorily demonstrated, has not the power of spontaneous pulsation which

^ For contrary opinion see Tnniiinzew and Dogiel, 1890, p. 494, and Berkeley, 1894, p. 90;
also the very beautiful plates of Lee, 1849, p. 43, showing subpericardial nerves and ganglia (?)
in the calf's heart.

^ Nikolajew, 1893, p. 73. ^ Heidenhain, 1854, p. 47.

* Bernstein, 1876, p. 386; Bowditch, 1879, p. 105.

5 Bowditch, 1871, p. 169 ; Merunowicz, 1875, p. 132; Bernstein, 1876, pp. 386, 435; Bowditch,
1879, p. 104 ; Aubert, 1881, p. 362 ; Ludwig and Luchsinger, 1881, p. 231 ; Langeudorff, 1884, p. 6.

442 AjV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

distinguislies the remainder of the lieart. This view is further .supported by
the observation that a slight stimulus applied to the base of a resting ventricle
M'ill often provoke a series of contractions, wliilc the same stinndus applied to
the apex will cause but a single contraction.'

The action of muscariu on the heart is often luld to indicate the nervous
origin of the heart-beat. Mu.scarin arrests the heart of the frog and other
vertebrates, but has no similar action on any other muscle either .striped or
smooth, nor does it arrest the heart of insects and mollusks. It follows that
rauscarin does not cause arrest by acting directly upon the contractile material
of the heart. The contractile material being excluded, the a.ssumption of a
nervous mechanism on the integrity of which the heart-beat depends seems
necessary to explain the effect of the poison.^

Further arguments are based on uncertain analogies between the heart and
othei' rhythmically contracting organs.

Muscular Theory of Heart-beat. — The evidence just stated cannot be re-
garded as proof of the nervous origin of the heart-beat. The most that can
be claimed is that it makes such a conception plausible. Even this claim has
been denied by not a few investigators who believe that the heart-beat is a
purely muscular phenomenon. Here again the properties of the apex are con-
sidered to be of the first importance. It has been shown that a strip of muscle
cut from the apex of the tortoise ventricle and suspended in a moist chamber
begins in a few hours to beat apparently of its own accord with a regular but
slow rhythm, which has been seen to continue as long as thirty hours. If the
strip is cut into pieces and placed on moistened glass slides each piece will con-
tract rhythmically.^ Yet in the apex of the heart no nerve-cells have been found.

The apex of the batrachian heart will beat rhythmically in response to a
constant stimulus. Thus if the apex is suspended in normal saline solution
and a constant electrical current kept passing through it, beats will appear
after a time, the frequency of pulsation increasing with the strength of the
current.^ Very strong currents cau.se tonic contraction. An apex made inac-
tive by Bernstein's crushing can be made to beat again by clamping the aorta
and thus raising the endocardiac pressure,* Chemical stimulation is also effect-
ive. Delphinin,* quinine,^ mu.scarin with atropin,^ atropin alone,' morphin
and various other alkaloids, dilute mineral acids, dilute alkalies, bile, .sodium
chloride, alcohol, and other bodies,'" when painted on the resting ventricle, call
forth a longer or shorter series of beats. Stimulation with induction shocks
gives a similar result."

• Scherhey, 1880, p. 260. ^ Ciishny, 1893, p. 451. » Gaskell, 1883, p. 54.

* Bernstein, 1871, p. 230 ; Foster and Dewsmitli, 1876, p. 737 ; von Basch, 1879, p. 71 ; Scher-
hey, 1880, p. 259; Langendorff. 1895, p. 336; Kaiser, 1895, p. 464.

^ Gaskell, 1880, p. 51 ; Aubcrt, 1881, p. 366; Liidwig and Luchsinger, 1881, p. 231 ; Dastre,
1882, p. 458: Biedermann, 1884, p. 24; Langendorff, 1884, p. 6.

« Bowditch, 1871, p. 169. ' Schtschepotjew, 1879, p. 56. « v. Basch, 1879, p. 73.

9 Lowit, 1881, p. 447. >» Langendorff, 1884, p. 21 ; 1895. p. 333; Kaiser, 1895, p. 6.

" Bowditch, 1871, p. 149; Kronecker, 1875, p. 178; 1879, p. 381; 1880, p. 285; v. Basch,
1879, p. 71 ; Ranvier, 1880, p. 46; Dastre, 1882, p. 433; Gaskell, 1883, p. 52.

CIBCULA TION. 443

Other muscles iu wliicli no nerve-cells have heeu discovered can contract
rhythmically. Tiius the hulbus aortaj of the frog beats regularly after its
removal from the body, even the smallest pieces showing under the microscope
rhvthmical contractions. Engelmann, who observed this fact, declares that
the entire bulbus is lacking in nerve-cells. This is contradicted by Dogiel ;
yet it seems hardly reasonable that these "smallest pieces" which Engelmann
mentions were each provided with ganglion-cells. It is more probable that the
contractions were the result of a constant artificial stimulus.^ Curarized stri-
ated muscles placed in certain saline solutions may contract from time to time.^
The hearts of many invertebrates in which ganglion-cells are apparently absent
beat rhythmically.^

Much has been made of the fact that the ganglion-cells grow into the heart
long after the cardiac rhythm is established/ showing that the embryonic heart
muscle has rhythmic contractile powers. The adult heart muscle, it is alleged,
retains certain embryonic peculiarities of structure, and as structure and func-
tion are correlated, should also retain the embryonic power of contraction
■without nerve-cells.^

It cannot be denied that these facts prove that the embryo heart muscle
possesses rhythmic contractility, that the apical half of the heart of the adult
frog and tortoise may be made to contract rhythmically, and that even fully
striated muscle will under some conditions show more or less periodic contrac-
tions. They can, however, hardly be said to prove that the beat of the mam-
malian or even the batrachian adult heart is not dependent on discharges from
the cardiac nerve-cells. Even the freedom of the apex from ganglion-cells,
which is the very foundation of the doctrine of muscular origin, has recently
been questioned.^ This problem is still unsolved.

The Excitation-wave. — The change in form which constitutes what com-
monly is called the cardiac contraction is preceded by a change in electrical
potential, supposed to be a manifestation of the unknown process by which the
heart-muscle is excited to contract. Both the contraction and the electrical
change sweep over the heart in the form of waves, and it has become the cus-
tom to speak of the electrical change as the excitation-wave. It should not be
forgotten, however, that this usage rests merely on an assumption, for the real
nature of the excitation is still a mystery. The contraction-wave begins nor-
mally at the great veins, travels rapidly through the auricle, and, after a dis-
tinct interval, spreads through the ventricle. The excitation-wave, which pre-
cedes and is the cause of the contraction, probably takes the same course,^ and
in fact it is possible to show that the change in electrical potential actually
begins under normal conditions at the great veins and passes thence over the
entire heart. But this sequence is not invariable. The ventricle under abnor-

1 Engelmann, 1882, p. 446; Dogiel, 1894, p. 225. ^ Biedermann, 1880, p. 2-59.

^ Concerning the cardiac apex in fishes, see Ludwig and Luchsinger, 1881, p. 247; Kazem-
Beck and Dogiel, 1882, p. 259 ; McWilliam, 1885, p. 197 ; Mills, 1886, p. 91.

* Wagner, 1854, p. 227 ; Schenck, 1867, p. Ill ; His, Jr., 1893, p. 25; Pickering, 1893, p. 391.

* Gaskell, 1883, p. 77. « Berkeley, 1894, p. 90. ' Compare Kaiser, 1895, p. 447.

444 AlV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

mal couditions has been seen to contract before the auricle, the normal sequence
of great veins, auricle, and ventricle being reversed.' The energy of the ven-
tricular muscle-cell may, therefore, be discharged by an excitation arising
within the ventricle itself. Evidence of this is afforded also by the experi-
ment of Wooldridge,^ who isolated the ventricles by drawing a silk ligature
tightly about the auricles at their junction with the ventricles, completely
crushing the muscle and nerves of the auricle in the track of the ligature with-
out tearing through the more resistant pericardium. This experiment was
rejwated the following year by Tigerstedt,' wiio devised a special clamp for
crushing the auricular tissues. Both observers found that the auricles and
ventricles continued to beat. The rhythm, however, was no longer the
same. The ventricular beat was slower than before * and was independent of
the beat of the auricle. Thus the ventricle, no longer connected physiologically
with the auricle, develops a rhythm of its own, an idio-ventricular rhythm. It
seems improbable that tlie very small part of the auricular tissue which cannot
be included in Wooldridge's ligature for fear of closing the coronary arteries
should be able to maintain the ventricular contractions.

Independent contraction is said to be secured by properly regulated excita-
tion of the cardiac end of the cut vagus nerve. Stimuli of one second duration
applied to the vagus at intervals of six to seven seconds arrest the auricles
completely, but do not stop the ventricles, except during the second of stimu-
lation. The ventricles, now dissociated from the auricles, beat with a rhythm
diiferent from that which characterized the normal heart,^ The force of this
demonstration is somewhat weakened by the possibility that the auricles,
although not beating themselves, might still excite the ventricles to contraction.

Conduction of the Excitation. — If the points of non-polarizable electrodes
are placed on the surface of the ventricle and connected with a delicate galvan-
ometer, a variation of the galvanometer needle will be seen with each ventric-
ular beat. If one electrode is placed near the Irase of the heart and the other
near the apex it is seen that the former electrode becomes negative before the
latter, indicating that the part of the heart muscle on which the basal electrode
rests is stimulated before the apical portion, and that the ditferenee in electrical
potential, or excitation-wave, according to the prevailing hypothesis, travels as
a wave over the ventricle from the base to the apex (see Fig. 112). Burdon-
Sanderson and Page^ have found that the duration of the ditferenee of poten-
tial is about two seconds in the frog's heart at ordinary temperatures. Cooling
lengthens the period of negativity, warming diminishes it. Some observers

' Recently studied by Engelmann, 1895, p. 275; see also Knoll, 1894, p. 306, who observed
fibrillary contraction of the auricle coincident with strong co-ordinated contractions of the ven-
tricles.

* Wooldridge, 1883, p. 527.

' Tigerstedt, 1884, p. 500; see also Krehl and Romberg, 1892, p. 54.

* The isolated ventricle may, however, beat as rapidly as the auricle, although independ-
ently of it (Bayliss and Starling, 1892, p. 408).

* Roy and Adami, 1892, p. 236; see also Knoll, 1884, p. 312.

* Burdon-Sanderson and Page, 1884, p. 338.

CIRCULA TION.

445

believe that the excitation-wave under certain conditions returns toward the
base after havinj^ reached the apex.' The sjieed of the excitation-wave has been
measuretl by the interval between the appearance of nei^ative variation in the
ventricle when the auricle is stimulated first near and then as far as possible

Fig. 112.— The electrical variation in the spontaneou.sly contracting heart of the frog, recorded by a
capillary electrometer, the apex being connected with the sulphuric acid and the base with the mercury
of the electrometer. The changes in electrical potential are shown by the line e, e, which is obtained by
throwing the shadow .of the mercury in the capillary on a travelling sheet of sensitized paper. The con-
traction of the heart is recorded by the line h, h ; time, in j'j second, by t, t. The curves read from left
to right. The electrical variation is diphasic ; in the first phase the base is negative to the apex ; in the
second, the apex is negative to the base ; the negative variation passes as a wave from base to apex
(Waller, 1887, p. 231).

from the non-polarizable electrodes. The interval is the time which the excita-
tion-wave requires to pass the distance between the two points stimulated. The
average rate is at least 50 millimeters per second.^ The negative variation
begins apparently instantly after the application of the stimulus. Its phases
and their characteristics have been described by Engelmann.^
The latent period of a frog's heart muscle is about 0.08 .second.*
Although the normal course of the excitation-wave is from base to apex, it
can be made to travel in any direction. If the frog's ventricle is cut with fine
scissors into a number of pieces in such a way as to leave small bridges of
heart-tissue between each piece, and any one of the pieces is stimulated, the
contraction will begin in the stimulated piece and then run from piece to piece
over the connectino- bridg-es until all have successively contracted. The direc-
tion in which the excitation-wave travels can thus be altered at the pleasure
of the operator.^

Whether the excitation is propagated from muscle-cell to muscle-cell or by
means of nerve-fibres has given rise to much discu.ssion. Anatomical evidence
can be adduced on both sides. On the one hand the rich plexus of nerve-
fibres everywhere present in the heart-muscle suggests conduction through
nerves ; on the other is the intimate contact of neighboring mu.scle-cells over

' Bayliss and Starling, 1892, pp. 260, 380.

2 Engelmann, 1878, p. 91 ; Burdon-Sanderson and Page, 1880, p. 426, give 150 millimeters
per second.

^ Engelmann, 1878, p. 74. * Ibid., 1874, p. 6.

* Ibid., p. 3; compare Bayliss and Starling, 1892, p. 262.

446 AN AMERICAN Ti: XT- HOOK OF PIIVSIOLOGY.

a part at least of their surfaee, thus hriiiging one mass of irritable protoplasm
against another ant.! ofTering a ])ath by whieh the excitation might travel from
cell to cell.*

If the excitation-wave were conducted by means of nerves, the difi'ereuce
between the moment of contraction of the ventricle when the auricle is stimu-
lated near the ventricle, and again as far as possible from the ventricle, should
be very slight, because of the gt-eat speed at which the nervous impulse travels
(about 33 raetei*s per second). If, on the contrary, the conduction were by
means of muscle, the difference would be relatively much greater, correspond-
ing to the much slower conductivity of muscular tissue. It has been found by
Engfelmann that the ventricle contracts later when the auricle is stimulated far
from the ventricle than when it is stimulated near the ventricle. The rate of
propagation being calculated from the dilference in the time of ventricular con-
traction was found to be 90 millimeters per second, which is about 300 times
less than the rate which would have been obtained had conduction over the
measured distance taken place through nerves.^ Hence the stimulus that trav-
els through the auricle to the ventricle and causes its contraction should be
propagated in the auricle by muscle-fibres and not by nerves.

Passage of Excitation-wave from Auricle to Ventricle. — The normal con-
traction of the heart begins, as has been said, at the junction of the great
veins and the auricle, spreads rapidly over the auricle and, after a distinct
pause, reaches the ventricle. The normal excitation-wave preceding the con-
traction passes likewise from the auricle to the ventricle and is delayed at or
near the auriculo- ventricular junction. The controversy over the nerv^ous or
muscular conduction of the excitation within the auricle and ventricle has
been extended to its passage from auricle to ventricle. A path for conduction
by nerves is presented by the numerous nerves which go from the auricle to
the ventricle. It has been shown recently that nuiscular connections also
exist.^ In the frog, muscle-bundles pass from the auricle to the ventricle
where the auricular septum adjoins the base of the ventricle. Muscular
bridges pass also from the sinus venosus to the auricles and from the ventricle
to the bulbus arteriosus.^ These muscle-fibres appear to be in intimate con-
tact with the muscle-cells of the divisions of the heart which they unite. Gas-
kell ^ believes that the connecting fibres are morphologically and physiologically
related to embryonic muscle, and therefore possess the power of contracting
rhythmically.

The delay experienced by the excitation in its passage from the auricle to
the ventricle — in other words, the normal interval between the contrac^tion of
the auricle and the contraction of the ventricle — is explained by those favoring

^ Engelmann, 1874, p. 7.

' Ibid., 1894, p. 188; 1890, p. 549; the measurements of Bayliss and Starling', 1892. p. 271,
on the mammalian heart are probably of little value because of the variation due to tempera-
ture (p. 272). See also Kaiser, 1895, p. 2, and Enselmann's reply, 1890, p. 547.

^Paladino, 1876; Gaskell, 1880, p. 70; Krehl and Komberg, 1892, p. 71 ; Kent, 1893, p.
240; Engelmann, 1894, p. 158.

* Engelmann, 1894, p. 158. » Gaskell, 1883, p. 77.

CIBCULA TION. 447

the nervous conduction as the delay wliidi the excitation experiences in dis-
charging the ganglion-cells of the ventricle, in accordance with the well-known
hypotheses of" the retardation of the nerve-impulse in sympathetic ganglia
and the slow passage of the nervous impulse through spinal cells.

The explanation given by those who believe in muscular conduction is that
the small number of nuiscular fibres composing the bridge between auricle
and ventricle acts as a " block " to the excitation-wave. If the auricle of the
tortoise heart is cut into two pieces connected by a small bridge of auricular
tissue, the stimulation of one piece will be followed immediately by the con-
traction of that piece, and after an interval by the contraction of the other.
The smaller the bridge, the longer the interval ; that is the longer the excita-
tion-wave will be in passing from one piece to another.^

The duration of the pause or " block " in the frog has been found to be from
0.15 to 0.30 second. The length of the muscle-fibres connecting auricle and
ventricle is about one millimeter. The speed of the excitation-wave in em-
bryonic heart muscle is from 3.6 to 11.5 millimeters per second. The duration
of the pause agrees, therefore, with the time which would be required for
muscular conduction.^

The extensive extirpations of the auricular nerves which have been made
without stopping conduction from auricle to ventricle ^ — for example, the ex-
tirpation of the entire auricular septum of the frog's heart — are of little
importance to this question, since the great number of nerve-cells revealed by
recent methods make it improbable that any extirpation short of total removal
of both auricles could cut off all the nerve-cells of the auricle.

Refractory Period and Compensatory Pause. — SchiflF* found in 1850
that the heart which contracted to each stimulus of a series of slowly repeated
mechanical stimuli would not contract to the same stimuli if they followed each
other in too rapid succession. Kronecker' got a similar result with induction
shocks. The heart contracted to every stimulus only when the interval between
them was not too brief. The following year Marey^ published a systematic
study of the phenomenon. He observed that the irritability of the heart sank
during a part of the systole, but returned during the remainder of the systole
and the following diastole.'^ The stimulus which fell between the beginning of
the systole and its maximum produced no extra contraction, whilst that which
fell between the maximum of one systole and the beginning of the next
called forth an extra contraction. During a part of the cardiac cycle therefore
the heart is " refractory " toward stimuli. The irritability of the heart is
removed for a time by an adequate stimulus.

Kronecker and Marey noticed further that stimulation with the induction
shock during the non-refractory period did not influence the total number of
systoles. The extra systole called forth by the artificial stimulus was followed
by a pause the length of which was that of the normal pause plus the interval

1 Gaskell, 1883, p. 64. '' Engelmann, 1894, p. 159.

^ Gaskell, 1883, p. 75; HoflFmann, 1895, p. 169. * Schiff, 1850, p. 50.

* Kronecker, 1875, p. 181. « Marey, 1876, p. 73. ' Cf. Engelmann, 1895, p. 313.

448 A!^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

between the appearance of the extra systole and what would have been the end
of the cardiac cycle in which the extra systole fell. The extra length of this
pause restored the normal frequency or rhythm. It was called the conij)ensa-
tory pause (see Fiij. 1 13).

Fig. 113.— The refractory period aiul compensatory pause. The curves are rccorrtefi by a writinfr lever
resting on the ventricle of the frog's heart. They read from left to right. A break in the horizontal line
below each curve indicates the moment at which an induction shock was sent through the ventricle. In
curves 1, 2, and .3 the ventricle proved refractory to this stimulus ; in the remaining curves, the stimulus
having fallen outside ihe refractory period, an extra contraction and compensatory pause are seen.
Many of the phenomena mentioned in the text are illustrated by this figure (Marey, 1876, p. 72).

If the heart, or the i.solated apex, is beating at a rate so slow that an extra
contraction falling in the interval between two normal contractions has time to
complete its entire phase before the next normal contraction is due, there will
be no compeu.satory pause.'

The refractory pha.se di.sapj>ears with sufficiently strong .stimuli, e.-jpecially
if the heart is warmed.'"^ In such a case an artificial stimulus falling in the
beginning of a spontaneous contraction produces an extra contraction. This
extra contraction, however, comes first after the end of the .systole during which
the artificial .stimulation is made,^ occurring in fact tt)ward the end of the

' Kaiser, 1895, p. 449.

* Engelmann, 1882, p. 453; compare Bnrdon-Sanderson and Page, 1880, p. 401.
' This is apparently true only of the whole heart, and not of the isolated apex (Engel-
mann, 1>^95, p. .317).

CIRCULA TION. 449

followiiif; diastole. The latent period of" such a contraction lengthens with
the length of the interval between the artificial stimulation and the end of the
systole.

A refractory period has been demonstrated in the auricle of the frog ' and
dog;- in the ventricle of the cat,'' rabbit and dog/ and in the sinus venosus'
and bulbu.s arteriosus " of the frog.

In some cases, the extra stimulus provokes not merely one, but two or three
extra contractions.^

The amplitude of the extra contraction increases with the length of the
interval between the maximum of contraction and the extra stimulus. If the
extra stimulus is given at the beginning of relaxation, the extra contraction is
exceedingly small ; on the other hand, the exti^a contraction may be greater
than the primary one, when the stimulus falls in the pause between two normal
beats.*

The supplementary systole of the auricle is sometimes followed by a sup-
plementary systole and compensatory pause of the ventricle, sometimes by the
compensatory pause alone, probably because the excitation wave reaches the
ventricle during its refractory period,' Multiple extra contractions of the
auricle are often followed by the same number of extra contractions of the
ventricle.^" If the frog's heart is made to beat in reversed order, ventricle
first, auricle second, extra contractions of the ventricle may be produced, and
will cause extra contractions of the auricle with compensatory pause. If the
reversed excitation wave travelling from the ventricle to the auricle reaches
the latter during auricular systole, the extra auricular contraction is omitted,
but a distinct though shortened compensatory pause is still observed. The
phenomena with reversed contraction are therefore similar to those seen under
the usual conditions."

Kaiser '- finds in frogs poisoned with muscarin that stimulation of the ven-
tricle during the refractory period causes the contraction in which the stimulus
falls to be more complete, as shown by the contraction curve rising above its
former level. He concludes that the ventricle is not wholly inexcitable even
during the refractory period.

The question whether the refractory state and compensatory pause are
properties of the muscle-substance or of the nervous system of the heart has
excited considerable attention. If the ganglion-free apex' of the frog's ven-
tricle is stimulated by rapidly repeated induction shocks it can be made to con-
tract periodically for a time. By momentarily increasing the strength of any
one induction shock an extra stimulus can be given from time to time. When

1 Hiklebrand, 1877, quoted by Lov^n, 1886, p. 5 ; Brnnton and Cash, 1883, p. 461 ; Kaiser,
1895, p. 15; Engelmann, 1895, p. 322. '^ Meyer, 1893, p. 185.

3 McWilliam, 1888, p. 169. * Gley, 1889, p. 501 ; 1890, p. 437.

5 Stromberg and Tigerstedt, 1888, p. 26 ; Brunton and Cash, 1883, p. 463.
« Engelmann, 1882, p. 453.

' Hildebrand, 1877; Stromberg and Tigerstedt, 1888, p. 33; Meyer, 1893, p. 187.
» Stromberg and Tigerstedt, 1888, p. 36. ' Kaiser, 1895, p. 16.

»» Mever, 1893, p. 188. " Kaiser, 1895, p. 19. '* Ihid., 1892, p. 219.

4o0 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the extra stimulus falls after the cuutraetion luaxiiuuui or during diastole an
extra contraction results, otherwise not. The refractory period exists, there-
fore, indei)endent]y of the cardiac ganglia/

The con)])ensatory pause can also, though not always, be secured with the
ganglion-free apex.'^

The refractory period has been used to show how a contijuious stinuilus
might produce a rhythmic heart-beat. The continuous stimulus cannot affect
the heart during tlie refractory period from the beginning to near the maxi-
mum of systole. At the close of the refractory period the constant stimulus
becomes effective, causing an extra contraction with long latent period. This
latent period is, according to this theory, the interval between the first and the
second contraction.^

A tonic contraction of the heart muscle is sometimes produced by strong,
rapidly repeated induction shocks* and by various other means, such as filling
the ventricle with old blood,^ by weak sodium hydrate solution,* and by certain
poisons, such as digitalin and voratrin,^

A. The Cardiac Nerves.

The cardiac nerves are branches of the vagus and the sympathetic nerves.

In the dog the vagus arises by about a dozen fine roots from the ventro-
lateral aspect of the medulla and passes outward to the jugular foramen in
company with the spinal accessory nerve. In the jugular canal the vagus
bears a ganglion called the jugular ganglion. The spinal accessory nerve
joins the vagus here, the spinal portion almost immediately leaving the vagus
to be distributed to certain muscles in the neck, while the medullary portion
passes to the heart through the trunk ganglion and thereafter in the substance
of the vagus. Directly after emerging from the skull, the vagus presents a
second ganglion, fusiform in shape and in a fairly large dog about one centi-
meter in length. From the caudal end or middle of this " ganglion of the
trunk " is given off" the superior laryngeal nerve, slightly behind which a
large nerve is seen passing from the sympathetic chain to the trunk of the
vagus. This nerve is in reality the main cord of the sympathetic chain, the
sympathetic nerve being bound up with the vagus from the " inferior" cervical
ganglion to the point just mentioned. Posterior to the trunk ganglion of the
vagus, the vago-sympathetic runs caudalward as a large nerv^e dorsal to the
common carotid artery as far as the first rib or near it, where it enters the
so-called inferior cervical ganglion. This ganglion belongs to the sympathetic
system and not to the vagus ; from a morphological point of view it is the
middle cervical sympathetic ganglion. The true inferior cervical sympathetic

' Dastre, 1882, p. 447 ; Kaiser, 1895, p. 449 ; Engelmann, 1895, p. 326 ; compare Kronecker,
1875, p. 181.

=* Kaiser, 1895, pp. 449, 457 ; Engelmann, 1895, p. 311 ; Dastre dissents, 1882, p. 464.
» Tigerstedt, 1893, p. 169. * Engelmann, 1882, p. 453.

* Aubert, 1881, p. 381 ; compare Rossbach, 1874, p. 97.
6 Gaskell, 1880, p. 53. ' Roy, 1879, p. 477.

CIRCULA TION.

451

ganglion is fused with tlio first ono or two thoracic ganglia to form the gan-
glion stellatiini, situated opposite the first intercostal space. At the " inferior
cervical " ganglion the vagus and the sympathetic part company, the vagus
passing cjiudalward behind the root of the lung and the sympathetic passing
to the stellate ganglion, dividing on its way into two portions (the annulus of
Vieussens), which embrace the subclavian artery. In many cases the lower loop
of the annulus of Vieussens joins the trunk of the vagus caudal to the ganglion.'
The cardiac nerves spring from the vagus and the sympathetic nerve in
the region of the inferior cervical ganglion. They n.ay be divided into an
inner and an outer group.

The inner group is composed of one medium, one ^hick, and from two to
three slender nerves. The nerve of medium thickness springs from the gan-
glion itself. The thick branch rises from the trunk of the vagus near the
origin of the inferior laryngeal nerve about 1.25 centimeters caudal to the

inferior cervical ganglion. It can be

easily followed to its final distribution. ^"""

It passes behind the vena cava superior,

perforates the pericardium, and runs

parallel with the ascending aorta across

the pulmonary artery, on which it lies

in the connective tissue already divided

into two or three tolerably thick twigs

or spread in a fan of smaller branches.

These now bend beneath the artery,

pass round its base on the inner side,

and reach the anterior inter- ventricular

groove. Here they spread over the

surface of the ventricle. The slender

branches leave the vagus trunk caudal

to the branch just described. ^^^ I14.-Cardiac plexus and stellate ganglion

The outer group comprises two thick of the cat, drawn from nature after the removal of

, the arteries and veins; about one and one-half times

branches — namely, an upper nerve, natural size (Boehm.isTS, p. 258):

springing from the ganglion or from R, right; i.left: 1,1, vagus nerve; 2 cervical

i^ o t? & t> _ sympathetic ; 2', annulus of Vieussens ; 2", thoracic

the trunk of the vagus near it, and a sympathetic; 3, recurrent laryngeal nerve; 4, de-

InwPr nerve from the lower loon of P'"e^«o'" "^^^^' entering the vagus on the right, on
lOWei nerve, irom tne JOWei luup ui ^^^ ^^^^ running a separate course to the heart;

the annulus, or from the vagus 1—1^ 5, middle (often called "inferior") cervical gan-

. , , J TT^^l, ^^ ^U^^^ glion ; 5', communicating branch between middle

centimeters lower down. Each of these S^^^. -^^ '^^^^uon and vagus nerve ; 6, stellate gan-

thick branches may be replaced by a glion ; 6', 6" &", spinal roots of stellate ganglion ;

,, p„ I'l i-^A?, communication between stellate ganglion and

bundle of finer branches, and in tact ^agus ; 8', 8", 8'", cardiac nerves.

the description of the cardiac nerves

here given can be regarded as a close approximation only, so frequent are the

individual variations.^

1 Schmiedeberg, 1871, p. 34.

2 Details concerning the composition of the cardiac plexuses in the dog are given by Lira
Boon Keng, 1893, p. 467.

452 AjV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Ill the rabbit the cervical sympathetic and the vaj^iis trunk are not joined,
as ill the dog, but run a separate course. Cardiac fibres from the spinal cord
reach the lower cervical and first thoracic ganglion (ganglion stellatum) along
their rami couiinunicantcs ' and pass to the heart by two sympathetic cardiac
nerves, one from the inferior cervical ganglion and one from the ganglion
stellatum.^

The arrangement of the cardiac nerves in the cat is shown in Figure 114.

In the frog the cardiac nerves, both vagal and sympathetic, reach the heart
through the splanchnic branch of the vagus. The sympathetic fibres pass out
of the spinal cord with the third spinal nerve, through the ramus comraunicaus
of this nerve into the third sympathetic ganglion,^ up the sympathetic chain
to the ganglion of the vagus, and down the vagus trunk to the heart.^

The Inhibitory Nerves.

In 1845, Ernst Heinrich and Eduard Weber '^ ann(Miiiced that stimulation
of the vagus nerves or the parts of the brain where they arise slows the heart
even to arrest. When one pole of an induction apparatus was placed in the
nasal cavity of a frog and the other on the spinal cord at the fourth or fifth
vertebra, the heart was completely arrested after one or tM'o pulsations and
remained motionless several seconds after the interruption of the current.
During the arrest, the heart was relaxed and filled gradually with blood.
When the stimulus was continued many seconds, the heart began to beat again,
at first weakly and with long intervals, then more strongly and frequently,
until at length the beats were as vigorous and as frequent as before, though all
this time the stimulation was uninterrupted.

In order to determine from what part of the brain this influence proceeds,
the electrodes were brought very near together and placed upon the cerebral
hemispheres. The movements of the heart were not affected. Negative results
followed also the stimulation of the spinal cord. Not until the medulla oblon-
gata between the corpora quadrigemina and the lower end of the calamus scrip-
torius was stimulated did the arrest take place. Cutting away the spinal cord
and the remainder of the brain did not alter the result.

Having determined that the inhibitory power had its seat in the medulla
oblongata, the question arose through what nerve the inhibitory influence is
transmitted to the heart. In a frog in which the stimulation of the medulla
had stopped the heart, the vagus nerves were cut and the ends in connection
with the heart stimulated. The heart was arrested as before.

Thus the fundamental fact of the inhibition of a peripheral motor mechan-
ism by the central nervous system through the agency of si)ecial inhibitory

1 Bever and von Bezold, 1867, pp. 236, 247.

" Ludwig and Thiry, 1864, p. 429; Bever, 1867, p. 249.

^ It is probable tliat the fibres of spinal origin end in the sympathetic ganglia, making con-
tacts there with sympathetic ganglion-cells, the axis-cylinder processes of which pass up the
cervical chain and descend to the heart in company with the vagus.

* Gaskell and Gadow, 1884, p. 369. * E. Weber, 1846, p. 42.

CIRCULATION.

453

nerves was firmly established. A great imniher of investigations have demon-
strated that this inhibitory power is found in many if not all vertebrates and
not a few invertebrates.'

The effect of vagus stinmlation on the heart is not immediate; a. latent
period is seen extending over one beat and sometimes two, according to the
moment of stimulation'- (see Fig. 115).

Fig. 115.— Pulsations of frog's heart, inhibited by the excitation of the left vagus nerve (TarchanoflF.
1876, p. 296) : C, pulsations of heart ; S, electric signal which vibrated during the passage of the stimu-
lating current, one vibration for each induction shock.

Changes in the Ventricle. — The periodicity of the ventricular contraction
is altered by vagus excitation, a weak excitation lengthening the duration of dias-
tole, while leaving the duration of systole unchanged (see Fig. 116). A
stronger excitation, capably of modifying largely the force of the contraction,
lengthens both systole and diastole.^ The difficulty of producing a continued
arrest in diastole is much greater in some animals than in others. Even when
easily produced, the arrest soon gives away in the manner described by E. H.
and E. Weber, the heart beginning to beat in spite of the vagus excitation.*

Fig. 116.— Showing the lengthened diastole and diminished force of ventricular contraction during
weak stimulation of the peripheral end of the cut vagus nerve. The heart (cat) was isolated from both
systemic and pulmonary vessels, and was kept beating by circulating defibrinated blood through the
coronary arteries : A, Pressure in left ventricle, which was filled with normal saline solution, and com-
municated with a Iliirthle membrane manometer by means of a cannula which was passed through the
auricular appendix and the mitral orifice ; B, line drawn by the armature of an electro-magnet in the
primary circuit; the heavy line indicates the duration of stimulation ; C, time in seconds.

The force of the contraction, measured by the height of the up-stroke of the
intra-ventricular pressure curve, or by placing a recording lever on the heart,

^ P'or literature see Tigerstedt, Physiologie des Kreislaufes, 1893.

^Schiff, 1849, p. 192; Pliiiser, 1865, p. 30; Czermak, 1868, p. 644; 1868, p. 32; Donders,
1868, p. 339; 1872, p. 6; Tarchanoff 1876, p. 300; Pruszynski, 1889, p. 569.

' Arloing, 1894, p. 88 ; Meyer, 1894, p. 698.

* Hough, 1895, p. 161. The terrapin heart is said not to escape, as a rule, from vagus inhibi-
tion. Compare Mills, 1885, p. 255 ; see also Laulanie, 1889, p. 409.

454 AN AMERICAN TEXT-BOOK' OF PHYSIOLOGY.

is lessened/ this diiuiiiution in force appearing often before any notiw-able
change in periodicity.

The d'uistolic pressure increases, as is shown by the lower level of the cnrve
gradually rising farther and farther above the atmospheric pressure line.*-

The volume of blood in the ventricle at the close of diastole is increased. So
also is the volume at the close of systole (residual blood) — sometimes to such
a degree that the volume of the heart at the end of systole may be greater than
the volume of the organ at the end of diastole before the vagus was excited.^

The oufjmf and the input of the ventricle, that is, the quantity of blood dis-
charged and received, are both diminished by vagus excitation.^

The ventricular tonus, or state of constant slight contraction on whic-h the
systolic contractions are superimposed, is also diminished, as is well shown by
an experiment of Stefani.^ In this experiment the pericardial sac is filled with
normal saline solution under a pressure just sufficient to prevent the expansion
of the heart in diastole. On stimulation of the vagus, the heart dilates fur-
ther. A considerably higher pressure is necessary to overcome this dilatation.
Stefani finds also that the pressure necessary to prevent diastolic expansion is
much greater with intact than with cut vagi. Furthermore, the heart is much
more easily distended by the rise of arterial pressure through compression of
the aorta when the vagi are severed than when they are intact. Franck has
noticed that the walls of the empty ventricle become softer when the vagus is
stimulated.*

The propagation of the cardiac excitation is more difficult during vagus
excitation.^ Bayliss and Starling^ demonstrate this on mammalian hearts
made to contract by exciting the auricle three or four times per second ; the ven-
tricle as a rule responds regularly to every auricular beat. If, then, the vagus
is stimulated with a weak induced current, the ventricle may drop every other
beat, or may for a short time cease to respond at all to the auricular contrac-
tions. The defective propagation is not due to changes in the auricular con-
traction, for even an almost inappreciable beat of the auricle can cause the
ventricle to contract. Nor is it due to lowered excitability of the ventricle,
for the effi?ct described is seen with currents too weak to depress the irrita-
bility of the ventricle to an appreciable extent.

The action of the vagus is accompanied by an electrical variation. This
has been shown in the muscular tissue of the resting auricle of the tortoise'
(see Fig. 117). The auricle is cut away from the sinus without injuring the
coronary nerve, which in the tortoise passes from the sinus to the auricle and
contains the cardiac fibres of the vagus. After this operation the auricle and
ventricle remain motionless for a time, -and this quiescent period is utilized for

1 Coats, 1869, p. 1S7 ; Niiel, 1874, p. 87 ; Gaskell, 1882, p. 1011 ; Heidenhain, 1882, p. 388;
Mills, 1885, p. 283. Roy and Adami, 1892, p. 224, are of contrary opinion.

2 Roy and Adami, 1892, p. 227.

" Roy and Adami, 1892, p. 218; compare Stefani, 1893, p. 136; 1895, p. 175.

♦ Roy and Adami, 1892, pp. 217, 228. * Stefani, 1891, p. 182.

6 Franck, 1891, p. 486. ' Gaskell, 1883, p. 100 ; McWilliam, 1888, p. 367.

» Bayliss and Starling, 1892, p. 412. « Gaskell, 1887, p. 116 ; 1887, p. 404.

CIRCULA TION.

455

the experiment. The tip of tlic aurich^ is injured by immersion in hot water,
and the demareation current (the injured tissue bein<^- negative toward tlie unin-
jured) is led oir to a galvanometer. On exciting the vagus in the neck, the
demarcation current is markedly increased. No visible change of form is seen
in the auricular strip.

Fig 117 -The tortoise heart prepared for the demonstration of the electrical change in the cardiac
muscle'accompanyingthe excitation of the vagus nerve: r, vagus nerve; ^'' ''^'^;^^'J^l''^l'l:^^2
and part of auricle in connection with it ; G, galvanometer, in the circuvt fo^ned by Uv o non-polanzable
electrodes and the part of the auricle between them ; E, induction coil (Gaskell. 1887).

Changes in the Auricle.— There is little probability that the action of
the vao-us on the auricle^ differs essentially from the action on the ventricle.
The force of the auricular contraction is diminished. The diastole is length-
ened The change in force appears earlier than in the change in periodicity
and sometimes without it. On the whole, the auricle is more easily affected
by vagus excitation than the ventricle. ^ i /• j

Action on Bulbus Arteriosus.— If the bulbus arteriosus of the Irog s
heart is extirpated in such a way as to leave untouched the nerve-fibres that
connect it with the auricular septum, the contractions of the isolated bulbus
will be arrested when the peripheral end of the vagus is excited.^

Diminished Irritability of Heart.-During vagus excitation with cur-
rents of moderate strength, the arrested heart will respond to direct stimula-
tion by a single contraction. With strong vagus excitation, however, the
directlv stimulated heart contracts not at all or less readily than before

Effects of Varying the Stimulus.-A single excitation of the vagus does
not stop the heart.^ IMorat has investigated the effect of excitations of varied
I Eckhard, 1860, p. 140; Nnel, 1874, p. 86; Gaskell, 1882, p. 1010; 1883 p. 89; Mills,
1885 p 250; 886, p. 550 ; McWillian., 1885, p. 225; 1887, p. 309; 1888 p. 348; Johansson
and Tigerst;dt, 1889; Franck, 1891, p. 581; Bayliss and ^^-1"^^^^^- J" /g^*^; ^^^j;.^"'
^^";85o!p.'64; 1877,p.494; Einbrodt, 1859. p. 353 ; Eckhard.T^ p. 25 ; McWil-

Uam, 1885, p. 222; 1888, p. 351 ; Mills, 1888, p. 3. „,o rr • , u • , 1889 n ^

* Donders, 1868, p. 344; 1872, p. 5 ; Tarchanofi; 1876, p. 303; Heidenhain, 1882, p. 386.

456 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

duration, uuinber, and frequency on the tortoise lieart.' With excitations of
the same duration, the effect was minimal at 2 per second, maximal at 7
per second, diminishing theroaftor as tiie frequency increased. The longer the
stinuilation, the longer (within limits) was the inhibition. An excitation that
is too feeble or too slow, or, on the contrary, is over-strong or over-frequent,
has no effect. Within limits, however, the degree of inhibition increases with
the strength of the stinudus."

Weak stimuli affect primarily the auricles, diminishing frequency and force
of contraction, and secondarily lower the frequency of the ventricle. Stronger
stimuli arrest the aiu'icle, the ventricles continuing to beat with almost undi-
minished force but with altered rhythm. Still stronger stimuli inhibit the
ventricles also.^

The frequencv can be kept comparatively small by continued moderate
stimulation.''

Arrest in Systole. — The excitation of the tortoise vagus in the upper or
middle cervical region is sometimes followed, according to Rouget,^ by a state
of continued, prolonged contraction — in short, an arrest in systole. The same
effect is observed in rabbits strongly curarized and in curarized frogs. Arloing *
noticed that the mechanical irritation produced by raising on a thread the left
vagus nerve of a horse caused the right ventricle to remain contracted during
seven seconds. The ventricular curve during this time presented the characters
of the tetanus curve of a striated muscle.'

Comparative Inhibitory Power. — One vagus often possesses more inhibi-
tory power than the other.^

Septal Nerves in Frog. — The electrical stimulation of the peripheral
stump of either of two large nerves of the inter-auricular septum in the frog
alters the tonus and the force of contraction of the ventricle, but not the fre-
quency. After section of these nerves, the excitation of the vagus has very
little effect on the tonus, and almost none on the force of the ventricular beat,
while the frequency is diminished in the characteristic manner. Evidently,
therefore, the two large septal nerves take no part in the regulation of fre-
quency, but leave this to the nerves diffusely distributed through the auricles.
There is then au anatomical division of the septal branches of the frog's vagus,
the fibres affecting periodicity running outside the septal nerves, while those
modifying the force of contraction and the tonusof the ventricle run within them.^

* Morat, 1894, p. 10; Legros and Onimus, 1872, p. 565.

2 V. Bezold, 1868, p. 50; Ptluger, 1859, p. 19; Bonders, 1868, p. 356.

'Johansson and Tigerstedt, 1889; Rov and Adami, 1892, p. 237 ; Bayliss and Starling,
1892, p. 411. ' Laulani^, 1889, p. 408.

* Rouget, 1894, p. 398. * Arloing, 1893, p. 112.

" For other unusual alterations in the heart-beat in consequence of vagus excitation see
Arloing, 1893, p. 163.

« Cold-blooded Anivmlx: Meyer, 1869, p. 61 ; Tarchanoff, 1876, p. 293; Gaskell, 1882, p. 82;
McWilliam, 1885, xvi. ; Mills," 188.5, p. 259; 18S7, p. 11 ; 1888, p. 2.

Mammals: Miusoin, 1S72, p. 410; Legros and Onimus, 1872, p. 575; Arloing and Tripier,
1872, p. 420; Langendortt", 1878, p. 68; compare Brown-S^quard, 1880, p. 211.

» Hofniann, 1895, p. 169; examine Pxkhard, 1876, p. 192; and Dogiel, 1890, p. 258.

CIRCULA TION. 457

Nature of Vagus Influence on Heart.— The nature of the terminal
apparatus by which the vagus inhibits the heart is unknown. It is probable
that the same iutracaidiac apparatus serves for both nerves, for Hiiflcr finds
that when the heart escapes from the inhibition caused by continued stimula-
tion of one vagus, the prolonged diastole growing shortca- again, the immediate
stinmlation of'' the second vagus has no effect upon the heart.^ Dogiel and
Grahe have recently observed that the lengthening of diastole which follows
stimulation of the peripheral stump of the vagus, the other vagus l)eing intact,
is less marked than when both vagi are cut.^

The question whether the vagus acts on the heart muscle directly or through
the medium of some nervous mechanism has not yet been answered. The only
fact bearing immediately on this problem is the diminution in the irritability of
the ventricle during vagus excitation, and this does not exclude an action upon
a nervous mechanism.^

The earlier attempts to form a satisfactory theory for the inhibitory power
of the vagus met with little success. The statement of the Webers' that the vagus
inhibits the movements of the heart gave to nerves a new attribute, but is
hardlv an explanation. The view of Budge ^ and Schiff,^ that the vagus is the
motor nerve of the heart and that inhibition is the expression of its exhaustion,
is now of only historical interest. Nor has a better fate overtaken the theory
of Brown-Sequard,« who saw in the vagus the vaso-motor nerve of the heart,
the stimulation of which, by narrowing the coronary arteries, deprived the
heart of the blood that, according to Brown-Sequard, is the exciting cause of the

contraction. ...

Of recent years, the explanation that has commanded most attention is the
one advanced by Stefani^ and Gaskell, namely, that the vagus is the trophic nerve
of the heart, producing a dis-assirailation or katabolism in systole and an
assimilation or anabolism in diastole. Gaskell supports this theory by the
observation that the after-effect of vagus excitation is to strengthen the force
of the cardiac contraction and to increase the speed with which the excitation
wave passes over the heart, while the contrary effects are witnessed after the
excitation of the augraentor nerves.^

Various attempts have been made to prove a trophic action of the vagus on

the heart by cutting the nerve in animals kept alive until degenerative changes

t Hiifler, 1889, p. 307 ; Hough, 1895, p. 198. Earlier experimenters obtained conflicting

results • see Tarchanoff and Puelma, 1875, p, 757 ; Tarchanoff, 1876, p 296 ; Eckhard 18-9 p.

r8T; Gamgee and Priestley, 1878, p. 39 ; Tscherepin, 1881 ; MoWilham, 188o, p. 217 ; Mills,

1885, p. 257 ; Laulanie, 1889, p. 377.

2 Dogiel and Grahe, 1895, p. 393. ^ ^ ,, „.•,,• iqqq „ i~'=.

3 Chlnges in the peripheral efficiency of the vagi are discussed by^M<^^^^ll--^1^93,^p. 4.5.

* Budge, 1846, p. 418. ' '^ " ' ' P'

; S:^^^^:'l^ M#; Eichhorst, I879, p. I8 ; GasUell, 1886, p. 49 ; Fantino, 1^8,
p. 243 ; Timofeew, 1889 ; Tigerstedt, 1893, p. 259. Gaskell gives a resume of his work on the
heart in Archives de Physiolog^e, 1888, pp. 56-68. , .^ ,„„„ ,« ^ «x^„.r^ 1880

« Gaskell, 1883, pp. 81, 94 ; also Gianuzzi, 1871 ; Schiff, 1878, p. 16; Brown-Sequard, 1880,
p. 211 ; Laffont, 1887, p. 1095; Konow and Stenbeck, 1889, p. 414.

458 yl.V AMERICAN TEXT-BOOK OF PHYSTOLOGY.

in the heait-niiLscle should have had time to appear. The important distril)u-
tion of the vagus nerve to many organs, and tlie consequently wide extent of
the loss of function following its section, makes it difficult to decide whether the
changes produced in the heart are not secondary to the alterations in other tis-
sues. The work of Fautino ^ will serve for an example of these investigations.
Fantino cut a single vagus to avoid the paralysis of deglutition aud the inani-
tion and occasional broncho-pueumouia that follow section of both nerves.
Young and perfectly healthy rabbits and guinea-pigs were selected. The opera-
tion was strictly ase])tic, and all cases in which the wound suppurated were
excluded. A piece of the nerve about one centimeter long was cut out, so that
no reunion could be possible. After the operation the animals were as a rule
lively, ate well, and gained weight. Post-mortem examination of animals
killed two days or more after section of the vagus nerve disclosed no patho-
logical changes in the lungs, spleen, liver, and stomach. In the heart, areas
were found in which the nuclei and the striation of the muscle-cells had disap-
peared. Eighteen days after section the atrophy of the cardiac muscle in these
areas was observed to be extreme. The degenerations following section of the
right vagus were situated in a different part of the ventricular wall from those
following: section of the left nerve.

The effects of stimulation of the vagus nerve in the new-boi'n do not differ
essentially from those seen in the adult.^

The relation between the action of the vagus and the intracardiac jwessure
has been recently studied by Stewart.^ He finds that an increase in the pressure
in the sinus or auricle makes it difficult to inhibit the heart through the vagus.

The inhibitory action of the vagus diminishes as the temperature*^ of the
heart falls. At a low limit the inhibitory power is lost, but may return when
the heart is warmed again. Even when the stimulation of the trunk of the
nerve has failed to affect the cooled heart, the direct stimulation of the sinus
can still cause distinct inhibition. The power of inhibiting the ventricle is
first lost. Loss of inhibitory power do&s not follow the raising of the heart
to high temperatures. The vagus remains active to the verge of heat rigor,
and resumes its power as soon as the rigor passes away.

The Augmentor Nerves.
V. Bezold' observed in 1862 that stimulation of the cervical spinal cord
caused an increased frequency of heart-beat. This seemed to him to prove
the existence of special accelerating nerves. Ludwig and Thiry,* however,
soon pointed out that stimulation of the s]Mnal cord in the cervical region
excited many vaso-constrictor fibres, leading to the narrowing of many vessels
and a corresponding rise of blood-pressure. The acceleration of the heart-beat

' Fantino, 1888, p. 239; see also Bidder, 1868, p. 41 ; Eichhorst, 1879, p. 18; Wa&silLeff,
1881, p. 317 ; King, 1881, p. 946.

" Compare Soltmann, 1877, p. 106; Bochefontaine, 1877, p. 226; Tarchanoff, 1878, p. 217;
Langendorfl; 1879, p. 247 ; von Anrep, 1880, p. 78; Meyer, 1893, p. 477.

3 Stewart, 1892, p. 138. * Stewart, 1892, p. SO.

* von Bezold, 1863, p. 191. « Ludwig and Thiry, 1804, p. 421.

CIRCULATION. 459

accompanying this rise in blood-pre&sure would alone explain the observation
of vou J>ezokl. Three years later Bever and von Bezold ' were more suc-
cessful. The intluence of the vaso-motor nerves was excluded by section of
the spinal cord between the first and second thoracic vertebrae. Stimulation
of the cervical cord now caused an increase \\\ the frequency of the heart-beat
without a sinmltaneous increase of blood-pressure. The fibres carrying the
accelerating impulse were traced from the spinal cord to the last cervical gan-
glion and from there toward the heart.

In the dof) the '' augmenting " or " accelerating " nerves thus discovered
leave the spinal cord mainly by the roots of the second dorsal nerves, and enter
the ganglion stellatum, whence they pass through the anterior and posterior
loops of the annulus of Vieussens into the inferior cervical ganglion, from
which they go, in tiie cardiac branches of the latter, to the heart.' Some of
the cardiac fibres in the annulus pass directly thence to the cardiac plexus and
do not enter the inferior cervical ganglion.

In the rabbit^ the course of the augmentor fibres is probably closely similar
to that in the dog.

In the cat,* the augmentor nerves spring from the ganglion stellatum, and
very rarely from the inferior cervical ganglion as well. The right cardiac
sympathetic nerve communicates with the vagus.

The stimulation of the sympathetic chain in the frog, " between ganglion 1
and the vagus ganglion, and also stimulation of the chain between ganglia 2
and 3, causes marked acceleration and
augmentation of the auricular and ven-
tricular contractions. Stimulation be-
tween ganglia 3 and 4 produces no effect y^y
whatever upon the heart." ^ This ex-
periment of Gaskell and Gadow's shows
that augmentor fibres enter the sympa-
thetic from the spinal cord along the
ramus communicans of the third spinal
nerve and pass upward in the sympa-
thetic chain. In this animal the sym-
pathetic chain, after dividing between

the first and second ganglia to form the Fig. llS— The cardiac sympathetic nerves in

1 n -i^- ^^^. r^:„-, +U^ t,..i.-,l- Rana temporaria (twice natural size): V-Sy,

annulus of \ leUSSens, joms the tlUUk ^.^^^.^^^^^.^.^^^^ , ^.,, arteria vertebralis; II,

of the vagus between- the united vagus ir, second and fourth spinal nerves (Gaskell
1 , , 1 T 1 ,1 and Gadow, 1884).

and glosso-pharyngeal ganglia and tne

vertebral column (see Fig. 118). Here the sympathetic again divides, some of

1 von Bezold, 1866, p. 834; Bever and von Bezold, 1867, p. 227.

- Eoy and Adanii, 1892, p. 238 ; compare Schmiedeberg, 1871, p. 38, and Langley, 1893, p.
108 ; the latter states on p. 108 the results of Bever and von Bezold, 1867, Schmiedeberg, 1871,
Boehm and Nussbaum, 1875, Strieker and Wagner, 1878, Bradford, 1889, and Bradford and
Dean, 1889.

3 Bever and von Bezold, 1867, p. 247 ; see remarks of Gaskell and Gadow, 1884, p. 370.
* Boehm, 1875, p. 260. ° Gaskell and Gadow, 1884, p. 369.

460

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

the fibres passing alongside the vagus into the cranial cavity, the rest accompany-
ing the vagus nerve perii)herally. The augmentor nerves for the heart are
anionff the latter, for the slinuilation of the intracranial vagus results in pure
inhibition,' while the stimulation of the vagus trunk after it is joined by the
sympathetic may give either inhibition or augmentation. We may say, there-
fore, that the augmentor nerves of the frog pass out of the spinal cord by the
third spinal nerve, through the ramus comnmnicans of this nerve, into the
third sympathetic ganglion, up the sympathetic chain to the ganglion of the
vagus, and down the vagus trunk to the heart.

Stimulation of Augmentor Nerves. — The most obvious effect of the stim-
ulation of the augmentor nerves is an increase of from 7 to 70 per cent, in the
frequency of the heart-beat (see Fig. 119). The quicker the heart is beating
before thn stimulation, the less marked is the acceleration. The absolute maxi-

Fig. 119.— Curve of blood-pressure in the cat, recorded by a mercury manometer, showing the
increase in frequency of heart-beat from excitation of the augmentor nerves. The curve reads from
right to left. The augmentor nerves were excited during thirty seconds, between the two stars. The
number of beats per ten seconds rose from 24 to 33 (Boehm, 1875, p. 258).

mum of frequency is, however, independent of the frequency before stimulation.^
The maximum of acceleration is largely independent of the duration of stimula-
tion. The duration of stimulation and the duration of acceleration are not
related, a long stimulation causing no greater acceleration than a short one.^

The /o>-ce of the ventricular beat is increased.* The ventricle is filled more
completely by the auricles, the volume of the ventricle being increased. The

^rr / 'yV /i'-c r/

Fig. 120.— Increase in the force of the ventricular contraction (curve of pressure in right ventricle) from
stimulation of angmentor fibres. There is little or no change in frequency (Franck, 1890, p. 819).

output of the heart is rai.sed.' There is no definite relation between the in-
crease of contraction volume or force of contraction and the increase in fre-
quency (see Fig. 120). Either may appear without the other, though this is

' Gaskell, 1884, p. 48. " Boehm, 1875, p. 277. ^ Baxt, 1877, p. 523.

* Heidenhain, 1882, p. 396; Ga-skell, 1884, p. 47; 1886, p. 42; Mills, 1886, p. 554; Franck,
1890, p. 814; Roy and Adami, 1892, p. 242; Baylies and Starling, 1892, p. 413.
5 Roy and Adami, 1892, p. 240.

CIRCULATION. 461

rare.* The simultaneous stimulation of the nerves'of Ijoth sides does not
give a greater maximum frequcncv than the stimulation of one nerve alone.^

The strength and the volume of the auricular contractions are also in-
creased. The increase in volume is not due to a rise of pressure in the veins
— in fact, the pressure falls in the veins — but to a change in the elasticitv of
tiie relaxed auricle, a lowering of its tonus. This change is not related to the
increase in the force of the auricular contractions that stimulation of the auo^-
mentor nerves also causes. It varies much in amount and is less constantly
met with than the change in force.^ The changes in the ventricle and auricle
probably account for the rise of blood-pressure in the systemic arteries and the
fall in both systemic and pulmonary veins observed by Roy and Adami.*

The speed of the cardiac excitation icave is increased. Its passage across
the auriculo- ventricular groove is also quickened, as is shown in the following
experiment of Bayliss and Starling.'^ In the dog, the artificial excitation of
the ventricle may cause the excitation wave to travel in a reverse direction,
namely, from ventricle to auricle. If the ventricles are excited rhythmically
and the rate of excitation is gradually increased, a limit will be reached beyond
which the auricle no longer beats in response to every ventricular contraction.
With intact vagi, a rate of 3 per second is generally the limit. If now the
augmentor nerve is stimulated, the "block" is partially removed, and the
auricle beats during and for a short time after the stimulation at the same
rapid rate as the ventricle.

The latent periocjAf the excitation is long. In the dog, about two seconds
pass between the beginning of stimulation and the beginning of acceleration,
and ten seconds may pass before the maximum acceleration is reached.^ The
after-effect mav continue two minutes or more." It consists of a weakenino; of
the contractions and an increase in the difficulty with M'hich the excitation
wave passes from the auricle to the ventricle. The return to the former fre-
quency is more rapid after short than after long stimulations.^

The simultaneous stimulation of the inhibitory and the augmenting nerves
of the heart, either in the vagus or separately, causes, in warm-blooded ani-
mals, inhibition and not auo-nientation. The inhibition overcomes the auo[-
mentation,^ but the vagus effect is diminished nevertheless. The acceleration
that is seen after the stimulation of the vagus is due to the after-effect of the
stimulation of accelerating filires in the vagus.

The simultaneous stimulation of the auo:;mentors and the vagi, the strength
of the current being sufficient to stop the auricular contractions, causes accel-
eration of the ventricular contractions.*''

1 Franck, 1S90, p. 819 ; Roy and Adami, 1892, p. 240. ^ Franck, 1880, p. 85.

^ Rov and Adami, 1892. p. 240. * Ibid.

» Bavliss and Starling, 1892, p. 415. « Baxt, 1877, p. 529.

' von Bezold and Bever, 1867, p. 245; Schraiedeberg, 1870, p. 136; 1871, p. 43; Boehm,
1875, p. 273. ^ Baxt, 1877, p. 536.

» Bowditch, 1873. p. 273; Bast, 1875, p. 204: Boehm, 1875, p. 278.

^° Bayliss and Starling, 1892, p. 414. For further discussion of the effects of simultaneous
stimulation, see Meltzer, 1892, p. 376.

402

^iV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Other Centrifugal Heart-nerves.

Ill the vago-sympathetic trunk and tlic annulus of Vieussens fibres pass to
the heart tliat cannot be chissed either with the vatj^us or the augmentor nerves.
Tlie evidence for their existence is furnished bv Roy and Adami's observation
that when the intracardiac vagus mechanism is acting strongly, so that the
auricles are more or less completely arrested, the stimulation of the vago-
sympathetic trunk sometimes causes a decided increase in the force both of
the ventricles and the auricles, usually accompanied by an acceleration of the
rhythm of the heart. These changes are too rapidly produced to be aiig-
mentor effects.'

Centrifugal inhibitory nerves have been found as an anomaly in the right
depressor nerve of a rabbit.^

Pawlow^ dividers the inhibitory and augmentor nerves into four classes —
(1) nerves inhibiting the frequency of the beat, (2) nerves inhibiting the force of

the contraction, (3) nerves augmenting
frequency, and (4) nerves augmenting
force. The origin of this subdivision
of the two groups generally recog-
nized was the observation that, in cer-
tain stages of convallaria poisoning, the
excitation of the vagus in the neck — all
the branches of the nerve except those
going to heart ancrlungs being cut — re-
duced the blood-pressure without alter-
ing the frequency of the beat. Further
researches showed that the stimulation
of branch 3 (Fig. 121) even in unpoi-
soned animals reduced the blood-pres-
sure independently of the variable al-
teration simultaneously produced in the
pulse-rate. Stimulation of branch 5
produced an acceleration of the heart-
beat without increase of blood-pressure.
Other branches brought about rise of
pressure without acceleration, and in-
creased discharge by the left ventricle without alteration in the }>ulse-rate.
These results are supported further by Wooldridge's observation that exci-
tation of the peripheral ends of certain nerves on the posterior surface of the
ventricle raised the blood-pressure without modifying the frequency of contrac-
tion,^ and by Roy and Adami's demonstration that certain branches of the first
thoracic ganglion lessen the force of the cardiac contraction without influencing
its rhythm.^ But the matter is as yet far from certain.

> Roy and Adami, 1892, p. 249. * Herins;, 1894, p. 78.

» Pawlow, 1887, p. 510. * Wooldridge, 1883, p. 537.

* Rot and Adami, 1892, p. 246.

Fig. 121. — Scheme of the centrifugal nerves of
the heart according to Pawlow : 1, vago-sympa-
thetic nerve ; 2, upper inner branch ; 3, strong
inner branch; 4, lower inner branch: 5, upper
and lower outer branches ; 6, ganglion stellatum ;
7, annulus of Vieussens ; 8, middle (inferior) cer-
vical ganglion ; 9, recurrent laryngeal nerve.

CIRCiJLA TIOX. 463

The Centripetal Nerves of the Heart.

The Ventricular Nerves. — When the nuiininalian heiirt is freed from
blood by wa.sliiii^- it out with normal saline solution and the ventricle is painted
with pure carbolic acid, liquefied by \varmiu<^, numerous nerves appear as
white threads on a i)rown back<2:;round. They are non-medullated, form many
plexuses, and run beneath the pericardium obliquely downward from the base
to the apex of the ventricle. They may be traced to the cardiac plexus.
These fibres are not centrifugal branches of the vagus or the augmentor nerves,
for the characteristic eifects of vagus and augmentoi' stimulation are seen after
section of the nerves in question. The stimulation of their peripheral ends,
moreover, the fibre being carefully dissected out from the subpericardial tissue,
cut across, and the cut end raised on a thread in the air, is without effect on
the blood-})ressure and pulse-rate. The stimulation of the central stumps of
these nerves, on the contrary, is followed by changes both in the blood-pressure
and the pulse, showing that they carry impulses from the heart to the cardiac
centres in the central nervous system, or perhaps, according to the views of
some recent investigators, to peripheral ganglia, thus modifying the action of
the heart reflexly.^

Sensory Nerves of the Heart. — The stimulation of intracardiac nerves
by the application of acids and other chemical agents to the surface of the
heart causes various reflex actions, such as movements of the limbs. The
afferent nerves in these reflexes are the vagi, for the reflex movements dis-
appear when the vagi are cut.^ On the strength of these experiments the
vagus has been believed to carry sensory impressions from the heart to the
brain. Direct stimulation of the human heart, in cases in which a defect in
the chest-wall has made the organ accessible, give evidence of a dim and very
limited recognition of cardiac events — for example, the compression of the
heart.^

Vagus. — The stimulation of the central end of the cut vagus nerve, the
other vagus being intact, causes a slowing of the pulse-rate. The section of
the second vagus causes this retardation of the pulse to disappear, indicating
that the stimulation of the central end of the one affects the heart reflexly
through the agency of the other vagus. The blood-pressure is simultaneously
affected, being sometimes lowered and sometimes raised, the difference seeming
to depend largely on the varying composition of the vagus in different ani-
mals and in different individuals of the same species.* The stimulation of the
pulmonary branches, by gently forcing air into the lungs, loud speaking, singing,
etc., is said to increase the frequency of the heart-beat.^ Yet the chemical
stimulation of. the raucous membrane of the lungs is alleged to slow the pulse-

1 Wooldridge, ia83, pp. 523, 529, 539 ; see also Lee, 1849, p. 43.

^ Budge, 1846, p. 588 ; Goltz, 1863, p. 5 ; Giirboki, 1872, p. 289; Franck, 1880, p. 382.

3 V. Ziemssen, 1882, p. 297 ; Nothnagel, 1891, p. 209.

* See Franck, 1880, p. 281 ; v. Bezold, 1863, p. 281 ; Dreschfeld, 1867, p. 326 ; Aubert and
Eoever, 1868, p. 211 ; Kowalewsky and Adamiik, 1868, p. 546; Cybulski and Wartanow, 1883;
Eey and Aducco, 1887, p. 188; Arendt, 1890, p. 11 ; Koy and Adami, 1892, p. 251.

5 Hering, 1871 ; Sommerbrodt, 1881, p. 602.

464 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

rate and lower the blood-pressure.' Observers differ as to the results of stim-
ulation of the central end of the laryngeal branches of the vagus on the pulse-
rate and blodd-prcssure.*

Depressor Nerve. — The earlier stiiiuilatii)iis of the nerves that pass
between the central nervous system and the iieart, with the exception of the
vao-us, altered neither the blood-pressiu'e nor the pulse-rate. Ludwig and ( yon ^
suspected that the negative results were owing to the fact that the stiMuilations
were confined to the end of the cut nerve in connection with the heart. Some
of the nerves, they thousrht, should carry impulses from the heart to the brain,
and such nerves could be found only by stimulation of the brain end of the
cut nerve. Thev began their research for these aflereut nerves with the branch
which springs from the rabbit's vagus high in the neck and passes downward
to the ganglion stoUatum. Their suspicion was at once confirmed. The stimu-
lation of the central end of this nerve, called by Ludwig and Cyon the depres-
sor, caused a considerable fall of the blood-pressure.

The depressor nerve arises in the rabbit by two roots, one of which comes
from the trunk of the vagus itself, the other from a branch of the vagus, the
superior laryngeal nerve. Frequently the origin is single ; in that case it is
usuallv from the nervus laryngeus.* The nervus depressor runs in company
with the svmpathetic nerve to the chest, where commuuicatious are made with
the branches of the ganglion stellatum.

The stimulation of the peripheral end of the depressor nerve is without
effect on |he blood-pressure and heart-beat. The stimulation of the central
end, on the contrary, causes a gradual fall of the general blood-pressure to the
half or the third of its former height. After the stimulation is stopped, the
blood-pressure returns gradually to its previous level.

Simultaneously with the fall in blood-pressure a lessening of the pulse-rate
sets in. The slowing is most marked at the beginning of stimulation, and after
rapidlv reaching its maximum gives way gradually until the rate is almost
what it was before the stimulation began. After stimulation the frequency is
commonly greater than previous to stimulation.

After section of both vagi, the stimulation of the depressor causes no change
in the pulse-rate, but the blood-pressure falls as usual. The alteration in fre-
quencv is therefore brought about through stimulation of the cardiac inhibitory
centre, acting on the heart through the vagi. The experiment teaches, further,
that the alteraticm in pressure is not dependent on the integrity of the vagi.

Poisoning with curare paralyzes all motor mechanisms except the heart and
the muscles of the blood-vessels. Yet curare-poisoning does not affect the
result of depressor stimulation. The cause of the fall in blood-jiressure must
be sought then either in the heart or the reflex dilatation of the blood-vessels.
It cannot be in the heart, for depressor stimulation lowers the blood-pressure
after all the nerves going to the heart have been .severed. It must therefore

> Franck, 1880, p. 378. * Aubert and Roever, 1868, p. 241 ; Franck, 1880, p. 357.

' Ludwig and Cyon, 1866, p. 128.

* Tschirwinsky, 1896, p. 778, gives a somewhat different account.

CIRCULATION. 465

lie in the blood-vessels. Liulwig and Cyou knew that the dilatation of
the intestinal vessels could produce a great fall in the blood-pressure and
turned at once to them. Section of the splanchnic nerve -caused a dilata-
tion of the abdominal vessels and a fall in the blood-pressure. Stimula-
tion of the peripheral end of the cut splanchnic caused the blood-pressure to
rise even beyond its former height. If now the depressor lowers the blood-
pressure chiefly by affecting the splanchnic nerve reflexly, the stimulation of
the central end of the depressor after section of the splanchnic nerves ought to
have little effect on the blood-pressure. This proved to be the case. The
depressor, therefore, reduces the blood-pressure chiefly by lessening the tonus
of the vessels governed by the splanchnic nerve, thus allowing their dilatation
and in consequence lessening the peripheral resistance.

It has already been said that .the depressor fibres pass from the heart to the
vaso-motor mechanism in the central nervous system. The cardiac fibres are
probably stimulated when the heart is overfilled through lack of expulsive
force or through excessive venous inflow, and, by reducing the peripheral resist-
ance, assist the engorged organ to empty itself.

The depressor nerve is not in continual action ; it has no tonus ; for the sec-
tion of both depressor nerves causes no alteration in the blood-pressure.

The many successors of Cyon and Ludwig have added relatively few im-
portant facts to their extraordinary investigation.

Sewall and Steiuer ^ have obtained in some cases a permanent rise in blood-
pressure following section of both depressors, yet they hesitate to say that the
depressor exercises a tonic action.

Spallita and Consiglio ^ have stimulated the depressor before and after the

rao

\

v^

^v^

'A.A

A A

,A

N

'■\

A

/V

Fig. 122.— Showing the fall in blood-pressure and the dilatation of peripheral vessels from stimula-
tion of the central end of the depressor nerve (Bayliss) : A, curve of blood-pressure in the carotid artery ;
B, volume of hind limb, recorded by a plethysmograph ; C, electro-magnet line, in which the elevation
shows the time of stimulation of the nerve ; D, atmospheric pressure-line ; E, time in seconds.

section of the spinal accessory nerve near its junction with the vagus. They
find that after section of the spinal accessory, the stimulation of the depressor
' Sewall and Steiner, 1885, p. 168. "^ Spallita and Consiglio, 1892, p. 42.

30

46G AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

docs not arteot the pulse, whence they conclude that the depressor fibres that
affect the blood-pressure are separate from those that affect the rate of beat, the
latter being derived from the spinal accessory nerve.

A recent study by JJayliss ' brings out several new facts. II' a limb is i)la(cd
in Mosso's plethysmogra])li and the central end of the depressor stinudated,
the volume of the lind) increases, showing an active dilatation of tiie vessels
that supply it. The latent period of this dilatation varies greatly, 'i'he vessels
of the skin play a large part in its production. A similar local action is seen
on the vessels of the head and neck (see Fig. 122).

The depressor fibres vary much in size in different animals. When the
nerve is small, a greater depressor effect can be obtained by stimulating the
central end of the vagus than from the depressor itself But the course of the
fall is different in the two cases. With the depressor, the fall is maintained at
a constant level during the whole excitation, however long it lasts, whereas
in the case of the vagus the pressure very soon returns to its original
hei^dit although the excitation still continues. Bayliss believes, therefore,
that there is a considerable difference between the central connections of
the depressor nerve itself and the depressor fibres sometimes found in other
nerves.

The left depressor nerve usually produces a greater fall of pressure than the
right. The excitation of the second nerve during the excitation of the first
produces a greater fall than the excitation of one alone.

The fibres of the depressor, in part at least, end in the wall of the ventricle.^
A similar nerve has been demonstrated in the cat,^ horse,* dog,* sheep,^ swine/
and in raan.^

Sensory Nerves. — The first and usually the only effect of the stimulation
of the central end of a mixed nerve like the sciatic, according to Roy and
Adami,^ is an increase in the force and the frequency of the heart-beat. Other
observers ^"^ have sometimes found quickening and sometimes slowing of the pulse-
rate, so that sensory nerves, as Tigerstedt" suggests, appear to affect both the
inhibitory and the augmenting heart-nerves. When a sensory nerve is weakly
excited the augmentor effect predominates, when strongly excited the inhibi-
tory. A well-known demonstration of the reflex action of the sensory nerves
on the heart is seen in the slowing of the rabbit's heart when the animal

1 Bayliss, 1893, p. 304. ' Kazem-Beck, 1888, p. 329.

' Bernhardt, 1868, p. 5; Auhert and Roever, 1868, p. 214; Kowalewsky and Adamiik, 1868,
p. 545; Roever, 1869, p. 68; Kazem-Beck, 1888, p. 331.

* Bernliardt, 1868, p. 5 ; Cyon, 1870, p. 262; Finkelstein, 1880, p. 350.

* Roever, 1869, p. 71 ; Langenbacher, 1877 ; Kreidniann, 1878, p. 411 ; Finkelstein, 1880, p.
248 ; Kazem-Beck, 1888, p. 332.

« Kriedmann, 1878, p. 407. ^

' Langenbacher, 1877; Kazem-Beck, 1888, p. 335; the latter describes also (p. .338) a de-
pressor nerve in cold-blooded animals; compare Ga.skell and Gadow, 1885, p. 362.

8 Bernhardt, 1868, p. 5; Kreidmann, 1878, p. 408; Finkelstein, 1880, p. 249; B^k^sy, 1888.

9 Roy and Adami, 1892. p. 254.

>•> Lov^n, 1866, p. 5 ; Bernard, 1858, p. 291 ; Asp, 1867, p. 173 ; Tranck, 1876, p. 246 ; Siman-
owskv, 1881. " Figerstedt, 1893, p. 287.

CIRCULA TION. 467

is mado to inhale oliloroform. Tlie superior laryngeal and the trigeminus
nerves, especially the latter, convey the stimulus to the nerve-centres.*

The stiiiuilation of the nenrs of special sense, optic, auditory, olfactory and
glosso-pharyngeal nerves, also sometimes slows and sometitues quickens the
heart.^

Sympathetic. — The reflex action of" the sympathetic nerve upon the heart
is well shown by the celebrated experiment of F. Goltz.^ In a medium-sized
frog, the [)ericardium was exposed by carefully cutting a small window in the
chest-wall. The pulsations of the heart could be seen through the thin peri-
cardial membrane. Goltz now began to beat upon the abdomen about 140
times a minute M'ith the handle of a scalpel. The heart gradually slowed, and
at length stood still in diastole. Goltz now ceased the rain of little blows.
The heart remained quiet for a time and then began to beat again, at first slowly
and then more rapidly. Some time after the experiment, the heart beat about
five strokes in the minute faster than before the experiment was begun. The
effect cannot be obtained after section of the vagi.

Bernstein * found that the afferent nerves in Goltz's experiment were branches
of the abdominal sym])athetic, and discovered that the stimulation of the cen-
tral end of the abdominal sympathetic in the rabbit was followed also by reflex
inhibition of the heart.

The stimulation of the central end of the splanchnic produces a reflex rise
of blood-pressure and, perhaps secondarily, a slowing of the heart.^ In some
cases acceleration has been observed.^ According to Roy and Adami splanch-
nic stimulation sometimes produces a combination of augmentor and vagus
effects, the augmentation appearing during stimulation and giving place
abruptly to well-marked inhibitory slowing at the close of stimulation,''

The results of stimulating various abdominal viscera have been studied by
Mayer and Pribram. One of the most interesting of the reflexes observed by
them was the inhibition of the heart called forth by dilating the stomach.^

The stimulation of the cervical sympathetic does not give any very constant
results on the action of the heart,^

B. The Centres op the Heart-nerves.

Inhibitory Centre. — It has been already mentioned that the brothers
Weber *" localized the cardiac inhibitory centre in the medulla oblongata. The
efforts to fix the exact location of the centre by stimulation of various parts,
either mechanically, by thrusting fine needles into the medulla,*' or electrically,

1 Dogiel, 1866, p. 236; Kratschmer, 1870, p. 159; Franck, 1876, p. 227; Simanowsky, 1881.

2 Couty and Charpentier, 1877, p. 563. * Goltz, 1863, p. 11.

* Bernstein, 1863, p. 818 ; 1864, pp. 617, 642. * Asp, 1867, p. 150.
6 V. Bezold, 1863, p. 252; Asp, 1867, p. 172; Sabbatini, 1891, p. 219.

' Roy and Adami, 1892, p. 258.

* Mayer and Pribram, 1872, p. 107 ; Simanowsky, 1881.

8 Bernstein, 1864, p. 630; Aubert and Roever, 1868, p. 240 ; 1869, p. 95; Bernstein, 1868,
p. 601. '" Weber, 1846, p. 45.

" Eckhard, 1878, p. 187 ; Klug, 1880, p. 516 ; Laborde, 1888, p. 400.

4GS AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cannot inspire great confidence becau.se of the difficulty of distinguishing
between rhe resuhs that follow the excitation of a nerve-path from or to the
centre and those following the excitation of the centre itself. According to
Laborde, who also used this method, the cardiac inhibitory centre is situated at
the level of the mass of cells known as the accessory nucleus of the hypoglossus
and the mixed nerves (vagus, spinal accessory, glosso-pharj'ngeal).^

Tiie localization of the centre by the method of successive sections is per-
haps more trustworthy. Frauck - has found that the separation of the bulb
from the spinal cord cuts off the reflexes c-alled forth by nerves that enter the
spinal cord, while leaving undisturbed the reflex produced by stimulation of
the trigeminus nerve.

On the whole, there seems to be no doubt that the cardiac inhibitory centre
is situated in the bulb.

Tonus of Cardiac Inhibitory Centre. — The cardiac inhibitory centre is prob-
ably always in action, for when the vagus nerves are cut, the heart-beat
becomes more frequent. The source of this continued or "tonic" activity
may lie in the continuous discharge of inhibitory impulses created by the
liberation of energy in the cell independeut of direct external influences, or
the cells may be disciiarged by the continuous stream of afferent impulses
that must constantly play upon them from the multitude of afferent nerves.
This latter theory, the conception of a reflex tonus, is made probable by the
observations that section of the vagi does not increase the rate of beat after
the greater part of the afferent impulses have been cut off" by division of the
spinal cord near its junction with the bulb,^ and that the sudden decrease in
the number of afferent impulses caused by section of the splanchnic nerve
quickens the pulse-rate,^

Irradiation. — The slowing of the rate of beat observed chiefly during the
expiratory i)ortion of respiration disappears after the section of both vagus
nerves. The slowing may perhaps be due to the stimulation of the cardiac
inhibitory centre by irradiation from the respiratory centre.'^

Origin of Cardiac Inhibitory Fibres. — Since the researches of "Waller^ and
others, it has been generally believed that the cardiac inhibitory fibres enter
the vagus from the spinal accessory nerve, for the reason that cardiac inhibi-
tion was not secured in animals in which the fibres in the vagus derived from
the spinal accessory nerve were made to degenerate by tearing out the latter
before its junction with the vagus. These results have lately been called in
question by Grossmann.^ The method employed by his predecessors, according
to him, probably involved the destruction of vagus roots as well as those of
the spinal accessory. Grossmann finds that the stimulation of the spinal
accessory nerve before its junction with the vagus does not inhibit the heart.
Nor does inhibition follow the stimulation of the bulbar roots supposed to be
contributed to the mixed nerve by the spinal accessory.

^ Laborde, 1888, p. 415. ' Franck, 1876, p. 255. ' Bernstein, 1864, p. 654.

♦ Asp. 1867. p. 136. ^ Laulanie. 1S93. p. 72.S.

•Waller, 1856, p. 420; Schiff, 1858; Heidenhain, 1865. p. 109; Gianuzzi. 1872; Franck,
1876, p. 264. ' Grossmann, 1895, p. 6.

CIRCULATION. 469

Augmentor Centre.— The situation (.f the centre for the augmentor
nerves of tlie heart is not definitely known, aUhough from analogy it seems
probable that it will be found in the bulb. That this centre is constantly in
action is indicated by the lowering of the pulse-rate after section of the vagi
followed bv the bilateral extirpation of the inferior cervical and first thoracic
gano:lia. The division of the spinal cord in the upper cervical region after the
section of the vagi has the same etfect.^ Vagus inhibition, moreover, is .said
to be moi-e readily i)roduced after section of the augmentor nerves.^

:McWilliam ^ has remarked that the latent period and the character of the
acceleration often accompanying the excitation of afferent nerves may differ
entirely from the characteristic effects of the excitation of augmentor nerves.
The stimulation of the latter is followed by a long latent period, after M-hich
the rate of beat gradually increases to its maximum and, after excitation is
over, as gradually declines. The excitation of an afferent nerve, on the con-
trary, causes often, with almost no latent jieriod, a remarkably sudden accel-
eration, that reaches at once a high value and often suddenly gives way to a
slow heart-beat. These facts seem to show that reflex acceleration of the heart-
beat is due to changes in the cardiac inhibitory centre, and not to augmentor
excitation. This view is strengthened by the fact that if the augmentor nerves
are cut, the vagi remaining intact, the stimulation of afferent fibres, fi)r exam-
ple in the brachial nerves, can still cause a marked quickening of the pulse-
rate. In short, the action of afferent nerves upon the rate of beat is essentially
the same, according to this observer, whether the augmentor nerves are divided

or intact.

Roy and Adami ' believe that the stimulation of afferent nerves, such as the
sciatic or the splanchnic, excites both augmentor and vagus centres. The
augmentor centre is almost always the more strongly excited of the two, so
that augmentor effects alone are usually obtained.

Action of Higher Parts of the Brain on Cardiac Centres.— Repeated
efforts have been made to find areas in the cortex of the brain especially
related to the inhibition or augmentation of the heart, but with results so con-
tradictory as to warrant the conclusion that the influence on the heart-beat
of the parts of the brain lying above the cardiac centres does not differ essen-
tially from that of other organs peripheral to those centres.*

Yoluntarv control of the heart, by which is meant the power to alter the
rate of beat bv the exercise of the will, is impossible except as a rare indi-
vidual peculiaritv, commonlv accompanied by an unusual control over muscles,
such as the platvsma, not usually subject to the will. Cases are described by
Tarchanoff^ and Pease,^ in which acceleration of the beat up to twenty-seven

1 Tschirjew, 1877, p. 164 ; Strieker and Wagner, 1878, p. 370.

^ Sustschinsky, 1868, p. 164. ' Mc^\ ilham, 1893, p. 472.

* Rov and Adami, 1892, p. 260.

5 See Danilew.kv, 1875, p. 130; Bochefontaine, 1876, p. 140; 1883, p. 33; Balogh,76;
Eckhard. 1878, p. 185; Bechterew and Mislawsky, 1886, p[.. 193, 416; Franck, 1887, p. 162.

6 Tarchanoff, 1884, p. 113.

7 Pease, 1889, p. 525.

470 AN A3IERICAN TEXT-BOOK OF PHYSIOLOGY.

in the minute was produced, together with increase of blood-pressure, from
vaso-constrictor action. The experiments are dangerous.

Peripheral Reflex Centres. — It is now much discussed wliethcr the periph-
eral ganglia can act as centres of rcHcx action. According to Franck ' the excita-
tion of the central stump of the divided left anterior limb of the annulus of
Vieussens is transformed within the first thoracic ganglion, isolated from the
spinal cord by section of its ramus communicans, into a motor impulse trans-
mitted by the posterior limb of the annulus. This motor impulse causes, inde-
pendently of the bulbo-spinal centres, a reflex augmtmtation in the action of the
heart, and a reflex constriction of the vessels in the external ear, the sul)maxil-
lary gland, and the nasal mucous membrane. This experiment, in conjunction
with the facts in favor of other .sympathetic ganglia acting as reflex centres,^
seems to demonstrate that some afferent impulses are transformed in the sym-
pathetic cardiac ganglia into efferent impulses modifying the action of the
heart. If this conclusion is confirmed by future investigations it will pro-
foundly modify the views now entertained regarding the innervation of the
heart.

Intra- ventricular Centre. — Kronecker and Schmey,^ finding that puncture
of the inter-ventricular septum at the junction of the upper and middle thirds
often caused arrest of the heart with fibrillary contractions, have set up the
hypothesis of a co-ordinating centre at that point, essential to the co-ordinated
contractions of the ventricle. Their results are possibly due to inhibition ;■* cer-
tainly they are not to be explained by the destruction of a co-ordinating centre.
The anatomical basis for such a conception is wanting, careful search having
failed to reveal any ganglion-cells in the locality in question,^ and the heart has
been observed to beat for hours and even days after the cardiac tissue of this
part of the septum liad been destroyed by infarction, caused by the ligation of
its nutrient arteries.^

The expenments of Stannius, published in 1852, have been the starting-
point of a very great number of researches on the innervation of the frog's
heart. Stannius observed, among other facts, that the heart remained for a
time arrested in diastole when a ligature was tied about the heart precisely at
the junction of the sinus venosus with the right auricle. No sufficient
explanation of this result has yet been giyen, nor is one likely to be found
until the innervation of the heart is better understood. Stannius^ further

1 Franck, 1894, p. 721.

''See Wertheimer, 1890, p. 519; Skabitschewsky, 1891, p. 15G ; Langley and Anderson,
1893, p. 435.

^ Kronecker and Schmey, 1884, p. 89; S^e and Gley, 1887, p. 827 ; the latter could not get
arrest in 11 out of 14 dogs.

* Knoll, 1894, p. 312, observed fibrillation of the auricles in consequence of vagus stimula-
tion ; escape of current into tlie heart was guarded against.

* Krehl and Romberg, 1892, p. 54.

* Porter, 1893, p. 366; for the effect of wounds of the heart upon its rhythm, see Rodet
and Nicolas, 1896, p. 167.

' A review of the Stannius literature is given by Tigerstedt, Physiobgie des Kreidaiifes,
1893, p. 196.

CIR CULA TION. 4 7 1

observed that after the ligature just described had been drawn tight, thus
arresting the heart, the placing of a second ligature around the heart at the
junction of the aui-icle and ventricle caused the latter to begin to beat again,
while the auricle remained at rest. This second ligature, it is generally
admitted, stimulates the ganglion of Bidder, and the ventricle responds by
rhythmic contractions to the constant excitation thus produced. Loosening the
ligature and so interrupting the excitation stops the ventricular beat.^

PART III.— THE NUTRITION OF THE HEART.

The cells of which the heart-wall are composed are nourished by contact
with a nutrient fluid. In hearts consisting of relatively few cells no special
means of bringing the nutrient fluid to the cells is required. The walls of the
minute globular heart of the small crustacean Daphnia, for example, are com-
posed of a single layer of cells, each of which is bathed by the fluid which the
heart pumps. In larger hearts with thicker w-alls only the innermost cells
could be fed in this way. Special means of distributing the blood throughout
the substance of the organ are necessary here.

Passages in the Prog's Heart. — In the frog this distribution is accom-
plished chiefly through the irregular passages which go out from the cavities
of the heart between the muscle-bundles to within even the fraction of a milli-
meter of the external surface.^ These passages vary greatly in size. Many are
mere capillaries. They are lined by a prolongation of the endothelium of the
heart. Filled by every diastole and emptied by every systole, they do the
work of blood-vessels and carry the blood to every part of the cardiac muscle.
Henri Martin^ describes a coronary artery in the frog, analogous to the
coronary arteries of higher vertebrates. This artery supplies a part of the
auricles and the upper fourth of the ventricle.

In the rabbit, cat and dog, and in man a well-developed system of cardiac
vessels exists, the coronary arteries and veins. Their distribution in the dog
deserves especial notice, because the physiological problems connected with these
vessels have been studied chiefly in this animal.

Coronary Arteries in the Dog. — In the dog the coronary arteries and
their larger branches lie upon the surface of the heart, covered as a rule only
by the pericardium and a varying quantity of connective tissue and fat. The
left coronary artery is extraordinarily short. A few millimeters after its origin
from the aorta it divides into the large ramus circumflex and the descen-
dens, nearly as large. The former runs in the auriculo-ventricular furrow
around the left side of the heart to the posterior surface, ending in the pos-
terior inter-ventricular furrow. The left auricle and the upper anterior and the
posterior portion of the left ventricle are supplied by this artery. The descen-
dens runs downward in the anterior inter- ventricular furrow to the apex. Close
to its origin the descendens gives off the arteria septi, which at once enters the

1 Goltz, 1861, p. 201. 2 Engelmann, 1874, p. 11. » Martin, 1893, p. 754 ; 1894, p. 46.

472 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

inter-veiitriciilar sei)tiiin and passes, sparsely covered with iiiiisele-buiidlcs,
obliquely downward and backward on the right side of the septum. The
descendens in its farther course gives off numerous branches to the left ventricle
and the anterior ])art of the septum. Only a few small branches go to tlie
right ventricle. Thus the descendens supplies the septum and the inferior
anterif)r part of the left ventricle. The right coronary artery, imbetlded in
fat, runs in the right auriculo-ventricular groove around tiie right side of the
heart, supplying the right auricle and ventricle. It is a much smaller artery
than either the circumflex or descendens. Each coronary artery kee|)S to its
own boundaries and does not, in the dog, pass into the field of another artery,
as sometimes happens in man.^

Terminal Nature of Coronary Arteries. — The coronary arteries in the
dog, as in man, are terminal arteries, that is, the anastomoses which their branches
have with neighboring vessels do not permit the making of a collateral circula-
tion. Their terminal nature in the human heart is shown by the formation of
infarcts in the areas supplied by arteries which have been plugged by embo-
lism or thrombosis. That part of the heart- wall supplied by the stopped arteiy
speedily decays. The bloodless area is of a dull white color, often faintly
tinged with yellow ; rarely it is red, being stained by luemoglobin from the
veins of neighboring capillaries. The cross section is coarsely gramdar. The
nuclei of the muscle-cells have lost their power of staining. The muscle-cells
are dead and connective tissue soon replaces them.^ This loss of function and
rapid decay of cardiac tissue would not take place did anastomoses permit the
establishment of collateral circulation between the artery going to the part and
neighboring arteries. The terminal nature of the coronary arteries in the dog
has been placed beyond doubt by direct experiment. It is possible to tie them
and keep the animal alive until a distinct infarct has formed.^

The objection that one of the coronary arteries can be injected from
another,* and that therefore they are not terminal, is based on the incorrect
premise that terminal arteries cannot l)e thus injected, and has no weight against
the positive evidence of the complete failure of nutrition following closure.
The |)assage of a fine injection-mass from one vascular area to another proves
nothing concerning the possibility of the one area receiving its blood-supply
from the other. Such supply is impossible if the resistance in the communi-
cating vessels is greater than the blood-pressure in the smallest branches of the
artery through which the supply nnist come. It is the fact of this high resist-
ance, due to the small size of the communicating branches, w'hich makes the
artery "terminal." This condition of high resistance is really j>resent during
life, or infarction could not take j^lace.

The terminal nature of the coronary arteries is of great importance w^ith
regard to the part taken by them in the nutrition of the heart. Being ter-

* Cohnheim and v. Schiilthess-Rechberg, 1881, p. 511.

* See also the description by Kolster, 1893, p. 14, of the infarctions produced experiment-
ally in the dog's heart.

» Kolster, 1893, p. 14; Porter, 1893, p. 366. * Miciiaelis, 1894, p. 289.

CIRCULA TION. 473

miual, their experimental closure enables us to study the effects of the sudden
stoppin*^ of tiie blood-supply (isfluLMuiu) of the heart muscle upon the action
of the heart.

Results of Closure of the Coronary Arteries. — The sudden closure of one
of the large coronary branches in the dog has as a rule cither no effect upon
the action of the heart beyond occasional and transient irregularity/ or is fol-
lowed af\er the lapse of seconds, or of minutes, by the arrest of the ventricu-
lar stroke, the ventricle falling a moment later into the rapid, fluttering,

Fig. 123.— J, curve of iiUra-vcntricular pressure, written by a manometer connected with the interior
of the left ventricle; 5, atmospheric pressure; C, time in two-second intervals. At the iirst arrow the
ramus circumflexus of the left coronary artery was ligated ; at the second arrow the heart fell into fibril-
lary contractions. The lessening height of the curve shows the gradual diminution of the force of con-
traction after ligation. The rise of the lower line of the curve above the atmospheric pressure indicates
a rise of intra-ventricular pressure during diastole. The small elevations in the pressure-curve after the
second arrow are caused by the left auricle, which continued to beat after the arrest of the ventricle
(Porter, 1893).

undulatory movements known as fibrillary contractions and produced by the
inco-ordinated, confused shortenings of individual muscle-cells, or groups of
cells. The auricles continue to beat for a time, but the power of the ventricles
to execute co-ordinated contractions is lost.

The Frequency of Arrest. — The frequency with which closure is fol-
lowed by ventricular arrest depends on at least two factors — namely, the size
of the artery ligated and the irritability of the heart. That the size of the
artery is of influence appears from a series of ligations performed on dogs,
arrest being never observed after ligation of the arteria septi alone, rarely
observed (14 per cent.) with the right coronary artery, more frequently (28
per cent.) with the descendens, and still more frequently (64 per cent.) with the
arteria circumflexa.^ The irritability of the heart is an important factor. In
animals cooled by long artificial respiration, or by section of the spinal cord at
its junction with the bulb, the ligation of the descendens arrests the heart less
frequently than in vigorous animals which have been operated upon quickly.
The frequency of arrest is increased by the use of morphia and curare.^

Changes in the Heart-beat. — Ligation destined to arrest the heart is fol-
lowed almost immediately by a continuous fall in the intra-ventricular pressure
during systole and a gradual rise in the pressure during diastole (see Fig. 123).
The contraction and relaxation of the ventricle are often slowed. The force
of the ventricular stroke is diminished. As arrest draws near, irregularities in
the force of the ventricular beat are seldom absent.* The frequency of beat is
sometimes unchanged throughout, but is usually diminished toward the end ;

* The changes produced by subsequent degeneration are not considered here.

"'' Porter, 1893, p. 131. ^ Ibid., 1896, p. 49. * Ibid., 1893, p. 133.

474

^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 12-1.— Showing fall in arte-
rial pressure and diminished out-
put of left ventricle in conse(iuenee
of the ligation of the circumflex
artery. The curve reads from left
to right. It is one-half the original
size. The upper curve is the pres-
sure in the carotid artery. The
unbroken line is atmospheric pres-
sure. The next curve is the meas-
urement of the outflow from the
left ventricle, each rise and each
fall indicating the passage of 50
c.cm. of blood into the aorta. The
lower line is a time-curve in sec-
onds. At * the circumflex artery
•was Ugated (Porter, 1896, p. 51).

occasionally the frequency is increased. iJoth ven-
tricles as a rule cease to beat at the same instant.
The work done by the heart, measured by the
blood thrown into the aorta in a unit of time, is
les.sened by ligation when followed by arre.st' (see
IV 124).

The Exciting Cause of Arrest. — There are
two opinions concerning the exciting cause of the
changes following closure of a coronary artery,
some investigators holding for anaemia and others
for mechanical injury of the cardiac muscle or its
nerves in the operation of ligation. The latter
ba.se their claim on the frequent failure of ligation
of even a main branch to stop the heart ; on the
fact that the heart of the dog has been seen to
beat from 115 to 150 seconds after the blood-pres-
sure in the aorta was so far reduced, by clamping
the auricle and opening the carotid artery, as to
make a continuance of the coronary circulation
very improbable;^ on the revival of the arrested
heart by the injection of defibrinated blood into
the coronary arteries from the aorta, by which
means the dog's heart and even the human heart
has been made to beat again many minutes after
the total arrest of the circulation,^ — it being as-
sumed, incorrectly, that the dog's heart cannot be
made to beat after arrest with fibrillary contrac-
tions; and, finally, on the arrest with fibrillary
contractions which some experimenters have caused
by mechanical injury to the heart.*

To sum up, the argument in favor of explain-
ing arrest with fibrillary contractions simply by
the mechanical injury done the heart in the jiro-
cess of ligation consists of two propositions : first,
that anaemia without mechanical injury does not
cause arrest with fibrillary contractions; and .sec-
ond, that mechanical injury without anaemia does
cause arrest.

Against the .second of these propositions must
be placed the extreme in frequency of arrest from
mechaniad injuries. In more than one hundred

' Porter, 1896, p. 52.

2 Tigerstedt, 1895, p. 87 ; Michaelis, 1894.
' Langendorff, 1895, p. 320; H^don and Gilis, 1892,
p. 760. * Martin and Sedgwick, 1882, p. 168.

CIRCULA TION. 475

ligations Porter* observed not a single arrest in consequence of laying the
artery bare and placing the ligature ready to be drawn, the only effect of the
nieolianical })ro(_'c<lure being an ocaisional si igiit irregularity in force. Ligation
of the periarterial tissues in ten dogs, the artery itself being excluded from the
ligature, directly injured both muscular and nervous substance, but was only
once followed by arrest." Nor does arrest follow the ligation of a vein, although
the mechanical injury is possibly as great as in tying an artery. The direct
stimulation of the superficial ventricular nerves exposed to injury in the opera-
tion of ligation does not produce the effects that appear after the ligation of
coronary arteries.^

Against the remaining proposition stated above — namely, that anaemia with-
out mechanical injury does not cause arrest with fibrillary contractions — it
should be said that the frequency of arrest after ligation is in proportion to
the size of the artery ligated, and hence to the size of the area made anaemic,
and is not in proportion to the injury done iu the preparation of the artery.
The circumflex and descendens may be prepared w'ithout injuring a single
muscle-fibre, yet their ligation frequently arrests the heart, while the ligation
of the arteria septi, which cannot be prepared without injuring the muscle-
substance, does not arrest the heart. It is, moreover, possible to close a coro-
nary artery without mechanical injury. Lycopodium spores mixed with de-
fibrinated blood are injected into the arch of the aorta during the momentary
closure of that vessel and are carried into the coronary arteries, the only way
left open for the blood. The lycopodium spores plug up the finer branches
of the coronary vessels. The coronary arteries are thus closed without the
operator having touched the heart. Prompt arrest with tumultuous fibrillary
contractions follows.^ There seems, then, to be no doubt that fibrillary contrac-
tions can be brought on by sudden anaemia of the heart muscle.

The gradual interruption of the circulation in the coronary vessels — by
bleeding from the carotid artery, for example — is followed by feeble inco-
ordinated contractions not essentially different in kind from those commonly
termed fibrillary contractions.^ The manner of interruption probably explains
the difference in result. In the former case, namely, ligation or other sudden
closure, the supply of blood to the heart muscle is suddenly stopped while the
heart continues to work against a high peripheral resistance ; in the latter, the
anaemia is gradual and the heart works against little or no peripheral resistance.

Recovery from Fibrillary Contractions. — Fibrillary contractions brought
on by clamping the left coronary artery in the rabbit's heart are often gradually
replaced by normal contractions when the clamp is removed.^ The isolated
cat's heart after showing marked fibrillary contractions during forty-five
minutes has given strong regular beats for more than an hour.'' The recovery

^ Porter, 1896, p. 58 ; see also Fenoglio and Drogoul, 1888, p. 49.

2 Porter, 1896, p. 57 ; see also Rodet and Nicolas, 1896, p. 167.

5 McWilliam, 1887, p. 298; Wooldridge, 1883, p. 532; compare Michaelis, 1894, p. 285.

* Porter, 1896, p. 65. * Porter, 1895, p. 482.

8 V. Bezold, 1867, pp. 263, 285. ' Magrath and Kennedy (about to be published).

47()

AN AMERICAN TENT-HOOK OF I'll YSK )L< X ; Y.

of" tho (loii's heart lias hccii supposed iin])ossil)le.^ MeA\'illiaiii, however, has
seen a number ot" regnhir heats after the termination ol' fihriHarv conlractioii.^
Recent rcsnhs suggest that llhrilhirv contractions even in the high(;st verte-
brates niav be removed by estabbshing an artitieial cireiihition of defibrinated
bhi()d through the coronary arteries.

Closure of the Coronary Veins. — Closure of all the coronary veins in
the rabbit jiroduced tibrillary contractions after from fifteen to twenty minutes
had passed.^ Their closure in the dog is said to be without effect ■* — a negative
result perhaps to be explained by the fact that a portion of the coronary blood
finds its wav to the cavities of the heart through the venae Thebesii.*

Volume of Coronary Circulation. — Bohr and Heuriques,^ taking the
average of six experiments on dogs, found that 16 cubic centimeters of blood
passed through the coronary arteries per minute for each 100 grams of heart
muscle. The (juantity passing through both coronary arteries varied in dif-
ferent animals from 20 to 64 cubic centimeters per minute ; the quantity
passing t broil <;h the left coronary artery varied from 22.5 to 60 cubic centi-

lliffiilllill^^

iMjijif^mmmmmmHH^

^lnnilnininninuMiiiiiiiiiiiimi\inniHHiuiuinMiiiiiuin

iii/flf^<|«tfjJ/Ui^/(//^^ . •■■ " " L"

Fig. 125.— Diminution of the force of contraction of the ventricle of the isohitcd cat's lieart in con-
sequence of dimini.shiug the supply of blood to the cardiac muscle : A, hlood-pressure at the root of the
aorta, recorded by a mercury manometer; 5, intra-ventricular pressure-curve, left ventricle: the indi-
vidual beats do not appear, because of the slow speed of the smoked surface ; C, time in seconds ; D, the
number of drops of blood passing through the coronary arteries, each vertical mark recording one drop.
As the number of drops of blood passing tlirough the coronary arteries diminishes, the contractions of
the left ventricle become weaker, but recover again when the former volume of the coronary circula-
tion is restored.

meters per minute. The hearts weighed from 51 to 350 grams. The method
which Bohr and Henriques found it neces.sary to employ placed the heart
under such abnormal conditions that their results can be regarded as only

1 Ck)hnheim and v. Schulthess-Rechberg, 1881, p. 519; Tisenstedt, 1895, p. 546; and others.

' It is not quite clear wlietlier McWilliam refers to fil)rillary contraotions produced by
closing a coronary artery or to those which follow strong faradic stimulation of the ventricle
(1887, p. 299).

3 V. Bezold and Breymann, 1807, p. 299. ' Michaelis, 1894, p. 291.

* Gad, 1886, p. 382. * Bohr and Henriques, 1895, pp. 233-236.

CIRCULA TION.

477

approximate. Porter ' supplied llic left coronary artery of the clog with blood
(lihitcd one-half with sodiinn cliloridc sohition (0.6 per cent.) by means of a
tube (lumen 2.75 millimeters) inserted into the aortic opening of the left coro-
nary artery and connected with a reservoir placed 150 centimeters above the
heart. In one dog, weighing 11,500 grams, 318 cubic centimeters flowed
through in eight minutes. In a second dog, weighing 9500 grams, 114 cubic
centimeters passed through in four minutes. In the isolated heart of the cat
strong and regular contractions are made on a circulation of about 4 cubic
centimeters per minute, or even less, through the coronary systeni. The
quantity passing through the veins of Thebesius into the left auricle and
ventricle is ,very slight.

Blood-supply and Heart-beat.— Tlie relation between the volume of
blood passing through the coronary arteries and the rate and force of the
ventricular contraction has been studied by Magrath and Kennedy (1896).
Variations in the volume of the coronary circulation in the isolated heart
of the cat, unless very considerable, are not accompanied by changes in the
rate of beat. The force of contraction, on the contrary, appears to be closely
dependent on the volume of the coronary circulation (Fig. 125).

Lymphatics of the Heart.— A rich plexus of lym])hatic vessels has been
demonstrated in the heart. Valuable information concerning the nutrition of
the heart could probably be gained by the systematic study of these vessels.

0. Solutions which Maintain the Beat of the Heart.
The beat of the heart is maintained during life by a constant supply of
oxygenated blood. The blood, however, is a very complex fluid, and it can
hardly be supposed that all of its constituents are of equal value to the heart.
The systematic search for those constituents of the blood which are of import-
ance to the nutrition of the heart was begun in Ludwig's laboratory in 1875
by Merunowicz.2 The first step toward the method used by Merunowicz and
his successors was taken by Cyon.^ Cyon tied cannulas in the vena cava
inferior and in one of the aort« of the extirpated heart of the frog, and
joined them by a bowed tube filled with serum. The ventricle pumped
the serum through the aortic cannula and the bowed tube into the vena
cava, whence it reached the ventricle again. The force of the contraction
was measured by a mercury manometer which was joined by a side branch
to one limb of the bowed tube.

The frog heart manometer method thus introduced by Ludwig and Cyon
has undergone various modifications at the hands of Blasius and Fick," Bow-
ditch,^ Luciani,« Kronecker,^ and others. Blasius and Fick were the first to
register changes in the volume of the heart by the plethysmographic method,
the organ being enclosed in a vessel filled with normal saline solution and

1 Porter, 1896, p. 64. ' Merunowicz, 1876, p. 132.

3 Cyon, 1867, p. 80. * Blasius, 1872, p. 9.

5 Bowditch, 1872, p. 139. ' Luciani, 18-3, p. 113.

' Kronecker, 1874, p. 174.

478

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

connected with a manometer. This idea reappears in the Strassburg apparatus
described below.

A valuable improvement was made by Kronecker, who invented a double
cannula, through one side of which the " nutrient " fluid enters the ventricle

while it passes out through the other (Fig. 126).
The contents of the ventricle are thus contin-
ually renewed. In 1878, Koy ^ constructed the •
instrument shown in Figure 127, by means of
which the changes in the volume of the heart at
each contraction are recorded on a moving cylin-
der. A great advance was made by Williams,^
in the invention known as " Williams's valve,"
which is the essential feature of the apparatus
devised by this investigator and others in
Schmiedeberg's laboratory at Strassburg. The
present form of this apparatus is illustrated in
Figure 128. A perfusion cannula is introduced
into the ventricle through the aorta. Through
one tube of the cannula the heart is fed from a
reservoir placed above it. Through the other
the heart pumps its contents into a higher reser-
voir or into the same reservoir. Thus the heart is " loaded " with a column
of liquid of known height and pumps against a measurable resistance. A

Fig. 126.— The perfusion cannula
of Kronecker. The ventricle is tied
on the cannula at d, a ring being
placed here to prevent the ligature
from slipping. The double tube,
shown in cross-section at e, divides
into the large branch a and the
small branch b. The nutrient solu-
tion enters the heart through b and
escapes through a. The silver wire
c can be connected with one pole of
a battery, the cannula serving as one
electrode, and the fluid surrounding
the heart as the other.

Fio. 127.— Roy's apparatus: the heart is tied on a
perfusion cannula and enclosed in a bell glass rest-
ing on a brass plate, 6, the centre of which presents
an opening covered by a rubber membrane. Vari-
ations in the volume of the heart cause the mem-
brane to rise and fall. The movements of the
membrane are recorded by a lever.

Fig. 128.— Williams's apparatus: H, frog's heart;
V, V, Williams's valves ; MS, millimeterscale. The
apparatus is arranged to feed the heart from the
reservoir into which the heart is pumping.

Williams's valve in the inflow tube prevents any flow except in the direction

of the heart. A similar valve reversed in the outflow tube prevents any flow

» Roy, 1879, p. 453. » Williams, 1881, p. 3.

CIRCULA TION. 479

except away from the heart. The ventricle is filled and emptied alternately as
is the normal heart, the artificial valves rei)laciiig the heart-valves, which are
often necessarily rendered useless by the introduction of the cannula and are at
best less certain in their action than the artificial valve. The changes in the
volume of the heart are shown by the movements of a liquid column in a
horizontal tube which communicates with the bottle filled with "nutrient"
fluid in which the heart is enclosed.

In the original method of Cyon the ventricle is left in connection with the
auricle, the ganglion-cells of the ventricle and the neighboring portions of the
auricle being kept intact. This *' whole heart " preparation is to be distin-
guished from the " apex " preparation of Bowditch, which has also been used
in studies of the effects of nutrient solutions on the heart. In Bowditch's
" apex " preparation,^ the ventricle is bound to the cannula by a thread tied at
the junction of the upper and middle thirds of the ventricle. By this means
the lower two-thirds of the ventricle, which contains no ganglion-cells, is cut
off from any physiological connection with the base of the ventricle and a
" ganglion-free apex " secured. The isolated " apex " at first stands still, but
after from ten to sixty minutes ^ commences to beat again and can then be kept
beating for several hours.

In the use of these various methods certain general precautions should be
kept in mind. Special attention should be directed to the difficulty of remov-
ing the blood from the capillary fissures in the wall of the frog's heart.^ A
small amount of blood remaining in these passages is frequently a source of
error. It should be remembered that, as Cyon * pointed out, a change in the
nutrient solution is of itself a stimulus to the heart, increasing or diminishing
the frequency of contraction and obliging the investigator to wait until the heart
has become accustomed to the new solution before making an observation. The
heart should, as a rule, be constantly supplied with fresh fluid, as in the natural
state. The resistance against which the heart works is also a factor of import-
ance. The water with which the solutions are made should be distilled in glass,
as the minutest trace of the compounds of heavy metals in non-colloidal solu-
tions affects the heart.'

Nutrient Solutions. — Cyon ^ found that the beat of the extirpated frog's
heart is very dependent on the nature of the solution with which the heart is
fed. Hearts supplied with normal saline solution (NaCl, 0.6 per cent.) ceased
to beat much sooner than those left empty. The serum of dog's blood seemed
almost poisonous. Rabbit's serum, on the contrary, postponed the exhaustion
of the heart for many hours, provided the limited quantity contained in the
apparatus was renewed from time to time. Serum used over and over again
caused the beats to lose force after an hour or two. The renewal of the serum
seemed a stimulus to the heart, causing it to contract very strongly during a
half minute or more, after which the contractions became less energetic.

1 Bowditch, 1872, p. 139. ^ Merunowicz, 1876, p. 135.

3 Martius and Kronecker, 1882, p. 547. * Cyon, 1867, p. 89.

5 Locke, 1895, p. 331 ; Naegeli, 1893, p. 12. « Cyon, 1867, p. 89.

480 ^l.V AMERICAN TKXT-UOOK OF PHYSIOLOGY.

Cvon's immediate successors, Bowditch, Liuiiuii, and Rossbacli/ confirmed
his observations. None of these investigators, however, was concerned pri-
marily with the nutrition of" the heart. The first systematic work on tiiis sub-
ject was done, as has been said, l)y Merunowiez, who attenij»ted to maintain
the beat ot" the iieart with nornuil saline solution containing; various (quantities
t)t' blood, with normal saline alone, with a watery solution ot the ash of an
alcholic extract of serum, and with a normal saline solutitju containing a
minute amount of sodium carbonate. The direction taken by him has been
pursued to the present day, the chief objects of stuily behig tin; importance to
the heart of sodium carbonate or other alkali, sodium and potassium chloride,
the salts of calcium, oxygen, proteids and some other organic bodies such as
dextrose, and, finally, of fluids possessing the physical characteristics of the
blood. The outcome of this work we must now consider.

The value of an alkaline reaction has been generally recognized. Sodium
carbonate is the alkali commonly preferred. The favorable influence of this
salt probably does not depend on any specific action, but simply upon its
alkalinity.^ The alkali promotes the beat of the heart by neutralizing the
carbon dioxide and other acids formed in the metabolism of the contracting
muscle; this, however, may not be its only use.

Certain of the salts normally present in the blood are necessary to main-
tain the beat of the heart. Sodium chloride is one of these. The solution
employed should contain a "physiological quantity." Such a solution is said
to be " isotonic." The amount required to make a sodium chloride solution
** normal" or "isotonic" for the frog is 0.6 per cent., for the mammal nearly
1 per cent. Enough of a calcium salt to prevent the washing out of lime
from the tissues is also essential for prolonged maintenance of the contractions.^
A heart fed with normal saline solution is before long brought to a stand ; the
addition of a calcium salt to the solution postpones the arrest. The character
of the contraction, however, is altered by the calcium, the relaxation of the
ventricle being sometimes so much delayed that the next contraction takes
place before the relaxation from the previous contraction has commenced, the
ventricle falling thereby into a state of persistent or " tonic " contraction. The
addition of a potassium salt restores the normal character of the contraction,*
calcium and potassium having an antagonistic action on the heart. The
importance of calciimi to the heart is said to be demonstrated by the disap-
pearance of the spontaneous contractions of the heart which follows the pre-
cipitation of the calcium in the circulating fluid by the addition to it of an
equivalent quantity of a soluble oxalate, and by the return of spontaneous
contractions which is seen when the calcium is restored to the solution.^

The antagonistic action of calcium and the oxalates was first pointed out
by Cyon."

1 Bowditch, 1872, p. 139; Luciani. 1873, p. 113; Rossbach, 1875, p. 90.

2 Gaiile, 1878, p. 294. ' Ringer, 1885, p. 252.

* Ringer, 1885, p. 247. * Ringer, 1885, p. 85; compare Howell, 1894, p. 478.

6 Cyon, 1807, p. 203; see also Sokoloff, 1881, p. 8; Ringer, 1885, p. 86; Howell and Cooke,
1893, p. 220 ; Howell, 1894, p. 478.

CIRCULA TION. 481

According to Riui!;er/ the substances thus far mentioned are effective in the
followinij; order: normal saline is the least effective; next is saline contaiuinir
sodium bicarbonate; then saline containing tricalcinm pho8})hate; and best of
all, saline containing tri(;alcinm phosphate together with potassium chloride.
He recommends the following mixture : Sodiutu chloride solution 0.6 per
cent., saturated with tribasic calcium phosphate, 100 cubic centimeters; solu-
tion potassium chloride 1 per cent., or acid potassium phosphate (HKgPOJ
1 per cent., 2 cubic centimeters.^

There has been considerable dispute over the part played by oxygen in
the beat of the frog's heart. McGuire^ and King* were of opinion that
the beat is largely independent of the amount of oxygen in the circulating
fluid. Yeo^ concluded that the contracting heart uses more oxygen than
the resting heart, and that the consumption of oxygen increases with the work
done. Kronecker and Handler,^ on the contrary, believe that the oxygen con-
sumption is increased by an increase in the rate of beat, but is independent of
the work done.^ More recent observers are united on the necessity of oxygen
to the working heart. Oehrwall's studies in this field are especially interesting.
He finds that a volume of blood sufficient to fill the frog's ventricle will main-
tain contractions for hours provided the heart is surrounded by an atmosphere of
oxygen. The heart is brought to a stand by lack of oxygen and may be made
to beat again, even after an arrest of twenty minutes, by giving it a fresh sup-
ply. The heart fails in oxygen-hunger probably because the chemical process
by which the stimulus to contraction is called forth no longer takes place, and
not because of a failure in contractility, for even after long inaction a gentle
touch on the pericardium will cause a vigorous contraction.

Carbon dioxide^ is injurious to the heart when present in the circulating
fluid in considerable quantities. The force of the contraction is reduced before
the rate of beat. The heart poisoned with carbon dioxide often falls into
irregular contractions, exhibiting at times '"grouping" and the "staircase"
phenomenon, a series of beats regularly increasing in strength.

Organic Substances. — An unsuccessful effort has been made to prove that
only solutions containing proteids, for example blood-serum, chyle, and milk,
can keep the heart active.^ Recent observers have shown the incorrectness of
this claim. The inorganic salts of serum alone suffice.''^ Locke" found that the
addition of 0.1 percent, of dextrose to a suitable inorganic solution kept a frog's

' Ringer, 1886, p. 294.

- Ringer, 1893, p. 128; for the action of rubidium, strontium, and caesium on the heart see
Ringer, 1884, p. 370.

3 McCluire, 1878, p. 321. * Klug, 1879, p. 478.

5 Yeo, 1886, p. 119. « Handler, 1890, p. 253.

' Heffter, 1892, p. 52 ; Albanese, 1893, p. 311 ; Oehrwall, 1893, pp. 42, 44.

8 See Kronecker and Stirling, 1874, p. 200 ; McGuire, 1878, p. 322; Klug, 1879. p. 478 ;
Saltet, 1882, p. 567 ; Kronecker and Mays, 1883, p. 263 ; Langendorff, 1893, p. 417 ; Ide, 1893,
p. 492; Ringer, 1893, p. 129.

9 Martius and Kronecker, 1882, p. 562; v. Ott, 1883, p. 26; Popoff, 1889, p. 438 ; Brinck,
1889, p. 472; White, 1896, p. 344 ; compare Stienon, 1878, p. 277, and Ringer, 1886, p. 363.

10 Merunowicz, 1876, p. 166; Howell and Cooke, 1893, p. 204. '^ Locke, 1895, p. 333.
.".1

482 .l.V AML'Ji'/CAy^ TEXT- HOOK OF PlIYSIOLOOY.

heart workinjj; iiiuler a load of 3.5 centigrams, and under aii "after-load " of 3
centiijranis iu spontaneous activity for more than twenty-four iiour.s. The
sustainin<»; action which dextrose appears to exercise is shared, according to him,
by various other organic substances.

Physical Characteristics. — Heflter' and Albanese,^ having observed that
the addition of gum-arabic to the circulating fluid was of advantage, declared
that the nutrient solutions should possess the viscosity of the blood. The
favorable action of giun-arabic may, however, more probably be ascribed to the
conijiounds w hich it contains rather than to its physical properties.^

Mammalian Heart. — The success attained within the past two years in the
isolation of the mammalian heart opens up an hitherto unexplored region in
which svstematic investigation will surely bring to light facts of wide interest
and value. At present, however, little is known as to the constituents of the
blood which are essential to the life of the mammalian heart. An abundant
supply of oxygen is certainly highly important.*

Blood of Various Animials. — Roy '' gives some data as to the effect on the
frotr's ventricle of the blood of various animals. The blood of the various her-
bivora (rabbit, guinea-pig, horse, cow, calf, sheep), as well as that of the pigeon,
were found to have nearly the same nutritive value in each case. That of the
dog, of the cat, and more especially of the pig, while in some instances equal in
effect to that from the hoi-se or rabbit, were in other examples (from the newly
killed animals) apparently almost poisonous. Cyon's early observation of the in-
jurious action of dog's blood on the frog's ventricle has already been mentioned.

Regarding the mammalian heart, experience has shown that it is best to
supply the heart with blood from the same species of animal.' The difficulties
attending the use of blood from a different species are seen in the case of the
dog's heart supplied with calf's blood. The heart dies sooner; ojdema of the
lungs takes place, impeding the pulmonary circulation and leading to engorge-
ment of the right heart and paralysis of the right auricle ; exudation into the
pericardium often seriously interferes with the beat of the heart; and, finally,
the elastic modulus of the cardiac muscle is apparently altered, permitting the
heart to swell until it tightly fills the pericardium, when the jn'opcr filling of
the heart is no longer possible through lack of room for diastolic expansion.

PART IV.— THE INNERVATION OF THE BLOOD-VESSELS.

About the middle of the eighteenth century more or less sagacious hypotheses
concerning the contractility of the blood-vessels began to appear in medical

1 Hefiler, 1892, p. 52. " Albanese, 1S93, p. 311.

» Howell and Cooke, 1893, p. 216; Locke, 1895, p. 333.

* Experiments on the artificial circulation of defibrinated blood through the coronary .irter-
ies have been performed by Martin and Applegarth, 1890, p. 275; Arnaud, 1891, p. 396;
H^don and Gilis, 1892, p. 760; Langendorff; 1895, p. 291; Porter, 1896, p. 46; Magrath and
Kennedy, 1896. * Roy, 1879, p. 460; compare Hefller, 1892, p. 44.

6 Cyon, 1867, p. 89. ' Martin, 1883, p. 676 ; see also Langendorfl', 1895, p. 293.

aiRCULA TION. 483

literature, but it was not until Honlo demonstrated the existence of muscular
elements in the middle coats of the arteries in 1840 that a secure foundation
was laid for the present knowledge of the mechanism by which that contractility
is made to control the distribution of the blood. More than a hundred years
before, indeed, Pourfonr du Petit had shown that redness of the conjunctiva
was one of the consc(|uenccs of the section of the cervical sympathetic, but iiad
called the ])rocess an inflammation, in which false idea he was supported by
C'ruikshank and others; and Dupuy of Alfort had noted redness of the con-
junctiva, increased warmth of the forehead, and sweat-drops on ears, forehead,
and neck following his extirpation of the superior cervical ganglia in the
horse; Brachet, also, cutting the cervical sympathetic in the dog, had gone so
far as to attribute the resulting congestion to a paralysis of the blood-vessels.
But these were merely clever speculations, for the anatomical basis necessary
for a real knowledge of this subject was wanting as yet. Henle furnished this
basis, and at the same time reached the modern point of view. " The part
taken by the contractility of the heart and the blood-vessels in the circulation,"
said Henle, " can be expressed in two words : the movement of the blood depends
on the heart, but its distribution depends on the vessels." Nor did Henle stop
here. It was now known that the vessels possessed contractile walls ; it was
known further that these walls contracted when mechanically stimulated ; for
example, by scraping them with the point of a scalpel ; and various observers
had traced sympathetic nerves from the greater vessels to the lesser until lost in
their finest ramifications. It was therefore easy to construct a reasonable
hypothesis of the control of the blood-vessels by the nerves. Henle declared
that the vessels contract because their nerves are stimulated, either directly,
or reflexly through the agency of a sensory a})paratus. The ground was
thus prepared for the physiological demonstration of the existence of " vaso-
motor" nerves, as Stilling began to call them. Four names are associated
with this great achievement — Schiff, Bernard, Brown-Sequard, and Waller,^
each of whom worked independently of the others. Foremost among them
is Claude Bernard, though not the first in point of time, for it was he who
put the new doctrine on a firm basis. In his first publication Bernard ^ stated
that section of the cervical sympathetic, or removal of the superior cervical
ganglion, in the rabbit, causes a more active circulation on the correspond-
ing side of the face together with an increase in its temperature. The greater
blood-supply manifests itself in the increased redness of the skin, particularly
noticeable in the skin of the ear. The elevation of temperature may be easily
felt by the hand. A thermometer placed in the nostril or in the ear of the
operated side shows a rise of from 4° to 6° 0. The elevation of temperature
may persist for several months. Similar results are obtained in the horse and
the dog.

The following year Brown-S^quard' announced that " if galvanism is applied

' Waller, 1853, p. 378. The literature of vaso-motor nerves is so large that only works of
the past fifteen years can be cited, except in a few important instances.

■'Bernard, 1851, p. 163. =■ Brown-S^quard, 1852, p. 490.

484 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

to the superior portion of the sympathetic after it has been cut in the neck, the
dihited vessels of the face and of the ear after a certain time begin to contract;
their contraction increases slowly, but at last it is evident that they resume
tlieir normal condition, if they are not even smaller. Then the temperature
diminishes in the face and the ear, and becomes in the palsied side the same as
in the sound side. AVhen the galvanic current ceases to act, the vessels begin
to dilate again, and all the phenomena discovered by Dr. Jiernard reapj)ear."
Brovvn-Sequard concludes that " the only direct efiect of tiie section of the
cervical part of the sympathetic is the paralysis, and consequently the dilata-
tion, of the blood-vessels. Another evident conclusion is that the cervical
sympathetic sends motor fibres to many of the blood-vessels of the head."

While Brown-S6quard was making these important investigations in
America, Bernard, in Paris, quite unaware of Brown-Sequard's labors, was
reaching the same result. The existence of nerve-fibres the stinmlation of
Avhich causes constriction of the blood-vessels to which they are distributed was
thus established.

A considerable addition to this knowledge was presently made by Schiff,^
who pointed out in 1856 that certain vaso-motor nerves take origin from the
spinal cord. The destruction of certain parts of the spinal cord causes the
same vascular dilatation and rise of temperature that follows the section of the
vaso-motor nerves outside the spinal cord.

At this time Schiff also offered evidence of vaso-dilator nerves. When
the left cervical sympathetic is cut in a dog, and the animal is kept in his
kennel, the left ear will always be found to be 5° to 9° warmer than the
right. If the dog is now taken out for a run in the warm sunshine, and
allowed to heat himself until he begins to pant with outstretched tongue, the
temperature of both ears will be found to have increased. The right ear is
now, however, the warmer of the two, being from 1° to 5° warmer than the
left. The blood-vessels of the right ear are, moreover, now fuller than those
of the left. When the animal is quiet again the former condition returns, the
redness and warmth in the right becoming again less than in the left ear. The
increase of the redness and warmth of the right ear over the left, in which the
vaso-constrictor nerves were paralyzed, must be the result of a dilatation of
the vessels of the right ear by some nervous mechanism. For if the dilatation
of the vessels was merely passive, the vessels in the right ear could not dilate to
a greater degree than those in the left ear which had been left in a passive state
by the section of their nerves. This experiment, however, is by no means con-
clusive.

The existence of vaso-dilator fibres was placed beyond doubt by the follow-
ing experiment of Bernard ^ on the chorda tympani nerve, new facts regarding
the vaso-constrictor nerves being also secured. Bernard exposed the submax-
illary gland of a digesting dog, removed the digastric muscle, isolated the
nerves going to the gland, introduced a tube into the duct, and, finally, sought

' Schiff, 1856, p. 69 ; 1859, p. 153.

"^ Bernard, 1858, p. '241 ; see also pp. 649 to 658.

CIRCULATION. 485

oat and opened the submaxillary vein. The blood contained in the vein was
dark. The nerve-braiieh coming to the gland from the sympathetic was now
ligated, whereupon the venous blo(Kl from the gland grew red and flowed more
abundantly ; no saliva was excreted. The sympathetic nerve was now stimu-
lated between the ligature and the gland. At this the blootl in the vein became
dark again, flowed in less abundance and Anally stopped entirely. On allow-
ing the animal to rest the venous blood' grew red once more. The chorda
tympani nerve, coming from the lingual nerve, was now ligated, and the end
in connection with the gland stimulated. Then almost at once saliva streamed
into the duct, and large quantities of bright scarlet blood flowe<l from the vein
in jets, synchronous with the pulse.

This experiment may be said to close the earlier history of the vaso-motor
nerves.' It was now established beyond question that tlie size of the blood-
vessels, and thus the quantity of blood carried by them to diiferent parts of the
body, is controlled by nerves which when stimulated either narrow the blood
vessels (vaso-constrictor nerves) and thus diminish the quantity of blood that
flows through them, or dilate the vessels (vaso-dilator nerves) and increase the
flow. The section of vaso-constrictor nerves, for example those found in the
cervical sympathetic, causes the vessels previously constricted by them to dilate.
The section of a vaso-dilator nerve, for example the chorda tympani, running
from the lingual nerve to the submaxillary gland, does not, however, cause the
constriction of the vessels to which it is distributed. And finally, it was now
determined that vaso-motor fibres are found in the sympathetic system as
well as in the spinal cord and the cerebro-spinal nerves.

It remained for a later day to show that vaso-motor nerves are present in
the veins as well as in the arteries. Mall ^ has found that when the aorta is
compressed below the left subclavian artery, the portal vein receives no more
blood from the arteries of the intestine, yet remains for a time moderately full,
because it cannot immediately empty its contents through the portal capil-
laries of the liver against the resistance which they offer. If the peripheral
end of the cut splanchnic nerve is now stimulated, the portal vein contracts
visibly and may be almost wholly emptied. Thompson^ has extended the
discovery of Mall to the superficial veins of the extremities. He finds that
the stimulation of the peripheral end of the cut sciatic nerve, the crural artery
being tied, causes the constriction of the superficial veins of the hind limb.
The contraction begins soon after the commencement of the stimulation, and
usually goes so far as to obliterate the lumen of the vein. Often the contrac-
tion begins nearer the proximal portion of the vein and advances toward the
periphery. More commonly, however, it is limited to band-like constrictions
between which the vein is filled with blood. After stimulation ceases the
constrictions gradually disappear. A second and third stimulation produce

^ Further information regarding the history of this subject is given by Vulpian, Lemons sur
I'appareil vaso-moieur, Paris, 1875; Longet, Trails de physiologic, Paris, 1869, t. ii. p. 199; and
Schiff, Untersuchungen zur Physiologie des Nenensy stems, P'rankfort-am-Main, 1855, Bd. i. p. 124.

2 Mall, 1890, p. 57 ; 1892, p. 409. '" Thompson, 1893, p. 104.

486 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

much less constriction. The superficial veins of" the rabbit's abdotncii are
constricted by the stinuihition of tlie cervical spinal cord at the second ver-
tebra.

The observations oi" liernard and his contemporaries led to a very great
number of researches on the general properties and the distribution of the
vaso-motor nerves, in the course of which a variety of ingenious methods of
observation liave been devised.

Methods of Observation. — One fruitful method of research has been
already incidentally mentioned, namely, the direct inspection of the vessel, or
region, the vaso-motor nerves of which are being studied.

A second method consists in accurately measuring the outflow from the
vein. If the blood-vessels of the area drained by the vein are constricted by
the stimulation of a vaso-motor nerve, the quantity escaping from the vein in
a given period previous to constriction will be greater than that escaping in an
equal period during constriction. This well-known method is especially avail-
able where an artificial circulation is kept up through the organ studied, as
the blood drained from the vein does not then weaken the animal and thus
disturb the accuracy of the observations.'

A third method is founded on the principle in hydraulics that the lateral
pressure at any point in a tube through which a liquid flows depends, other
things being equal, on the resistance to be overcome below the point at which
the pressure is measured. In the animal body the resistance to be overcome
by the blood-stream varies with the state of contraction of the smaller vessels,
and thus the variations in the lateral pressure of a given artery may, under
certain restrictions, be used to determine variations in the size of the smaller
vessels distal to the artery. The restrictions are, that the variations in the
lateral pressure in the artery are indicative of changes in the size of the distal
vessels only when the general blood-pressure remains unaltered, or alters in a
direction opposite to the change in the artery investigated.^ An example will
make this plain. Dastre and Morat,^ in order to demonstrate the presence of
vaso-motor fibres for the hind limb in the sciatic nerve, connected a manometer
with the central end of the left femoral artery, and a second manometer with
the peripheral end of the right femoral artery, distal to the origin of the pro-
funda femoris. The anastomoses between the principal branches of the fem-
oral artery are so numerous and so large that the circulation in the limb can
be maintained by the profunda femoris alone. Dastre and Morat could there-
fore compare the general blood-pressure with the blood-pressure in the right
hind limb. On stimulating the peripheral end of the right sciatic nerve, the
blood-pressure rose in the arteries of the limb, but remained stationary in the
arteries of the trunk, connected with the first manometer through the central
end of the left femoral artery. The rise of blood-pressure in the operated
limb, while the blood-pressure in the rest of the body remained unchanged,
proved that the vessels in the operated limb were constricted.

* Cavazzani and Manca, 1895, p. 33. ' llurthle, 188&, p. 563.

' Dastre and Morat, 1883, p. 556.

CIRCULATION. 487

Many investigators liave studied vaso- motor phenomena by means of the
plethysmograph, an apparatus invented by Mosso for recording the changes in
the volume of {\\v extremities. The member, the vaso-motor nerves of which
are to be studied, is placed within a cylinder filled with water, from which a
tube leads to a recording tambour.' An increase in the volume of the member,
such as would be brctught about by the expansion of its vessels, causes a corre-
sponding vt)lume of water to enter the tambour tube, thus raising the pressure
in the tambour and forcing its lever to rise. A constriction of the vessels, on
the contrary, causes the recording lever to fall.

In addition to these general methods, special devices have been employed
in the researches into the vaso-motor nerves of the brain.

In considerino- the observations made Avith these various methods it will
be advisable to beo-in with the differences between the two kinds of vaso-motor
nerves.

Differences bet^ween Vaso-constrictor and Vaso-dilator Nerves. — The
differences between vaso-constrictor and vaso-dilator nerves are particularly
interesting for the reason that both vaso-constrictor and vaso-dilator fibres are
often found in one and the same anatomical nerve. The sciatic nerve is a
good example of this. By taking advantage of these differences the investi-
gator may determine whether one or both kinds of fibres are present in any
anatomical nerve; whereas, without this knowledge, the effects produced by
the stimulation of the one might be wholly masked by the effects produced by
the stimulation of the other.

The vaso-constrictors are less easily excited than the vaso-dilators. The
simultaneous and equal stimulation of the dilator and constrictor nerves going
to the submaxillary gland causes vaso-constrictiou, dilatation appearing after
the stimulation ceases, for the after-effect of excitation is of shorter duration
with the constrictors than with the dilators.^ ^yarming increases and cooling
diminishes the excitability of the vaso-constrictors to a greater degree than is
the case with the vaso-dilators. Thus if the hind limb of an animal be
warmed, the stimulation of the sciatic nerve will cause vaso-constriction ;
while if it be cooled the same stimulation will cause vaso-dilatation.^ Vaso-
constrictors are more sensitive to rapidly repeated induction shocks (tetaniza-
tion) and less sensitive to single induction shocks than are vaso-dilators. Thus
if the sciatic nerve is stimulated with induction shocks of the same strength, it
will be found that a rapid repetition of the stimuli will give vaso-constriction,
while with single shocks at intervals of five seconds vaso-dilatation is the result.'*
Vaso-constrictors degenerate more rapidly than vaso-dilators after separation
from their cells of origin. The stimulation of the peripheral end of the frog's
sciatic nerve immediately afler section causes constriction. Several days later
the same stimulation causes vaso-dilatation, the oonstrictor nerves having already

' An. improved inetliod of recording is given by Bowditch and Warren, 18S6, p. 420.

^ Anrep and Cybulski, 1884.

'■" Lepine, 1876, p. 26; Howell, Budgett, and Leonard, 1894, p. 306.

♦ Ostroumoff, 1876, p. 232; Bowditch and Warren, 1886, p. 436; Bradford, 1889, p. 390.

488 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

degenerated' (sec Fig. 129, H). The maxiinuni effect of stimulation is more
quickly reached with the vaso-constrictor than with the vaso-dilator nerves.
Tiiere is also a difference in the latent period, or interval between stinudatiim

.1 It

Kiii. 12'.t.— Curvi-s olitaiiKMl by enclosiiifj llie hiiifl limb of a cut in the plethysni()t,'ra|)li and stimu-
lating the peripheral end of the cut sciatic nerve (Bowditch and Warren, 18)5t;, p. 4-17). The curves read
from right to left. In each case the vertical lines show the duration of the stimulus— namely, fifteen
induction shocks per second during twenty seconds. Curve A shows the contraction of the vessels pro-
duced by the excitation of the freshly-divided nerve ; curve B, the dilatation produced by an equal
excitation of the nerve of the opposite side four days after section, the vaso-constrictor nerves having
degenerated more rapidly than the vaso-dilators.

and response. Bowditch and Warren^ have found the latent period of the
vaso-constrictor fibres in the sciatic to be about 1.5 seconds, while that of the
vaso-dilators is 3.5 seconds. Finally, the two sorts of nerves have been said
to differ in the manner in which they are distributed. The vaso-constrictor
nerves leave the cord as medullated fibres, enter the sympathetic chain of gan-
glia and end in terminal branches probably in contact with a sympathetic
ganglion-cell. The constrictor impulse is forwarded to the vessel by a
process of this cell, either directly or by means of still other sympathetic
ganglion-cells. The vaso-dilator fibre, on the contrary, was thought to run
directly from the cord to the blood-ves.sel ; ^ but the latest investigations make
it probable that all spinal vaso-motor fibres end in sympathetic ganglia.*

Origin and Course. — The vaso-motor nerves the general i)roperties of
which have just been .studied are axis-cylinder processes of .sympathetic gan-
glion-cells. They follow, for a time at least, the course of the corresponding
spinal nerve. According to Langley,® they do not differ from the pilo-motor
and secretory nerves except in the nature of the structure in which they termi-
nate. They are not interrupted by other nerve-cells on their coui^e. The
action of the sympathetic vaso-motor cells is influenced by the vaso-motor
cells of the spinal cord and bulb. These arc probably small cells situated at
various levels in the anterior horn and lateral gray substance.^ Their axi.s-
cylinder processes leave the cerebro-spinal axis by the anterior roots ^ of

' Ostroiimoff, 1876, p. 228; Bowditch and A\'arren, 1886, p. 444.

2 Bowditch and Warren, 1886, p. 440. ^ Kolliker, 1894, p. 2.

* Lansley, 1895, p. 314. * I^angley, 1895, p. 314. « Kolliker, 1894, p. 6 (reprint).

' Biuljje, 1853, p. 378 Some investifiators hold that va-so-niotor nerves leave the cord in the
posterior as well as tlie anterior roots. Strieker' observed that excitation of the peripheral end
of the posterior roots of the sciatic nerve is followed by a rise of temperature in ilie Iiind limb.
This was denied bv Kiihlwetter.* Bonuzzi^ and Gartner* agreed with Strieker. Moral* found

» Strieker, 1877, p. 279. 2 Kiihlwettcr, ]HS.\ p. in. 3 Bonuzzi, 1885, p. 473. < Giirtner. lb»9, p. 980.
6 Morat, 189-2, pp. 1499, 694; see also Bradford, 1889, p. 363, and Moral, 1890, p. 473.

CIRCULATION. 489

certain spinal and by certain cranial nerves, and enter sympathetic ganglia,
wiiere they end in terminal twigs probably in contact with the sympathetic
vaso-motor cells. The vaso-motor cells lying at various levels in the cerebro-
spinal axis are in turn largely controlled by an association of cells situated in
the bulb and termed the vaso-motor centre. The neuraxons (axis-cylinder
processes) of the cells composing this " centre " pass in part to the nuclei of
certain cranial nerves and in part down the lateral columns' of the cord, to
end in contact with the spinal vaso-motor cells. The vaso-motor apparatus
consists, then, of three classes of nerve-cells.^ The cell-bodies of the first class
lie in sympathetic ganglia, their neuraxons passing directly to the smooth mus-
cles in the walls of the vessels ; the second are situated at different levels in
the cerebro-spinal axis, their neuraxons passing thence to the sympathetic gan-
glia by way of the spinal and cranial nerves ; and the third are placed in the
bulb and control the second through intraspinal and intracranial paths. The
nerve-cell of the first class lies wholly without the cerebro-spinal axis, the third
wholly witliin it, while the second is partly within and partly without, and
binds together the refmaining two.

The evidence for the existence of these vaso-motor nerve-cells must now
be considered. We shall begin with those of the third class, constituting the
so-called bulbar vaso-motor centre.

Bulbar Vaso-motor Centre. — The section of the spinal cord near its
junction with the bulb is followed by the general dilatation of the blood-
vessels of the trunk and limbs.^ The dilated vessels are again constricted
when the severed fibres in the spinal cord are artificially stimulated. Hence
the section caused the dilatation by interrupting the vaso-constrictor impulses
passing from the bulb to parts below. The position of the bulbar vaso-
constrictor centre has been determined by Owsjannikow and Dittmar. The
former observer * divided the bulb transversely at various levels. When the
section fell immediately caudal to the corpora quadrigemina, only a slight
temporary rise in blood-pressure was observed. When, however, the section
fell a millimeter or two nearer the cord, a considerable and permanent fall in
the blood-pressure was noted. Further lowering was seen as the sections
were carried still farther toward the spinal cord, until at length, about four
millimeters from the corpora quadrigemina, no further fall took place. The
area from which the vaso-constrictor nerves receive a constant excitation
extends, therefore, in the rabbit, over about three millimeters of the bulb not
far from the corpora quadrigemina. Two yeajs after this investigation Ditt-
mar added to the observations of Owsjannikow the fact that the vaso-con-

in a ciirarized dog that excitation of the peripherai end of certain lumbo-sacral posterior roots
causes primary vascular dilatation in the pulp of the hind paw corresponding to the nerves
stimulated. The fibres in question, do not degenerate after section of the root containing them,
and are therefore not of spinal origin.

' Compare Nicolaides, 1882, p. 28; Helweg, 1886, quoted by Tigerstedt, 1893, p. 536.

^ By "nerve-cells" is meant the cell-body with all its processes, namely, the neuraxon, or
axis-cylinder process, and the dendrites, or protoplasma processes.

^ Waller, 1853, p. 381. ♦ Owsjannikow, 1871, p. 25.

490 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

strictor centre is bilateral, lyint!; in tlio aiitoiior pari of tlu- lateral eoliiniiis on
both sides of the median line.' At this site is i'oiind a t!:n»u}) of nantrjion-celle
known as the antero-lateral nneleus of Clarke. It is possible, tlionj:;h far
from certain, that these are tlic cells of the vaso-eonstrictor centre.

The vaso-constrictor centre in the bulb is always in a state of action, or
"tonic" excitation, as is shown by the dilatation of the vessels when deprived
of their constrictor impulses through the section of the spinal cord.

It is not definitely known whether a vaso-dilator centre is present in the
bulb.

Spinal Centres. — A complete demonstration of the existence of vaso-raotor
centres in the spinal coi'd, first suggested by Marshall Hall, was made by Goltz
and Freusberg- in their experiments on dogs which had been kept alive after
the division of the spinal cord at the junction of the dorsal and the lumbar
regions. This operation cuts off both sensory and motor communication
between the parts lying above and below the plane of section, and divides the
animal ]>hysiologically into a fore dog and a hind dog, to use the author's
expression. The investigator can now explore the lumbar cord unvexed by
cerebral impulses. A great number of motor reflexes formerly thought to have
their centres exclusively in ^he brain are by this means found to take place
in the absence of the brain. '^ That vaso-motor reflexes were among them was
discovered by accident. It was noticed that the mechanical stimulation of the
skin of the abdomen and penis while the animal was being washed provoked
erection, M'hich, as Eckhard^ had discovered some years before, is a reflex action
due to the dilatation of the arteries of the penis through impulses conveyed by
the nervi erigentes. Pressure on the bladder, or the walls of the rectum, also
had this effect. After the destruction of the lumbar cord this reflex was no
longer possible. The vessels of the hind limb are also connected with vaso-
motor cells in the lumbar cord. Soon after the section of the cord in the dorsal
region the hind paws are observed to be warmer than the fore paws, and the
arteries of the hind limb are seen to beat more strongly. This is the result of
cutting off* the vaso-constrictor impulses from the bulbar centre to the vessels
in question. If the animal survives a considerable time the hind paws will
be observed to grow cooler from day to day until they are again no warmer
than the fore paws. Destruction of the lumbar cord now causes the tempera-
ture of the hind limbs to rise again.

The conclusion drawn from these observations is that vaso-motor cells are
present in the spinal cord. It is probable that they are normally subordinated
to the bulbar nerve-cells and require a certain time after separation from the
bulb in order to develop their previously rudimentary powers. Hence the

^ Dittmar, 1873, pp. 110, 114. Otiier literature : Sohitf, 1855, p. 198 ; Heidenhain. 1870,
510; Latschenberger and Dealma, 1876, p. 183; Strieker, 1886, p. 13.

'Goltz and Freusberg, 1874, p. 463. Other literature: Smirnow, 1886, p. 145; Ustimo-
witsch, 1887, p. 187 ; Thayer and Pal, 1888, p. 29 ; Konow and Stenbeck, 1889, p. 409.

' Later experiments by Goltz and Ewald, showing the decree of independence of the spinal
cord possessed by sympathetic vaso-motor neurons will presently be cited.

* Eckhard, 1863, p. 144.

CIRCULA TION. 491

interval of many days between the section and the return of arterial tone in areas
distal to tiie section. It has been suggested tliat during this period the power
of tiie spinal nerve-cell is inhibited by impulses proceeding from the cut sur-
face of the cord/ but this long inhibition is questionable in view of the fact
that transverse section of the cord in ral)bits and dogs does not inhil)it the
phrenic nuclei.^

The spinal nerve-cell takes part in vaso-motor reflexes. Thus the stimu-
lation of the central end of the brachial nerves after section of the spinal cord
at the third vertebra causes a dilatation of the vessels of the fore limb.^ The
stimulation of the central end of the sciatic nerve after the division of the
spinal cord causes a general rise of blood-pressure indicating the constriction
of many vessels. The sensory stimulation of one hind limb may cause reflexly
a narrowing of the vessels in the other, after the spinal cord is severed in the
mid-thoracic region.^ In asphyxia, after the separation of the cord from the
brain, vascular constriction is produced reflexly through the spinal centres.^
This constriction is not observed if the cord is previously destroyed.^ Goltz
and Ewald ^ find that the tonic constriction of the vessels of the hind limbs
returns after the extirpation of the lower part of the spinal cord.

Sympathetic Vaso-motor Centres. — Gley ^ finds that after the destruc-
tion of both bulbar and spinal centres some degree of vascular tone is still
maintained. The extraordinary experiments of Goltz and Ewald ' place this
fact beyond question. These physiologists remove the lower part of the spinal
cord completely, taking away 80 millimeters or more. For a few days after
the operation the hind limbs are hot and red, from dilatation of their blood-
vessels. Soon, however, the hind limbs become as cool, and sometimes even
cooler, than the fore limbs, their arterial tonus being re-established and main-
tained without the help of the spinal cord.

The sympathetic ganglia are probably also centres of reflex vaso-motor
action. The fact that these ganglia act as centres for other motor reflexes
would itself suggest this possibility. A direct proof of the vaso-motor reflex '"
function of the first thoracic ganglion has been given recently by Fran9ois
Franck." The two branches composing the annulus of Vieussens contain both
afierent and efferent fibres. If one of the branches is cut, and the end in con-
nection with the first thoracic ganglion is stimulated, the ganglion having been
separated from the spinal cord by the section of the communicating branches,
a constriction of the vessels of the ear, the submaxillary gland, and the nasal
mucous membrane may be observed.

1 Goltz and Ewald, 1896, p. 397. = Porter, 1895, p. 459.

3 Smirnow, 1886, p. 147; compare Thayer and Pal, 1888, p. 29.
* Vulpian, 1875, p. 290. ' Knwalewsky and Adamiik, 1868, p. 582.

« Konow and Stenbeck, 1889, p. 409. ' Goltz and Ewald. 1891, p. 496 ; 1896, p. 388.

8 Gley, 1894, p. 704. » Goltz and Ewald, 1896, p. 389.

*•' See Wertheimer, 1890, p. 519 ; Navrocki and Skabitschewsky, 1891, p. 156 ; Langley and
Anderson, 1893, p. 417 ; Franck, 1894, p. 717 ; compare Mosso and Pellacani, 1882, p. 300; also
Goltz and Ewald, 1896, p. 391.

" Franck, 1894, p. 721 ; see also Roschansky, 1889, p. 162.

492 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Tliis evidence, together with the j)robability that tlie neiiraxons of all the
spinal vaso-motor cells end in sympathetic ganglia/ makes it fairly credible
that the syni})athetie vaso-motor nerve-coll possesses central functions.

There has been much discussion over the meaning of the rhythmic con-
tractions observed in certain blood-vessels apparently independent of the cen-
tral nervous system.^ The median artery of the rabbit's ear, the arteria
saphena in the same animal, and the vessels in the frog's web and frog's mes-
entery, slowly contract and relax. This rhythmic contraction is easily seen in
the car of a white rabbit. The movements are possibly of purely muscular
origin, but are more probably the result of periodical discharges by vaso-motor
nerve-cells.

Rhythmical variations in the tonus of the vaso-constridor centres are often
held to explain the oscillations seen in the blood-pressure curve after the
influence of thoracic aspiration has been eliminated by opening the chest and
cutting the vagus nerves. These oscillations are of two sorts. In the one,
the blood-pressure sinks with every inspiration and rises with every expiration,
though the rise and fall are not precisely synchronous with the respiratory
movements ; in the other, the so-called Traube-Hering waves, the oscillations
embrace several resj)i rations. It has also been suggested that these phenomena
are due to periodical changes in the respiratory centre affecting the vaso-con-
strictor centre by "irradiation."^

Vaso-motor Reflexes. — The vaso-motor nerves can be excited reflexly by
afferent impulses conveyed either from the blood-vessels themselves or from
the end-organs of sensory nerves in general. The existence of reflexes from
the blood-vessels may be shown by Heger's experiment. Heger* observed a
rise of general blood-pressure with a subsequent fall, and at times a primary
fall, after the injection of nitrate of silver into the peripheral end of the crural
artery of a rabbit. The limb, with the exception of the sciatic nerve, was
severed from the trunk. The quantity injected was so small that it probably
was decomposed before passing the capillaries or escaping from the blood-
vessels. Thus the eflfect exerted by the nitrate of silver on the general blood-
pressure was probably caused by afferent impulses set up in the blood-vessels
themselves and transmitted through the sciatic nerve to the vaso-motor cen-
tres. Vaso-motor reflexes are, however, much more commonly produced
by the stimulation of sensory nerves other than those present in the blood-
vessels.

The reflex constriction or dilatation ' appears usually in the vascular area

* See the statement of Langley's results with the nicotin method on pape 500.

^ Literature: Schiff, 1854, p. 508; Mosso, 1880, p. 66; Pye-Sinitli, 1887, p. 48; Fredericq,
1887, p. 351; Konow and Stenbeck, 1889, p. 406. Discussion of the active dilatation of the
blood-vessels has been recently revived by Piotrowski, 1892. p. 701 ; (iriinhagen, 1892, p. 829;
Franck, 1893, p. 729; Biedl, 1894; Stefani, 1894, pp. 237, 245; Lui, 1894, p. 410; Goltz and
Ewald, 1896, p. 396.

' Compare Fredericq, 1882, p. 71; Knoll, 1885, p. 439. * Heger, 1887, p. 197.

^ For a study of reflex constriction and dilatation produced by stimulating the skin see
Maragliano and Lusona, 1889, p. 246 ; compare Hegglin, 1894, p. 25.

CIRCULA TION. 493

from wliich the afferent impulses arise. For example, the stimulation of the
central end of the posterior auricular nerve in the ral)bit causes a ])assing con-
striction followed by dilatation, or a primary dilatation often followed by
constriction of the vessels in the ear. The stimulation of the nervi erigentes
causes dilatation of the vessels of the penis.' Gaskell ^ found that the vessels
of the mylo-hyoid muscle widened on stimulating the mucous membrane at
the entrance of the glottis.

The vascular reflex ^ may appear in a part associated in function with the
sensory surface stimulated. Thus the stimulation of the tongue causes dilata-
tion of the blood-vessels in the submaxillary gland.* Frequently the vascular
reflex is seen on both sides of the body. The stimulation of the mucous
membrane on one side of the nose may cause vascular dilatation in the whole
head;* the effect in this case is usually more marked on the side stimulated.
The vessels of one hand contract when the other hand is put in cold water.®
Sometimes distant and apparently unrelated parts are affected. Vulpian^
noticed that the stimulation of the central end of the sciatic caused the vessels
of the tongue to contract.

The vascular changes produced reflexly in the splanchnic area are of
especial importance because of the great number of vessels innervated through
these nerves and the great changes in the blood-pressure that can follow dilata-
tion or constriction on so large a scale.

There is in some degree an inverse relaiion between the vessels of the skin
and deeper parts on reflex stimulation of the vaso-raotor centres. The super-
ficial vessels are often dilated while those of deeper parts are constricted.*
Thus the stimulation of the central end of the sciatic nerve may cause a dilata-
tion of the vessels of the lips, hand in hand with a rise in general blood-pres-
sure.' Exposing a loop of intestine dilates the intestinal vessels in the rabbit,
but constricts those of the ear.'" In asphyxia, the superficial vessels of the ear,
face, and extremities dilate, while the vessels of the intestine, spleen, kidneys
and uterus are constricted."

Relation of Cerebruin to Vaso-motor Centres. — A rise of general blood-
pressure has been produced by the stimulation of different regions of the cortex
and of various other parts of the brain ; for example, the crura cerebri and
corpora quadrigemina. Vaso-dilatation has also been observed. The motor
area of the cortex especially seems closely connected w' ith the bulbar vaso-
motor centres. There is, however, no conclusive evidence that special vaso-

» Eckhard, 1863, p. 144. ^ Qaskell, 1877, p. 742.

' The general arrangement of the matter in this paragraph is that given by Tigerstedt,
1893, p. 519. * Bernard, 1858, p. 656. * Franck, 1889, p. 555.

* Brown-S^quard and Tholozan, 1858, p. 500; compare Teissier and Kaufmann, 1881, p.
1302; and Ranvier, 1892, p. 629.

'' Vulpian, 1875, p. 238; compare Sergejew, 1894, p. 162.

* Griitzner and Heidenhain, 1878, p. 20 ; Dastre and Morat, 1884, p. 329 ; "Wertheimer,
1893, p. 595; 1894, p. 724; Franck, 1896, p. 502; compare Bayliss and Bradford, 1894, p. 17.

* Wertheimer, 1891, p. 548 ; compare Isergin, 1894, p. 448.

1° Pawlow, 1878, p. 268. " Heidenhain, 1872, p. 100.

494 AN AMERICAN TEXT-BOOK OF PIIYSTOLOGY.

motor centres exist in the brain aside I'loni llie bulbar centres already described.
At present the safer view is that the changes iu blood-pressure called forth by
the stimulation of various jiarts of the brain are reflex actions, the afferent im-
pulse starting in the brain as it might in any other tissue peripheral to the
vaso-motor centres.'

Pressor and Depressor Fibres. — The stimulation of the same aflerent
nerve sometimes causes reflex dilation of the vessels of a part, instead of the
more usual reflex constriction. Two explanations of this fact have been sug-
gested. The first assumes that the condition of the vaso-motor centre varies in
such a way that the same stimuli might produce contrary effects, depending
on the relation between the time of stimulation and tlie condition of the centre.
The second assumes the existence of special reflex constrictor or " pressor "
fibres, and reflex dilator or "depressor" fibres. The existence of at least one
depressor nerve is beyond question, namely the cardiac depressor nerve, which
it will be remembered runs from the heart to the bulb and when stimulated
causes a dilatation of the splanchnic and other vessels reflexly through the
bulbar vaso-motor centre. Evidence of other reflex vaso-dilator nerves and of
reflex vaso-constrictor fibres as well has been offered by Latschenberger and
Deahna,^ Howell,^ and others. Howell, for example, has found that if u part of
the sciatic nerve is cooled to near 0° C. and the central end stimulated periph-
erally to this part, the blood-pressure falls, instead of rising, as it does when
the nerve is stimulated without previous cooling. Howell's experiments have
been recently extended by Hunt,* who finds that the stimulation of the sciatic
during its regeneration after section gives at first vaso-dilatation only, but when
regeneration has progressed still further, vaso-constriction is secured. These
results point to the existence of both pressor and depressor fibres, the latter
being the first to regenerate after section. A reflex fall in blood-pressure is
also produced by stimulating various mixed nerves with weak currents' and
by the mechanical stimulation of the nerve-endings in muscle. The fiill is
more readily obtained when the animal is under ether, cliloroform, or chloral,
less readily under curare.

Topography. — "We pass now to the vaso-motor nerves of various regions.

Brain.^ — The study of the innervation of the intracranial vessels is ren-
dered exceptionally difficult by the fact that the brain and its blood-vessels are
placed in a closed cavity surrounded by walls of unyielding bone. The funda-
mental difference created by this arrangement between the vascular phenomena

1 Literature: Dogiel, 1880, p. 420; Strieker, 1886, p. 9; Bechterew and Mislawsky, 1886,
p. 193; Franck, 1887, p. 1G2.

* Latschenberger and Dealina. ISTfi, p. 165.

» Howell, Budgett, and Leonard, 1894, p. 310. Other literature : Belfield, 1882, p. 298 ; Knoll,
1885, p. 447, 1889, p. 249 : Kleen, 1887, p. 247 ; Bayliss, 1893, p. 317 ; Bradford and Dean,
1894, p. 67 ; Hunt, 1895, p. 381.

♦ Hunt, 1895, p. 381.

5 See also Knoll, 1885, p. 451.

6 Literature: Mosso, 1880, p. 1-127 ; Franck, 1887, p. 199 ; Gaertner and Wagner, 1887, p. 602;
Corin, 1888, p. 185; Hiirthle, 1889, p. 561 ; Eoy and Sherrington, 1890, p. 85; Cavazzani, 1891,
p. 23; 1893, pp. 54, 214; Bayliss and Hill, 1895, p. 334; Gulland, 1895, p. 361.

CIRCULA TION. 495

of the brain and those of otlier organs was recoj^iiized in part at least by
the yonngor INIonro as long ago as 1783. Monro declared that tiie quantity
of blood within the cranium is almost invariable, " for, being enclosed in a
case of bone, the blood must be continually flowing out of the veins that room
may be given to the blood which is entering l)y the arteries, — as the substance
of the brain, like that of the other solids of our body, is nearly incompress-
ible." Further differences between the circulation in the brain and in other
organs are introduced by the presence of the cerebro-spinal fluid in the ventri-
cles and in the arachnoidal spaces at the base of the brain. This fluid may pass
out into tiie spinal canal and thus leave room for an increase in the amount
of blood in the cranium. Finally, a rise of pressure in the arteries too great
to be compensated by the outflow of cerebro-spinal fluid may lead to com-
pression of the venous sinuses and a decided change in the relative distri-
bution of the blood in the arteries, capillaries and veins — conditions which are
not present in extracranial tissues. It is evident, therefore, that the methods
emj)loyed in the search for vaso-motor nerves within the cranium must take
into account many sources of error that are absent in vaso-motor studies of
other regions. It is, indeed, probable that incompleteness of method will go
far toward explaining the disagreement of authors as to the presence of vaso-
motor nerves in the brain. According to Bayliss and Hill,^ the most recent
investigators of this subject, it is necessary to record simultaneously the arterial
pressure, the general venous pressure, the intracranial pressure and the cerebral
venous pressure, the cranium as in the normal condition being kept a closed
cavity. In their experiments, " a cannula was placed in the central end of the
carotid artery. A second long cannula was passed down the external jugular
vein, and on the same side, into the right auricle. The torcular Herophili was
trephined, and a third cannula, this time of brass, was screwed into the hole
thus made." The intracranial pressure was recorded by a cannula connected
through another trephine-hole with the subdural space.

Bayliss and Hill could find no evidence of the existence of cerebral vaso-
motor nerves. The cerebral circulation, according to them, passively follows
the changes in the general arterial and venous pressure. Gulland ^ has examined
the cerebral vessels by the Golgi, Ehrlich, and other methods, to determine
whether nerve-fibres could be demonstrated in them. None were found. It
is probable that the blood-supply to the brain is regulated through the bulbar
vaso-constrictor centre.' Anaemia or asphyxia of the brain stinmlates the cells
composing this centre, vascular constriction of many vessels follows, and more
blood enters the cranial cavity. The vessels of the splanchnic area play a
chief part in this regulative process.* Their importance to the circulation in
the brain is shown by the fatal effect of the section of the splanchnic nerves
in the rabbit. On placing the animal on its feet, so much blood flows
into the relaxed abdominal vessels that death may follow from anaemia of the
brain.

' Bayliss and Hill, 1895, p. S37. ^ Gulland, 1895, p. 36L

» Bayliss and Hill, 1895, p. 358. * Wertheimer, 1893, p. 297.

496 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Vaso-rnotor Nerves of Head. — Tlie cervical .sympathetic contains vaso-con-
strictor fibres for the corresponding side of the face, the eye, ear, salivary
glands' and tongne, and possibly the brain. The spinal vaso-constrictor
fibres for the vessels of the lioad in the cat and dog leave the cord in the
first five thoracic nerves;^ in the rabbit, in the second to eighth thoracic, seven
in all.^

Vaso-dilator fibres for the face and month have been found in the cervical
sympathetic by Dastre and jNIorat,"* leaving the cord in the second to fifth
dorsal nerves, and uniting (at least for the most part) \vith the trigeminus by
passing, according to Morat,^ from the superior cervical sympathetic ganglion
to the ganglion of Gasser. Other dilator fibres for the skin and mucous
membrane of the face and mouth arise apparently in the trigeminus, for the
stimulation of this nerve between the brain and Gasser's ganglion causes dila-
tation of the vessels of the face,^ and in the nerve of Wrisberg/

The vaso-motor nerves of the tongue have been recently studied by Isergin.*
The lingual and the glosso-pharyngeal nerves are recognized by all authors as
dilators of the lingual vessels. The sympathetic and the hypoglossus contain
constrictor fibres for the tongue. It is possible that the lingual contains also
a small number of constrictor fibres. Most if not all these vaso-motor fibres
arise in the sympathetic and reach the above-mentioned nerves by Avay of the
superior cervical ganglion.® They degenerate in from three to five weeks after
the extirpation of the ganglion.

Morat and Doyon '" cut the cervical sympathetic in a curarized rabbit and
examined the retinal arteries with the ophthalmoscope. They were found
dilated. The excitation of the cervical sympathetic caused constriction, the
excitation of the thoracic sympathetic dilatation of these vessels. The retinal
fibres leave the sympathetic at the superior cervical ganglion and pass along
the communicating ramus to the ganglion of Gasser, whence they reach the
eye through the ophthalmic branch of the fifth nerve, the gray root of the
ophthalmic ganglion, and the ciliary nerves. Most, or all, of" the fibres for
the anterior part of the eye are found in the fifth nerve.

Lungs. — The methods ordinarily employed for the demonstration of vaso-
motor nerves cannot without danger be used in the study of the innervation

1 Compare Vulpian, 1885, p. 853. ' Langley, 1892, p. 102.

2 Langley, 1892, p. 104.

* Da,stre and Morat, 1884, pp. 116, 129; see also Pye-Smith, 1887. p. 25; Langley, 1890, p.
146; Langley and Dickinson, 1890, p. 380; Morat, 1891, p. 87; Piotrowski, 1892, p. 464;
Langley, 1892, p. 97.

* Morat, 1889, p. 201.

6 Vulpian, 1885, p. 982; compare Dastre and Morat, 1884, p. 118; Langley, 1893, iv.; Pio-
trowski, 1894, p. 278.

' Vulpian, 1885, p. 1038.

^ Isergin, 1894, p. 441 ; other literature: Anrep and Cybulski, 1884; Vulpian, 1885, pp. 854,
1038; Piotrowski, 1887, p. 454; 1894, p. 246.

® For evidence that probably all vaso-constrictor fibres to the head (nerve-cells of the second
class) end in thfi superior cervical ganglion, see Langley and Dickinson, 1889, p. 425.

'» Morat and Doyon, 1892, p. 60 ; see also Langley, 1893, iv. ; Doyon, 1890, p. 774 ; 1891, p. 154.

CIRCULA TION.

497

of tlic pulmonary vessels.' A fall in the blood-pressure in the pulmonary
artery, lor example, procluecd by stimulating any nerve cannot be taken as
final evidence that the stimulation caused the constriction of the pulmonary
vessels. The lesser circulation is so connected that changes in the calibre of
the vessels of a distant part, the liver for cxam])le, may alter the quantity of
blood in the Inngs.^ The method of Cava/zani'' avoids these dilhculties.
Cavazzani establishes an artificial circulation through one lobe of a lung in
a living animal, and measures the outflow per unit of time. An increase in
the outflow means a dilatation of the vessels, diminution means constriction.
He finds that the outflow diminishes in the rabbit when the vagus is stimulated
in the neck, and increases when the cervical sympathetic is stimulated. Franck
measures the pressure simultaneously in the pulmonary artery and left auricle,
a method apparently also trustworthy. The stimulation of the inner surface
of the aorta causes a rise of pressure in the pulmonary artery and a simul-
taneous fall in the left auricle, indicating, according to Franck,* the vaso-con-
strictor power of the sympathetic nerve over the pulmonary vessels. A reflex
constriction is also produced by the stimulation of the central end of a branch

■•'■^—'>

if \^-

PrA.F.H

LujLLimi.JLliJ,?i^'[ff.

Fig. 130.— The excitation of the central end of the inguinal branch of the crural (sciatic) nerve causes
a rise in the aortic pressure {Pr.A.F.), a rise in the pressure in the pulmonary artery (Pr.A.P.) of 10 to 16
mm. Hg, accompanied by a falling pressure in the left auricle (Pr.O.O.) (Franck, 1896, p. 184). The rise
of pressure in the pulmonary artery, together with the fall in the left auricle, demonstrate, according
to Franck, a constriction of the pulmonary vessels.

of the sciatic, intercostal, abdominal pneumogastric, and abdominal sympa-
thetic nerves^ (see Fig. 130).

Heart — Vaso-motor fibres for the coronary arteries of the heart have been
described in the vagus of the dog ^ and cat,''

1 Literature: Openchowski, 1882, p. 233; Franck, 1889, p. 555; Bradford and Dean, 1889,
i.-iv. ; 1889, p. 369; Couvreur, 1889, p. 731 ; Franck, 1890, p. 550; Arthaud and Butte, 1890,
p. 12; Knoll, 1890, p. 13; Cavazzani, 1891, p. 32; Doyon, 1893, p. 101 ; Henriques, 1893, p.
229; Bradford and Dean, 1894, p. 34; Franck, 1895, pp. 744, 816, 1896, p. 178.

2 Tigerstedt, 1893, p. 493. ' "^ Cavazzani, 1891, p. 35.
* Franck, 1896, p. 178. » Franck,' 1896, p. 184.

6 Martin, 1891, p. 291. ' Porter, 1896, p. 39.

32

498 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Intestines} — The mesenteric vessels receive vaso-constrictor fibres from tlie
sympathetic chiefly tliroiigh the s|>l:iii(linic nerve. ^ The vaso-constrictoi-.s of"
the jejunum, as a rule, begin to be lound in tiic rami of the fiftii dorsal nerves;
a little lower down, those for the ileum come off; and still lower down, those
for the colon ; none arise below the second lumbar pair.^ A(;cor(ling to Ilal-
lion and Franek, vaso-dilator fibres are present in the same sympathetic nerves
that contain vaso-constrictors. The dilator fibres are most abundant or most
powerful in the rami of the last three dorsal and first two lumbar nerves.
There is some evidence of the presence of vaso-dilator fibres in the vagus.
The excitation of the vaso-constrictor centres by the blood in asphyxia pro-
duces constriction of the abdominal vessels/ The vaso-dilator as well as the
vaso-constrictor fibres of the splanchnic probably end in the solar and renal
plexuses/

Liver. — Cavazzani and Manca ® have recently attempted to show the pres-
ence of vaso-motor fibres in the liver. Their method consists in passing warm
normal saline solution from a Mariotte's flask at a pressure of 8 to 10 milli-
meters Hg through the hepatic branches of the portal vein and measuring
the outflow in a unit of time from the ascending vena cava. On stimulating
the splanchnic nerve they observed that the outflow was usually diminished
though sometimes increased, indicating perhaps that the splanchnics contain
both vaso-constrictor and vaso-dilator fibres for the hepatic branches of the
portal vein. The vagus appeared to contain vaso-dilator fibres. Further
studies are necessary, however, before pronouncing definitely upon these
questions.

Kidney? — The vaso-motor nerves of the kidney leave the cord from the
sixth dorsal to the second lumbar nerve.^ In the dog, most of the renal vaso-
motor fibres are found in the eleventh, twelfth, and thirteenth dorsal nerves.'
The stimulation of the nerves entering the hilus of the kidney between the
artery and vein causes a marked and sudden renal contraction, but the organ
soon regains its former volume.'" Constriction follows also the stimulation of
the peripheral end of the cut splanchnic nerve." Bradfi)rd has demonstrated
renal vaso-dilator fibres for certain nerves by stimulating at the rate of one
induction shock per second. For example, the excitation of the thirteenth
dorsal nerve with 50 to 5 induction shocks per second gave always a constric-

• Literature: Cyon and Ludwig, 1866, p. 136; Cohnlieim and Roy, 1883, p. 440: Dastre
and Morat, 1884, p. 294; Waters, 1885, p. 460; Bradford, 1889, p. 390; Hallion and Franek,
1896, p. 478. ^ Cyon and Ludwig, 1866, p. 136.

» Hallion and Franek, 1896, p. 496.

* Dastre and Morat, 1884, p. 294; Hallion and Franek, 1896, p. 506.
' * Langley and Dickinson, 1889, p. 429.

« Cavazzani and Manca, 1895, p. 33: see also Pal, 1888, p. 73.

^Literature: Nicolaides, 1S82, p. 28; Cohnlieim and Roy, 1883, p. 345; Klemensiewicz.
1886, p. 84; Masius, 1888, p. 539; Bradford, 1889, p. 404; Arthaud and Butte, 1890, p. 379;
Preobrascbensky, 1892; Wertlieimer, 1893, p. 1024; 1894, p. 308; Bayliss and Bradford, 1894,
p. 17. ' « Bayliss and Bradford, 1894, p. I7. « Bradford, 1889, p. 404.

»» Cobnbeini and Roy, 1883, p. 345; and Bradford, 1889, p. 364.

" Cohnheim and Roy, 1883, p. 440.

CIRCULATION. 499

tiou of the kidney, but when a single shock per second was employed, the
kidney diluted.' If the cells connected with the renal vaso-niotor fibres are
stimulated directly by venous blood as in asphyxia, the animal being curarized,
a decided constriction of the kidney results.^ The reflex excitation of these
cells is of especial importance. The stimulation of the central end of the
sciatic or the splanchnic nerves causes renal constriction.^ The same effect is
easily produced by stimulating the skin, for example, by the application of
cold.'* The stinuilation of the sole of the foot in a curarized dog caused
contraction of the renal vessels.* There is some evidence that the
splanchnic vaso-motor fibres for the kidney end in the cells of the renal
plexus.*"

Spleen. — The stimulation of the peripheral end of the splanchnic nerves
causes a sudden and large diminution in the volume of the spleen.'' It
is, however, not certain Avhether the constriction of the spleen is to be
referred primarily to a constriction of its blood-vessels or to the contraction
of the intrinsic muscular fibres which play so large a part in the changes of
volume of this organ. The doubt is strengthened by the fact that section of
the splanchnic nerves does not alter the volume of the spleen ; dilatation
would be expected were these nerves the pathway of vaso-constrictor fibres
for the spleen.

External Generative Organs.^ — The recent history of the vaso-motor nerves
of the external generative organs — namely, those developed from the urogenital
sinus and the skin surrounding the urogenital opening^ — begins with Eck-
hard,'" who showed that the stimulation of certain branches of the first and
second, and occasionally the third, sacral nerves (dog) caused a dilatation of the
blood-vessels of the penis and erection of that organ, and with Goltz," who
found an erection centre in the lumbo-sacral cord. Numerous researches in
recent years, among which the reader is referred especially to the work of
Langley and Langley and Anderson,'^ have shown that the vaso-motor nerves
of the external generative organs of both sexes may be divided into a lumbar
and a sacral group.

The lumbar fibres pass out of the cord in the anterior roots of the second,
third, fourth, and fifth lumbar nerves, and run in the white rami communi-
cantes to the sympathetic chain, from which they reach the periphery either by
way of the pudic nerves or by the pelvic plexus. The greater number take

^Bradford, 1889, p. 387. * Coljnheim and Roy, 1883, p. 437.

3 Cohnheim and Roy, 1883, p. 439.

* Preobraschensky, 1892; Wertheimer, 1894, p. 308. ^ Wertheimer, 1893, p. 1024.
« Langley and Dickinson, 1889, p. 429.

' Roy, 1882, p. 225 ; Schiifer and Moore, 1896, pp. 229, 287.

* Literature: Goltz and Freusberg, 1874, p. 460; Kaes, 1883, p. 1; Anrep and Cybulski,
1884; Gaskell, 1887, iv. ; Morat, 1890, p. 480; Piotrowski, 1892, p. 464; Sherrington, 1892, p.
686; Franck, 1894, p. 740; Piotrowski, 1894, p. 284; Franck, 1895, p. 122; Langley and
Anderson, 1895, p. 5; 1895, p. 76.

* Langley and Anderson, 1895, p. 76; 1895, p. 85. i" Eckhard, 1863, p. 145.
*' Goltz and Freusberg, 1874, p. 460. ^^ Langley and Anderson, 1895, p. 120.

500 AN AMEBIC AN TEXT-BOOK OF PHYSIOLOGY.

the former course, runniug down the sympathetic chain to the sacral ganglia,
and passing from these ganglia through the gray rami communicantes to the
sacral nerves. None of the fibres thus derived enter the nervi erigentes of
Eckhard. Of the various branches of the pudic nerves (rabbit), the nervus
dorsalis causes constriction of the blood-vessels of the penis and the peri-
neal nerve contraction of the blood-vessels of the scrotum. The course by
way of the pelvic plexus is taken by relatively few fibres. They run for
the most part in the hypogastric nerves, a few sometimes joining the plexus
from the lower lumbar or upper sacral sym])atlietic chain, or from the
aortic plexus. The presence of vaso-dilator fibres in the lumbar group is
disputed.^

The sacral group of nerves leave the spinal cord in the sacral nerve roots.
Their stimulation causes dilatation of the vessels of the penis and vulva.

Internal Generative Organs (those developed from the Miillerian, or the
Wolffian, ducts). — Langley and Anderson ^ find vaso-constrictor fibres for the
Fallopian tubes, uterus, and vagina in the female, and the vasa deferentia and
seminal vesicles in the male, in the second, third, fourth, and fifth lumbar
nerves. The internal generative organs receive no afferent, and probably no
efferent, fibres from the sacral nerves.^

The position of the sympathetic ganglion-cells, the processes of which carry
to their peripheral distribution the efferent impulses brought to them by the
efferent vaso-motor fibres of the spinal cord, may be determined by the nicotin
method of Langley. About 10 milligrams of nicotin injected into a vein of a
cat prevent for a time, according to Langley,^ any passage of nerve-impulses
through a sympathetic cell. Painting the ganglion with a brush dipped in
nicotin solution has a similar effect. The fibres peripheral to the cell, on the
contrary, are not paralyzed by nicotin. Now, after the injection of nicotin the
stimulation of the lumbar nerves in the spinal canal has no effect on the vessels
of the generative organs.* Hence all the vaso-motor fibres of the lumbar
nerves must be connected with nerve-cells somewhere on their course. The
lumbar fibres which run outward to the inferior mesenteric ganglia are for the
most part connected with the cells of these ganglia. A lesser number is con-
nected with small ganglia lyitig as a rule near the organs to which the nerves
are distributed. The remaining division of lumbar fibres running downward
in the sympathetic chain, and including the majority of the nerve-fibres to the
external generative organs are connected with nerve-cells in the sacral gan-
glia of the sympathetic.

The sacral group of nerves enter ganglion-cells scattered on their course,
most of the nerve-cells for any one organ being in ganglia near that organ.

Bladder. — Neither lumbar nor sacral nerves send vaso-motor fibres to the
vessels of the bladder.®

1 Franck, 1895, p. 143 ; Langley and Anderson, 1895, p. 93.

* Langley and Anderson, 1895, p. 129. ^ Langley and Anderson, 1896, p. 372.

* Langley, 1894, p. 420, also Langley and Dickinson, 1889, p. 423.

6 Langley and Anderson, 1895, p- 131. ® Langley and Anderson, 1895, P- 84.

CIRCULATION. 501

Portal System. — It has already been said that vaso-constrictor fibres for the
portal vein were discovered by Mall ^ in the splanchnic nerve. Constrictor fibres
have been Ibund by Bayliss and Starling^ in the nerve-roots from the third to
the eleventh dorsal inclusive. Most of the constrictor nerves pass out from
the fifth to the ninth dorsal.

Back. — The dorsal branches of the lumbar and intercostal arteries, issuing
from the dorsal nmscles to supply the skin of the back,^ can be seen to con-
tract when the gray ramus of the corresponding sympathetic ganglia are
stimulated.

Limbs.* — The vaso-motor nerves of the limbs in the dog leave the spinal
cord from the second dorsal to the third lumbar nerves.^ The area for the hind
limb, according to Bayliss and Bradford," is less extensive than that for the
fore limb, the former receiving constrictor fibres from nine roots, namely the
third to the eleventh dorsal, the latter from six roots, the eleventh dorsal to
third lumbar. Langley^ finds that the sympathetic constrictor and dilator
fibres for the fore foot are connected with nerve-cells in the ganglion stella-
tum ; while those for the hind foot are connected with nerve-cells in the sixth
and seventh lumbar, and the first, and possibly the second, sacral ganglia.

Tail.^ — Stimulation of any part of the sympathetic from about the third
lumbar ganglion downward almost completely stops the flow of blood from
w^ounds in the tail. The vaso-motor fibres for the tail leave the cord chiefly
in the third and fourth lumbar nerves. Their stimulation may cause primary
dilatation followed by constriction.

Muscles.^ — According to Gaskell,^" the section of the nerve belonging to
any particular muscle or group of muscles causes a temporary increase in the
amount of blood which flows from the muscle vein. The stimulation of the
peripheral end of the nerve also increases the rate of flow through the muscle.
The same increase is seen on stimulation of the nerve when the muscle is kept
from contracting by curare, provided the drug is not used in amounts sufiicient
to paralyze the vaso-dilator nerves." Mechanical stimulation by crimping the
peripheral end of the nerve gives also an increase.^^ The existence of vaso-
dilator nerves to muscles must therefore be conceded. The presence of vaso-con-
strictor fibres is shown by the diminution in outflow from the left femoral vein
which followed Gaskell's stimulation of the peripheral end of the abdominal
sympathetic in a thoroughly curarized dog,^^ but the supply of constrictor fibres

1 Mall, 1890, p. 57 ; 1892, p. 409. ' Bayliss and Starling, 1895, p. 125.

3 Langley, 1895, p. 314.

* Literature : Lewaschew, 1882, p. 389 ; 1884 ; Laffont, 1882, p. 864 ; Bowditch and Warren,
1886, p. 416; Humilewski, 1886, p. 126; Langley, 1891, p. 375; Jegorow, 1892, p. 69; Pio-
trowski, 1892, p. 464 ; Thompson, 1893, p. 104 ; Langley, 1893, p. 227 ; Piotrowski, 1894, p.
258 ; Wertheimer, 1894, p. 724 ; Bayliss and Bradford, 1894, p. 16 ; Langley, 1895, p. 307.

* Bayliss and Bradford, 1894, p. 22.

* Bayliss and Bradford, 1894, pp. 16, 17 ; compare Langley, 1895, p. 307.

^ Langley, 1891, p. 375. ^ Langley, 1895, p. 311.

9 Literature : Sadler, 1869, p. 77 ; Gaskell, 1876, p. 45 ; 1877, pp. 360, 720 ; Griitzner and
Heidenhain, 1878, p. 1 ; Gaskell, 1878, p. 262.

>» Gaskell, 1878, p. 262. " Ibid., p. 274. >^ Ibid., p. 275. ^^ Ibid., p. 277.

502 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

is comparatively small. In tiirarizetl auimalt^ reflex dilatation ai)parently follows
the stimulation of the nerves tlie excitation of which would have caused the
contraction of the muscles observed, had not the occurrence of actual contrac-
tion been prevented by the curare. The stimulation of the central end of
nerves not capable of calling forth reflex contractions in the muscles observed
— for example, the vagus — seems to cause constriction of the muscle- vessels.'

' Gaskell, 1878, p. 289.

VIII. RESPIRATION.

A STUDY of the plienomena of animal life teaches us that a supply of
oxygen and an elimination of carbon dioxide are essential to existence. Oxy-
gen is indispensable to life; carbon dioxide is inimical to life. One serves for
the disintegration of complex molecules whereby energy is evolved, while the
other is one of the main effete products of this dissociation. We therefore find
an intimate relationship between the ingress of the one and the egress of the
other. During the entire life of the individual there is this continual inter-
change, which we term respiration. This term embraces two acts which, while
different, are nevertheless co-operative — first, the interchange of O and COgj
second, the movements of certain parts of the body, having for their object the
inflow and outflow of air to and from the lungs. The former, properly speak-
ing, is respiration ; the latter, movements of respiration.

Respiration is spoken of as internal and as external respiration. In the
very lowest forms of life the interchange of gases takes place directly between
the various parts of the organism and the air or the water in which the organ-
ism lives; but in higher beings a circulating fluid' becomes a means of
exchange between the bodily structures and the surrounding medium, so that
in these beings there is first an interchange between the air or the water in
which the animal lives and the circulating medium, and subsequently an inter-
change between the circulating medium and the tissues. Therefore in the most
primitive forms of life respiration is a single process, while in higher organ-
isms it is a dual process, or one consisting of two stages, the first being the
interchange between the atmosphere or the water surrounding the body and
the circulating medium, and the second between the circulating medium and
the bodily structures. In man, external respiration is the interchange taking
place between the blood and the gases in the lungs and between the blood and
the air through the skin ; while internal respiration is the interchange between
the blood and the tissues. In external respiration O is absorbed and COj is
given off by the blood ; in internal respiration the blood absorbs CO2 and
gives off O.

A. The Respiratory Mechanism in Man.

The respiratory apparatus in man consists (1) of the lungs and the air-
passages leading to them, the thorax and the muscular mechanisms by means
of which the lungs are inflated and emptied, and the nervous mechanisms con-
nected therewith ; and (2) the skin, whicli, however, plays a subsidiary part in
man, and need not here be considered.

503

604 AJV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Tlio lungs limy lie regarded as two large bags broken up into saccular
divisions and subdivisions which ultimately consist of a vast number of little
pouches, or infundibuli, each of which is, as the name implies, funnel-shaped,
the walls being hollowed out into alveoli, or air-vesicles. These alveoli vary
in size from 120// to 380//, the average diameter being about 250// (y^ inch).
Each infundibulum communicates by means of a small air-passage with a
bronchiole, which in turn communicates with a smaller air-tube or bronchus,
and filially, through successive unions, with the common air-duct or trachea.
It is estimated that tiie alveoli numl)er about 725,000,000, and that the total
superficies exposed by them to the gases iu the lungs is about 200 square
meters, or from one hundred to one hundred and thirty times greater than
the surface of the body (1.5 to 2 square meters). The wall of each alveolus
forms a delicate partition between the air in the lungs and an intricate net-
work of blood-vessels ; this netw'ork is so dense that the spaces between the
capillaries are, as a rule, smaller than the diameters of the vessels. The
lungs, therefore, are exceedingly vascular, and it is estimated that the vessels
contain on an average about 1.5 kilograms of blood. Owing to the minute-
ness of the capillaries and the density of the network, the air-cells may be
said to be surrounded by a film of l)lood which is about 10/^ in thickness and
has an area of about 150 square meters.

The lungs are highly elastic, and their elasticity is perfect, as is shown by
the fact that they immediately regain their passive condition as soon as the
dilating or distending force has been removed. Before birth the lungs are air-
less (atelectatic) and the walls of the bronchioles and the infundibuli are in
contact, yet in the child before birth, as iu the adult, the lungs are in apposi-
tion with the thoracic walls, being separated only by two layers of the pleurae.
As soon as the child is born a few respiratory movements are sufficient to
inflate them, and thereafter they never regain their atelectatic condition, since
after the most complete colla])se, such as occurs when the thorax is opened,
some air remains in the alveoli, owing to the fact that the walls of the bron-
chioles come together before all of the air can escape. As the child grows the
thorax increases in size more rapidly than the lungs, and becomes too large, as
it were, for the lungs, which, as a consequence, become permanently distended
because of their being in an air-tight cavity. If the chest of a cadaver be
punctured, the lungs immediately shrink so that a considerable air-sj)ace will
be formed between them and the walls of the thorax. This collapse is due to
the condition of elastic tension which exists from the moment air is introduced
into the alveoli, and which increases with the degree of ex])ansion. Therefore,
after the lungs are inflated they exhibit a persistent tendency to collapse; con-
sequently they must exercise upon the thoracic walls and diaj)hragm a constant
traction or " pull " which is in proportion to the amount of tension. It is
therefore obvious that there must exist within the thorax, under ordinary
circumstances, a state of negative pressure (pressure below tliat of the atmo-
sphere). This can be proven by connecting a trocar with a manometer and
then forcing the trocar into one of the pleural sacs.

BESPIRA TION. 505

Doiiders found that the pressure at the end of quiet expiration was —6 mil-
limeters of Hg, and at the end of quiet inspiration —9 millimeters. Accord-
ing to these figures, the pressure on the heart, great i)lood-vessels, and other
thoracic structures lying between the lungs and the thoracic walls would be
754 millimeters of Hg (one atmosphere, 760 millimeters, —6 millimeters) at
the end of quiet expiration, and 751 millimeters of Hg at the end of quiet
inspiration. Corresponding values by Hutchinson are —3 millimeters and
—4.5 millimeters. Arron ' found in a case of a woman with emphysema that
the ])ressure at the end of expiration ranged from —1.9 to —3.9 millimeters,
and at the end of inspiration from —4 to —6.85 millimeters, according to the
position of the body, the pressure being lowest in the lying posture, higher
when sitting in bed, still higher when sitting on a chair, and highest when sit-
ting and when inspiration on the well side was hindered, thus throwing a larger
portion of the work on tiie diseased side, on which the measurements were
made. During inspiration negative pressure increases in proportion to the
depth of inspiration — or, in other words, in relation to the amount of expan-
sion of the lungs — while during expiration it gradually falls to the standard at
the beginning of inspiration. During forced inspiration it may reach —30 to
—40 millimeters or more. The pressure thus observed within the thorax {out-
side of the lungs) is known as intratlwracic pressure, and must not be con-
founded with intrapulmonary or respiratory pressure, which exists within the
lungs and the respiratory passages (see p. 516).

The thorax is capable of enlargement in all directions. It is cone-shaped,
the top of the cone being closed in by the structures of the neck ; the sides,
by the vertebral column, ribs, costal cartilages, sternum, and intercostal sheets
of muscular and other tissues ; and the bottom, by the arched diaphragm. It
is obvious that, since the thorax is an air-tight cavity and completely filled
by various structures, enlargement in any direction must cause a diminution of
pressure within the lungs, while a shrinkage would operate to bring about an
opposite condition of increased pressure. Since the trachea is the only means of
communication between the lungs and the atmosphere, it is evident that such
alterations in pressure must encourage either the inflow or the outflow of air, as
the case may be ; consequently, when the thoracic cavity is expanded the pres-
sui-e within the lungs is less than that of the atmosphere, and air is forced into
the lungs; and when the thorax is decreased in size the reverse of the above
pressure relation exists, and the air is expelled. In fact, the thorax and the
lungs behave as a pair of bellows — just as air is drawn into the expanding
bellows, so is air drawn into the lungs by the enlargement of the thorax ;
similarly, as the air is forced from the bellows by compression, so is air
forced from the lungs bv the shrinkage of the lung's and the thorax.

During the expansion of the thorax the lungs are entirely passive, and by
virtue of their perfect elasticity merely follow the thoracic walls, from which
they are separated only by the two layers of the pleurae, which, being moist-
ened with lymph, slide over each other without appreciable friction. That
^ Virchow's Arckiv, 1891, vol. 126, p. 523.

506 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the lungs arc entirelv passive is shown by the fact that when the thorax is
punctured, so as to allow a free communication with the atmosphere, expan-
sion of the chest is no longer followed by dilatation of the lungs. During the
shrinkage of the thorax the elastic reaction of the lungs plays an active part.

Respiration, Inspiration, and Expiration. — Each respiration or respiratory
act consists of an inspiration (enlargement of the thorax and inflation of the
lungs) and an expiration (shrinkage of the thorax and the lungs). Accord-
ing to some observers, a pause exists after expiration {expiratory pause), but
during quiet breathing no such interval can be detected. A pause may be
present when the respirations are deep and infrequent. Under certain abnor-
mal circumstances a pause may exist between inspiration and cx])i ration
(inspiratory pause).

Inspiration is accomplished by the contraction of certain muscles which are
designated inspiratory muscles. Expiration during quiet breathing is essen-
tially a passive act, but during forced breathing various muscles are active;
these muscles are distinguished as expiratory muscles.

During inspiration the thorax is enlarged in the vertical, transverse, and
antero-posterior diameters. During quiet breathing the vertical diameter is
increased by the descent of the diaphragm, and during deep inspiration it is
further increased by the backward and slightly downward movement of the
floating ribs, and by the extension of the vertebral column, which raises the
sternum with its costal cartilages and ribs. The transverse diameter is in-
creased by the elevation and eversion (rotation outward and upward) of the
ribs. The antero-posterior diameter is increased by the uj)ward and outward
movement of the sternum, costal cartilages, and ribs. During quiet inspiration
in men the sternum is not raised to a higher level, but the lower end is rotated
forward and upward. It is only during deep inspiration in the male and in
quiet or deep inspiration in women that the sternum as a whole is elevated.

The movements of the anterior and lateral walls constitute costal respira-
tion, and those of the diaphragm diaphragmatic or, as it is sometimes called,
abdominal respiration, since the descent of the diapiiragm causes protrusion
of the abdominal walls. Both types coexist during ordinary resjiiratory move-
ments, but one may be more prominent than the other. The costal type is well
marked in women, and the diaphragmatic type in men. These peculiarities
are not, however, due to inherent sexual differences, but to dress and heredity.
Young children of both sexes exhibit, as a rule, the diaphragmatic type, and
it is only near or at puberty that the costal type is developed in the female.

The chief muscles of inspiration are the diaphragm, the quadrati Imnborum,
the serrati postici infer iores, the scaleni, the serrati postici super iores, the leva-
tores costarum longi et brevea, and the intercostales externi et intercartilaginei.

Movements of the Diaphragm. — The diaphragm is attached by its two
crura to the first three or four lumbar vertebrte, to the lower six or seven cos-
tal cartilages and adjoining parts of the corresponding ribs, and to the poste-
rior surface of the ensiform appendix. It projects into the thoracic cavity in
the form of a flattened dome, the highest part being formed by the central

RESPIRATION. 507

tendon. Tlie tendon consists of three lobes which are partially separated by
deprcs^sions. The right lobe, or largest, is the highest portion and lies over
tiie liver; the leit lobe, which is the smallest, lies over the stomach and the
spleen ; while the central lobe is situated anteriorly, the upper surface blending
with the pericardium. The central tendon is a common point of insertion
of all the muscular fibres of the diaphragm. In the passive condition the
lower portions of the diaphragm are in apposition to the thoracic walls.
During contraction the whole dome is drawn downward, while the parts of
the muscle in contact with the chest are pulled inward. According to Hult-
krauz, the cardiac part of the diaphragm descends from 5.5 to 11.5 millimeters
during quiet inspiration, and as much as 42 millimeters during deep inspira-
tion. Not only is the height of the arch lessened, but there is also a tendency,
owing to the points of attachment of the diaphragm, toward the pulling of the
lower ribs with their costal cju'tilages and the lower end of the sternum inward
and upward ; this traction, however, is counterbalanced by the pressure of the
abdominal viscera, the latter being forced downward and outward against the
thoracic and abdominal walls. If this counterbalancing pressure be removed
by freely opening the abdominal cavity, especially after removing the viscera,
the lower lateral portions of the thorax will be seen during each inspiration to
be drawn inward. It is during labored inspiration only that this movement
occui'S in the intact individual.

AVhen the diaphragm ceases to contract, the negative intrathoracic pressure
is sufficient to draw the sunken dome upward into the passive position. This
upward movement of the diaphragm is aided by the positive intra-abdominal
pressure exerted by the elastic tension of the abdominal walls through the
medium of the abdominal viscera. In forced expiration the contraction of
the abdominal muscles (p. 515) adds additional force.

The quadrati lumborum are believed to assist the diaphragm by fixing
the twelfth ribs, or even lowering them during deep inspiration. Each of
these muscles arises from the ilio-lumbar ligament and the iliac crest, and
is inserted into the transverse processes of the first, second, third, and
fourth lumbar vertebrae and the lower border of one-half of the length
of the last rib. These muscles are regarded by some physiologists as
expiratory agents.

The serrati postici inferiores similarly assist the diaphragm by drawing the
lower four ribs backward, and in deep inspiration also downward. They not
only thus oppose the tendency of the diaphragm to pull the lower ribs
upward, which would lessen its effectiveness in enlarging the vertical diam-
eter of the thorax, but they contribute to this enlargement by their down-
ward and backward traction upon the ribs and the attached portions of the
diaphragm. These muscles pass from the spines of the eleventh and twelfth
dorsal and first two or three lumbar vertebra and the supraspinous ligament
to the lower borders of the ninth, tenth, eleventh, and twelfth ribs, beyond
their angles.

Simultaneously with the contraction of the diaphragm the thoracic walls

508

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

are drawn upward and outward Ity tlie contractions of other inspiratory mus-
cles, thus enlarging the thorax in the antero-posterior and lateral diameters.

Movements of the Ribs. — Tiie movements of the rii)> during inspiration
are, as a whole, essentially rotations upward and outward ujwn axes which are
directed obliquely outward and backward, each axis being directed through
the costo-vertebral articulation and a little anterior to the costo-transverse
articulation. The vertebral ends of the ribs lie higher than their sternal
extremities, so that when the ribs are elevated the anterior ends are advanced
forward and upward. The arches of the ribs are inclined downward and
outward, and, owing to the obliquity of the axes of rotation, the convexities
are rotated upward and outward, or everted. Thus both the antero-posterior
and lateral diameters are increased.

The degree of obliquity of the axes of rotation of the different ribs varies.
The axis of the first rib is almost transverse (Fig. 1.31), while that of each
succeeding rib to the ninth, inclusive, becomes more oblique (Fig. 132). The

Fig. 131.— First dorsal vertebra and rib.

Fig. 132.— Sixth dorsal vertebra and rib.

more oblique the axis, the greater the degree of eversion ; consequently the
first rib is capable of but slight eversion, while the lower ribs may be everted
to a relatively marked extent. iSIoreover, the peculiarities or the absence of
the costo-transverse articulations materially affect the character of the move-
ments of the different ribs. Thus, the facets on the transverse processes of the
first and second dor.sal vertebrre are cup-shaped, and into them are inserted
the conical tuberosities of the ribs, thus materially limiting the rotation of the
ribs ; wliile the facets for the articulations of the third to the tenth ribs, inclu-
sive, assume a plane character which admits of larger movement. The facets
for the third to the fifth ribs are almost vertical, thus allowing a free move-
ment upon the oblique axis ; while the facets for the sixth to the ninth ribs,
inclusive, are directed obliquely upward and backward, and admit of a move-

RESPIRATION. 509

inent upward aud backward as well as a rotation upon the oblique axis.
Finally, the eleventh and twelfth ribs (and generally the tenth) have no costo-
transverse articulations, allowing a movement backward aud ibrward as well
as rotation upon their oblique axes. While, therefore, the movements of the
ribs are essentially rotations upward, forward, and outward upon oblique axes
directed through the costo- vertebral articulations and a little anterior to the
costo-transverse articulation, they are more or less modified by reason of the
motion permitted by the nature or the absence of the costo-transverse articu-
lations. Thus, the essential character of the movement of the first to the
fifth ribs is a rotation upward, forward, and outward ; that of the sixth to
the ninth ribs, a rotation upward, forward, and outward combined with a
movement u])ward and backward ; that of the tenth and eleventh ribs, a
rotation upward, forward, aud outward with a rotation backward; that of
the twelfth rib, chiefly a rotation backward and rather downward. The
character of the movement of each rib differs somewhat as we pass from
the first to the twelfth ribs.

During forced inspiration the sternum and its attached costal cartilages
with their ribs are pulled upward and outward, while the ninth, tenth,
eleventh, and twelfth ribs are drawn backward and downward. During
expiration these movements are of course reversed.

The intercostal spaces during inspiration, except the first two, are widened.^
The reason for this opening out must be apparent when we remember that
the ribs are arranged in the form of a series of parallel curved bars directed
obliquely downward, and the fact may be demonstrated by means of a very sim-
ple model (Fig. 133) consisting of a vertical support and two parallel bars, a, b,
placed obliquely. If, after measuring the distance c, d, w^e
raise the bars to a horizontal position, the distance e,f will
be found to be greater than c, rf, since the bars rotate around
fixed points placed in the same vertical line. This widening
of the intercostal spaces is readily accomplished because of
the elasticity of the costal cartilages.

The muscles involved in the movements of the ribs
during quiet inspiration include the scaleni, the serrafi
postid superior es, the levator es costarum longi et breves, and
the intei'costales extcrni et iniercartUaginei.

The scaleni are active in fixing the first and second ribs, lustrate the widening
thus establishing, as it were, a firm basis from which the during?nspi"rluon.*^^^
external intercostal muscles may act. The scalenus anticus
passes between the tubercles of the transverse processes of the third, fourth,
fifth, and sixth cervical vertebrae to the scalene tubercle on the first rib.
The scalenus medius passes from the posterior tubercles of the transverse
l)rocesses of the lower six cervical vertebrae to the upper surface of the
first rib, extending from the tubercle to just behind the groove for the
subclavian artery. The scalenus posticus passes from the transverse pro-
' Ebner : Archivfiir Anatomie und Physiologic, Anatomische Abtheilung, 1886, p. 199.

Fig. 133— Model to il-

510 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cesses of the two or three lower cervical vertebrte to the outer surface of the
second rib.

The scrrati postici supcriores aid iu fixing the second ribs and raise the third,
fourth, and fifth ribs. The muscles })ass from the ligamentum nuchie and the
spines of the seventh cervical and first two or three dorsal vertebrae to the upper
borders of the second, third, fourth, and fifth ribs, beyond their angles.

The levatores costarum breves con.sist of twelve pairs which pass from the
tips of the transvei-se processes of the seventh cervical and first to the eleventh
dorsal vertebrae downward and outward, each being inserted between the
tubercle and the angle of the next rib below. Those ari.<iug from the lower
ribs send fibres to the second rib below {levatores costarum longiores). They
assist iu the elevation and evei'sion of the first to the tenth ribs, inclusive, and
co-operate with the quadrati lumborum and the serrati postici inferiores to
draw the lower ribs backward.

The functions of the intercostale.9 have been a matter of dispute for centu-
ries, and the problem is still unsettled. For instance, Galen looked upon the
external iutercostals as being expiratory. Vesalius asserted that both the
external and the internal iutercostals are expiratory, while Haller expr&ssed
the opposite belief. Hamberger and Hutchinson regarded the external iuter-
costals and the interchoudrals as being inspiratory, and the interosseous portion
of the internal iutercostals as being expiratory. Finally, Landois believes that
while the external iutercostals and the interchondrals are active during inspira-
tion, and the interosseous portion of the internal iutercostals during expiration,
their chief actions are not to enlarge nor to diminish the volume of the thoracic
cavitv, but to maintain a pro]>er degree of tension of the intercostal spaces.
Each view still has its adherents.

The actions of the intercostal muscles are generally demonstrated by means
of rods and elastic bands arranged in imitation of the ribs and the origins and
insertions of the muscles, or by geometric diagrams. The well-known model
of Bernouilli consists of a vertical bar representing the vertebral column, upon
which bar move two parallel straight rods in imitation of the ribs (Fig. 134).
Tf the rods be placed at an oblique angle and a tense rublier band (a, h) be
affixed to represent the relations of the external iutercostals, the rods M-ill be
pulled upward and the space between them will be widened. The interchon-
dral portion of the internal iutercostals bears the same ol)lique relation to the
costal cartilages, and theoretically should have the same action. The action
of the interosseous portion of the internal iutercostals is demonstrated in this
wav: If the rubber baud be placed at right angles to the rods (Fig. 130, a, 6)
and the rods be raised to a horizontal position, the rubber is put on the stretch
(c, d), so that when the rods are released they will be pulled downward by the
elastic reaction of the rubber. This last demonstration has been held to indi-
cate that during inspiration the interosseous portion of the internal intercostals
is put on the stretch and in an oblique position, and therefore in a relation
favorable for effective action during contraction. The ribs, however, differ
essentially from such a model in the fiict that they are curved bai-s, that their

RESPIRA TIOX.

511

ends are not free, and that the movement of rotation is materially different.
In fact, the meolianii'ul conditions are so complex that deductions from phe-
nomena observed in .such gross demonstrations or by means of geometric figures
such as suggested by Rosenthal and others must be accepted with caution.

There is no doubt that stimulation of any of the intercostal fibres causes
au elevation of the rib below if the rib above be fixed, and that if the excita-
tion i)e sufficiently strong and the area be large, the effect may extend from rib
to rib, and thus a large part of the thoracic cage will be elevated. Conse-
quently, it has been assumed that, should the upper ribs be fixed, the contrac-
tions of both sets of intercostals would elevate the system of ribs below. But
the experiments of Martin and Hartwcll ' show that during forced inspiration
the ijiternal intercostals contract alternately with the diaphragm and the exter-
nal intercostals, and therefore are expiratory. Moreover, Ebuer^ has found,
as a result of elaborate measurements, that the intercostal spaces, excepting the
first two, are, instead of being narrowed, actually widened during inspiration.

Fig. 134.— Model to illustrate the action of the
external intercostals and interchondrals.

Fig. 135.— Model to illustrate the action of the inter-
osseous portion of the internal intercostals.

An examination of the origins and insertions of the external intercostals and
the interos.seous portion of the internal intercostals, and of their actions during
contraction, renders it apparent that it is possible for the externi to elevate the
ribs and to widen the intercostal spaces, but that such effects are impossible in
the case of the interosseous portion of the internal intercostals. Thus, if we
take the model described above (Fig. 134), project a line «, b in imitation of
the relation of the external intercostals to the ribs, and raise the parallel bars
to a horizontal position, the distance between e, d is shorter than that between
a, b. It is but a logical step from this demonstration to assume that, .should a
strip of muscle be placed between a, b, the muscle in shortening would pull the
bars upward, at the same time widening the intercostal spaces. If now the
upper ribs be fixed, it is obvious that the external intercostals must raise the
ribs and open up the intercostal spaces during contraction. This same reason-
ing applies to the interchondrals, and the experiments of Hough ^ show that
they contract synchronously with the diaphragm, and therefore with the exter-
nal intercostals.

' Journal of Physiology, 1879-80, vol. 2, p. 24. * Loc. eit.

' Studies from (he Biological Laboratory, Johns Hopkins University, March, 1894.

512 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

In considering:: the interosseous portion of the internal intercostals we find
that (lininir the ])as.sive condition they are placed nearly at rijjjht angles to the
ribs. If contraction takes place, it is obvious that the mechanical response
must be an ap|)roxiniati()n of the ribs and a lessening of the width of the inter-
costal spaces. It must also be ai)parent that during the movement of inspira-
tion these fibres are put on the stretch, which can be demonstrated in the above
model. Thus, if we put a rubber band at right angles to the parallel rods.
(Fig. 135), we will find that when the rods are in the horizontal position, in
imitation of the position of the ril)s at the beginning of expiration, the distance
between c, d is greater than that between «, b ; therefore if we lessen the dis-
tance between c, d, as when the muscle-fibres contract, the mechanical result of
contraction must be approximation, the opposite to that which occurs during
ins])iration.

While the whole subject of the actions of the intercostal muscles must still
be regarded as in an unsettled condition, yet there is no reasonable doubt that
the externi and the intercartilaginei contract during inspiration, and the inter-
osseous portion of the internal intercostals during expiration. Admitting this
to be true, it is, however, by no means clear whether or not these muscles are
for the purpose of altering the volume of the thorax. It is probable, as sug-
gested by Landois, that their chief function is to maintain, during all phases
of the respiratory movements, a proper degree of tension of the intercostal
tissues. If this view be correct, the external intercostals and interchondrals con-
tract during inspiration chiefly for the purpose of causing greater tension of
the intercostal tissues, so as to counteract the influence of the increase of
negative intrathoracic pressure ; while during expiration, when their relax-
ation occurs, a substitution for this relaxation is jirovided by the contraction
of the interosseous portion of the internal intercostals, so that the tension of
the intercostal tissues is maintained. The internal intercostals must prove
most effective during forced expiratory efforts — for example, in coughing,
when the intercostal tissues arc subjected to high positive intrathoracic pres-
sure, and there is a consequent tendency to outward displacement, which is
met and counteracted by the internal intercostals.

During forced inspiration the scalcni and the serratl posticl siiperiores con-
tract vigorously, so that the sternum and the first five ribs are elevated, thus
raising the thoracic cage as a whole. At the same time the serratl poslici
inferiores, the quadrati lumborum, and the sacro-lnmbales are active in pulling
the lower ribs downward and backward. Besides these muscles there are a
number of others which directly or indirectly affect the size of the thorax and
which may be brought into activity ; chief among these are the sferno-cfeido-
mastoidci, the irapezei, the pectorales minores, the jjectorales majores (costal
portion), the rhomboidei, and the erectores spinoe.

The .stcrno-cJeldo-mafttoid passes from the mastoid process and the superior
curved line of the occipital bone to the upper front surface of the manubrium
and the upper border of the inner third of the clavicle. These muscles ele-
vate the upper jiart of the chest when the head and neck are fixed. The

RESPIRATION. . 513

trapezius passes from the occipital bone, the liganientum nucha, the spines of
the seventh cervical and of all the dorsal vcrtci>ne, and the supraspinous liga-
ment to the posterior border of the outer third of the clavicle, the inner border
of the acromion process, the crest of the spine of the scapula, and to the
tubei-cle near the root. The trapezei help to fix the shoulders. The rfiomboid-
eus minor passes from the ligamentum nucha? and the spines of the seventh
cervical and first dorsal vertebne to the root of the spine of the scapula. The
rhomboideus major passes from the spines of the first four or five dorsal vertebrae
and the supraspinous ligament to the inferior angle of the scapula. The trapezei
and rhomboidei fix the shoulders, affording ii base of action from which the
pectorales act. The pectoralis major passes from the pectoral ridge of the
humerus to the inner half of the anterior surface of the clavicle, the corre-
sponding half of the anterior surfVice of the sternum, the cartilages of the
first six'inbs, and the aponeurosis of the' external oblique muscle. The pedo-
ralis minor passes from the coracoid process of the scapula to the upper margin
and outer surface of the third, fourth, and fifth ribs close to the cartilages and
to the intercostal aponeuroses. The pectorales minores and the costal portion
of the pectorales majores raise the ribs when the shoulders are fixed. The
eredorc^ spince are composite muscles extending along each side of the spinal
column, each consisting of the sacro-lumbalis, the musculus accessorius, the
cervicalis ascendens, the longissimus dorsi, the transversalis cervicis, the trachelo-
mastoid, and the spinalis dorsi. The erectores spinse straighten and extend the
spine and the neck, and thus tend to raise the sternum, the costal cartilages,
and the ribs. The infrahyoidei may also be included among the muscles
engaged in forced inspiration, since they may aid in the elevation of the sternum.
Summary of the Actions of the Chief Muscles of Inspiration.— Dur-
ing quid inspiration the diaphragm contracts, thus increasing the vertical diam-
eter of the thorax, its effectiveness being augmented by the associated actions
of the quadrati lumborum and the serrafi postici inferiores, the former fixing
the twelfth ribs, and the latter fixing the ninth, tenth, eleventh, and twelfth
ribs, and thus preventing the muscular slips of the diaphragm attached to these
ribs from drawing them inward and upward and thus diminishing the cavity
of the thorax. Coincidently with the contractions of these muscles the scaleni
fix the first and second ribs, and the serrati postici superiores aid in fixing the
second ribs and elevate the third, fourth, and fifth ribs ; the intercostaks extemi
d intercartilaginei and the levatores costarum longi d breves elevate and evert the
first to the tenth ribs, inclusive, throwing the lower end of the sternum for-
ward ; and the levatores, in conjunction with the quadrati lumborum and the
serrati postici inferiores, aid in fixing the lower ribs and even draw them back-
ward. The intercostales extemi also serve to maintain a proper degree of tension
of the intercostal tissues.

During forced inspiration the scaleni and the serrati postici s^iperiores act
more powerfully and thus raise the sternum with its attached costal cartilages
and ribs, being assisted bv the sterno-deido-mastoidei and the infrahyoidei
when the head and neck are fixed, and by the pectorales majores d minores

33

514 A.y AMERICAN TEXT-BOOK OE PHYSIOLOGY.

when tlie shoulders are fixetl l)y {\\ctrapezei aiul the rhomboidei. The eredores
spincc further assist this action by extending the spinal column.

Movements of Expiration. — During (piiet breathing expiration is effected
mainly or solely by tliL' passive return of the (lis[)laeed parts. Normal expi-
ration is therefore essentially a passive act, although it may be assisted by the
contraction of the interosseous portion of the internal intercostals. The most
important factors are unquestionably the elastic tension of the lungs, costal
cartilages, intercostal spaces, and abdominal walls, together with the weight of
the chest.

The lungs after quiet expiration are in a state of elastic tension equal to a
pressure of -f 1.9 to +3.9 millimeters of mercury (see p. 505), which pressure
during inspiration is increased in proportion to the depth of the movement.
As soon, therefore, as the inspiratory muscles cease to contract, this tension
comes into play, and, aided by elastic and mechanical reactions below noted,
forces air from the lungs. This elasticity, and the facility with which the air
is expelled, may be demonstrated by inflating a pair of excised lungs and then
suddenly allowing a free egrass of the air: collapse occurs with remarkable
rapidity, with a force proportionate to the degree of distention. The elastic
costal cartilages are similarly put on the stretch : the lower borders are drawn
outward and upward and are thus twisted out of position, so that as soon as
the inspiratory forces are withdrawn they must untwist themselves, further
aiding the elastic reaction of the lungs. The intercostal spaces, excepting the
first two, are widened and the tissues are stretched, and the diaphragm during
its descent presses upon the abdominal viscera, rendering the abdominal walls
tense. AVhen, therefore, inspiration ceases the reaction of the tense and elastic
intercostal tissues aids in bringing the chest into the position of rest, while the
stretched abdominal walls press upon the abdominal viscera and thus force
the diaphragm upward. Finally, the chest-walls by their weight tend to fall
from the positi<jn to which they have been raised, adding thus another factor
toward the elastic reaction of the lungs, costal cartilages, intercostal tissues, and
abdominal walls.

Whether or not the interosseous portion of the internal intercostal nmscles
assists in expiration cannot be stated with positiveness. The fact that these
muscles contract during the expiratory phase and that the contraction results
in an approximation of the ribs leads to the belief that they are expiratory.
But, as before stated (p. 512), this activity may be primarily for the purpose
of maintaining a proper degree of tension of the intercostal tissues. In the
dog these muscles are not active until dyspnoea appeal's, while in the cat they
do not come into play until extreme dyspnoea has set in (Martin and Hartwell).
These facts certainly militate against regarding them as active expiratory fac-
tors during quiet breathing, while during forced expiration they may with
accuracv be considered as being in part at least ex]iiratory in function. We are
therefore justified in concluding that normal quiet expiration is essentially a
jiassivc act due to elastic reaction and to the mechanical replacement of dis-
placed parts.

RESPTRA TTOX. 51o

During forced expiration c-ertain muscles may l)e active, the chief being the
intereodales intcrni interossei, tiie Ir'uuKjalarcH .stmii, tiie inujicnti abdoiainalcs,
and the levatovcs aid. The intercostalcs interni inkrossei are pr(jl)ably active
expiratory muscles during forced expiration, but they can ]»rove effective only
when the lower part of the thoracic cagi; is fixed or drawn down — an act which
is accomplished chiefiy by the abdominal muscles.

Tiie triangulares stenii pass outward and upward from the lower j)art of
the sternum, the inner surface of the ensiform cartilage, and the sternal
ends of the costal cartilages of the two or three lower sternal ribs, to the lower
and inner surfaces of the cartilages of the second to the sixth ribs, inclusive.
They draw the attached costal cartilages downward during expiration.

The abdominales during quiet expiration are passive, and aid in the expul-
sion of air from the lungs simply by their elasticity ; but during forced expi-
ration, by contraction, they are active expiratory factors.

The ob/iqum e.rterniis arises by slips on the outer surface and lower borders
of the lower eight ribs, and is inserted into the outer lip of the anterior half
of the crest of the ilium and into the broad aponeurosis which blends with
that of the opposite side in the linea alba. The obliqmis internus passes
from the outer half or two-thirds of Poupart's ligament, the anterior two-thirds
of the middle lip of the crest of the ilium, and the posterior layer of the lumbar
fascia to the cartilages of the last three ribs and the aponeurosis of the anterior
part of the abdominal wall. The rectus abdominis passes from the crest of the
pubes and the ligaments in front of the symphysis pubis to the cartilages of
the fifth, sixth, and seventh ribs, and usually to the bone of the fifth rib. The
transversalis abdominis passes from the outer third of Poupart's ligament, the
anterior three-fourths of the inner lip of the iliac crest, by an aponeurosis
from the transverse and spinous processes of the lumbar vertebrae, and from
the inner surface of the sixth lower costal cartilages to the jiubic crest and the
linea alba. The fibres for the most part have a horizontal direction. The pyram-
idalis passes from the anterior surface of the pubes and the pubic ligament
to the linea alba. It is obvious from the points of origin and insertion of the
abdominal muscles that during contraction they co-operate toward diminishing
the volume of the thorax in three ways : (1) By offering a base of action for
the internal intercostals, and thus aiding in the approximation of the ribs;
(2) by depressing and drawing inward the lower end of the sternum and the
lower costal cartilages and rii)S ; (3) by forcing the abdominal viscera against
the diaphragm, thrusting it upward. The alxlominales are unquestionably
the chief expiratory muscles.

The levatores ani converge from the pelvic wall to the inner part of the rec-
tum and the prostate gland. They form the largest part of the muscular floor
of the pelvic cavity. The levatores ani are important during forcible exj>i-
ration by resisting the downward pressure of the pelvic viscera caused by the
powerful contractions of the abdominal muscles, but they must be regarded rather
as associatefl in the act of ex])iration, and not as true expiratory muscles.

Summary of the Actions of the Chief Muscles of Expiration. — During

510 ^i;\^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

quiet expiration uo muscular factors arc involved, unless it be the contraction
of the intcreostalcs intei'ni interossei, in which event they are more probably
engaged in maintaining the tension of the intercostal tissues tlian in actually
diminishing the capacity of the thorax.

During forced expiration the abdominales flex the thorax upon the pelvis,
force (he abdominal viscera against the diaphragm, thrusting it uj)\vard, and
by })ulling u})()n the lower margins of the thoracic cage draw them inward
and at the same time oifer a base from which the intercostales intenii inter-
ossei act to i)ull the ribs downward ; the triangidares sterni contract at the
same time and pull downward the cartilages of the second to the sixth ribs,
inclusive.

Associated Respiratory Movements. — Associated with the thoracic and
abdominal movements of respiration are movements of the face, pharynx, and
larynx. The nostrils are slightly dilated during insj)iration and passively
return to their condition of rest during expiration ; the soft palate moves to
and fro with the inflow and outflow of air, and the glottis is widened during
inspiration and narrowed during expiration. During labored inspiration,
besides the above movements, the mouth is usually opened ; the muscles con-
cerned in facial expression may be active, giving the individual an apjwarance
of distress; the soft palate is raised, and the larynx descends. The widening
of the nares and the glottis, the opening of the mouth, the elevation of the soft
palate, and the descent of the larynx during inspiration are obviously for the
purpose of lessening the resistance to the inflow of air.

Intrapulmonary or Respiratory Pressure and Intrathoracic Pressure.
— The tidal flow of air to and from the lungs during the respiratory move-
ments is due, as already stated, to the differences between the jircssure within
the lungs and that outside the body. During inspiration the enlargement of
the thorax causes an expansion of the lungs and a consequent diminution of
pressure within them, so the air is forced through the air-passages until the
pressure within the lungs equals that of the atmosphere; during cx})iration
there occur elastic and mechanical reactions whereby the pressure within the
lungs is greater tlian that of the atmosphere, consequently air is expelled until
an equilibrium is again established. It is apparent, then, that during inspira-
tion there exists within the lungs a condition of negative pressure, and that
during expiration the pressure is positive. If a manometer be so arranged as
in no way to interfere with the ingress and egress of air, it will be found that
during inspiration the column of mercury sinks, while during expiration it
rises. Donders found by connecting a manometer with the nasal ])assage that
the pressure during quiet inspiration was — 1 millimeter of Hg, and during
expiration -}-2 to 3 millimeters. Ewald gives as corresponding values — 0.1
millimeter and -fO.lB millimeter, and IMundhorst, — 0.5 millimeter and -1-5
millimeters. During deep inspiration Donders noted a pressure of — 30 milli-
meters, and when the mouth and nose were closed, — 57 millimeters. During
forced expiration, with respiratory passage closed, it was -}-87 millimeters; but
these figures have been exceeded.

nESPTRATTOX. 517

It will be observed that during quiet respiration intrapulmonary pr&ssure
(pressure 7cithin the lungs) oscillates between negative and ])ositive and vice
versd, whereas intrathoracic pressure (pressure out.skJe the lungs) is pei'sistently
negative, the amount by which it differs from atmospheric pressure becoming
greater during inspiration and diminishing to the j)revious level during expi-
ration (p. 5U5). Under forced expirati(»n, however, when the air-i)assages are
obstructed intrathoracic pressure may become positive. This may be demon-
strated in this way: If a manometer be connected with the mediastinum of
a cadaver, and the chest be pulled u])ward in imitation of deep inspiration,
intrathoracic pre&sure will be found to be about — 30 millimeters. If now a
second manometer be connected with the trachea, and air be forced into the
lungs through a tracheal tube, as intrapulmonary pressure rises intrathoracic
pressure falls, so that when the former reaches +30 millimeters the intratho-
racic negative pressure exerted by the elastic traction of the lungs is counter-
balanced and the pressure within and outside the lungs is equal. If intra-
pulmonary pressure now rise above this limit, intrathoracic pressure must
proportionately become positive. During violent coughing, when the expira-
tory blast is obstructed and the muscular effort is powerful, intrapulmonary
pressure may rise to +80 millimeters or more.

The intercostal tissues tend to be drawn inward as long as negative intra-
thoracic pressure exists, and to be forced outward when there is positive intra-
thoracic pressure ; hence during inspiration the traction becomes more marked
with the rise of intrathoracic pressure, and during expiration the reverse;
while during forced expiration with obstructed air-pa&sages the pressure exerted
by the effort of the expiratory muscles, together with the weight of the chest
and the elastic reaction of the costal cartilages, etc., may be, as above stated,
far more than sufficient to counterbalance the traction exerted by the distended
elastic lungs, and thus cause positive intrathoracic pressure.

The influences exerted by changes in intrathoracic and intrapulmonary
pressure upon the circulation are marked and important, and may be so pro-
nounced as to cause an obliteration of the pulse.

Respiratory Sounds. — During the respiratory acts characteristic sounds
are heard in the lungs. A study of these sounds, however, properly belongs
to physical diagnosis.

The Value of Nasal Breathing-. — Xasal breathing has a value above
breathing through the mouth, inasmuch as the air is warmed and moistened
and thus rendered more acceptable to the lungs, more or less of the foreign
particles in the air are removed, and noxious odors may be detected.

B. The Gases in the Lungs, Blood, and Tissues.
Alterations in the Gases in the Lungs. — The object of respiratory
movements is to renew the air within the lungs, which air is constantly being
vitiated, and thus supply O and remove COj and other effete substances. The
lungs of the average adult man after quiet expiration contain about 2800 cubic
centimeters (170 cubic inches) of air. During quiet respiration there is an

518

A.X AMERICAN TKXT-JiOOK OF PHYSIOLOGY.

iiiHow ami outflow of about 500 cubic centimeters (30 cubic inches), therefore
from one-sixth to one-fifth of the air in the kings is renewed by each act.
Since tlie respirations occur at so frequent a rate as 16 to 20 per minute, it
seems apparent tiiat there nnist be a rapid loss of O and a gain of CO^. This
is proven by analyses of inspired and ex])irc(l air. Inspired air is under
normal circumstances atmospheric air, composed of oxygen, nitrogen, argon, and
carbon dioxide, with more or less moisture, traces of ammonia and nitric acid,
dust and micro-organisms, etc. The es.sential diflFerences between insj)ired
and expired air are shown by the following table, the figures for the gases
being in volumes per cent. Argon constitutes about 1 per cent, of the nitrogen
as ffiven in the table :

Inspired air .
Expired air .

0

COa

N

20.81
16.03

0.04
4.38

79.15
79.30

4.78

4.34

0.15

Watery Vapor.

Variable.
Saturated.

Temperature.

Average, about 20°
Average, about 36.3°

Volume
(Actual).

Diminished

2to2i%.

Expired air is therefore 4.78 volumes per cent, poorer in O, 4.34 volumes per

cent, richer in COj, and 0.15 volume per cent, richer in N; it is saturated

with watery vapor, and is of higher temperature and of less actual volume.

In addition, expired air contains various effete bodies, such as organic matter

("crowd-poison"), hydrogen, marsh-gas, etc.

The relative quantities of O absorbed and of COg given oif are not constant,

and the ratio is known as the respiratory quotient. This is obtained by dividing

CO 4.34
the volume of COj given off by that of O absorbed, ^ ^' '' = 0.908. Hence,

for each volume of O that is lost 0.908 volume of CO, is gained. Various
circumstances affect the quotient (p. 544). The quantity of N given oft' is
about 7 grams per diem.

The quantity of watery vapor lost by the lungs varies inversely with the
amount contained in the atmosphere and with the volume of air respired. The
less the moisture in the atmospheric air and the larger the volume of air
respired, the greater the lo.ss. Valentine, in experiments on eight young men,
records a dailv loss varvine; from 349.9 to 773.3 grrams, or an average of 540
grams. Vierordt records a loss of 330 grams, while Aschenbrandt estimates
a daily loss of 526 grams.

The temperature of the expired air varies with the temperature and volume
of the inspired air and with the temperature of the body. Valentine and
Bruner found that when the temperature, of inspired air was from 15° to 20°,
that of expired air was 37.3° ; when that of inspired air was — 6.3°, expired
air had a temperature of 29.8° ; while when the inspired air was at»41.9°, that
of expired air was 38.1°. When the air is respired through the nose the
expired air is warmer than when respiration occurs through the mouth, l^loch '

^ Zeitschrijt fur OhrenheilJcunde, 1888, vol. xviii. p. 215.

RESPIIIATION. 519

records ;i differoiicc of 1.5° to 2°, The fiii|;ures by other observers vary froai
0.5° to 1.5°. The larger tlie volume of air respired, other tliiugs being equal,
the less the increase of temperature.

The volume of expired air is from 10 to 12 per cent, greater than that of
inspired air, this increase being due to expansion caused by the increase of tem-
perature. When proper deductions are made for tempei'ature and barometric
pressure, the actual or corrected volume is less by 2 to 2^ per cent.

Lossen estimated that 0.0204 gram of ammonia is eliminated per diem in
the expired air, but Voit's investigations indicate that expired air usually does
not contain even a trace of ammonia.

Alterations in the Gases in the Blood. — The blood in the pulmonary
artery is of the typical venous color — that is, deep bluish-red. During its
passage through the lungs it becomes scarlet-red, or, commonly speaking, arte-
rialized or aerated. If we take arterial blood and deprive it of oxygen, the
color changes to a venous hue ; if now we shake the bluish-red blood in air or
O, the scarlet- red color is restored. AVe have here the suggestion that the blood
while passing the lungs absorbs O. Analyses show that not only does absorp-
tion of O occur, but that there is simultaneously with this an elimination from
the blood of CO2.

Arterial and venous blood each contains approximately 60 per cent, volumes
of O and CO2 ; that is, for about every 100 volumes of blood 60 volumes of gas
will be obtained. Such analyses demonstrate also that while the total volumes
per cent, of O and COg are about the same, the proportions are different. The
following table, after Ellenberger,^ gives the volumes per cent, of gases in the
arterial blood of various animals :

Animal. Total. O. CO2. N.

Dog 57.9 19.8 37.0 1.9

Cat 43.2 13.1 28.8 1.3

Sheep 57.6 10.7 45.1 1.8

Rabbit 49.3 13.2 34.0 2.1

Man 63.5 21.6 40.3 1.6

Fowl 58.8 10.7 48.1

Pfliiger obtained as averages of analyses of arterial blood of dogs 58.3
volumes per cent., consisting of 22.2 volumes per cent, of O, 34.3 volumes
per cent, of COg, and 1.8 volumes per cent, of N. Venous blood, according
to estimates by Zuntz based on a large number of analyses, contains 7.15 vol-
umes per cent, less of O and 8.2 volumes per cent, more of CO2. The quantity
of N is practically the same in both arterial and venous blood.

The proportions of O and CO2 in arterial blood vary but little in speci-
mens taken at random from the arterial system, while those of venous blood,
on the contrary, differ considerably according to the locality of the vessel as
well as to the degree of activity of the structures whence the blood comes.
Thus, venous blood from an active secreting gland differs very little in its
composition, gaseous and otherwise, from typical arterial blood, whereas when
' Physiologie der Haussdugethiere, 1890, vol. i. p. 204.

020 AX AMKRTCAX TKXT-JiOOK OF PHYSIOLOGY.

the gland is inactive tlie l)lo(xl is distinctly venous. The arterial character of
the venous blood in tlie former case is due to the considerable increase in the
(jnantitv of blood j)assing through the gland during activity, the result i)eing
that the loss and gain of substances are not so noticeable, although the total
quantities of O and CO, exchanged are actually greater than when the gland
is at rest and the blood coming from it has the typical venous characters.

The venous blood during its passage through the lungs acquires O and loses
CO.,. After the blood is arterialized it passes from the lungs into the left side
of the heart, from which it is forced to the aorta and its ramiiications and ulti-
mately into the capillaries. Here it undergoes a retrograde change, parting
with some of its O and taking in exchange COg ; consequently the gaseous
interchange between the blood and the tissues is the reverse of that occurring
between the blood and the air. Thus we find that the interchange of O and COj
occurs in a distinct series of events: (1) Oxygen is carried as a constituent of
the atmospheric air to the alveoli ; (2) here it is absorbed by the venous blood,
which at the same time gives oif CO, to the air in the alveoli; (3) O is now in
major part conveyed to the ti&sues, in which it is taken up and utilized in pro-
ce&ses of oxidation, CO, being the chief effete product, which is formed immedi-
ately or ultimately and given to the blood (a part of the O is consumed by the
blood, COg being one of the results) ; (4) the venous blood is now conveyed
to the lungs, COg is given off' and O is received in exchange, and the series of
events is repeated.

The Forces Concerned in the Diffusion of O and CO, in the Lungs. —
If the air expired be collected in a number of parts, each successive portion will
be found to contain a smaller percentage of O and a larger percentage of COg.
The air in the beginning of the respiratory tract (nose and mouth) varies from
atmospheric air but little in composition, while that in the alveoli contains con-
siderably less O and nuich more COg. With each quiet act of insj)iration the
quantity of air breathed is from three to four times greater than the cajiacity of
the trachea and bronchi, so that with each respiratory act two-thirds or more
of the fresh air is carried into the alveoli. "When expiration occurs a similar
volume of the vitiated air within the alveoli is driven into the bronchi and
trachea, and thus a certain percentage is expelled from the body. Thus the
mere volume and force of the air-currents must obviously be of great value in
equalizing the composition of the air in the different parts of the respiratory
tract.

The contractions of the heart exert similar mechanical influences. With each
contraction intrathoracic pressure is lessened, so that there is a slight expansion
of the lungs, just as would be caused had the thorax been slightly enlarged,
and consequently there is a movement of air toward and into the alveoli. Dur-
ing diastole intrathoracic pressure returns to the jn-evious level, the volume
of the lungs is diminished, and the air is driven from the alveoli. Thus
each heart-beat causes a to-and-fro movement (jf the air. These oscilla-
tions, which are termed carcJio-pnrinnntic vwvemeyifs, are of more importance
than might seem at first sight, for it has been shown that in cases of suspended

BESPIRA TION. 521

animation and in hybernating animals they aid materially in pnlmonary ven-
tilation.

Besides these mechanical factors there is present the important factor of the
ditt'nsion of gases, O diffnsing toward the alveoli and COj toward the anterior
nares. The ra])idity with which difFnsion occnrs, other things being equal,
depends upon the differences in the " partial pressure " of the gas at various
regions. Each gas forming part of a mechanical mixture exerts a partial
pressure proportional to its percentage of the mixture. Thus, atmosj)heric air
contains 20.81 volumes per cent, of (), 0.04 volumes })er cent, of COg, and 79.15
volumes per cent, of N. If the air exists at 760 millimeters barometric pressure,
each gas w'ill exert a jx;/-^ of the total pressure, or a " partial pressure," equivalent
to its respective volume. Should we wish to find the partial pressure of O, it

. , . , , , . 20.81 ^ , , 20.81 X 760
may be ascertained simply by taking oi the total pressure= —^

= 158.15 millimeters; similarly, the partial pressure of COg would be

0.04 X 760 ^^_ .„. ^ 1 ., . i. AT 79.15X760 ._^ _ .
r-— = 0.30 mdhmeter ; and that of N, ^r^ = 601.54

millimeters. Knowing, then, the composition of any mixture of gases and the
total pressure under which it exists, it is a matter of very simple calculation
to determine the partial pressure of each of the various gases constituting the
atmosphere. Expired air is poorer in O and richer in COg than inspired air,
and alveolar air is altered even to a greater extent than expired air; hence
the partial pressures must be affected similarly.

The first portion of the air expired contains a maximum amount of inspired
air and a minimum amount of the air contained in the air-passages previous to
the inspiratory act ; but as expiration continues the mixture becomes poorer and
poorer in inspired air and similarly richer in the vitiated air from the smaller
air-passages and the alveoli ; in fact, the last portion of expired air is very
similar to, if not identical in its composition with, that in the alveoli. The
following partial pressures of O and CO2 in inspired air and alveolar air
indicate the extent to which the composition varies in different parts of the
respiratory tract :

Gas. Inspired Air. Alveolar Air.

O 158.15 millimeters. 122 millimeters.^

COj 0.30 millimeter. 38 millimeters.

Since the partial pressure of O in inspired air is about 158.15 millimeters, and
as it is but about 122 millimeters in the alveoli, and as the air is poorer in O as
we pass from the nares to the alveoli, it is obvious that a force must be exerted
constantly to cause a diffusion of O from the larger air-passages to the bron-
chioles and from the bronchioles to the alveoli — that the O must diffuse
from the region of highest pressure to that of lowest pressure. During life
an equilibrium can never be established, because of the constant supply of
fresh air and the continual passage of O from the alveoli to the blood. The

• ^ The exact per cent, composition of alveolar air is not known ; these figures are estimates.

522 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

same relations of partial pressure are observed in connection with COj, except
that the air in the alveoli is inces-santly acquiring; this gas from the blood, causing
the per cent, composition of COj to be much in excess of that found in the
atmosphere. The partial pressure of CO2 in the alveolar air is about 38.00
niillimetci-s, while in inspired air it is only 0.30 millimeter ; hence COj must
diffuse from the alveoli outward.

There are, therefore, three important factors concerned in the admixture
and purification of the air in the lungs: (1) The tidal movements caused
by inspiration and expiration, which movements bv the mere force of air-cur-
rents cause a partial niixture of the air ; (2) the smaller wave-movements (car-
dio-pneumatic) produced by the heart-beats, and similar in effect to, Ijut much
less effective than, the first ; (3) the diffusion of O and CO^, depending upon dif-
ferences in their partial pressures in the various parts of the respiratory tract.

The Forces Concerned in the Interchange of O and COj between
the Alveoli and the Blood. — The gases in the lungs are in the form of
a mechanical mixture, while in the blo(Kl they are in solution or in chemical
combination ; hence we now have to deal with conditions quite different, involv-
ing the consideration of the relations of gases to liquids — a relationship of
twofold nature, inasmuch as the gas may be found not only in solution, but
in chemical association.

When an atmosphere consisting of O, COj, and N is brought in contact
with water, each gas is absorbed independently not only of the others, but
of the nature and quantity of all other gases which may happen to be in
solution. The quantity of each gas dissolved depends upon its relative solu-
bilitv as well as upon the temperature and the barometric pressure. The
coefficient of absorption of any fluid is the quantity of gas dissolved at a given
temperature and pressure, and is in inverse relation to temperature and in direct
relation to pressure. The following absorption-coefficients of water for O, CO^,
and X at 760 millimeters of Hg have been obtained by Winkler:'

Temperature. O. COj. N.

0° 0.04890 1.7967 0.02348

15° 0.03415 1.0020 0.01682

40° 0.02306 . 0.01183

Thus, at 0° C and 760 millimetei"s pressure each volume of water absorbs 0.0489
volume of O; at 15°, 0.03415 volume; and at 40°, 0.02306 volume. The
absorption-coefficient falls, it will be observed, with the increase of temperature.
Comparing the solubilities of the three gases, it will be seen that at the same
temperature and pressure a considerably larger quantity of COj is absorbed
than of O — nearly four times more — whereas the quantity of N absorbed is
less than one-half as much as that of O.

The quantity of a gas absorbed by a given liquid at a given temperature is
proportionate to its coefficient of solubility and to the pressure, and is the same
whether the gas exist free or as a constituent of a complex atmosphere, pro-
' Zeitschrift fur physikalische Chemie, 1892, vol. 9, p. 173.

BESPTRA TION. 523

vicled that the pressure exerted by the gas in both cases be the same. Thus,
atmospheric air consists of 20.81 volumes per cent, of O, 0.04 volume per
cent, of CO2, and 79.15 volumes per cent, of N. Each gas exerts a partial
pressure iu proportion to its percentage of the mixture. Assuming that the
air is at standard atmospheric pressure, the ])artial pressure of O is 20.81 per
cent, of 760 millimeters of Hg, or 158.15 millimeters. The quantity of O
absorbed from the air at 0° C and 760 millimeters pressure is therefore the same
as when the atmosphere consists of pure O at a pressure of 158.15 millimeters.

, , 20.81 X 0.0489 ^ ^, ,
The absorption-coefficient must consequently be :^ = 0.01 vol-
ume. Therefore 100 volumes of water at 0° C. and 760 millimeters pressure
absorb from the air 1 volume of O.

If the partial pressure of O be increased or decreased, the quantity absorbed
will rise or fall accordingly. From this it is obvious that O must exist under
a certain degree of pressure to prevent its passing out of solution, which
is expressed by the term tension of solution, meaning, in a word, the pres-
sure required to keep the gas in solution. If the partial pressure of the gas
diminishes, the gas in solution is given off until the jxirtkd jy-essure of the
gas in the air and the tension of the gas in solution are equal. Conversely, as
the partial pressure of the gas in the air increases, the gas in solution will be
under correspondingly higher tension.

Tension of 0.— The absorption-coefficient of blood for O is nearly the same
as that of water, so that blood at 0° should absorb from the atmosphere about
1 volume per cent, of O, but less than one-half as much at the temperature
of the body. The results of experiments show, however, that blood contains
considerably more than this, the average for arterial blood being 22.2 volumes
per cent., or very much more than can be accounted for by the laws of partial
pressures and tensions. Moreover, when the blood is subjected to a vacuum
pump there is evolved a small amount of gas consistent with the diminution of
pressure, but the great bulk of it does not come off until the pressure has been
reduced to Jg- to j\ of an atmosphere. Finally, the quantity absorbed is
affected but little by changes in pressure above a certain standard. These
facts indicate that almost all of the O must be in chemical combination, the
combination being with haemoglobin in the form of oxyhseraoglobin. This
chemical union is readily dissociated at a constant minimal pressure which is
termed the tension of dissociation. There is a persistent tendency of the gas in
such a compound to become disengaged, so that when oxyhsemoglobin is placed
under circumstances where the tension or the partial pressure of O is less than
that in the compound, dissociation occurs; conversely, when htemoglobin is
brought in contact with O at a pressure above the minimal constant of dissocia-
tion (^ to ^ of an atmosphere), the two unite to form oxyhemoglobin. One
gram of hemoglobin combines, according to Hiifner,^ with 1.59 cubic centimeters
of O at 0° and 760 millimeters pressure. Assuming that 100 volumes of blood
contain 15 grams of hemoglobin (p. 335), if oxidized into oxyhemoglobin the
1 Zeitschriftfur physiobgische Chemie, 1877-78, vol. ii. p. 389.

524 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

quantity of gas combined witii the hfcmoglobiu would be equal to 23.38 vol-
umes per cent, of the blood ; in other words, arterial blood should contain
23.38 volumes per cent, of O. This, however, is more than is found, but the
deficit is accounted for by the fact that only from ^V (Pfliiger) to -|-i (Hiifner)
of the haemoglobin is .saturated.

Tiie plasma and the serum absorb but very small quantities of O — according
to Pfiiiger, only 0.26 volume per cent. Owing to the relatively low absor})tion-
coefficient of the plasma compared with the O-capacity of the hsemoglobiu, as
well as to the fact that the haemoglobin is practically saturated at a relatively low
pressure, the quantity of O absorbed is not materially affected by an increase of
pressure above the level of the tension of dissociation : the slight increase which
does occur is due chiefly to absorption by the j)lasma.

The tension of O in arterial and venous blood must be ascertained separately,
inasmuch as each contains a different percentage. Following tliis method,
Strassburg^ records the following averages: Arterial blood, 29.64 millimeters
of Hg, or 3.9 percent, of an atmosphere; and venous blood, 22.04 millimeters,
or 2.9 per cent, of an atmosphere.

Tension of CO^. — Venous blood contains about 45 volumes per cent, of
COg. The results of experiments prove that only about 5 per cent, of this
CO2 is in simple solution, that from 10 to 20 per cent, is in firm chemical
combination, and that from 75 to 85 per cent, is in loose combination.

When the blood at the temperature of the liody is sulijected to a vacuum;
all of the CO2 is given off; but if the blood-corpuscles be removed and the
plasma and corpuscles each in turn be submitted to the pump, both will give
off COj, the plasma yielding a larger volume than the corpuscles, but not so
much as when they are together. Plasma and serum in vacuo give off only a
portion of their COg ; the remainder may, however, be dissociated by adding
acid or red corpuscles. The red corpuscles therefore act as an acid and cause the
disengagement of all the gas from the plasma ; consequently, not only do the
corpuscles yield up the CO2 contained in them, but they are also active agents
in bringing about the dissociation of COj which is in chemical combination in
the plasma. The dissociation is due in part, perhaps, to the presence of phos-
phates in the stromata of the red cor})uscles, and to certain proteids, but the
observations of Preyer and Hoppe-Seyler lead to the conviction that it is due
chiefly to oxyh?emoglobin and haemoglobin. Phosphates, proteids, lijemoglubin,
and oxyhsemoglobiu all have the power of expelling COj from sodium car-
bonate in solution in vacuo, but this fact leaves us none the wiser as to which,
if any, is active in this way in the blood. Arterial blood gives off its COj
more readily than venous blood.

Of the total quantity of CO,, about 5 per cent, is in simple solution and
from 10 to 20 per cent, is in firm chemical combination in the plasma, the latter
requiring the addition of acid or of haemoglobin, etc. to cause its dissociation
in vacuo; while the remainder, constituting nuich the larger proportion, is in
loose chemical union in both the plasma and the corpuscles. That which is in

' Pfiiiger' s Archlv fiir Physiologic, vol. vi. p. 65.

RESPIRATION. 525

chemical combination in the plasma is. probably in part combined with glob-
ulin and alkali, and in part with sodium as carbonate and bicarbonate, tiie
proportion of each varying with the tension of the COg. The wliite blood-
corpuscles, so far as they contain any of the C()2, hold it probably in combina-
tion with globulin and alkali and as carbonates of sodium. Tiie great bulk of
the gas disengaged from the corpuscles is derived from the red cells, but in what
combination or combinations it exists is not positively known. The experiments
of Setschenow, Zuntz, Boiir,^ and others indicate that it is associated in some
obscure way with haemoglobin, and probably with a third body, such as globulin
or alkaline phosphates; and yet haemoglobin seems to have the power to hold
the CO2 in tiie absence of a third body. This latter fact has been shown by
the experiments of Bohr, who compared the quantities of COj absorbed by
pure water and by solutions of pure crystallized haemoglobin at constant tem-
perature and varied pressure. He found that the weight of COg absorbed by
the water increased regularly with the increase of pressure, whereas the quan-
tity absorbed by the solution of haemoglobin was very large relatively to the
lower pressures and small for higher pressures, and that the increments of
absorption were in decreasing ratio to the rise of pressure. The absorption
curve is therefore steep at first, becoming less and less so with the increase of
pressure, and entirely different from the absorption line for pure water, which
is straight. Moreover, the quantity of CO2 dissolved was considerably in
excess of that which physical laws could admit. The CO2, in \vhatever form
or forms it may exist in the red corpuscles, is in looser combination than in
serum.

Strassburg's experiments show that the average tension of COg in arterial
blood is 21.28 millimeters of Hg, or 2.8 per cent, of an atmosphere, and in
venous blood 41.04 millimeters, or 5.4 per cent, of an atmosphere.

Tension of N. — The quantity of nitrogen in the blood is about 1.8 volumes
per cent. It is in simple solution in the blood-plasma, and the quantity in
both venous and arterial blood is practically the same. Its presence and quan-
tity are not of physiological importance.

The Interchang-e of O and COg between the Alveoli and the Blood. —
Let us now inquire into the factors which bring about the passage of O from
the alveoli to the blood and of CO2 from the blood to the alveoli. If we have
two mixtures of the same gases, but in unlike proportions, and separate them
by means of an animal membrane, diffusion will occur through the membrane
until the partial pressures of the two gases are the same on the two sides of the
membrane. Now modify this experiment by bringing an atmosphere of air
in contact with water containing O, COj, and X in solution or in chemical
combination : if the partial pressure of O in the air be greater than the tension
of O in the water, O will pass to the water ; if the partial pressure of CO2 in
the air be less than the tension of CO2 in the water, COg will pass to the air.
If now we interpose an animal membrane between the atmosphere and the

1 Erper. Uniermch. u. d. Sauersioffaufnahme d. Blutfarbsioffes, Kopenhagen, 1885 ; Beitrdge zwr
Physiologic, Festschr. f. C. Ludwig, 1887, pp. 164-172.

526 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

water, the interchange of gases will continue as before. In this case we have
conditions analogous totho.se which exist iu the living organism : In the alveoli
tliere is an atmosphere consisting of O, COj, and X ; each gas is under a par-
tial pressure proportional to its volume per cent, of the mixture; the pul-
monary membrane and the walls of the capillaries may be regarded as a sini])le
animal membrane separating the air in the alveoli from the blood ; finallv, the
blood contains O, CO,, and N, each of which is in a definite and inde])eiident
degree of tension. Whether or not any or all of these gases will pass in one
direction or the other must obviously depend upon the conditions of partial
pressure and tension of each gas on the two sides of the membrane. The ten-
sion of O in venous blood, as above stated, is 22.04 millimeters of Hg, and of
CO,, 41.04 millimeters. What are the partial pressures of these gases in the
alveoli? The precise pressures are not known, but it is estimated that the
partial pressure of O is about 122 millimeters, and of COg about 38 millimeters.
Comparing the partial pressures and the tensions of these two gases in the
alveoli and the blood respectively, it is obvious that the conditions on the two
sides of the membrane are favorable to the diffusion of O and COg, and in
definite but opposite directions. This is illustrated in the following diagram-
matic presentation :

O. COj.

Tensions in alveolar air 122.00 38.00

Pulmonary membrane + —\ —

Tensions in venous blood 22.04 41.04

Since the gases diffuse from the point of higher pressure or tension to that
of lower pressure or tension, O passes from the alveoli to the blood, while CO,
pas.ses from the blood to the alveoli.

It is, however, impo.ssible under certain circumstances to account for the
transmi.ssion of all of either the O or the CO., by the laws of diffusion. In
regard to O, physical forces are active to the extent that they cause a diffusion
of O to the blood-plasma, where it is brought in contact with the haemoglobin
of the blood-corjniscles. The chemical union of O Mith haemoglobin takes
place at a low tension, hence the quantity of O taken up by the blood does
not vaiy matel'ially with the amount of O in the air breathed, no more O
being taken up when pure O is respired than from atmospheric air, in which O
constitutes only about 20 volumes per cent. ; and Frjinkel and Geppert record
that the quantity of O in arterial blood is but little dimini.shed even when the
air-pressure is reduced as low as 378-36o millimeters. But Rolir found in
experiments on dogs that the tension of O in arterial blood may even be higher
than it.-^ partial pressure in the alveolar air; and Pfliiger long since determined
that when animals breathe pure N or H, no O passes from the blood into the
alveoli. It is apparent from the^e latter facts tliat the transmi.'^'sion of O may
not be entirely a matter of diffusion. In addition to the phvsical and chemi-
cal factors, it is poasible, as suggested by Bohr, that the ]uilmonary tissue
takes an active part as a specific secretory membrane in this transmission.

The problem in connection with COj is also complex. It is commonly

RESPIRATION. 527

believed tliat the passage of CO2 from the blood to the alveoli is determined
simply by the laws of ditUision, but Bohr^ has found in experiments in which
analyses of the blood and alveolar air were made simultaneously that the par-
tial pressure of COg in the alveolar air may be less than the average tension in
the blood. Moreover, Bohr found in a series of experiments that even when
the quantity of COj in the atmosphere in contact with the blood was very
small, but little more COg diffused from the blood. Facts of this kind are
explicable on the hypothesis that the pulmonary membrane is, as contended by
Ludwig, Bohr, and others, actively engaged in the process, playing a specific
excretory role, but our knowledge is as yet too incomplete to require the
acceptance of such an hypothesis. Under ordinary conditions the tension of
CO2 in the alveoli is less than in the blood, and the transmission of CO^ from
the blood to air-cells may be explained satisfactorily by the laws of diffusion.

The Forces Concerned in the Interchange of O and CO2 between the
Blood and the Tissues. — Innumerable facts show that the chief seat of the
chemical processes in the body is in the tissues, and that the decompositions
are essentially of an oxidizing character whereby COg is formed as one of
the most important effete products; consequently the blood as it is carried
through the capillaries gives up O and receives COj.

Experiments show that the tissues exert a strong reducing action, and that
their avidity for O is so great that they will take it up at extremely low
pressures. Moreover, never more than mere traces of O can be obtained
from the tissues, because the gas upon its absorption immediately enters into
chemical combination.

The tension of COg in the tissues is considerably higher than in blood.
Strassburg,^ in a loop of intestine into which he injected atmospheric air, fcmnd
that the tension was 58.52 millimeters of Hg, which is considerably greater
than in either arterial or venous blood. Thus we find that the tension of O in
the tissues is nil, owing to their greediness for this gas, while that of CO2 is
very high. Comparing the tensions of these two gases in the blood and the
tissues, it will be observed that there are present conditions which are highly
favorable to the passage of O to the tissues and of CO2 in the reverse direction :

O. COo.

Tensions in arterial blood 29.64 21.28

Blood-vessel walls — + 1

Tensions in tis.sues 0.00 58!25

It is manifest from the above that O should pass from the blood to the tissues,
and CO, from the tissues to the blood.

The lymph is probably merely a passive medium in this interchange. It
contains, according to Haramarsten, only traces of O, from 37.5 to 47.1 vol-
umes per cent, of CO2, and from 1.1 to 1.63 volumes per cent, of N. The
mean percentage of COg is lower than in serum, but Gaule has shown that the
tension is higher. Doubtless the same relations hold good for the plasma and

' Loc. cit. ** Loc, cit.

628

AN AMElilCAN TEXT-BOOK OF PllYSlOLOaY.

the hlood, so that, uotwithstaiuling a smaller volume per cent, of CO2 in the
Ivmph, CO2 passes to the blood because of the higher tension in the Iyin])h.

Extraction of Gases from the Blood. — We have found that in the l)lood
both O and CO2 cxi.st partly in solution and partly in chemical combination.
The portion in solution comes off regularly with a diminution of pressure, but
that which is in chemical combination remains so until the pressure is reduced
to the level of the tension of dissociation. Since there are several of these
combinations, such as O in oxyhemoglobin and CO2 in carbonates, bicarbon-
ates, alkali })hos2)hates, etc., portions of each of these gases come off at different
pressures in accordance with their different tensions in the several chemical
combinations. The portions in solution may be removed by the use of an

ordinary air-pump, i)ut those in
chemical condjination are held so
firndy that the more powerful mer-
curial j)um]) is required. A con-
venient pump of this kind has been
devised by Dr. Geo. T. Kemp, the
description of which he gives as
follows :

" To use the pump the reservoir
bulb lib (Fig. 136), the bulb /, the
cylinder SR and S'R' ^ and the ves-
sel Pare filled with mercury. When
the bulb Bli is raised the mercury
rises in the tube AC and fills B,
driving the air out by the path
FHOP, the stopcock Q being closed.
When Bb is lowered again the mer-
cury flows back from B into Bb,
creating a Torricellian vacuum in
B. As soon as the mercury has
fallen below the joint D, this
vacuum in B becomes connected
by the path DEG with the tubes
TGIJG'T' and the tube VWYX, and
thence, when the stopcock is open,
with the vessel to be exhausted. The air in this then diffuses to fill the
vacuum in B, and becomes rarefied, so that the mercury rises from the cylin-
ders SR and S'R' in the outer tubes TG and T'G'. The small inner tubes
RG and R'G' are made so high that even when there is a complete vacuum in
the outer tubes TG and T'G' the mercury will not rise high enough to cover
them.

"On raising Bb again the mercury rises in AC, and as soon as the joint D is.
covered, all the air which has been caught in B is forced out by the path FHOP.
Each time the bulb Bb is raised and lowered a certain amount of air is ex-

FiG. 136.— Kemp's gas pump.

BESPIRA TION.

529

tracted from the receiver, until finally a vacuum is produced. In a similar
way, when the receiver connected with the pump at Z contains any gas which
we wish to analyze — as, for example, the gases given off by the blood in a
vacuum — we put a eudiometer {Eii) over the bend of the tube at P, which, of
course, is always under the mercury, and collect the gases as they are forced out.

" The extraction of the last traces of gas by raising and lowering Bh is a
very tedious and laborious process, so that the final extraction of the gases can
best be accomplished by the Sprengel jnimp LTKLMNIIOP. The bulb and stop-
cock UK are made separate, as shown in the figure, and are connected with
LMN by a piece of rubber tubing, the whole being under mercury. This is
accomplished by the bend JKLM, which is made so as to allow a narrow wooden
box filled with the mercury to be slipped up over the bend high enough to
cover the stopcock and thus prevent leakage of air. The same arrangement is
shown at X, aud is indicated by a dotted line in each instance. When the
stopcock K is opened the mercury flows in, drops down the tube NHOF, and
extracts the gases at H in the well-known manner of the Sprengel pump. The
large bulb is for rapid exhaustion down to the last few millimeters of pressure,
the rest being accomplished more slowly but more perfectly by the Sprengel.
In extracting blood-gases the oxygen is given off suddenly and the CO2 slowly.
The great desideratum is to keep the tension of the gases in the blood-chamber
down as near zero as possible — certainly below 20 millimeters of Hg. This
is readily done with the large bulb when the O is evolved, while the Sprengel
is able to remove the COg as it is given oif, thus obviating the continued rais-
ing and lowering of the reservoir bulb."

The gases collected are driven through the tube P into a
eudiometer previously filled with mercury and inverted.
The eudiometer (Fig. 137) is a calibrated tube in which the
gases are measured. In the upper part of it are two plati-
num wires by means of which an electric spark is brought
in contact with the gases. Hydrogen is introduced into the
eudiometer in. definite quantity (more than sufficient to com-
bine with all of the O to form HgO), and a spark is gen-
erated between the ends of the platinum wires, causing the
O and the H to combine. The diminution in volume is now
noted, one-third of which diminution is equal to the total
volume of O obtained from the sample of blood. The quan-
tity of CO2 may be estimated by introducing into the eudi-
ometer a piece of moistened fused potassium hydrate, which
absorbs the COg, forming potassium carbonate. The loss in
volume is the volume of COg obtained from the blood. The

residual gas consists of N and H, the latter being the excess

not combined with O. The total quantity of H introduced

being known, and also the quantity which combined with

O, the difference is deducted from the volume N and H, the remainder being

the volume N. Accurate analysis necessitates corrections for temperature, for
34

Fig. 137.— Eudiometer.

530 .Lv AMKiurAN TEXT-IK i< >K OF PTfYsrnr.oa Y.

tension of aqueous vapor, and for atnios])heric pressure, as well as adnition to
the nianv details connected with jjas-analysis.

Cutaneous Respiration. — In froj:;s the skin is a nioic important i('sj)i-
ratorv organ than th(^ lungs, as is illustrated i)y the tact that asphyxia is
more rapidly })rodnced hy dipping the animal in oil, and thus preventing the
interehangeof O and CO2 through the skiu, than by ligature of the trachea;
moreover, the investigations of Regnault and Reiset show that in these animals
nearly the same quantities of O are absorbed and COg eliminated after the
lungs are excised as in the intact animal. In man the reverse is the case, the
cutaneous interchange being insignificant as compared with that in the lungs.

The quantity of COg exhaled through the skin during twenty-four hours
has been estimated by different ob-servers from 2.23 grams to as much as 32.08
grams. Compared with pulmonary interchange, the ratio of O absorbed is
probably about 1 : 100-200, and of CO2 eliminated, 1 : 200-250.

Cutaneous respiration is, as a rule, subject to the same circumstances that
aifect the interchange in the lungs, and is accomplished, moreover, in the same
w^ay. In some instances, however, it is influenced in the opposite direction ;
for instance, it is increased by circumstances that hinder pulmonary respiration.
Cutaneous respiration is favored by moist skin, and Ronehi found that it was
inerea.sed by higher external temperature.

Internal or Tissue-respiration. — The main object of the respiratory mech-
anism is to supply the organism with O and to remove the CO2 resulting from
tissue-activity. The organism may be regarded as an aggregation of living
cells, each of which during life consumes O and gives off COg. Activity
depends essentially upon processes of oxidation ; consequently, not only is oxi-
dation necessary for existence, but the quantity of O absorbed must bear a direct
relation to the degree of activity. The avidity of the different tissues for O
varies greatly, and the differences are doubtless expressions, broadly speaking,
of the relative intensities of their respiratory processes. Quinquaud ' records
the following absorption-capacities of 100 grams of each tissue, submitted for
three hours to a temperature of 38° :

Muscle 23 c.c.

Heart 21 "

Brain 12 "

Spleen 8 c.c.

Lungs 7.2 "

Adipose tissue 6 "

Liver 10 " Bone 5

Kidney 10 " I Blood 0.8 "

The quantity of CO2 formed in each case was approximately proportional to
the quantity of O absorbed. The respiratory value of blood is doubtless too
low. The blood is not merely a carrier of O and COg to and from the tissues,
but is itself the .seat of active disintegrations which involve the consumption
of O and the production of COj and other effete matters. Ludwig and his
pupils long ago showed that when readily-oxidizable substances, such as lactate
of sodium, are mixed with the blood, and the blood is transfused through the
lungs or other living tissues, more O is consumed and COj given off than by

' Compter rendus de la Societe de hiologie (9), 1890, 2, pp. 29, 30.

RESPIBA TION. 531

blood free from tlieni. Tliese results Imvc been substantiated by the recent
researches of Bohr and Ilenriquez' on dogs; tliese experiments have further
shown that a considerable portion of O may disappear as a result of processes
occurring in the blood during its passage through the lungs, and a large
amount of COg be formed as one of the products. Thus they found that con-
siderably more O was absorbed from the lungs than could be pumj)ed from the
blood, and that more CO2 was givx'u to the air in the lungs than was lost
by the venous blood. They believe that the tissues deliver to the blood j)ar-
tially-oxidized substances which undergo a final splitting up when the blood
reaches the lungs. If this be so, the respiratory capacity of the blood, apart
from its capacity as a carrier of 0 and COj to and from the tissues, must be
considerably greater than indicated by Quinquaud's figures.

The chief chemical product of the oxidative decompositions in the blood
and tissues is CO2 ; but the quantity of O absorbed is not necessarily related
to the amount of CO2 eliminated ; that is, during a given interval the quantity
of O may be out of proportion to the elimination of CO2, and vice versd.
Thus, in a muscle during rest, at normal bodily temperature, the consumption
of O is greater than the elimination of COg, while during activity the propor-
tion of CO2 to O increases and may exceed that of O. Rubuer's^ experiments
on the resting muscle at various temperatures accentuate the fact that the for-
mation of CO2 may be independent of the quantity of O absorbed. Thus, at
8.4° the respiratory quotient was 3.28 ; at 28.2°, 1.01 ; at 33.8°, 1.18 ; and at
38.8'^, 0.91. The high respiratory quotient at low temperatures is to be
explained partly by direct oxidation and partly by intramolecular splitting,
which is independent of oxidation. It is probable that during rest O is util-
ized to some extent in oxidations which are not at once carried to their final
stage and in which relatively little CO2 is formed; hence during activity com-
paratively little O is required to cause a final disintegration of the now par-
tially broken-down substances, and thus to give rise to a relatively large
formation of CO2. (See Effects of Muscular Activity on Respiration and
Metabolism of Muscle, etc.)

0. The Rhythm, Frequency, and Depth op the Respiratory

Movements.

The Rhythm of the Respiratory Movements. — During normal breathing
the respiratory movements follow each other in regular sequence or rhythm.
Various instruments have been devised for the study of these movements
in man ; the form most commonly used is the stethograph or pneumo-
graph of Marey. The respiratory movements are communicated by a system
of levers to a tambour, thence through a rubber tube to a second tambour
having attached a lever which records upon a moving surface. In animals
a tracheal cannula or tube (p. 554) is usually inserted into the trachea, and
a tube is led from it to a recording tambour. In case the movements

1 Comptes rendus, 1892, vol. 114, pp. 1496-99.

^ DuBoui-Reymond^ s Archivfiir Physioloffie, 1885, pp. 38-66.

532 ^l^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of the ribs are especially to be studied, the stethograph may be employed ;
if the movements of the diaphragm, a loDg probe may be inserted
through the abdominal walls so that one end rests between the liver and the
diaphragm and the other end connects with a recording lever, the abdominal
walls serving as a fulcrum. A tracing obtained by one of the above methods
shows : (1) That inspiration passes into expiration without an appreciable in-
tervening pause ; (2) that inspiration is shorter than expiration; (3) that the
curves of inspiration and expiration diifer in certain characters. The relative
periods of inspiration aud expiration vary with age, sex, and other conditions.
The inspiratory phase is shorter relatively in women than in men, and in chil-
dren and the aged than iu those of middle life. The length of inspiration as
compared to expiration is subject to variations, but these relations are affected
chiefly by disease and by other abnormal conditions. After section of the
pneumogastric nerves, and in diseased conditions which narrow any part of the
air-passages, inspiration is longer than expiration, while in emphysema the
expiratory phase is prolonged. The relative periods occupied by inspiration
and by expiration in the adult differ according to various observers ; at one
extreme, the ratio according to Yierordt aud Ludwig is 10 : 19-20, and at
the other extreme, according to Ewald, 11:12. A mean ratio is 5:6.
Renuebaum found that the expiratory phase is relatively prolonged by an
increase in the respiration-rate, the ratio being 9 : 10 at 13 respirations per
minute, aud 9 : 13 at 46 per minute. In the new-born the ratio is 1 : 2-3.
Mosso found that during sleep the inspiratory phase is lengthened one-fourth.

Inspiration is more abrupt than expiration, the lever moving more rapidly
during inspiration than during expiration ; consequently the curves differ in
character. We may volitionally affect the rhythm and the various phases of
each respiratory act.

A pause may exist between expiration and inspiration (expiratory ])ause)
when the respirations are abnormally infrequent. In certain diseases an inter-
val may be observed between inspiration and ex])iration (inspiratory pause).
Some observers look upon the nearly horizontal part of the respiratory curve
as a record of a pause, but an examination of tracings of normal respirations
shows that one phase passes into the other without an appreciable interval.

The respiratory acts while we are awake and quiet are rhytimiical, but this
rhythm is more or less disturbed during sleep, especially in young children
and in the aged. In the latter there may not only be an irregularity in
the time-intervals between successive acts, but occasionally long expiratory
pauses, giving the movements a peculiar periodical character. In the so-called
" Cheyne-Stokes respiration " the rhythm is greatly disturbed. This type is
characterized by groups of respiratory movements, each grouj) being separated
from the preceding and succeeding ones by more or less marked pauses. The
first respiration in each group is very shallow and is followed by movements
which successively become deeper and deeper until a maximum is reached;
then the successive movements become more and more shallow and finally
cease. Each group commonly consists of about 10 to 30 respirations, and is

RESriRA TIOX. 53:^

separated from the preceding aud siicceetling groups by a variable interval,
usually 30 to 45 -seconds. This form of respiration is frcfjuently observed in
urtemia, after severe hemorrhage, and in certain diseases of the heart and brain.
Periodical alterations in tlie respiratory rhythm may be observed in the last
stages of asphyxia, in poisoning by chloral, opium, curare, and digitalis, in cer-
tain septic level's, in certain animals during hybernation, etc. In the human
organism, excepting during sleep and in the aged and the very young, such
non-rhythmical respirations are always indicative of abnormal conditions.

In Nvarm-blooded animals the movements are generally of a much more
rhythmical character than in cold-blooded animals.

The Frequency and Depth of the Respiratory Movements. — The
respiratory rate is afiected by a number of conditions, chiefly species, age,
posture, time of day, digestion, activity, internal and external temperature,
season, barometric pressure, emotions, the composition of the air, the composi-
tion of the blood, the state of the respiratory centres and nerves, etc.

The following figures, compiled from various sources, indicate the wide
differences in various species y the rates being per minute :

Horse 6-10 I Pig 15-20 i Kabbit .... 50-60

Ox 10-15 Man 16-24 i Sparrow ... 90

Sheep 12-20 Cat 20-30 Guinea-pig . . 100-150

Dog 15-25 Pigeon 30 ■ Eat 100-200

The average rate in man varies according to different investigators, from
11.9 by Yierordt to 19.35 by Ruef. Hutchinson noted 16-24 per minute as
a mean of 2000 observations. There is a general, but not an absolute, rela-
tionship between the rate and the size of the body, as regards both different
species and different individuals of the same species : as a rule, the smaller the
species the more frequent the respirations; the same holding good for indi-
viduals of the same species.

The marked influence of age is illustrated by the records of the observa-
tions by Quetelet on 300 individuals :

Rate per Minute.

Age. Maximum. Minimum. Mean.

New-born 70 23 44

1- 5 years 32 . . 26

15-20 ' " 24 16 20

20-25 " 24 14 18.7

25-30 " 21 15 16

30-50 " 23 11 18.1

Posture exerts a marked influence, especially in those enfeebled by disease.
Guy records, in normal individuals, 13 while lying, 19 while sitting, and 22
while standing.

The diurnal changes are in close accord with those of the pulse-rate (p. 412).
The rate is less frequent by about one-fourth during the night than during the
day, and more frequent after meals, especially after the mid-day meal. Yier-
ordt noted the following variations: 9 a.m., 12.1; 12 M., 11.5; 2 p.m., 13;

531 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

7 P.M., 11.1. Ciiiy gives tlie mean rate in tiie morning as 17 and in the
evening as 18.

Tlie rate increases with an increase in inuscular adivUy (p. 41 o).

Changes in extermd (surnxnuling) tempcratare have very little iiiHuence.
Vierordt noted a rate of 12.16 at 8.47° C. and one of 11.57 at 19.4° C, and
that an increase of each degree C. decreases the period of each respiration
0.054. Alterations of into'nal temperature are associated with marked
changes, as is well illustrated in the increase in the rate observed in fevers,
which increase, in turn, is closely related to the rise in the pulse-rate and
the bodily temperature.

Season is not without its influence. In the spring the rate, according to E.
Smith, is 32 per cent, greater than at the end of summer.

Ordinary changes in atmospheric pressure exert no influence, but under con-
siderable variations the rate rises and falls inversely with the pressure.

The frequency of the respirations may be profoundly affected by our emo-
tions and by our u-ill. Mental excitement may increase or decrease the rate,
and, as is well known, we may greatly modify not only the rate but the depth
of the movements by volitional effort.

If the composition of the inspired air becomes so altered that O falls below
13 volumes per cent., the respirations ^re increased in frequency and in depth.
In the same way, if the blood becomes deficient in O or overcharged with CO2,
movements of respiration are increased.

Excitation and depression of the respiratory centres and nerves through the
agency of operations, disease, poisons, etc. effect changes in the respiratory rate.

The rate and the depth of the respirations bear generally an inverse relation
to each other : the greater the rate the less the depth, and vice versd ; but the
quantity of air respired during a given period does not necessarily bear any
direct relation to either the rate or the depth alone, but rather to both.

A general relationship exists between the frequency of the respirations and
the pulse-rate. Comparisons of a large number of observations by different
investigators give a ratio at twenty-five to thirty-five years, 1 : 4-4.5 ; at
fifteen to twenty years, 1 : 3.5 ; at six weeks, 1 : 2.5.

D. The Volumes of Air, O, and CO.. Respired.
During quiet respiration there occurs an inflow and outflow of air, desig-
nated tidal air, equal to about 500 cubic centimeters, or 30 cubic inches. The
volume of ex})ired air is a little in excess of inspired air, owing to the expan-
sion caused by the increase of tenijierature, although the actual volume is less
(p. 519). The volume of air respired during each respiration bears generally
an inverse relation to the respiration-rate, and is affected by the position of the
body; thus, if in the lying posture the volume be 1, when sitting it will be
1.11, and when standing 1.13 (Hutchinson). Besides the term tidal air,
others are used to express definite volumes associated with the capacity
of the lungs under certain circumstances. Thus, Hutchins<Mi distinguishes

RESPIRA TION.

535

complemental (lir, or the volume tlmt cuii he inspired after the completion of an
ordinary inspiration (1500 ciihic centimeters); reserve or supplemental air, or
the vohime that can ho expelled after an ordinary expiration (1 240-1 .SOO ciil)ic
centimeters); residual air, or the vohinie remaining in the lungs after the most
forcible expiration (1 230-1040 cubic centimeters); and stationary air, or the
volume remaining in tlie lungs after ordinary expiration, and equal to
reserve air j)lus residual air (2470-3440 cubic centimeters). The volume of
residual air is different according to various observers, the estimates ranging
from 538 cubic centimeters by Kochs to 19,800 cubic centimeters by Neupauer.
The recent researches of Hermann and Jacobson ' give 914.5 cubic centimeters
as the average of nine observations, the lowest measurement being 434 (;ubic
centimeters, and the highest 1023.2 cubic centimeters.

Lung-capacity is the tt)tal quantity of air the lungs contain after the most
forcible inspiration, and is equal to the vital capacity plus the residual air.

Bronchial capacity is the capacity of the
trachea and bronchi, and is equal to about 140
cubic centimeters.

Alveolar capacity is the volume of air in
the smallest air-passages and alveoli, and is
greater during inspiration than during expira-
tion, and, of course, is altered in proportion to
the depth of these movements. After quiet
expiration it is equal to about 2000 to 3000
cubic centimeters ; during quiet inspiration it
is increased about 500 cubic centimeters, and
during forced inspiration about 2000 cubic cen-
timeters; during forced expiration it is dimin-
ished about 1500 cubic centimeters. Between
the extremes of forced inspiration and forced
expiration the volume diifers about 3J times.

Vital capacity is the volume of air that can
be expired after the most forcible inspiration.
Averages obtained by Vierordt from the results
of the observations by various investigators are
3400 cubic centimeters for men and 2500 cubic
centimeters for women. Such investigations
are conducted by the aid of a spirometer (Fig.
138), Avhich is a calibrated gasometer consisting
of a bell-jar submerged in water and counter-
poised. Communicating with the interior of
the jar is a tube through which the expired air

is conducted. The subject makes the deepest possible inspiration and then
forcibly expires into the tube : the jar rises in proportion to the volume of
air admitted, and the extent of this rise may be read from the scale.
* Pfliiger's An-hiv J'iir Physiolor/ie, 1888, vol. 43, pp. 23G, 440.

Fig. 138.— Wintrich's modification of
Hutchinson's spirometer.

530 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Vital capacity is affected by various circumstances, especially age, stature,
sex, po.-turc, occupation, and disease. It increases with age, reaching a maxi-
mum at about thirty-five years, after which there occurs an annual decrease of
about 32 cubic centimeters uj) to about sixty-five years. In proi)ortion to
the length of the body it increases up to twenty-five years and then dimin-
ishes. Wintrich has shown that vital capacity for each centimeter of height
varies at different ages; thus at eight to ten years it is 9 to 11 cubic
centimeters for each centimeter of height, at sixteen to eighteen years
20.65 cubic centimeters, and at fifty years 21 cubic centimeters. Arnold
estimates that in the adult for each centimeter of increase or decrease of
height beyond a mean standard there is a corresponding rise or fall of 60 cubic
centimeters in men and of 40 cubic centimeters in women. It is greater in
men than in women of the same height, the ratio being about 10 : 7.5. Hutch-
inson found that it was affected by posture, the ratios being as follows : Lying
on chest and abdomen, 0.96; lying on back or sitting, 1.11; and standing,
1.13. Wintrich and Arnold both have found that vital capacity is diminished
during starvation 100 to 200 cubic centimeters. Physical exercise, such as
running and other forms of violent exertion that increase the rate and depth
of respiration, tends to increase the vital capacity. Occupation also exerts
an influence upon vital capacity, it being proportionately greater in those en-
gaged in active physical work than in those leading a sedentary life. All cir-
cumstances which interfere w^ith the full and free expansion of the thoracic
cavity diminish vital capacity, as, for instance, tight clothing, visceral tumors,
tuberculosis of the lungs, pneumothorax, etc.

The Volumes of O and COg Respired. — The quantity of air re-
spired during each respiratory act is about 500 cubic centimeters, or 30 cubic
inches ; and since the normal respiration-rate in man is, we may say, for the
twenty-four hours about 15, the total quantity of air respired per diem may
readily be calculated :

Per minute, 500 c.c. x 15 = 7,500 c.c, or 7.5 liters.
Per hour, 7.5 liters x 60 = 450 liters.

Per day, 450 liters x 24 = 10,800 liters, or about 380 cubic feet, which is equal to a volume

about 220 centimeters (7^ feet) in height,width, and thickness.

With these figures as standards, and knowing the per cent, composition of
inspired and expired air, the volumes of O absorbed and of COj eliminated
are easily found. The inspired air loses 4.78 volumes per cent, of O; it is
obvious, then, that the quantity absorbed per diem is 4.78 volumes per cent,
of 10,800 liters, which is 516 liters, or about 740 grams; likewise, the ex-
pired air contains an exce&s of 4.34 volumes per cent, of COj; the quantity
expired per diem is 4.34 volumes per cent, of 10,800 liters, or 470 liters or
925 grams. These figm-es, while not strictly accurate, are in accord with those
obtained by other methods of estimation and by experiments. The amount of
O varies from 600 to 1200 grams per diem, and that of CO^ from 700 to
1400 grams — approximate averages being about 750 grams of O and 875
grams of COj.

RESPIRA TION.

637

Tlie quantities of O and of CO2 exchanged, although in a general way
closely related, are in a measure independent of each other, but, as a rule, an
increase or a decrease in one is accompanied by a rise or a fall in the other.
The most important conditions affecting the quantities of O absorbed and CO,
given off are species, body-weight and body-surface, age, sex, constitution, rate
and depth of the respirations, the period of the day, digestion, food, internal
and external temperature, activity, atmospheric pressure, the composition of
the inspired air, and the condition of the nervous system.

Most of the studies have been made solely by determinations of the quan-
tities of CO, given off, the results being taken as standards for tlie relative
volumes of O absorbed ; but such deductions are of very uncertain value and
may be entirely misleading. (See Respiratory Quotient, p. 544.)

Respiratory activity in different species in proportion to body-weight is less
in cold-blooded than in warm-blooded animals, the difference being due chiefly
to the larger supply of O demanded by the more active heat-producing pro-
cesses in the latter, and in part to the more active character generally of the
bodily operations. If we take as a standard for cold-blooded animals the
respiratory activity in the frog (which is 0.07 gram of O per kilogram of body-
weight per hour), and compare this with the standards for warm-blooded ani-
mals, in the latter it will be from 6 to 18 times greater, according to the species.
Respiratory activity is higher in proportion to body-weight in birds than in
mammals. The following tabular statement of the intensity of the respiratory
interchange per kilogram of body-weight per hour, compiled chiefly from the
researches of Regnault and Reiset, Zuutz and Lehmann, Bossignault, Herzog,
and Grouven, illustrates these differences :

Animal.

Finch .
Sparrow

Fowl . .

Frog . .

Dog . .

Cat . .

Ox. . .

Ass . .

Calf . .

Horse .

Sheep .

Rabbit .
Man

Pig . .

0.

CO2.

Grams.

C.c.

Grams.

C.c.

11.635

1837

11.540

5857

9.595

6710

10.492

5334

1.189

831 ■

1.271

678

0.070

49

0.062

37

1.191

847

1.281

652

1.001

699

1.082

549

0.550

382

0.757

383

0.566

394

0.393

394

0.481

336

0.571

290

0.437

303

0.640

323

0.499

347

0.599

304

0.920

642

1.158

588

0.434

302

0.507

257

0.474

331

0.594

302

C02
o

0.72
0.79
0.82
0.76
0.77
0.80
1.00
1.00
0.86
0.91
0.88
0.90
0.85
0.91

As a rule, the smaller the species the greater (relatively, but not absolutely)
is the intensity of respiratory activity ; for instance, the consumption of O
for each kilogram of body- weight is for the horse, 0.437; ass, 0.566; sheep,
0.499; rabbit, 0.92; and for birds, as high as 12.58. For different species
of the same class the same variations are observed ; thus, Richet records, as
the result of investigations on birds, the following figures as the number of

538

A.\ AMERICAN TEXT- BOOK OF PHYSTOLOGY.

grains of COg given oil" per kilogram ol" hotly-w eight })er lioiir: Goijse, 1.4*J;
fowl, 1.66; duck, 2.27; pigeon, 3.36; and finch, 12.58.

In the same species, other things being equal, the respiratory interchange is
greater in smaller animals, because in relation to body-icciyht the body-surface
is greater, causing a greater })roportional heat-loss, which in turn necessitates a
larger consumption of O for oxidative processes to produce heat, and a conse-
quent increase in the production of COg. Richet' has shown that in the same
species the quantity of COg exhaled (indicating the intensity of the oxidation-
processes) is inversely proportional to the body-weight and is directly ])r()p()r-
tional to the body-surface. The following figures illustrate these imiwrtant
facts :

Mean Body-weight
(kilograms).

CO2 per Kilogram
per Hour
(grams).

Body-surface
(sq. cm.).

CO., per 100
sq. cm.
(grams).

24

11.5
6.5
3.i

1.020
1.880
1.624
1.964

9296
5656
3940
2341

2.65
2.81
2.69
2.71

Thus, an animal weighing 24 kilograms will give off 1.026 grams of COj
per hour for each kilogram of body-weight, while one weighing 3.1 kilograms
will give off 1.964 grams, or nearly twice as much, for equal increments of
weight. It will be observed by comparing the quantity of CO2 and the body-
surface that for each 100 square centimeters of surface the elimination is about
the same.

Age exercises an important influence. Until full growth respiratory activity
is higher than in middle life, and in middle life it is higher than in old age.
In children the absolute quantities of O consumed and CO2 formed are less
than in the adult, but in relation to body-weight they are about twice as much.
During middle life respiratory activity is about one-sixth higher than during
old age. In the young the quantity of O in relation to COj is higher than in
the adult.

Andral and Gavarret have shown, in investigations relative to sex, that
after the eighth year males give off from one-third to one-half more COg than
females, the difference being most pronounced at puberty. During pregnancy
and after the menopause the relative quantity of COg rises.

The influence of constitution is manifest by a greater intensity of respi-
ratory activity in the robust than in the weak, other conditions being the
same.

The rate and depth of the respiratory movehients do not appreciably affect
the volumes of O and COj interchanged, although the removal of COj is facili-
tated by an increase of the volume of air respired, because of the better ven-
tilation of the lungis. An increase in the rate, the depth remaining constant,
increases the volume of air respired and the ab.solute quantity of CO, given
off, but the quantity of COj in relation to the total volume of air is Ic^s. If
' Archiv de Physiologic noi-male et pathologicpie, vol. 22, pp. 17-30.

RESPTR , 1 T/O X. 539

the rate remain constant ;iiul tlio clci)th be increased, similar results are
obtained.

The quantity of CO.^ eliminated during slow, deep respirations is larger
than during rapid, shallow respirations.

The diunidl rdriafions are in accord with the changes in the respiratory
rate — rising after we awake, falling during the forenoon, again rising after the
mid-day meal, again falling during the afternoon, increasing after the evening
meal, and falling to a minimum during the night.

Sunli(/Iit exercises a marked influence, as is proven by the results obtained
by a number of investigators. In frogs the elimination of COj is increased
by sunlight, even after excision of the lungs. Fubini and Benedicenti,' in
experiments upon hybernating animals, found that the comparative quantities
of CO2 eliminated under the influence of sunlight and of darkness were as
100 : 93.48. Confirmatory results have been obtained by Ewald on curarized
frogs.

Respiratory activity is affected by the character and quantity of the food.
The following results, obtained by Pettenkofer and Voit, are very instructive :

Non-nitrogenous Nitrogenous

Fasting. Mixed Diet. j^jg^^ » pj^j.

O 743 grams. 867 grams. 808 grams. 1083 grams.

CO., 695 " 930 " 839 " 850 "

It will be observed that respiratory activity is lowest during fasting, higher
when the diet is non-nitrogenous, still higher when the diet is mixed, anJ
highest when the diet is purely nitrogenous. The respiratory quotient is
higher when the diet is rich in carbohydrates (p. 545), while it falls in propor-
tion to the percentage of nitrogenous food. Fasting reduces the quotient con-
siderably, and if coupled with inactivity (hybernation) causes it to fall to a
minimum.

During digestion the gaseous exchange is increased, according to Loewy,''
from 7 to 30 per cent. Joylet, Bergonie, and Sigalas^ obtained the following
averages of seven experiments on a man weighing 52 kilograms, the increase
of O being about 7 per cent., and of CO2 about 6 per cent. :

o. CO,

CO2
o

Before food 259 grams. 298.4 grams. 0.869

After food 275 " 317 " 0.867

The increase of respiratory activity during digestion may be due to the
chemical processes involved in the production of the digestive secretions, to
the oxidation of the products of digestion after absorption, or to muscular
activity of the gastro-intestinal walls. Zuntz and Mering^ endeavored to

1 MolescMis Untermch. z. Naturl., 1887, vol. 14, pp. 623-629.
^ Pfliir/ei-'s Archivf. Physiologle, 1888, vol. 43, pp. 515-532.
s Compt. rend., 1887, vol. 105, pp. 380, 675.
* Pfluyer's Archiv f. Phy&iologie, 1883, vol. 32, pp. 173-221.

540 AN AMERICAN TEXT-liOOK OF PHYSIOLOGY.

settle tliis point hv making three series of expcriiuciits : in one they injected
certain readily oxidizable substances into the blood ; in another the substances
were injected into the stomach ; and in another sulphate of sodium or other
purgative was given. When the snbstances were injected into the blood, Zuntz
and Mering found as a general result that the absorption of O was not increased,
while the formation of VO., was slightly increased ; when injected into the stom-
ach, no marked increase in respiratory activity occurred unless the substances were
given in large quantities. When, however, in addition to the readily oxidiz-
able substances, a purgative was injected, or when the purgative was given
alone, the absorption of O and the elimination of COg were considerably in-
creased. They were therefore led to conclude that the increased respiratory
interchange during digestion is due chiefly to the muscular activity of the
intestinal walls. Loewy^ has confirmed this conclusion, and has clearly shown
that the increase in respiratory activity is chiefly related to the intensity of
})eristalsis, the most marked increase being associated with excessive peristaltic
activity. There can be no reasonable doubt, however, that an insignificant
portion of the increase is due both to glandular activity and to the oxidation
of the absorbed products of digestion.

The volumes of O absorbed and of COj produced rise with an increase of
bodily temperature. This fact has been illustrated by the experiments of
Pfliiger and Colasanti on guinea-pigs, in which they found that the quantity
of O absorbed at a bodily temperature of 37.1° was 948.17 grams; at 38.5°,
1137.3 grams; at 39.7°, 1242.6 grams. Similar results have been obtained
by other investigators in experiments both upon the human subject and upon
the lower animals under the pathological conditions of fever. A fall of bodily
temperature is accompanied by a decrease in the intensity of respiration, unless
the fall is accompanied by muscular excitement, such as shivering. Speck ^
has seen shivering cause the consumption of () to rise from 302 to 496 cubic
centimeters, and the exhalation of COj from 287 to 439 cubic centimeters.
The primary and fundamental effect of lowering the bodily temperature is to
diminish respiratory activity, but this may be more than compensated for by
involuntary or voluntary excitement of the muscles (p. 541 ; see also Tissue-
respiration).

The effects of external temperature upon warm- and cold-blooded animals
are different: Moleschott found that frogs produced three times more COj at
38.7° than at 6°, while in warm-blooded animals the opposite is the cast — that
is, three times more COg is formed at the lower temperature. The frog's tem-
])erature rises and falls with changes in the temperature of the surroundings,
while that of warm-blooded animals remains at a fairly constant standard ;
he""ce the respiratory intensity in the frog increases with the rise of external
temperature, while in warm-blooded animals it decreases, owing to diminished
heat-production. But in warm-blooded animals the alterations in respiratory
activity caused by changes of external temperature are not always in inverse
relation. Thus, Voit has shown, as a result of studies in man, that the exhala-

• Loc. cit. » Deutsehes Archiv f. klin. Med., 1889, vol. 33, pp. 375, 424.

RESPIRATION. 541

tion of COj diminishes with the rise of external temperature from 4.4° uiiiil
the temperature reaehes 14.3°, when it rises slowly. These results have been
substantiated by the more recent investigations of Page/ who found in ex])eri-
ments on dogs that the discharge of COg was at a mininuim at about 25° ;
that below this temperature the quantity increased as the temperature fell ;
and that above this temperature the discharge increased, and became greatly
augmented at temperatures of 40° to 42°. At the latter temperatures the
increase may reach 3^ times the normal, but the bodily temperature is also
incretised. If the elimination of CO^ at 23° to 24° be represented by 100 as
a standard, at 13° it will be about 128 ; at 10°, 141 ; and at 18°, 177. The
researches of Speck,^ of Loewy,^ and of Quinquaud * all show that external
cold increases respiratory activity, chiefly by causing involuntary muscular
excitement (shivering). If shivering and other forms of nuiscular activity be
absent, the exchange of O and COj is unaffected or diminished, but when
present the increase of respiratory activity may amount to 100 per cent, not-
withstanding a fall of bodily temperature below the normal.

Muscidar activity is one of the most important of all the circumstances
affecting the quantities of O and CO2 exchanged. Involuntary excitement,
such as shivering, may of itself double the consumption of O and increase
by one-half the elimination of CO^, but the volitional effort may increase
the interchange even beyond these limits. Hirn, in investigations on
four men, noted during rest an hourly absorption of 30.2 grams of O, and
during work 120.9 grams; and Pettenkofer and Voit, in similar studies,
found an increase of O from 867 grams during rest to 1006 grams during
moderate work, and from 930 grams* of CO2 to 1137 grams. In experiments
on the horse Zuntz and Lehmanu^ obtained the following results, which show
to what a marked extent the respiratory interchange may be increased by
muscular activity :

Liters per Minute.

CO2

O. CO,. -^^

Besting 1.722 1.570 0.92

Walking ". . 4.766 4.342 0.90

Trotting 8.093 7.516 0.93

Speck ^ has added some interesting facts to our knowledge of the effects of
muscular activity on the respiratory interchange. Thus, he found that the
increase of O and CO2 reaches a maximum before exertion reaches its maxi-
mum ; that the increase for the same amount of work can be varied by chang-
ing the position of the body ; that if a given amount of work be divided into
two equal parts, the increase of respiratory activity during the first period is
greater than during the second ; that the greater the increase of CO^, the less,

1 Journal of Physiology, 1879-80, vol. 2, p. 228. ^ Loc. cit.

" Pfluger^s Arcfiiv f. Pliysiologie, 1890, vol. 46, pp. 189-224.

* Compt. rend., 1887, vol. 104, pp. 1542-1544.

* Journal of Physiology, 1890, vol. 2, p. 396.

* Deutsches Archiv f. klin. Med., 1889, vol. 45, pp. 460-528.

642 ^l.V A3fEniCAN TEXT-JiOOK OF PHYSIOLOGY.

projx^rtioiiatcly, is tlic iuoreasc of O, so that the respiratory (juotient rises
more and more, and to such an extent that the COj contains more O than is at
the time absorbed ; and that the quantity of air respired is so intimately related
to the amount of CO^ given off that he regards the fpiantitv of this gas
formed as the regulator, as it were, of the degree of activity of the respii-atory
movements.

Griiber ^ states that while resj)iratory activity is proportional to the inten-
sity of muscular activity, "training" diminishes tlu." (piaiitity (»f C()2 given
off for the same amount of work. Thus, taking 1 as a standard of the
amount of CO^ eliminated during rest, he obtained the following ratios in two
series of observations :

Climbing hills Climbing hills
Resting. Walking. when not used when used to

to it. it.

First series 1 1.89 4.1 3.3

Second series J_ 1.75 3.05 2.42

Mean 1 1.82 3.07 2^86

Training therefore reduces the output about 20 per cent.

The elimination of COg is about one-fifth less during sleep than while
awake and quiet ; from one-fifth to one-half greater during ordinary exertion ;
from two to two and a half times greater during violent exercise ; and about
three times greater during tetanus.

During hybernation the absorption of O falls to -^^ and the elimination of
CO2 to ^ of the normal for the period of activity (Valentine). Relatively
more O Ls absorbed than CO2 given off, hence the respiratory quotient falls,
reaching as low as 0.50 to 0.75.

A diminution of the barometric pressure increases the respiration-rate and
the volume of air respired, but both Mosso and Marcet have shown that if
allowances be made for the increase of volume of the air at the lower pressure,
the actual volume respired is less. Conversely, an increase of pressure lowers
the rate and the volume of air respired. Extremes of pressure severely affect
the respiratory and other functions (p. 559).

The integrity of the nervous apparatus which governs the metabolic pro-
cesses in the tis.sues is obviously of fundamental importance. If the efferent
nerve-fibres of a muscle be cut, the interchange of O and'COg at once sinks,
as illustrated by the following results obtained by Zuntz :

O consumed. CO... given off.

Before section 13.2 c.c. 14.4 c.c.

After section 10.45 c.c. 10.1 c.c.

After section (less) 2.75 c.c. 4.3 c.c.

The consumption of O was therefore lessened about 20 per cent., and the
formation of COj about 30 jier cent.

After section of the spinal cord in the dorsal region Quinquaud ^ obtained

' Zeiischrift f. Biolof/ie, 1891, vol. 28, pp. 466-491.
* Cmipt. rend. Soc. Biologic, 1887, pp. 340-342.

RESPIRATrOX. 643

similar results. Before the section the hloml in the crural vein contained 9.5
per cent, of () and 60 per cent, of COj ; after section it contained l.'i.o per
cent, of O and 40 per cent, of COj, showinj^ that the consumption of O by
the tissues and the formation of COg were c(jnsiderably leasened. After de-
struction of the spinal cord res})iratory activity falls to a minimum.

The study of the eti'ects of a/fcrations in the compo.sitlon of the inspired air
on the absorptiou of O and the elimination of CO2 are of great importance.
Nitrogen is merely a mechanical diluent of the inspired air, and may be
replaced by H or by other inert gas, so that alterations in its percentage do
not, -per se, aifect the respiratory phenomena ; but changes in the percentages
of O and COj may cause marked disturbances both of the respiratory move-
ments and of the gaseous interchange.

When the percentage of O in the inspired air is increased up to 40 volumes
per cent., Bert found that there occurred an increase in the quantity absorbed,
and both Speck and Fredericq have noted merely a transient increase under
similar circumstances ; but the results of most experimenters, on the contrary,
seem to show quite conclusively that an increase of the ])er cent, of O above
the normal does not affect the quantity absorbed. Lnkjanow ^ in a large
number of experiments could not detect any increase, and Saint-Martin,^ in
researches on guinea-pigs and rats with an atmosphere containing from 20 to
75 volumes per cent, of O, noted the same result. Even in an atmosphere of
pure O animals breathe as though they were respiring normal atmospheric air.

A decrease in the percentage of O is without influence until the proportion
falls below 13 volumes per cent. Worra-Miiller long ago showed that animals
breathe quietly in air containing 14,8 volumes per cent, of O, and that if the
proportion fell to 7 volumes per cent., respiration became slow, deep, and diffi-
cult ; with 4.5 volumes per cent, marked dyspnoea occurred ; and when there
was but 3 volumes per cent, asphyxia rapidly supervened. The more recent
results of Speck ^ not only confirm the main facts of Worm-Miiller's observa-
tions, but furnish other important data. He has shown that Avhen the
atmosphere contains 18 volumes per cent, of O, respiration is quiet and the
quantity of O absorbed is but slightly, if at all, diminished, and that even
when the proportion falls to 9.65 volumes per cent, breathing is carried on for
a long time without inconvenience, the amount of O absorbed, however, being
diminished. He shows, moreover, that when the volume of O in the atmo-
sphere falls to 8 per cent, the respiratory movements are deep and are but
slightly accelerated, the quantity of O absorbed being very much diminished,
and that the animal subjected to such an atmosphere succumbs in a few
moments. The quantity of O taken into the lungs falls proportionately with
the diminution of O in the inspired air until the reduction reaches 11.26 vol-
umes per cent., but further diminution is compensated for by an increase in
the volume of air respired. As the volume per cent, of O in the inspired air

1 Zeitschrifl f. Physiolog. Oiemie, 1883-1884, vol. 8, pp. 31«-355.

» Compt. rend., 1885, vol. 98, pp. 241-243.

' Zeitschrift f. klin. Med., 1887, vol. 12, pp. 447-532.

544 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

diminishes the relative percentage of O absorbed increases, and tliis continues
until the volume in the inspired air is reduced to 11.26 per cent., 27 per cent,
of which is absorbed ; below this point no further increase of absorption
occurs. As the (piantity of O absorbed is reduced the respiratory (piotiont
becomes greaier, and may reach as iiigh as 2.218.

When the quantity of O remains at the normal standard and the jK'rcentage
of COj is much increased, the elimination of the hitter is interfered witli ; and
Pfliiger has shown that if the percentage of COg be high, dyspncea ensues,
notwithstanding the fact that the blood contains a normal amount of O.
When air contains 3 to 4 volumes per cent, of COg, the quantity of COg
given off is diminished about one-half. Speck ^ and others have found that
the elimination of COg during a given period may be independent of b(»th
the percentage of O in the inspired air and the quantity absorbed. An atmo-
sphere containing 10 volumes per cent, of COg is generally believed to be toxic,
but Wilson's^ investigations show that air having even as much as 25 to 30
volumes per cent, may be inhaled with impunity. It is quite probable that
in those cases in which small percentages of COg in the inspired air have
proven poisonous the gases were contaminated with CO (carbon monoxide).
Respiration of an atmosphere of pure COg is followed within two or three
minutes by death.

Worm-Miiller found that when animals breathe atmospheric air in a large
closed chamber O disappears and COg accumulates, and death finally occurs,
not from a lack of O, but from the increase of COg, as is shown by the fact
that at the time of death the quantity of O in the air is sufficient to sustain
life. He has also shown that animals placed in an atmosphere of pure O die
from an accumulation of COg in the blood, rabbits succumbing after the reten-
tion of a volume of COj equal to one-half the volume of the body, and at a
time when the atmosphere contained as much as 50 volumes per cent, of O.

The dyspnoea occurring in an animal confined in an air-tight chamber of
miall size is due to the lack of O, nearly all of the gas being ab^^orbed before
the animal dies. If a cold-blooded animal, such as a frog, be similarly ex-
posed, the attraction of hemoglobin for O is so strong that almo><t every ])ar-
ticle of gas will pass into the blood long before death occurs ; and even after
the total disappearance of O the elimination of COj is said to continue at the
normal rate.

Animals placed in a confined space become accustomed, as it were, to the
vitiated air, and survive longer than a fresh animal suddenly thrust into the
poisonous atmosphere.

The Respiratory Quotient. — The relation between the (|uantities of O
absorbed and Ci\ given off during a given period is expressed as the respira-
tory quotient. The air during its sojourn in the lungs loses 4.78 volumes per
cent, of O and acquires 4.34 volumes per cent, of COj, hence the respiratory

quotient is —~- ._ -^ = 0.901. This quotient is subject to considerable

• Loc. cit. ' Amerimn Joum. Pharmacy, 1893, p. 5(51.

BESPJIiA TION. 545

variatioDS not only in tlifferont species, but in difTcrcnt individuals under
varied cireun»stances. The elilef reasons for the diHerences are:

First, the produetion of CO^ is in a measure independent of the O absorbed,
as is proven by tlie records of various investigators, showing that CO2 results
both from oxidation-processes and from intramolecular splitting (analogous to
fermentation-processes) which may be entirely independent of each other;
that the quantity of COg eliminated may continue under certain circumstances
at the normal standard even after the absor[)tion of O has ceased ; and that
the quantity of O contained in the CO2 eliminated during a given time may
be larger than the actual quantity absorbed. This may be understood in a
general way when we remember that the COg formed in the body is not the
result of an innnediate oxidation of the carbon-containing material of the
body ; on the contrary, some of the O absorbed may be stored, as it were, in
the form of complex compounds, which at some later time may undergo disin-
tegration, with the formation of CO2 ; or the complex materials introduced as
food may undergo a similar disintegration and splitting of the molecules, with
the formation of COg independently of the direct actiou of the O upon them.

Second, a larger quantity of CO2 is formed per unit of oxygen from the
disintegration of certain substances than from others, consequently the quotient
must be affected by the nature of the substances broken down. Thus, in the
formation of COg from carbohydrates all of the O consumed in the disinte-
gration of the molecules is used in forming COj, the H already liaving suffi-
cient O to satisfy it ; but in the case of fats and proteids a portion of the O
is utilized in the oxidation of H to form HjO. 6 molecules of O will oxidize
1 molecule of grape-sugar (CgHijOg) into 6CO2 + GHgO ; hence the quotient is

^^P- = 1. In regard to fat, if we take olein, C3H5 (0,8113302)3, as an ex-

6O2

ample, 80 molecules of O are required to reduce each molecule of the fat to

5 7 CO
57 molecules of COg and 52 molecules of H2O ; hence the quotient is ^^^ ^

= 0.712. In the disintegration of proteid only a part of the C is oxidized
into CO2, the remainder being eliminated as a constituent of various complex
effete bodies ; but it is estimated that the quotient for proteids (albumin) is
from 0.75 to 0.81, depending upon the completeness of disintegration.

The respiratory quotient varies with species, food, age, the time of day,
internal and external temperature, muscular activity, the composition of the
inspired air, etc.

In regard to species, the quotient is higher in warm-blooded (0.70 to 1.00)
than in cold-blooded animals (0.65 to 0.75); in herbivora (0.90 to 1.00) than
in carnivora (0.75 to 0.80) ; and in omnivora (0.80 to 0.90) than in carnivora,
but lower than in herbivora. These differences are due essentially to diet,
herbivora feeding largely upon carbohydrates, omnivora using carbohydrates
to a less extent, and carnivora practically not at all. These observations are
substantiated by the fact that during fasting, when the animal is feeding ujion
its own tissues, the respiratory quotient in all species is the same (0.7 to 0.75).
35

540 AN AMERICAN TEXT-HOOK OF PHYSIOLOGY.

The quotient is lowered bv an animal diet and increased by a vegetable diet,
the ratio approximating unity if the diet be sufficiently rich in carbohydrates.
Hanriot and Ricliet ' in observations on man noted that before feeding the quo-
tient was 0.84 to 0.89; when meat or fat was given tiie consumption of () was
increased, but there was no increase in COg, and the quotient fell to 0.76 ; when
given potatoes it was 0.93; and when the diet Was of glucose it reached 1.03.
During fasting the quotient falls rapidly. The exi)eriments of Zunt/ and
Lehmann^ show that in dogs it falls as low as 0.65 to 0.68 on the second day
of fasting, and that on the resumption of food it rises to 0.73 to 0.81.

The influence of age is manifest in the fact that in children the quotient is
lower than in the adult, more O being absorbed in proportion to the COg given
off than after full growth has been reached.

The quotient undergoes a diurnal variation. The day-time is more favor-
able than the night for the discharge of CO2, as well as for the absor})tion of
O, owing mainly to greater muscular activity :luring the day, but the COj
is more affected than the O ; hence the respirator}' quotient is higher during
the day. In the recent experiments by Saint-lNIartin '^ on birds, the mean quo-
tient during the day was 0.83 and during the night 0.72 ; the ratio for CO2
for the day and night was 1 : 0.78, and for O 1 : 0.9. During the night the
elimination of COg was diminished about 20 per cent., while the absorption of
O fell only about 10 per cent.

The quotient is increased by a rise of external temper atm-e. Thus, Pfliiger
and Finkler found in guinea-pigs that the quotient was 0.83 at 3.64° and 0.94
at 26.21°. AVhen the bodily temperature is increased, as in fever, the respira-
tory quotient remains practically unaltered. When the temperature falls below
the normal the respiratory quotient increases.

Muscular activity is also an important factor. During rest the consumption
of O by muscles is greater than the production of CO2, while during contrac-
tion the difference becomes less and less in proportion to the degree of activity,
until finally more CO2 may be given off than there is O consumed. Sczelkow
found in experiments on muscles of rabbits at rest and in tetanus that the
respiratory quotient was decidedly increased, A mean of six experiments
gives as the quotient during rest 0.543 and during tetanus 0.933 ; in one-half
of the experiments it went above 1, and in one instance to 1.13.

During sleep the output of CO2 is diminished more than the consumption
of O (p. 542), so that the respiratory quotient is less than when awake and
quiet.

During hybernation the quotient falls to a minimum — in the marmot as low
as 0.49. This is due chiefly to the more decided falling off in the quantity of
CO2, the CO2 being reduced to j\, and the O to only ^L; the animal, however,
is not only in a state of muscular' quiet, but fasting, which, it will be remem-
bered, is an important factor in lowering the quotient.

' Compt. rend., 1888, vol. 106, pp. 496-498.
. « Berliner klin. Woch., 1887, p. 428.
» Compt. rend., 1887, vol. 105, pp. 1124-1128.

RESPIRATION. 547

When the paxentage of 0 in the inspired air falls so low as to cause marked
(lyspiKjea, the respiratory quotient ra[)i(lly rises. This is owing ou the one
hand to the diminished quantity of O absorbed, and on the other hand to the
increased production of COj as a consequence of excessive activity of the
muscles of respiration. Speck (p. 543) found that when the proportion of O
was very low the quotient rose as high as 2.258.

E. Principles of Ventilation.

Breathing within a confined space, as in a small unventilated room or in a
large room in which a considerable number of persons are assembled, causes
a gradual diminution in the quantity of O and an accumulation of CO,, moist-
ure, and organic matter. In regard to O, even in the worst ventilated rooms
the atmosphere seldom contains as little as 15 volumes per cent., which is suffi-
cient to permit of undisturbed respiration. When the proportion of CO2
exceeds 0.07 volume per cent, the air becomes disagreeable, close, and stuffy —
oflPensive characters which are due neither to the increase of COg nor to a
deficiency of O, but to the presence of organic matter termed ^' crowd-poison."
Air from which this organic exhalation is absent may contain considerably
more COg without causing any unpleasant etfects. In well- ventilated rooms
the proportion of COg does not exceed 0.05 to 0.07 volume per cent. ; in
badly-ventilated rooms it may reach 0.25 to 0.30 volume per cent. ; while
when a large number of individuals are crowded together, as in lecture-
rooms, it may be as high as 0.70 to 0.80 volume per cent. This vitiation is
further increased by the burning of gas or oil, 150 liters of ordinary coal-gas
(enough to supply a large burner for about an hour) consuming all the O in
1200 liters of air, or as much O as is required by the average individual
in eight hours, besides loading the air with various deleterious products of
combustion.

While the accumulation of CO2 even in the worst ventilated rooms is not
in itself pernicious, its percentage is a practical working index of the amount
of organic matter present, and therefore of the degree of vitiation. It has
long been recognized that the atmosphere of crowded, badly-ventilated rooms
is poisonous, but the precise nature of the toxic element is unknown. Brown-
Sequard and d'Arsonval condensed the moisture of the expired air and found
that from 20 to 40 cubic centimeters would kill a guinea-pig; but their results
have been contradicted positively by Dastre and Loye, Lehmann, Geyer, and
others. The poison in expired air, whatever it may be, is of an impalpable
nature, and is neither dissolved nor condensed in the moisture exhaled.

The quantity of fresh air required during a given period depends upon the
size of the individual, the degree of activity, and the size of the air-space.
Assuming that an individual eliminates 900 grams, or 458 liters, of COj per
diem, and that the percentage of CO, is to be kept at a standard not exceeding
0.07 volume per cent., there would be required at least 1,440,000 liters of
fresh air during twenty-four hours, or about 60,000 liters (2000 cubic feet) per

548 AN AMUR/CAN TEXT-BOOK OF PHYSIOLOGY.

hour. All circumstances, such as muscular activity, which increase the outj)ut
of CO2 augment the demand for fresh air. When confined in rooms, every
pei-sou should have an air-space equal to about 28,000 litei-s, or 1000 cubic
feet, the floor-space should not be less than -^ of the cubic capacity of the
room, and the air should be renewed as often as twice an hour. In lecture-
rooms, school-rooms, etc. the air-space per individual is usually very small, so
that the renewal nnist be more frequent and in proportion to the limitation of
space per individual.

Ventilation is accomplished by natural and artificial means. The forces of
the wind, the differences in temperature within and without the building, the
natural diffusion of gases owing to variations in composition, etc., all cause
more or less circulation. Artificial ventilation is effected by the use of proper
appliances for the forced introduction of air into and expulsion from apartments.

F. The Effects of the Respiration of Various Gases.

The respiration of pure O takes place without disturbance of the respiratory
processes, but dyspnoea is developed when the inspired air contains less than 13
volumes per cent. (p. 543). Respiration of pure CO2 (p. 544) is fatal within
two or three minutes, but an atmosphere containing as much as 25 to 30 per
cent, may be respired for a few minutes without ill effect (p. 544). Nitrogen,
hydrogen, and carburetted hydrogen (CHJ may be inhaled with impunity if
they contain not less than 13 volumes per cent, of O. The respiration of
nitrous oxide or of air containing much ozone rapidly produces anaesthesia,
unconsciousness, and death. Carbon monoxide (CO) and cyanogen are decid-
edly toxic, combining with haemoglobin and displacing oxygen. Sulphuretted
hydrogen, phosphoretted hydrogen, arseniuretted hydrogen, and antimoniu-
retted hydrogen are all poisonous and are all destructive to ha?moglobin. An
atmosphere containing 0.4 volume per cent, of sulphuretted hydrogen is said
to be toxic. Air containing 2 volumes per cent, of CO (carbon monoxide) is
quickly fatal. Certain gases and vapors — as, for instance, ammonia, chlorine,
bromine, ozone, etc. — produce serious irritation of the respiratory passages, and
may in this way cause death.

G. Effects of the Gaseous Composition of the Blood on the

Respiratory Movements.

Certain terms are employed to express peculiarities in the respiratory phe-
nomena : Eupncea is normal, fpiict, and easy breathing, ^pnoga is a suspen-
sion of the respiratory movements. Hijperpnoea is a condition of increased
respiratory activity. Poli/pnoea, thcrmopoli/pnfra, and hcat-dyspncca are forms
of hyperpnoea due to heating the blood or the skin. Dyspnoea is distinguished
by deep and labored breathing ; the respiratory rate is usually less than the
normal, but in some forms it may be higher. Asphyxia (suffocation) is cha-
racterized by infrequent, feeble, and shallow respirations.

Eupnoea is the condition of respiration observed during bodily and mental

BESPIRA TION. 549

([iiiet, the quantities of O and CO^ in tlit' hloocl being within the normal mean
limits.

Apnoca may bo produced l)y lapidly repeated respirations of atmospheric
air, under \vhi<;li circumstances the respiratory movements may be arrested for
a period vurvin*;- from a few seconds to a minute or more. This condition is
produced most easily upon animals which have been tracheotomized and con-
nected with an artificial respiration apparatus. If under these conditions the
lungs are repeatedly inflated with sufficient frequency, and the blasts are then
suspended, the animal will lie quietly for a certain period in a condition of
apncea. The respirations after a time begin, usually with very feeble move-
ments which quickly increase in strength and depth to the normal type. The
ultimate cause of apncea is still a mooted question, and the heretofore prevalent
belief that it is due to hyperoxygenatiou of the blood is almost entirely dis-
carded. The connection between the quantity of O in the blood and apnoea
is, however, suggested by several facts : thus, apnoea is more marked after the
respiration of pure O than after that of atmospheric air, and less marked if the
air is deficient in O ; moreover, Ewald states that the arterial blood of apnoeic
animals is saturated with O. These facts naturally lead to the inference that the
blood is surcharged with O, and that the respiratory movements are arrested
until the excess of O is consumed or until sufficient COg accumulates in the
blood to excite respiratory movements. But Head ^ has shown that apnoea can
be caused by the inflation of the lungs with pure hydrogen as well as by infla-
tion with air or with pure O, although the apnoeic pause after the cessation of
the infliations is not so long or may be absent altogether ; while Ewald's asser-
tion as to the saturation of the blood with O is contradicted by Hoppe-Seyler,
Gad, and others. The fact that the apnoeic pause exists for a longer period
when O is respired lends confirmation to Gad's theory that it is due in part to
the large amount of O carried into and stored up, as it were, in the alveoli —
an amount sufficient to supply the blood for a certain period and thus to dis-
pense with respiratory movements. Gad found that even when apncea follows
the inflation of the lungs with air, the air in the lungs contains enough O to
supply the blood during the period occupied by the blood in making a com-
plete circuit of the system. The fact, however, that apnoea can be caused
by the inflation of the lungs by an indifferent gas such as hydrogen, by
which every particle of O may be driven from the lungs, certainly shows
that there exists some important factor apart from theO; and this assump-
tion receives support in the observation that after section of the pneumo-
gastric nerves (the channels for the conveyance of sensory impulses from
the lungs to the respiratory centre) it is very difficult to cause apnoea by in-
flation of the lungs with air, while if pure hydrogen is used violent dyspnoea
results. It seems, then, that apnoea cannot be produced after division of the
vagi unless there be an accumulation of O in the lungs. These facts suggest
that the frequent forced inflations of the lungs excite the pulmonic peripheries
of the pneumogastric nerves, thus generating impulses which inhibit the inspi-
^ Journ. Physiology, 1889, vol. 10, pp. 1, 279.

ooO ^.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ratoiy discharges from the respiratory centre. This view receives further su[i-
port in several facts : first, that the same number of inflations, whether of pure
O, of air, or of H, causes apncea, the only difference l)eing the length of the
apna?ic pause after the cessation of artificial respiration, which pause lasts for
the longest period when O is used, and for the shortest period, or not at all,
when II is employed; second, that apiuea cannot be caused by inflation of the
lungs with H if the pneumogastric nerves be previously divided ; third, that the
arrest of respiration which occurs during swallowing (" deglutition-apncea ")
is due to an inhibition of the respiratory centre by impulses generated in the
terminations of the glosso-pharyngeal nerves (p. 570). It therefore seems evi-
dent that apncea may be due to either gaseous or mechanical factors, or to both,
the former being effective, not because of the blood being saturated with O,
but because of the increased amount of O in the alveoli — a quantity sufficient
for a time to aerate the blood ; while the mechanical factors give rise to inhibi-
tory impulses which suspend for a longer or shorter period the rhythmical
inspiratory discharges from the respiratory centre, doubtless by depressing the
irritability of this centre (p. 563). From the experiment quoted it seems that
the first of these factoi'S may alone be sufficient to cause apnoea, but that apncea
is more easily produced, and lasts longer, when both factors act together, as is
usually the case.

Polypnoea, thermopolypnoea, and heat-dyspncea are due to a direct excitation
of the respiratory centres through an increase of the temperature of the blood,
or reflexly by excitation of the cutaneous nerves by external heat. This con-
dition may be produced, as was done by Goldstein, by exposing the carotids
and placing them in warm tubes, thus heating the blood ; or, as was done by
Richet and others, by subjecting the body to high external heat. Richet in
employing this latter method found that dogs so exposed may have a respira-
tory rate as high as 400 per minute. Ott records marked polypncea as a result
of direct irritation of the tuber cinereum. This form of hyperpn(ea is entirely
independent of the gaseous composition of the Ijlood ; moreover, an animal in
heat-dyspnoea cannot be rendered apnoeic, even though the blood be so thor-
oughly oxygenated that the venous blood is of a bright arterial hue.

Dyspnoea is generally characterized by slow, deep, and labored respiratory
movements, although in some instances the rate may be increased. Several
distinct forms are observed : " O-dyspnnoa," due to a deficiency of O ;
" COj-dyspnoea," due to an excess of COg in the blood ; a form of dyspnoea
due to substances imparted to the blood by the muscles during activity ; and
cardiac and hemorrhar/ic dyspnoeas, belonging to the O category.

Dys])noeas due to the gaseous composition of the blood maybe caused either
by a deficiency of O or by an excess of CO^, but are generally due to both.
Dyspnoea from a deficit of O is observed when an animal is j^laeod within a
small closed chamber, or when an indifferent gas, such as pure hydrogen or
nitrogen, is respired. Under the latter circumstances dyspnoea occurs even
though the quantity of COj in the blood be below the normal. If, on the
contrary, the animal be compelled to breathe an atmosphere containing 10 vol-

RESPIRA TION. 551

limes per cent, of COg, dyspnoea occurs, notwithstanding an abundance of O
(p. 544) both in the air and in the blood ; indeed, the quantity of O in the
blood maybe above the normal. Fredericq • in ingenious experiments has
directly demonstrated the influence of the quantity of CO^ in the blood upon
the respiratory movements. He took two rab))its or dogs, A and H, ligated the
vertebral arteries in each, exposed the carotids, and ligated one in each animal.
The other carotid in each was cut, and the peripheral end of the vessel of one
was connected by means of a cannula with the central end of the vessel of the
other, so that the blood of animal A supi)lied the head (respiratory centre) of
animal B, and vice versd. When the trachea of animal A was ligated or com-
pressed the animal b showed signs of dyspnoea, because its respiratory centre
was now supplied with the venous blood from A. Ou the contrary, animal a
exhibited (piiet respirations, almost apnoeic, because its centre received the
thoroughly arterialized blood from B, in which the respiratory movements were
augmented. In a second series of experiments blood was transfused through
the head : when the blood was laden with COa marked dyspnoea resulted ;
when arterial blood was transfused the normal respirations were restored.

While dyspnoea may be caused by the respiration of an atmosphere either
deficient in O (" O-dyspnoea ") or containing an excess of CO^ (" C^Og-dysp-
noea "), the phenomena in the two cases are in certain respects different : When
an animal breathes pure N, thus causing O-dyspnoea, the dyspnoea is character-
ized especially by frequent respiratory movements with vigorous insjjirations,
whereas if the atmosphere be rich in O and contain an excess of COg the
respirations are especially marked by a slower rate and by the depth and vigor
of the expirations ; O-dyspnoea continues for a long time before death ensues,
and is more severe ; in O-dyspnoea the absorption of O is diminished, but the
excretion of COg is practically unaffected ; in O-dyspnoea the attendant rise of
blood-pressure (p. 555) is more marked and lasting ; in O-dyspnoea death is
preceded by violent motor disturbauces which are absent in COg-dyspnoea.
Blood poor in O (O-dyspnoea) affects chiefly the inspiratory portion of the
respiratory centre (p. 565), while blood rich in COg (COa-dyspnooa) affects
chiefly the expiratory portion ; hence in the former the dyspnoea is manifest
especially in an increase in the fi-eqnency of the respirations (hyperpnoea) and
in the vigor of the inspirations, while in the latter it is manifest in a lessened
rate, strong expirations, and expiratory pauses.

The marked increase in the depth of the respiratory movements in COg-
dyspnoea is not solely due to the direct action of COg upon the respiratory
centre, for Gad and Zagari^ have shown that COj in abundance in inspired air
acts upon the terminations of the sensory nerves of the larger bronchi and
thus reflexly excites the respiratory centre. In a research on dogs these ob-
servers opened the trachea and passed glass tubes through the trachea and the
larger bronchi to the smaller bronchi. Before the tubes were inserted the
inhalation of COg caused a considerable deepening of the respiratory move-

i Bull. Acnd. Roy. Med. Belgique, vol. 13, pp. 417-421.
* DuBois-Reymond's Archiv f. Pkysiologie, 1890, p. 588.

5r)2 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

nieuts, l)iit after tlio insertion of the tubes, by means of \vbi( li the gas was
earried directly to the smaller brondii, the characteristic action of the CO^ wits
no lon<;er observed. From the results of these experiments we may con-
clude that the marked increase in the depth of" the respiratory mctvements
in COg-dyspnoea is due in part to the irritation of the sensory nerve-fibres of
the mucous membrane of the larger bronchi.

Till' form of dyspnani due to miisoular activifi/ is owing to the action upon
the re.si)iratory centre of certain substances which are formed in the muscles
during contraction and are given to the blootl. Muscular activity, as is well
known, is accompanied by an increase in the rate and depth of the respiratory
movements, and when the exercise is violent more or less marked dyspuwa
may occur. Some physiologists have been led to the belief that the respiratory
centre is connected directly or indirectly with the muscles by means of afferent
nerve-fibres which convey im})ulses to the centre and thus excite it to activity;
while others have regarded a ditninution of O and an increase of COg in the
blood as the cause, the active nmscles rapidly consuming the O in the blocxl
and giving oil" COg in great abundance; but Gepj)ert and Zuntz ^ have clearly
shown that neither of these theories is tenable, and that the respiratory excita-
tion is due to products of muscular activity which are given to the blood and
which act as powerful excitants to the respiratory centre. The precise nature
of the bodies is unknown, but it is probable that they are of an acid character,
for Lehmann ^ found that there was a distinct lessening of the alkalinity of
the blood after muscular exercise. It is likely that the bodies are broken up
in the system, because the results of Loewy's' investigations indicate that they
are not removed by the kidneys.

Cardiac and hemorrharjic dyspnoeas are chiefly due to tlie deficiency in the
supplv of O — the former, to the poor supply of blood due to the enfeebled action
of the heart ; and the latter, l)oth to this and to the reduced quantity of blood
(haemoglobin). All circumstances which enfeeble the circulation or lessen the
quantity of hrcmoglobin therefore tend to cause dyspnoea ; hence individuals
Avith heart troubles or weakened by disease or with certain forms of anaemia
are apt to suffer from dyspmea uj)on the least exertion.

All circumstances which interfere with the interchange of O and the
elimination of CO2 in the lungs are favorable to the production of dyspnoea,
as in pneumonia, pulmonary tuberculosis, growths of the larnyx, abdominal
tumors, etc., especially so upon exertion.

Asphyxia is literally a state of pidselcssness, but the term is now used to
express a series of phenomena caused by the deprivation of air, as by j)lacing
an animal in a closed chamber of moderate size. These phenomena may be
divided into three stages: the first is one of hyperpnoea ; the second, of
developing dyspnoea, and finally of convidsions ; and the third, of collapse.
During the first stage the ins])iratory portion of the respiratory centre
especially is excited, the respirations being increased in frequency and dejUh.

' Pfluger's Archiv f. Physiologic, 1888, vol. A2, p. 189. '' Ibid., p. 284.

'IbicLy,. -JSl.

RESPIRA TION. 553

During the second stage the excitation of the expiratory portion of the respiratory
centre is more intense tlian that of the inspiratory portion, so that the respira-
tions become slow and deep, prolonged and convnlsive, and tiie moven)ents of
inspiration are feeble and in striking contrast to the violent spasmodic expira-
tory efforts. During the third stage the dyspno'a is followed by general
exhaustion ; the resi)irations are shallow and occur at longer and longer inter-
vals, the pupils become dilated, the motor reflexes disappear, consciousness is
lost, the inspiratory muscles contract spasmodically with each ins})iratory act,
convulsive twitches are observed in the muscles of the extremities and else-
where, gasping and snapping respiratory movenients may be present, the legs
are rigidly outstretched and the head and body are arched backward, feces and
urine are usually voided, respiratory movements cease, and finally the heart
stops beating. During these stages the circulation has undergone considerable
disturbances. During the first and second stages the blood has been robbed
of nearly all its O, the gums, lips, and skin become cyanosed, and, owing to the
venous condition of the blood, the cardio-inhibitory centre has been decidedly
excited, so that the heart's contractions are rendered less frequent ; the vaso-
constrictor centre for the same reason has also been excited, causing a con-
striction of the capillaries and an increase of blood-pressure. During the
third stage these centres are depressed and finally are paralyzed.

If asphyxia be caused by ligating the trachea, the whole series of events
covers a period of four to five minutes, the first stage lasting for about one
minute, the second a little longer, and the third from two to three minutes.
If asphyxia be produced gradually, as by placing an animal within a relatively
large confined air-space, death may occur without the appearance of any motor
disturbances (p. 544).

The heart usually continues beating feebly for several minutes after the
cessation of respiration, so that by means of artificial respiration it is possible
to restore the respiratory movements and other suspended functions. After
death the blood is very dark, almost black. The arteries are almost if not
entirely empty, while the veins and lungs are engorged.

Death from drowning occurs generally from the failure of respiration,
occasionally from a cessation of the heart's contractions. It is more difficult
to revive an animal asphyxiated in this way than one which, out of water, has
simply been deprived of air for the same length of time. Dogs submerged
lor one and a half minutes can rarely be revived, but recovery can usually be
accomplished after deprivation of air, out of water, for a period four to
five times longer. After a person has been submerged for five minutes it is
extremely difficult to effect resuscitation.

H. Artificial Respiration.

Effective methods for maintaining ventilation of the lungs are important
alike to the experimenter and to the clinician. In the laboratory the usual
method is to expose the trachea, insert a cannula (Fig. 139), and then period-
ically force air into the lungs by means of a pair of bellows or a pump. Some

554 ^AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of the forms of ajiparatus arc very simple, wliile others are complicated. An
ordinarv pair of bellows does very well for short experiments, but for longer

study, especially when it is necessjuy
that the supply of air should be uniform,
the bellows are operated by power.
Some of these instruments are so con-
structed that air is alternately forced
into and withdrawn from the lungs.

Periodical in Hat ion of the lungs is

termed po.sitire ventilation ; the period-

Fi.;. i:'.'.i.-r;iiiiiuhL for au-s ^-M aiui for cats ical withdrawal of air from the lungs

rabbits (b). y^^^ suction is negative ventilation ; and

alternate inflation and suction is compound ventilation.

In practising artificial respiration we should imitate the normal rate and
depth of the respiratory movements. Long-continued positive ventilation
causes cerebral anaemia, a fall of blood-pressure, and decrease of bodily tem-
perature.

In human beings it is not practicable, except under extraordinary circum-
stances, to inflate the lungs by the above methods, so that we are dependent
upon such means as Avill enable us to expand and contract the thoracic cavity
without resorting to the knife. One method is to place the individual on his
back, the operator taking a position on his knees at the head, facing the feet.
The lower ribs are grasped by both hands and the lower antero-latei'al portions
of the thorax are elevated, thus increasing the thoracic capacity, with a conse-
quent drawing of air into the lungs; the ribs and the abdominal muscles are
then pressed upon in imitation of expiration. These alternate movements are
kept up as long as necessary.

The methods of Marshall Hall and Sylvester are now classic, and should
be learned thoroughly by every jihysician. Marshall Hall's method is as
follows : " After clearing the mouth and throat, place the patient on the face,
raising and supporting the chest well on a folded coat or other article of dress.
Turn the body very gently on the side and a little beyond, and then briskly
on the face, back again, repeating these measures cautiously, efficiently, and
perseveringly about fifteen times in the minute, or one every four or five
seconds, occasionally varying the side. By placing the patient on the chest
the weight of the body forces the air out ; when turned on the side this pres-
sure is removed and air enters the chest. On each occasion that the body is
replaced on the face, make uniform but efficient pressure with brisk move-
ments on the back, between and below the shoulder-blades or bones on each
side, removing the })ressure immediately before turning the body on the side.
During the whole of the operations let one person attend solely to the move-
ments of the head and of the arm placed under it."

The following is Sylvester's method : " Place the patient on the back, on a
flat surface inclined a little upward from the feet; raise and support the head
and shoulders on a small firm cushion or folded article of dress placed under

BESPIRA TION. 555

the shoulder-blades. Draw forward the patient's tongue, and keep it project-
ing bevond the lips ; an elastic band over the tongue and under the chin will
answer this purpose, or a piece of string or tape may l)e tied around them, or
bv raising the lower jaw tiic teeth may be made to retain the tongue in that
position. Remove all tight clothing from about tlie neck and chest, especially
the braces ",...*' To imitate the movements of breathing : {Standing at the
patient's head, grasp the arms just above the elbows, and draw the arras gently
and steadily upward above the head, and keep them stretched u])\\ard for two
seconds. By this means air is drawn into the lungs. Then turn down the
patient's arms, and press them gently and firndy for two seconds against the
sides of the chest. By this means air is pressed out of the lungs. Repeat
these measures alternately, deliberately, and perseveringly about fifteen times
in a minute, until a spontaneous effort to respire is perceived, immediately
upon Avhich cease to imitate the movements of breathing, and proceed to
induce circulation and warmth."

The restoration of respiratory movements is usually facilitated by periodical
traction of the tongue, which acts as a reflex stimulus to the respiratory centre.

I. The Effects of the Respiratory Movements on the

Circulation.

The respiratory movements are accompanied by marked changes in the cir-
culation. If a tracing be made of the blood-pressure and the pulse (Fig. 140),
and at the same time the inspiratory and expiratory movements be noted, it

Fig. 140.— Blood-pressure and pulse tracing showing the changes during inspiration (is.) and expi-
ration (EX.).

will be seen that the blood-pressure begins to rise shortly after the onset of
inspiration, commonly after a period occupied by one to three heart-beats, and
reaches a maximum after the lapse of a similar brief interval after the begin-
ning of expiration, when it begins to fall, reaching a minimum after the
beginning of the next inspiration. During inspiration the pulse-rate is more
frequent than during expiration and the character of tlie pulse-curve is some-
what different.

The Effects on Blood-pressure. — The changes in blood-pressure are
mechanical effects due to the actions of the respiratory movements. When it
is remembered that the lungs and the heart with their great blood-vessels are
placed within an air-tight cavity, that the lungs become inflated through the
aspiratory action of the muscles of inspiration, and that during inspiration

55(3 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

intrathoracic negative pressure is increased, it is easy to understniid liuw the
action wliich causes inflation oi" the hnigs must affect in like manner such
hollow clastic structures as the heart and the great blood-vessels, and tlms
influence the circulation. It is obvious, however, that this influence must make
itself felt to a more marked degree n])on the vessels than upon the heart, and
upon tlie flaccid Avails of the veins than upon the comparatively rigid walls of
the arteries. JNIoreover, the effects upon the flow of blood tlirough the vessels
entering and leaving the thoracic cavity must be different : the inflow through
the veins must be favored, and the outflow through the arteries hindered ; but
it is upon the flaccid veins chiefly that the mechanical influences of insj)i ration
are exerted. If the thoracic cavity be freely opened, movements of ins])iration
no longer cause an expansion of the lungs, nor is there a tendency to distend
the heart and the large blood-vessels; if, however, in an intact animal the out-
let of the thorax be restricted, as by pressure upon the trachea, the force of the
inspiratory movement would make itself felt chiefly u])on the heart and the
vessels, and it is under such circumstances that the maximal influences of in-
spiration upon the circulation are observed. The lungs on the one hand and
the heart and its large vessels on the other may be regarded as two sacs placed
within a closed expansible cavity, the former having an outlet communicating
with the external air, and the latter having inlets and outlets communicating
with the extrathoracic blood-vessels, both being dilated when the thorax ex-
pands and constricted when it contracts. Moreover, the blood-vessels in the
lungs may be compared to a system of delicate tubes jilaccd within a closed
distensible bag and communicating with tubes outside of the bag, simulating
the communication of the vense cavse and the aorta with the extrathoracic
vessels. "When such a bag is distended the tubes also must be distended
and their lumina in consequence be enlarged. The lungs in the same way,
when expanded by the act of inspiration, are accompanied by a simultaneous
dilatation of the intrapulmonary vessels, increasing their capacity, with the
natural physical result of lessened resistance to the flow of blood.

During expiration negative intrathoracic pressure becomes less, so that there
is a gradual return of the expanded intrathoracic vessels to that condition
wdiich existed at the beginning of ins})iration ; at the same time the intrajiul-
monary vessels are not only subjected to the passiv^e influence of the declining
intrathoracic pressure, but are actively squeezed, as it were, between the air in
the lungs on one side and the expiratory forces expelling the air on the other.
Thus we have during ex})iration passive and active agents combining to bring
about constriction of the intrapulmonary vessels.

The mechanical effects of the movements of respiration upon blood-pressure
maybe demonstrated by means of Hering's device (Fig. 141). The chamber
A represents the thorax ; the rubber bottom b, the diaphragm ; c, the opening
of the trachea; ED, a tube leading from the thoracic cavity to the manometer
I, by means of which intrathoracic pressure is measured; G is a vessel contain-
ing water, colored blue in imitation of venous blood, communicating by means
of a tube with an oblong flaccid bag f, in imitation of the heart and the intra-

RESPIRATION. 557

thoracic vessels, and iiiially witli tla- vessel ii ; v' and v arc valves in imitation
of valves in the heart and j)ulnu)naiv vein and aorta. Jt' now the knob K
which is fastened to the centre of the diaiihra^m he pidled down, rarefaction
of the air witiiin the chamber occnrs, so that the greater external pressure
forces air throngh the tube c into the two rubber bags (lungs); at the same
time and for the same reason water is forced from tlie vessel G iuto f, which is
distended. The diaphragm upou being released is drawn up in [)art by virtue
of its own elasticity and in part by the negative pressure within the chamber.
The rubber bags are emptied by their own natural elastic reaction. At the

Fig. 141. — Hering's device to illustrate the influence of respiratory movements upon the circulation.

same time the distended bag F contracts on its contained fluid, forcing it into
the vessel h, the valve v preventing a back-flow into g. The degree of force
exerted by the traction on the diaphragm is read from the scale on the man-
ometer.

This simple contrivance teaches us that during the entire phase of in.spira-
tion there is a condition of progressively increasing negative pressure within
the thorax, and that not only is air aspirated into the lungs, but that blood is
drawn into the large, flaccid vense cavse ; and that during expiration there is a
gradual diminution of negative pressure during which air is expelled from the
lungs and blood from the expanded venae cavte.

The increased flow iuto the thoracic cavity during inspiration is favored in
its progress through the pulmonary vessels by the attendant dilatation of the
lung-capillaries and by the fact that the increased negative pressure affects the

558 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tliiu-walled and sliglitly distended pulinuiiary veins mure than the thiei<-\valled
and more distended puhnonary arteries, so that the "driving force" of the lung
circulation, which is essentially the difference in pressure between the blood in
the pulmonary arteries and that in the veins, is thereby increased during inspi-
ration and the blood-current is driven with greater velocity. More blood thus
l>eing brought into the chest, and consequently to the heart, during ingpiration,
and less resistance being offered to the flow of the blood through the lungs,
more blood must ultimately find its way to the left side of the heart, and con-
sequently into the general circulation. If, therefore, the general capillary
resistance in the systemic circulation remains the same, it is evident that an
increased blood-supply to the left ventricle must cause the general blood-pres-
sure to "rise. That this rise does not become manifest immediately at the
beginning of inspiration is doubtless owing to the filling of the flaccid and
partially collapsed large veins and to the dilatation of the pulmonary capil-
laries. The continuance of the rise for a short time after the cessation of in-
spiration is due apparently to the partial emptying of the now distended lung-
vessels, whereby, owing to the arrangement of the heart-valves, the excess of
blood is forced toward the left side of the heart.

Besides the above factors, the flow of blood to the right side of the heart is
favored bv the pressure transmitted from the conjoint actions of the diaphragm
and the abdominal walls tlirough the abdominal viscera to the al)dominal
vessels. The pressure upon the arteries tends to drive the Ijlood toward the
lower extremities and to hinder the flow from the heart ; in the veins, however,
the flow toward the heart is encouraged, Avhile that from the extremities is
hindered. The rigid walls of the arteries protect them from being materially
affected, but the flaccid veins are influenced to a marked degree; while, there-
fore, the flow from the left side of the heart is not materially interfered with,
that through the veins toward the right side is appreciably facilitated, and thus
the supply of blood to the heart is increased. The effects of these movements
may be seen after section of the phrenic nerves, which causes paralysis of the
diaphragm, when it will be noted that the blood-pressure curves are much re-
duced.. This diminution is attributed to two causes — the enfeebled respiratory
movements, which are now confined to the ribs and the sternum, and the
absence of the pressure transmitted from the diaphragm through the abdominal
organs to the veins. If in such an/ animal the abdomen be periodically com-
pressed, in imitation of the effects produced by the contraction of the dia-
]ihragm, the respiratory curves may be restored to their normal height.

During expiration, since the conditions are reversed the effects also must be
reversed. The increased negative intrathoracic pressure occasioned by inspira-
tion now gives place to a gradual diminution, and with this a lessening of the
aspiratory action due to the sub-atmospheric intrathoracic pressure ; the blood-
supply is further reduced because of the lessened amount of blood coming
through the inferior vena cava; the abdominal veins, instead of being com-
pressed and their contents forced chiefly toward the heart, are now being
filled; finally, during the shrinkage of the lungs the intrapulmonary vessels

BESPIRA TION. 559

become constricted, and tlius offer greater i-esistance to the flow from the right
side of the heart through the lungs to tlie left side of the heart, and subse-
quently into the general circulation.

Another factor believed by some to be involved in the respiratory undula-
tions in blood-pressure is a rhythmical excitation of the vaso-constrictor centre
in the medulla oblongata, asserted to occur coincidently with the inspiratory
discharge from the respiratory centre. This has, however, been disproved.
Others have held that the blood-pressure changes are due to the pressure ex-
erted by the expanding lungs u[)on the heart; while others contend that
rhythmical alterations in the heart-beats are important. This latter factor is
of importance in man and in the dog, in which there is a distinct increase in
the rate of the heart-beat during inspiration, and co-operates in producing the
general rise of pressure during inspiration.

The Effects on the Pulse. — During inspiration the pulse-rate is more
rapid than during expiration. If we cut the pneumogastric nerves, it will be
seen that, while the rate is increased as the result of the section, the diiference
during ins[)iration and expiration is abolished ; on the other hand, if the thorax
be widely opened, but the pneumogastric nerves are left intact, the inspiratory
increase in the rate still occurs. This indicates that the cardio-inhibitory
centre is either less active during inspiration or more active during expiration,
and that there is an associated activity of the respiratory and cardio-inhibitory
centres. Why this sympathy sliould exist between the respiratory and cardio-
inhibitory centres we do not know, but it has been suggested that during expi-
ration the blood reaching the centres is less highly arterialized than during
the inspiratory phase, and that the cardiac centre is so sensitive to the difference
as to be affected, and thus its activity is somewhat increased during the expira-
tory phase, W'itli the consequent decrease in the pulse-rate.

During inspiration the pulse-rate is not only higher than during expiration,
but the form of the ])ulse-wave is affected. The systolic, dicrotic, and sec-
ondary waves are smaller and the dicrotic notch is more pronounced, so that
the dicrotic character of the curves is better marked.

The Effects of Obstruction of the Air-passag-es and of the Respira-
tion of Rarefied and Compressed Air on the Circulation. — The blood-
pressure undulations produced during quiet breathing become marked in pro-
portion to the depth of the respiratory movements. Inspiration or expiration
against extraordinary resistance — as after closing the mouth and nostrils, or
respiring rarefied or compressed air — may materially modify the eircul»t<jry phe-
nomena. When we make the most forcible inspiratory effort, the air passages
being fully open, not only is there a full expansion of the lungs, but great
diastolic distention of the heart and dilatation of the intrajjulmonary and intra-
thoracic vessels; yet, notwithstanding that this powerful aspiratory action en-
courages the flow of an extraordinarily large amount of blood into the thoracic
vessels, the heart-beats may be very small, because intrathoracic negative
pressure is so great that the thin-walled auricles meet with great resistance
while contracting; in consequence, then, of this forced inspiratory effort little

5G0 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

blood is driven throiiiih tho lungs to the left auricle and by the left ventricle
into the general circulation. If we make the greatest possible expiratory
effort, and niaintaiu the expiratory phase with air-passages open, the heart-
beats are small, owini; to the small amount of blood which flows throuirh
the vena^ cavjo to the right auricle, and to the resistance ofVered by the con-
stricted intrapulmouary vessels.

If, after a most p(i\verful expiration, we close the mouth and nostrils and
make a powerful inspiratory etibrt, the aspiratory effect of inspiration on the
heart and the blood-vessels is manifest to its utmost degree : the heart and the
vessels tend to undergo great dilatation, the blood-flow to the right auricle and
ventricle is increased, the intrapulmouary vessels and the heart become en-
gorged, and, owing to the powerful traction of the negative pressure upon the
heart, especially upon the right auricle, very little blood is forced through the
lungs to the left auricle and ventricle and subsequently into the general circu-
lation, thus causing a fall of blood-pressure ; indeed, the heart-sounds and the
pulse may disappear. If now we make the most forcible inspiratory effort,
close the glottis, and make a powerful expiratory effort, not only is the air in
the lungs subjected to high positive pressure, but the heart and the great
vessels partake in the pressure-effects, the blood being forced from the pul-
monic circulation into the left auricle, thence by the v^entricle into the aorta,
with the result of a temporary rise of blood-pressure. The pressure upon the
intrathoracic veins is so great that the flow of blood into the chest is almost
shut off, hence the veins outside the thorax become very much distended, as
seen in the superficial veins of the neck, and the heart is pressed upon to such
an extent that, together with the lessened supply of blood, the heart-sounds
and the radial pulse may disappear and the blood-pressure falls.

The respiration into or from a spirometer (p. 535) containing rarefied or
compressed air modifies the blood-pressure curves. Inspiration of rarefied air
causes a greater rise of blood-pressure than when respiration occurs at normal
pressure, while during expiration, although the blood-pressure falls, it may
remain somewhat above the normal. The increase of pressure is due to the
aspiratory effort required to draw the air into the lungs, which effort also makes
itself felt to a more marked degree upon the heart and the intrathoracic and
intrapulmouary vessels, thus increasing the blood-flow through the pulmonary
circulation. During expiration air is aspirated from the lungs into the spi-
rometer, tending to dilate the intrathoracic and intrapulmouary vessels and the
heart and thus to aid the pulmonary circulation. After a time, however, there
is a fall of blood-pressure on account both of the engorgement of the thoracic
vessels and the accompanying depletion of the general circulation, :u)d of the
distention of the heart and interference with its contractions.

Inspiration of compressed air lessens the extent of, and may prevent, the
inspiratory rise, or it may cause a fall. If, U})()n the respiration of compressed
air, the pressure of the air be above that exerted by the elastic tension of the
lungs, no effort of the inspiratory muscles is required, the chest being expanded
by the pressure of the air. Therefore, instead of an increase of negative intra-

BESPIRA TION. 56 1

thoracic pressure, as in normal inspiration, there is a decrease, and negative
intrathoracic pressure is replaced by positive pressure. As a result, the blood-
vessels and the heart, instead of being dilated by an as[»irat()rv action, are
pressed upon, forcing the blood into the general circulation, and thus causing a
transient rise of pressure, which is, however, succeeded by a iall (hu; to obstruc-
tion to the flow of blood through the heart and the pulmonary vessels. Ex-
piration into compressed air causes at first a transient increase of blood-pressure
followed by a fall, the former being due to the forcing of some of the blood
from the intrathoracic and intrapulmonary vessels into the general circulation,
and the latter to obstruction to the blood-flow through the heart and the pul-
monary circulation.

When individuals are exposed to compressed air, as in a pneumatic cabinet,
or to rarefied air, as in ballooning, the effects on the circulation become of a
very complex character, owing chiefly to the additional influences of the
abnormal pressure upon the peripheral circulation ; moreover, the effects of
breathing against obstructions or of respiring rarefied or compressed air may
be materially influenced by secondary effects resulting from excitation of the
cardiac and vaso-motor mechanisms.

In artificial respiration, as ordinarily performed in the laboratory, air is
periodically forced into the lungs by a pair of bellows or a pump, and is ex-
pelled from the lungs by the normal elastic and mechanical factors of expira-
tion. When the lungs are inflated the pulmonary capillaries are subjected to
opposing forces — the positive pressure of the air within the lungs on one hand,
and the resistance of the thoracic walls on the other — so that the blood is
squeezed out, thus momentarily increasing the blood-pressure, but subsequently
retarding the current and consequently lowering the pressure. During expira-
tion the pressure is removed and the blood-flow is encouraged ; there is, there-
fore, a temporary fall during the filling of the pulmonary vessels, followed by
a rise due to the removal of the obstruction. If the air is aspirated from the
lungs, the rise of the pressure is augmented, owing to the further dilatation of
the intrapulmonary capillaries ; hence, in artificial respiration, during the in-
spiratory phase the blood-pressure curves are reversed, there being a primary
transient rise followed by a fall, and during the expiratory phase a transient
fall followed by a rise. In normal respiration the oscillations are due essen-
tially to changes in negative intrathoracic pressure, while in artificial respira-
tion, as above noted, they are due to changes in positive intrapulmonary
pressure.

J. Special Respiratory Movements.

The rhythmical expansions and contractions of the thorax which we under-
stand as respiratory movements have for their object the ventilation of the
lungs. There are, however, other movements which possess certain respiratory
characters, but which are for entirely different purposes, hence they are spoken
of as special or modified respiratory movements. Some of these movements
are purposeful in character, others are spasmodic ; some are voluntary or in-

36

502 .l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

vi»liintarv, or possess both volitional and iiivolitional characteristics; some are
peculiar to certain species, etc. Ainoiit; such movements are coughing, hawking,
sneezing, laughing, crying, sobbing, sighing, yawning, snoring, gargling, hic-
cough, neighing, braying, growling, etc.

In coughing a preliminary inspiration is followed by an expiialion which is
frequently interrupted, the glottis being partially closed at the time of the
occurrence of each interruption, so that a series of characteristic sounds are
cau.sed. The air is forcibly ejected through the mouth, and thus foreign parti-
cles, such as mucus in the respiratory passages, may be expelled. Coughing
may be either voluntary or reflex.

Hawking is somewhat similar to coughing. The glottis is, however, open
during the expiratory act, and the expiration is continuous. The current of
air is forced through the contracted j>assage between the root of the tongue
and the soft palate. Hawking is a vohmtary act.

In sneezing a deep inspiration is followed by a forcible expiratory blast
directed through the nose; the glottis is open, and should the oral passage be
open, which is not usually the case, a portion of the blast is forced through the
mouth. Sneezing is usually a reflex act commonly excited by irritation of the
fibres of the nasal branches of the fifth pair, of cranial nerves. Peculiar sen-
sations in the nose give us a premonition of sneezing; at such a time the act
may be prevented by firmly pressing the finger upon the upper lip.

In laughing there is an inspiration followed, as in coughing, by a repeatedly-
interrupted expiration during which the glottis is open and the vocal cords are
thrown into vibration with each expiratory movement. The expirations are
not as forcible as in coughing, the mouth is wide open, and the face has a
characteristic expression due to the contraction of the muscles of expression.

Crying bears a close relationship to laughing — so much so that at times it
is impossible to distinguish between the two ; hence one may readily pass into
the other, as frequently occurs in cases of hysteria and in young children.
The chief differences between the two are in the rhythm and the facial expres-
sion. A secretion of tears is an accompaniment of crying, but not so of
laughing, except during very hearty laughter. Crying normally is involun-
tary; laughing may be cither voluntary or involuntary.

Sobbing, which is apt to follow a long period of crying, is characterized as
being a series of spasmodic inspirations during each of which the glottis is
partially closed, and the series is followed by a long, quiet ex]>iration. This is
usually involuntary, but may sometimes be arrested volitionally. In sighing
there is a long inspiration attended by a peculiar plaintive sound. The mouth
may be either closed or partially open. Sighing is usually voluntary.

Yawning has certain features like the j)receding. There occurs a long,
deep inspiration during which the mouth is stretched wide open, and there is
usually a simultaneous strong contraction of certain of the muscles of the
shoulders and the back ; the glottis is wide open, and inspiration is accompa-
nied by a peculiar sound ; expiration is short. Yawning may be either volun-
tary or involuntary.

RESPIRA TION. 563

In snoring the mouth is open, and the inflow and outflow of air throws the
uvuhi and tiie soft palate into vibration. The sound produced is more marked
during inspiration, and may even he absent during exj)iration. It is more apt
to occur when the individual is lying on his back than wlien in any other
posture. Snoring is usually involuntary, but it may be volitional.

In gargling the fluid is held between the tongue and the soft palate and air
is exj)ire(l through it in the form of bul)bles.

In hiccough there is a sudden inspiratory effort caused by a spasmodic
twitch of the diaphragm and attended by a sudden closure of the glottis, so
that the inspiratory movement is suddenly arrested, thus causing a characteris-
tic sound. Hiccough is sometimes not only distressing, but may be even seri-
ous or fatal in its consequences. It is especially apt to occur in cases of gastric
irritation, in certain forms of hysteria, in alcoholism, in urremia, etc.

Besides the above special respiratory movements, others are observed in
certain species of animals, such as whining, neighing, braying, roaring, bellow-
ing, bawling, barking, purring, growding, etc.

Of all these modified respiratory movements, coughing possesses to the
clinician the most interest, because it not only may express an abnormal condi-
tion of some portion of the lungs, trachea, or larynx, but may indicate irrita-
tion in even remote and entirely unassociated parts. Thus, coughing may be
the result of irritation in the nose, ear, pharynx, stomach, liver, spleen, intes-
tines, ovaries, testicle, uterus, or mamma. Coughs which are not dependent
upon irritation of the larynx, trachea, or lungs are distinguished as sympa-
thetic or reflex coughs. The term "■ reflex " is a bad one, however, inasmuch
as all coughs are essentially or solely reflex.

K. The Nervous Mechanism of the Respiratory Movements.

The movements of respiration are carried on involuntarily and automati-
cally— that is, they recur by virtue of the activity of a self-governing mech-
anism. Each respiratory act necessitates a finely co-ordinated adjustment of
the contractions of a number of muscles, which adjustment is dependent upon
the operations of a dominating or controlling nerve-centre located in the
medulla oblongata, and known as the resjyiratory centre. Besides this centre,
others of minor importance have been asserted to exist in certain parts of the
cerebro-spinal axis; these centres are distinguished as subsidiary or subordinate
respiratory centres. Connected with the respiratory centre are afferent and
efferent respiratory nerves.

The Respiratory Centres. — After removal of all parts of the brain except
the spinal bulb, rhythmical respiratory movements may still continue, but after
destruction of the lower part of the bulb they at once cease. These facts indi-
cate that the centre for these movements is in the medulla oblongata, and this
conclusion is substantiated by the results of other experiments upon this
region. According to the observations of Flourens, the respiratory centre is
located in an area about 5 millimeters wide between the nuclei of the pneumo-
gastric and spinal accessory nerves in the lower end of the calamus scriptorius.

564 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

When this region was destroyed he found that respiratory movements ceased
and death ensued, consequently he termed it the nceud vital, or vital knot.
The results of various investigations show, however, that Flourens' area, as
well as certain other parts of the medulla oblongata that have been looked
upon by others as being respiratory centres, are nut such, but arc largely or
wholly collections of nerve-fibres which arise chiefly in the roots of the vagal,
s])inal accessory, glosso-pharyngcal, and trigeminal nerves, and which there-
fore are probably nerve-paths to and from the respiratory centre. Moreover,
excitation of the no^id vital does not excite respiratory movements, but simply
increases the tonicity of the diaphragm ; nor is the destruction of the area
always followed by a cessation of respiration. While the precise location of
the centre is still in doubt, there is abundant evidence to justify the belief in
its existence in the lower portion of the spinal bulb.

The centre is bilateral, one half being situated on each side of the median
line, the two parts being intimately connected by commissural fibres, thus con-
stituting physiologically a single centre. This union may be destroyed by
section along the median line. Each half acts more or less independently of,
although synchronously with, the other, and each is connected with the lungs
and the muscles of respiration of the corresponding side. These facts are
rendered manifest in the following observations : If a section be made in the
median line so as to cut the commissural fibres, the respiratory movements on
the two sides continue synchronously ; if now the portion of the centre on the
one side be destroyed, the respiratory movements on the corresponding side tem-
porarily or permanently cease. If after section in the median line one pneumo-
gastric nerve be divided, the sensory impulses conveyed from the lungs on the
side of section to the corresponding half of the respiratory centre are prevented
from reaching the centre, causing the movements of the respiratory muscles on
the same side to be slower and the inspirations stronger as compared with those
on the opposite side ; if both pneumogastrics be divided, and the central end of
one of the cut nerves be excited high in the neck by a strong current, the respi-
ratory movements on the same side may be arrested, yet they may continue on
the opposite side. These facts indicate that each half is in a measure inde-
pendent of the other. The operations in the two parts are, however, inti-
mately related, as shown by the fact that if the commissural fibres between
the halves are intact, excitation or depression of one half is to a certain degree
shared by the other. Thus, after section of one vagus not only are the respi-
ratory movements less frequent and the inspirations stronger on the side of
the section, but there is a corresponding condition on the opposite side; simi-
larly, excitation of the central end of the cut nerv€ increases the respiratory
rate both on the same and on the opposite side. Consequently, while there is
more or less indej)endence of the halves, the two are physiologically so
intimately associated as to constitute a common or single centre.

Moreover, each of the halves may be supposed to consist of two distinct
portions, one of M^hich, upon excitation, gives rise to contraction of insi)irat()ry
muscles, the other to contraction of expiratory muscles ; hence they are spoken

RESPIRA TION. 565

of IIS ins})iratorv and expiratory j)arts of the respiratory centre, or as inspi-
nitory and expiratory ventres. Moderate e.\<'itati()n of the inspiratory centre
causes not only contraction of inspiratory muscles, but an increase in the
respiratory rate ; and if tiie irritation be sufficiently strong, there occurs a
spasmodic arrest of the res})iratory movements in the inspiratory phase. On
the contrary, excitation of the expiratory centre causes couti'action of expi-
ratory nuiscles and diminishes the respiratory rate; powerful excitation of the
same centre is followed by arrest of movements in the expiratory phase.
The inspiratory portion may therefore be regarded not only as being spe-
cifically connected with ins])irat()i"v nuiscles, but in the sense of an accelerator
centre; and the expiratory portion maybe regarded as being similarly con-
nected Avith expiratory nuiscles, and as being an Inliihitory centre. When the
two are conjointly excited the accelerator eifcct prevails, because under ordinary
circumstances the accelerator element of the centre seems more excitable and
potent than the inhibitory ; therefore, when the centre as a whole is irritated,
it manifests an accelerator character.

In addition to this centre, the existence of subsidiary centres is claimed,
situated both in the brain and in the spinal cord. One centre has been located
in the rabbit in the tuber cinereum, which has been named a polypnosic centre,
because when excited the respirations are rendered extremely frequent. The
sensitiveness of this centre is readily demonstrated by subjecting an animal
to a high external tem])erature, when a marked' increase of the respiratory rate
follows; if now the tuber cinereum be destroyed, there occurs an immediate
cesssation of the accelerated movements. Another area has been located in
the optic thalamus in the floor of the thii'd ventricle ; this centre is believed
to be excited by impulses carried by the nerves of sight and hearing, and
when irritated causes an acceleration of the respiratory rate, and when strongly
excited arrests respiration during the inspiratory phase ; hence it is regarded
as an inspiratory or accelerator centre. Another centre has been located in
the anterior pair of the corpora quadrigemina ; it causes expiratory and inhibi-
tory eifects, and may therefore be placed among the expiratory or inhibitory
centres. An inspiratory or accelerator centre has been recorded as existing in
the posterior pair of the corpora quadrigemina and the j^ons Varolii. The
nuclei of the trigemini are also said to act as inspiratory or accelerator centres.
Respiratory centres are likewise claimed to exist in the brain-corte.v. It is
very doubtful, however, whether or not these so-called subsidiary respiratory
centres should be regarded as being of a specific character. In any event, we
cannot suppose that these centres are capable of evoking directly respiratory
movements. If they exist, they are probably connected with the medullary
centre, through which they exert their influence on the respiratory movements.
The existence of a respiratory centre in the spinal cord, is also doubtful.
The chief reasons for the claim of its existence is that respiratory movements
may for a time be observed after section of the cerebro-spinal axis at the junc-
tion of the spinal cord and bulb. In new-born animals after such section
respiratory movements may continue for some time, strychnine rendering them

5GG AX AM ERICA X TEXT-BOOK OF PHYSIOLOGY.

moi'C proiioLinccil, Again, animals in which respiration has been artilieially
maiutoiued for a long time may, after section of the cord at the junction with
the bulb, exhibit respiratory movements after artificial respiration has been
suspended. The resjiiratory movements mider these circumstiinces are, how-
ever, of a spasmodic character, and distinctly unlike the co-ordinated rhythmi-
cal movements observed in normal animals ; the movements are rather of the
nature of spasms simulating normal respirations.

The Wiytlnnie Acticlty of the Retiipiriitory Centre. — The rhythmic sequence
of the respiratory movements is due to periodic discharges from the respiratory
centre. The cause of this periodicity is still obscure, but the fact that the
rhythm continues after the combined section of the vagi and the glosso-pharyu-
geal nerves, of the spinal cord in the lower cervical region, of the posterior
roots of the cervical spinal nerves, and of the spinal bulb from the parts
above, indicates that the rhythm is inherent in the nerve-cells, and is not
caused by external stimuli carried to the centre through afferent nerve-fibres.
Loewy ^ has shown that under the above circumstances, when the centre is iso-
lated from afferent nerve-impulses, the rhythmical activity of the centre is due to
the blood, which, while acting as a continuous excitant, causes discontinuous or
periodic discharges, so that, although we usually speak of the activity of the
respiratory centre as being automatic — that is, not immediately dependent upon
external stimuli — yet as a mutter of fact the apparently automatic discharges
are in reality due to the stimulation by the blood ; the centre is therefore auto-
matic only with reference to external nerve-stimulation.

The rhythm as well as the rate, force, and other characters of the discharges
may be affected materially by the will and emotions ; by the composition,
supply, and temperature of the blood ; and especially by certain afferent im-
pulses, pre-eminently those originating in the pneumogastric nerves. As to
the influence of the Avill and emotions, we are able, as is well known, to modify
voluntarily to a certain extent the rhythm and other characters of the respira-
tions, while the striking effect of emotions upon respiratory movements is a
matter of almost daily observation. The importance of the composition of
the blood is manifested by the marked effect upon the respirations when the
blood is deficient in O, when it contains an exce&s of COo, ;^nd during muscu-
lar activity, when in the blood. there is a relative abundance of certain products
resulting from muscular metabolism. If the blood-supply to the centre is
diminished, as after severe hemorrhage or after clamping the aorta so as to
interfere with the cerebral circulation, the respirations are less frequent and
the rhythm is affected, the form of breathing having a Cheyne-Stokes char-
acter (p. 532) ; conversely, an increase in the blood-supply causes an increase
in the rate. An increase or decrease in the temperature of the blood induces
corresponding changes in the rate; thus, in fever tiie frequency of the move-
ments increases almost pari passu\\\t\\ the augmentation of temperature, while
if the temperature of the blood be reduced by applying ice to the carotids, the
rate is lessened.

> Pjiuger's Archivf. Physiologie, 1889, vol. xlii. pp. 245-281.

RESPIRA TION. 567

Afferent impulses exercise an important, and practically a continuous, influ-
ence. After section of one pneunioj^astric iicrve the respirations are somewhat
less frequent; after section of botli nerves the respirations become considerably
less frequent and deei^er and otherwise changed. If we stinudate the central
end of one of these cut nerves below the origin of the laryngeal branches by
a current of electricity of moderate intensity, the respiratory rate may be in-
creased, and we may be able to restore, or even exceed, the normal frequency.
The fact that section of these nerves is followed by a dimiimtion of tiie rate
and that excitation of the central end of the cut nerve causes an increase leads
us to l)elicve that the pneumogastric nerves are continually conveying impulses
from the lungs to the respiratory centre, which impulses in some way increase
the number of discharges, and thus the respiratory rate. The centre may be
excited or depressed by excitaticm of the cutaneous nerves and the sensory
nerves in general ; thus, external heat accelerates, while a dash of cold water
may either accelerate or inhibit, respiratory movements. Excitation of the
glosso-pharvngeal nerves inhibits the respirations. Such inhibition occurs
during deglutition to avoid the risk of introducing foreign bodies into the
larynx. Similar respiratory inhibition may be induced by excitation of the
superior laryngeal nerves, when, if the degree of irritation be sufficiently
strono-, complete arrest of the respiratory movements may occur. Strong irri-
tation of the olfactory nerves and of the fibres of the trigemini distributed to
the nasal chambers excites expiration and may be fcjUowed by complete inhibi-
tion of the respiratory movements ; strong irritation of the optic and auditory
nerves excites inspiratory activity ; and irritation of the sciatic nerve causes an
increase of the rate, and may or may not affect the depth of breathing.

The study of the rhythmic activity of the respiratory centre is further
complicated Ijy the fact that there is not only a rhythmic sequence of the res-
pirations, but a rhythmic alternation of iusi)iratory and expiratory move-
ments. While it is true that in ordinary quiet expiration but little of the
muscular element is present, yet forced ex])iration is a well-defined co-ordinated
muscular act. The mechanism whereby this alternation is brought about is
not understood. Some believe that the pneumogastric nerves contain both
■ inspiratory and exj)iratory fibres which are connected with corresponding parts
of the respiratory centre and alternately convey their respective impulses to
the centre, inspiratory impulses being excited during expiration and expiratory
impulses during inspiration (p. 505). These impulses are, however, not indis-
pensable to the alternation of inspiration and expiration, because these acts
follow each other regularly, even after the isolation of the respiratory centre
from the lungs by section of the pneumogastric nerves.

Thus we may conclude that the rhythmical discharges from the centre are
due primarily to an inherent property of periwlic activity of the nerve-cells
constituting the respiratory centre and maintained by the blood, and that the
rhythm, ra'te, and other Characters of these discharges may be affected by the
will and the emotions, by the composition, supply, and temperature of the
blood, and bv various afferent impulses. The chief factors are,' under ordi-

568 A.X AMERICAN TEXT-BOOK OE PJIYSIOLOGY.

iiarv circumstances, the quantities of O and COj in the blood, and the inipnlses
conveyed from tlie lungs by tiie fibres of the pneumogastric nerves.

The Afferent Respiratory Nerves. — The chief of these nerv(is are the
■pncuinoijnstrH', (jlosxo-plmryngcdl, triytiainal, and cidaneoua 'iirrvcs. The im-
j)()rtant part taken by them in the regulation of the respiratory movements has
frequently been alluded to in connection with the respiratory centres. Their
functions, however, are of sufficient importance to demand special and detailed
consideration.

The j)neuinogastvic verves are pre-eminently the most important. Their
functions juay be studied by comparing the ])lienomena before and after section
of one or of both nerves, and from the results following excitation by stimuli
of varying quality and strength under normal and abnormal conditions.

Section of ojie pneumogastric may be without effi'ct or be followed by a
transitory, slight diminution of the resi)iratory rate ; by slower and deeper
movements; by stronger, deeper, and longer inspirations; by unaltered or
longer or shorter expirations; and probably by active expirations. Tliese
effects are transient, and the normal respiratory niovements are usually restored
within a half hour. Section of both nerves is sooner or later followed by a
diminution of the resi)iratorv rate ; by slow, deep, ]iowerful inspirations ; by
active expiration ; and by a pause between ex])iration and inspiration. The
immediate results are variable unless certain precautions are taken to prevent
irritation of the central ends of the cut nerves. If the ends are allowed to
fall back into the wound, the respirations may become irregular ; or they may
be le&s frequent, with weakened inspirations, spasmodic expirations, and pro-
longed expiratory pauses. The explanation of these variable results is found
in the fact that the expiratory fibres are more sensitive to vev}/ veak stimidus
than the inspiratory fibres, and that the mechanical irritation caused by the
section, and the excitation due to the electric current in the cut ends of the
nerves that is established when the central end of the nerve is replaced in the
wound, excite ex})iratorv impulses and cause expiratory phenomena; if the
irritation be stronger, both inspiratory and expiratory impulses are excited,
thus causing uncertain results, varying as one or the other is the stronger. If
irritation be prevented, section is at once followed by typical slow, deep
respirations.

Stimulation of the central end of the cut vagus, the other nerve being
intact, is followed by variable results dependent ujwn the character of the
stimulus. Chemical stimuli, such as a solution of sodium carbonate, excite
the expiratory fibres; mechanical stimuli, the inspiratory fibres; electrical
stimuli, expiratory or ins]Mratory fibres or both, according to the strength of
tha current. Single induction shocks are without cfTect, but a tetanizing
current is very effective. Should that current which will elicit the least
response be used, the breathing is rendered less frequent, the inspirations are
weakened, and the expirations may be active and lengthened ; in other words,
there are present the same phenomena which often immediately follow section
of both nerves when the cut ends are allowed to fall back into the wound and

resi'/hatiox. 500

thus establish an exciting electric current whidi affects expiratory fibres. If
the strcnoftli of the current bo increascil, these elfects give place to those of an
ojjpo.site ciiaracter, the respirations becoming more freijucnt and tiie inspi-
rations more marked in depth and force, the exi)hiiiati<)M of this difference
being that the stronger current has also excited inspiratory fibres, so that now
both expiratory and inspiratory impulses are generated, Ijut the latter, being
more potent in their influences, cause acceleration of the rate and accentuated
inspirations. The effects following stimulation of the central end of the cut
vagus by a current of moderate strength are best observed after l)oth nerves have
been divided and when there exist slow, deep, powerful respirations. Under
such circumstances stimulation of the central end of one of the vagi is followed
at once by an increase in the respiratory rate and a return of the general char-
acters of the inspiratory and expiratory phases toward the normal ; and if the
degree of excitation be properly adjusted, the normal rate and normal charac-
ter of breathing mav be restored. Still stronger excitation further accelerates
the rate, causing the respiratory acts to follow each other with sucii frequency
that inspiration begins before the expiratory act (relaxation of the inspiratory
muscles) has been completed. The inspiratory muscles are therefore never
completely relaxed. With a further increase of stimulus the expiratory
relaxation becomes less and less, until finally the respirations are brought to a
standstill in the inspiratory phase, the inspiratory muscles being in tetanus.

If the nerves be fatigued from over-excitation or if the animal be
tiioroughly chloralized, stimuhition of the central end of the cut nerve by a
strong current is no longer followed by inspiratory stimulation, but is followed
by expiratory stimulation (the inspirations being shortened and weakened, the
expirations prolonged and spasmodic) and by long pauses between expiration
and inspiration. If the excitation be sufficiently strong, arrest of respiration
occurs in the expiratory phase.

It will be observed from the above results that electrical irritation of the
central end of the cut pneumogastric may be followed by eftects of an oppo-
site character, extremely w^eak irritation causing expiratory stimulation (weaker
and shorter inspirations, prolonged and active expirations, expiratory pauses,
and diminished respiratory rate) ; whereas moderate irritation causes inspiratory
stimulation (stronger and deeper inspirations and increased respiratory rate).
These diverse results are explained by the fact that tliese nerves contain two
kinds of fibres having opposite functions : fibres of one kind convey impulses
which affect the expiratory centre ; those of the other kind convey impulses
which affect the inspiratory centre. The former are more susceptible to weak
electrical stimulation, and thus their presence may be elicited by the weakest
stimulus capable of causing any response. At the same time they are less
readily exhausted, so that if the vagi be subjected to prolonged stimulation
by a strong current, the inspiratory fibres are exhausted before the expiratory
fibres. For moderate and strong currents the inspiratory fibres are affected
to a greater degree than the expiratory fibres, therefore inspiratory stimula-
tion predominates.

570 ^.V AMERICAN TEXT- BOOK OF PIIYSIOLOdY.

Both sets of fibres convey iiupulses which liavc their origin essentiallv in
the peripheries of the pneuniogastric nerves in the kings; but expiratory
impulses may arise in tlie fibres of the supei-ior and inferior huyngeal nerves,
especially in the former. The impulses which arise in the lungs are under
ordinary circumstances produced mechanical ly by the movements of the lungs,
although it is believed by some that the composition of the gases in the alveoli
is an important factor. According to the latter view, when the lungs are in
the expiratory phase the accummulation of CO^ in the air-cells excites the
peripheries of the inspiratory fibres, thus giving rise to impulses which are
carried to the inspiratory ])ortion of the res])iratory centre, and exciting inspi-
ration ; whereas the stretching of the lungs during inspiration is held to excite
the peripherics of the expiratory fibres, generating impuses which are conveyed
to the ex})irutory portion of the ex])iratory centre, causing expiration. There
is, however, no sufficient evidence to lead us to believe that the presence of
CO2 in normal percentages influences in any way either set of fibres. On the
contrary, the mechanical eifects of the movements of the lungs are of great
importance, as is apparent from the fact that inflation excites active expi-
ration, whereas aspiration or collapse excites inspiration; moreover, if the
movements of one lung be prevented by occlusion of the bronchi or by free
opening of the pleural sac, the effects are the same as though the vagus of the
same side were cut ; if now the other nerve be severed, the results are the same
as when both nerves are cut. The movements of the lungs therefore generate
alternate inspiratory and exj)iratory impulses, collavpse causing inspiratory
impulses, and expansion causing expiratory impulses. The inspiratory
impulses, however, not only excite inspiration, but concurrently limit the
duration of expiration ; Mdiile the expiratory impulses excite expiration and
concurrently limit inspiration.

Excitation of the snperior laryngeal nerve causes expiratory stimulation,
and there may occur respiratory arrest in the expiratory phase. These fibres
are extremely sensitive; and they are of considerable physiological import-
ance, as is illustrated by the fact that the entrance of foreign bodies into
the larynx during deglutition causes an immediate arrest of inspiration, and
even a forced, spasmodic expiration. The foreign particles, coming in
contact with the keenly sensitive fibres of these nerves, generate impulses
which arrest inspiration, thus being prevented from being carried to the
lungs.

The fibres of the r/losso-pharyngeal nerves act similarly. Their excitation
is followed by an arrest of respiration which lasts for a period e(|ual to that
occupied bv al)OUt three of the preceding respiratory acts. The value of such
an inhibitory influence is obvious: During swallowing breathing is arrested,
evidently for the purpose of preventing the aspiration of food and drink into
the larynx. This act is purely reflex, and is due to the excitation of fibres of
these nerves by the fluid or the bolus of food after the act of deglutition has
begun. Such impulses flow to the respiratory centre, immediately arresting
the inspiratory discharge in whatever phase the inspiratory movement may

RESPlHATrOX. 571

happen to bo. Wlien ^^wallowinj; has bwii accoinphshed the inhibitory influ-
ence is removed and respiration is resumed.

The inhalation of irritating gases may cauM' respiratory arrest by excituig
either the sensory fibres of the trigeminal iierves in the nose or the pueumo-
gastric fibres in the larynx and lungs. Some gases affect the former, some
the latter, others both. In the rabbit, for example, the introduction of tobacco-
smoke into the lungs through a tracheal opening produces no effect upon the
respirations, but if injected into the nose respiration is at once arrested. When
ammonia is similarly introduced into the lungs the respirations may be either
accelerated or diminished, and may be arrested in the inspiratory or the expi-
ratory phase, but when drawn into the nose expiratory arrest follows. Some
irritating gases arrest respiration in the inspiratory phase, others in the expi-
ratory phase. Odorous gases which are powerful and disagreeable may simi-
larly cause arrest by acting upon the olfactory nerves. Excitation of the
splanchnic nerves causes expiratory arrest ; stimulation of the sciatic and sea-
sonj nerves in general usually increases the number of respirations, yet under
certain circumstances it may cause a decrease and final arrest during expi-
ration.

Stimulation of the cutaneous nerves, as by a cold douche, slapping, etc.,
causes primarily a tendency to an increase in the number and depth of the res-
pirations, but finally causes cessation in the expiratory phase. It is stated that
excitation of these nerves is more effective in causing respiratory movements
than irritation of the vagi. The influence of external heat is very powerful,
and is perhaps the most potent means, under ordinary circumstances, of exciting
the respiratory centre. The respiratory movements caused by cutaneous irrita-
tion, are, however, of the character of reflex spasms rather than of normal
movements, and when the excitation is sufficiently strong the movements may
be distinctly convulsive.

Finally, afferent (intercentral) fibres connect the brain-cortex, and probably
the ganglia at the base of the brain, with the respiratory centres.

The Efferent Respiratory Nerves.— During ordinary respiration the only
efferent or motor nerves necessarily involved are the phrenics, and certain other
of the spinal nerves, and the pneumogastrics. Section of one phrenic nerve causes
paralysis of the corresponding side of the diaphragm ; section of both phrenics
is followed by paralysis of the entire diaphragm. So important are these
nerves in respiration that in most cases after section death occurs from asphyxia
wathin several hours. In such cases not only is the work of inspiration thrown
upon the other inspiratory muscles, but the effectiveness of the latter is greatly
compromised by the relaxed condition of the diaphragm, which permits of its
being drawn into the thoracic cavity with each inspiration, thus hindering the
expansion of the lungs. If section be made of the spinal cord just below the
exit of the fifth cervical nerve, costal movements cease, but diaphragmatic con-
tractions continue. The level of the section is just below the origin of the roots
of the phrenics, so that the motor fibres for the diaphragm are left intact, but
the motor impulses which would have gone out to other inspiratory muscles

r>72 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tliroiigli the spinal nerves below the point of section are cut off. If the cord
be out just below the medulla oblongata or above the origin of the phrenics,
both costal and diai)liragniatic movements immediately or very soon cease, but
respiratorv movements may continue in the larynx, and when dyspntt-a occurs
thev may be observed in the muscles of the face, neck, and mouth. In rare
cases, after section at the junction of tlie mcidulla ()l)l(»ngata and the spinal cord,
respiratory movements may continue in tlu; thorax and the abdomen, but these
instances are exceptional and the movements are of the nature of reflex spasms.

During each respiratory act there flow to the larynx impulses which open
the glottis during inspiration. The pathway of these impulses is through the
laryngeal branches of the vagi, almost solely through the recurrent or inferior
laryngeal nerves. (See section on the Physiology of the Voice.) If the pneu-
mogastrics are cut above the origin of these brancdies, res[)iratory movements
in the larynx cease, and, owing to the paralysis of the laryngeal muscles, the
vocal cords are flaccid, the glottis is no longer widened, and thus great resist-
ance is offered to the inflow of air, causing difflculty during ins})iration.

During forced breathing, besides the above nerves a number of others may
be involved, especially the spinal nerves, which supply the extraordijaary respi-
ratory muscles of the chest, abdomen, pelvis, and vertebral column, and the
facial, hypoglossal, and spinal aecessorii nerves.

L. The Condition of the Respiratory Centre in the Fetus.

During intra-uterine life the child receives O from and gives CO2 to the
blood of the mother. No attempt is made by the child to breathe, because the
centre is in an apnoeic condition, due to a low condition of irritability and to
the relatively large amount of O in the blood. The fetal blood contains a
larger percentage of haemoglobin than the blood of the mother; Quinquaud
has shown that the fetal blood has a larger respiratory capacity than adidt's
blood ; and Regnard and Dubois have proven the same to be true of the calf
and the cow. Were it not for these two conditions, the child would continu-
ally attempt to breathe. While such efforts do not occur under normal cir-
cumstances, they may be present if we interfere in any way with the supj)ly of
oxygen, as by pressure upon the umbilical vessels. The child has been seen
to make respiratory efforts while within the intact fetal membranes. It seems
evident, therefore, that all that is necessary to excite the respiratory centre to
activity is a venous condition of the blood. In utero, and as long as the child
is bathed in the amniotic fluid, respiratory movements cannot be carried on
even though the res])iratory centre be excited to activity, the reason being that
with the first movement of inspiration amniotic fluid is drawn into the nasal
chamber; the fluid acts as a powerful excitant to the sensory fibres of the
nmcous membrane, thus causing inhibitory resjiiratory impulses. From this
fact we learn the practical application that it is desirable immediately after birth
of a child, if spontaneous respirations do not immediately and effectively occur,
to carefully remove mucus or other matter from the nose, so that the inhibitory
influences generated by nasal irritation shall be discontinued.

BESPIBA TION. 573

When the exchange of O and COg is interfered witli for a long period, as
in cases of prolonged labor, the respiratory centre may become so de})ressed
that spontaneous respirations do not occur upon the birth of the child. In
such a case respirations may usually be initiated by irritation of the skin, as
by slapping, sprinkling with iced water, etc. Respirations may also be carried
on successfully by artificial means (see p. 553).

In utero the lungs arc devoid of air ; the sides of the alveoli and of the
small air-passages are in apposition, although the lungs completely fill the
compressed thoracic cavity. During the first inspiration comparatively little
air is taken into the lungs, because of the force necessary to overcome the
adhesion of the sides of the alveoli and of the smaller air-tubes, but as one
inspiration follows another inflation increases more and more until full disten-
tion is accomplished. The vigorous crying which so generally occurs immedi-
ately after birth doubtless is of value in facilitating this expansion. If once
the lungs have been filled with air, they are never completely emptied of it,
either by volitional effort or by collapse after excision.

M. The Innervation of the Lungs.

The nerves of the lungs are derived from the pneumogastrics, the sympa-
thetics, and the upper dorsal nerves. Scattered along the paths of distribution
of these fibres are many small ganglia.

The Pneumogastric Nerves. — The pulmonary branches of the pneumogas-
tric nerves contain not only fibres which convey impulses that affect the gen-
eral characters of the respiratory movements, but other fibres that are of
great importance to the respiratory mechanism. Setting aside the effects on
the respiratory movements following section and stimulation of one or of both
vagi, there are observed phenomena which are of an entirely different character,
and which are due to excitation or paralysis of certain other specific nerve-
fibres. Among: these fibres are efferent and afferent broncho-constrictors and
broncho-dilators. Roy and Brown ^ found in investigations upon dogs that
stimulation of one vagus caused constriction of the bronchi in both lungs;
section of one vagus was followed by expansion of the bronchi in the corre-
sponding lung, which expansion was sometimes preceded by a slight contraction
owing to the temporary irritation caused by the section ; stimulation of the
peripheral end of the cut nerve caused a contraction of the bronchi in both
lungs; stimulation of the central end of the cut nerve was followed by a con-
traction of the bronchi in both lungs, but not so marked as when the peripheral
end was stimulated ; stimulation of sensory nerves other than the vagus rarely,
and then only to a slight extent, caused contraction ; atropine paralyzed the
constrictor fibres ; nicotine in small doses had a powerful expansive effect on
the bronchi ; after etherization stimulation of either the central or the periph-
eral end of the cut pneumogastric nerve was often followed by broncho-dilata-

1 Journal of Physiologrj, vol. 6, 1885 {Proceedings of the Phydologkal Society, iii. p. xxi.) ;
Einthoven, Pftiiger's Archiv fiir Physiologie, 1892, vol. 51, p. 367 ; Sandeman, Bu Bois-ReymomT a
Archiv fiir Physiologie, 1890, p. 252.

57 4 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tion ; asphyxia causes broncho-constrict iun, hut not after section of the pnou-
niogastric nerves ; after section of bt)th vagi it is impossible to rause reflex
bronclio-coustriction or broncho-dihitation ; the constriction of tlie bronchi
niav be so great as to reduce their calibres to one-half or one-third, or even
more. The above results are very instructive, and show — (1) That broncho-
constriction or broncho-dilatation can l)e obtained bv stimulating the peri])heral
end of the vagus, and tliat these changes occur in the bronchi of both lungs
when only one nerve is excited, thus })roving tliat each nerve supplies l)Oth
kinds of fibres to both lungs; (2) that the same results can be obtained by ex-
citation of the central end of the cut nerve, tiuis showing that the ])iienmogas-
trics contain both atfereut constrictor and afferent dilator fibres ; (3) that reflex
broncho-constriction and broncho-dilatation cannot be produced after section
of the vagi, thus proving that all of the efferent fibres pass through the pneu-
mogastrics; (4) that asphyxia and the inhalation of COg cause broncho-con-
striction, but not after section of the vagi, thus indicating that under these
circumstances the effects on the bronchi are reflex ; (5) that certain poisons
affect one or the other of these two sets of fibres.

The presence of efferent vaso-motor fibres in the vagi has been disproved by
the results of experiments by Bradford and Dean,^ and others. These observers
have shown, however, that the vagi contain afferent prei^sor fibres, irritation of
which is followed by constriction of the pulmonary vessels that may or may
not be accompanied by constriction of the systemic vessels, the efferent fibres
in this case reaching the lungs through the sympathetic nerves.

The existence of trophic fibres is generally admitted. After section of one
pneumogastric nutritive changes immediately begin in the lung of the corre-
sponding side, which changes are manifest in the appearance of inflammation
in the middle and lower lobes. Section of both nerves is followed by inflam-
mation in the middle and lower lobes of both lungs.

The vagi contain sensori/ fibres for the larynx, trachea, and lungs, after sec-
tion of which fibras there is an absolute loss of sensibility in these parts.

It is probable that the vagi contain secretori/ fibres for the mucous glands.

Thus we find that the pneumogastric nerves supply the lungs with (1)
afferent inspirator)/ and expiratorn fibres ; (2) afferent and efferent broncho-
constrictor and broncho-dilator fibres; (3) afferent pressor fibres; (4) general
sensory fibres; (5) trophic fibres; (6) and probably secretory fibres for the
mucous glands.

The Sympathetic Xerves. — The sympathetics supply trophic and efferent
vaso-motor fibres. The efferent vaso-motor fibres pass from the spinal cord in
the anterior roots of the second to the seventh dorsal nerve, inclusive, to join
the sympathetics, thence through the fii-st thoracic ganglia to the lungs.

The Ganglia. — Nothing is known of the functions of the ganglia.
' Jow-nal of Physiology, 1894, vol. 16, p. 70.

IX. ANIMAL HEAT.

A. Bodily Temperature.

Homothermous and Poikilothermous Animals. — Animal organisms are
divided as regards bodily temperature into two classes, homothermous and
poikilothermous. The temperature of homothermous (warm-blooded) animals
is constant within narrow limits and is not materially aifected by alterations
of the temperature of the medium in which the organism lives. The tempera-
ture of poikilothermous (cold-blooded) animals normally ranges from a frac-
tion of a degree to several degrees above that of the surrounding medium, and
under ordinary circumstances rises and falls with corresponding changes of sur-
rounding temperature. The old terms warm-blooded and cold-blooded imply
that the difference between the two classes is one of absolute temperature, the
•former having a temperature higher than the latter, and although this is gener-
ally the case it is not necessarily so. For instance, Landois has recorded that a
frog (cold-blooded) in water at a temperature of 20.6"^ C. had a temperature of
about 20.7° C, and that when the water was at 41° C. his temperature rose to
about 38° C, which is higher than the mean temperature of man (warm-
blooded). The temperature of cold-blooded animals may, therefore, be higher
than that of warm-blooded animals. The difference therefore is relative and
not absolute, the chief distinguishing feature being that the temperature of
homothermous animals is practically constant, while that of poikilothermous
animals fluctuates with the temperature of the medium in which the organism
exists. The class of homothermous animals includes mammals and birds ; and
that of poikilothermous animals, fish, reptiles, amphibia, and invertebrates.

Temperatures of Different Species of Animals. — The temperature of
every animal varies in different parts of the organism, so that in making com-
parisons it is necessary that the observations be made in the same region of the
body of the different individuals, and as far as possible under the same internal
and external conditions. As a rule, rectal temperatures are preferable, and
in making them it is especially desirable, in order to ensure practical accuracy,
that the bulb of the thermometer be inserted well into the pelvis, and that it
does not rest within a mass of fecal matter. The depth to which the bulb is
inserted is also of importance, as shown by Finkler, who found in experiments
on a guinea-pig that the temperature was 36.1° C. at a depth of 2.5 centimeters,
38.7° C. at 6 centimeters, and 38.9° C. at 9 centimeters. The following records
of mean bodily temperature of various species have been derived from various
sources, chiefly from the compilations of Gavarret :

575

576

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Mammals.

Centigrade.

Mouse 41.1"

Sheep 37.3-40.5°

Ape 35.5-39.7°

Rabbit 39.6-40.0°

Guinea-pig .... 38.4^39.0°

Dog 37.4-39.6°

Cat 38.3-38.9°

Horse 36.8-37.5°

Rat 38.8°

Ox 37.5°

Ass 36.95°

Birds.

Centigrade.

Birds 44.03"

Duck 42.50-43.90"

Goose 41.7°

Gull 37.8°

Guinea 43.90°

Turkey 42.70°

Sparrow .... 39.08-42.10°
Chicken .... 43.0°
Crow 41.17°

Reptiles and Fish.*

Centigrade.

Frog 0.32-2.44°

Snakes 2.5-12.0°

Fish 0.5-3.0°

Invertebrates.!

Crustacea 0.6°

Cephalopods - . . 0.57°

Medusa 0.27°

Polyps 0.21°

Molluscs 0.46°

The Temperature of the Different Regions of the Body. — The quanti-
ties ol" lieat produced aud di.'^sipated bv different parts of the eeonomv vary,
con.sequently there must continually be a transmission of heat from the warmer
to the cooler parts to establi.'^h throughout the organism an equilibrium of tem-
perature. Heat is distributed by direct conduction from part to part, but prob-
ably chiefly by the circulating blood and lymph. The.se means of distril>utiun
are, however, not sufficiently active to establish a uniform temperature. Thus
we find that the internal parts of the body have a higher temperature than the
external parts; that some internal organs are considerably warmer than others;
that every organ is warmer when active than when at rest ; that the tempera-
ture varies in different regions of the surface of the body, etc. The following
figures by Kunkel '" instance some of these differences, the temperature of the
room being 20° C. :

Centigrade.

Sternum 34.4°

Pectorales 34.7°

Right iliac fossa 34.4^

Left iliac fossa 34.6°

Os sacrum 34.2°

Eleventh rib (back) 34.5°

Tuberosity of ischium 32.0°

Upper part of thigh 34.2°

! Calf 33.0°

The temperature of the skin is higher over an artery than at some di.'^tauce
from it ; it is higher over muscle than over sinew ; it is higher over an organ
in activity than when at rest; it is higher in the frontal than in the parietal
region of the head, and on the left side of the head than on the right, etc.

Temperature observations are usually made in the rectum, in the mouth
under the tongue, in the axilla, and in the vagina, the rectum being preferable,
although in the human being the temperature is usually obtained in the mouth
and axilla. In the same individual when records are taken .'simultaneously in
all four regions appreciable differences will be noted. The temperature in the
axilla is, according to Hunter 37.2° C, to Davy 37.3° C.,to Wunderlich 36.5°
to 37.25° C. (mean 37.1° C), to Liebermeister 36.89° C, to Jiirgensen 37.2° C,

^ Temperatures above that of the surrounding medium.
* Zeitschrift fur Biologie, 1889, vol. 25, pp. 69-73.

Centigrade.

Forehead 34.1°-34.4°

Cheek under the zygoma .... 34.4°

Tip of ear 28.8°

Back of hand 32.5°-33.2°

Hollow of the hand (closed) . . . 34.8°-35.1°
Hollow of the hand (open) .... 34.4°-34.8°

Forearm 33.7°

Forearm (higher) 34.3°

ANIMAL HEAT. 577

and to Jaeger 37.3° C. 'V\\v inean axillary temperature may be put down as
being about 37.1° C. (98.8° F.), the normal limits being 3(5.25° to 37.5° C.
(97.2° to 99.5° F.) The temperature in tiie mouth is about 0.2° to 0.5° C.
higher than in the axilla, in the reetura from 0.3° to 1.5° C. higher, and in the
vagina from 0.5° to 1.8° C. higher.

The temperature of different tissues varies. Davy, as results of observa-
tions on a fresh-killed sheep, gives the temperature of the brain as about 40°
C; of the left ventriele 41.G7° C; of the right ventricle 41.11° C. ; of the
liver 41.39° C. ; of the rectum 40.56° C. According to Bernard, the liver is
the warmest organ in the body, and then the following in the order named-
brain, glands, muscles, and lungs.

The temperature of the blood varies considerably in different vessels. In
the carotid it is from 0.5° to 2° C. higher than in the jugular vein; in the
crural artery, from 0.75° to 1° C. higher than in the corresponding vein ; in
the right side of the heart about 0.2° C. higher than in the left ; in the hepatic
vein 0.6° C. higher than in the portal vein during the intervals of digestion,
and as much as 1.5° to 2° C or more during periods of digestion ; the venous
blood coming from internal organs is warmer than the arterial blood going to
them, but the blood coming from the skin is cooler than that going to it ; the
blood coming from a muscle in a state of rest is about 0.2° C, and during
activity as much as 0.6° to 0.7° C, warmer than that supplied to the muscle.
The mean temperature of the blood as a whole is about 39° C. (102° F.) ; of
venous blood about 1° C. (1.8° F.) lower than of arterial blood. The warm-
est blood in the body is that coming from the liver during the period of diges-
tion ; the coolest blood is that coming from the tips of the ears and nose and
similarly exposed parts.

Conditions affecting Bodily Temperature.— The mean temperature of
the body is subjected to variations which depend chiefly upon age, sex, consti-
tution, the time of day, diet, activity, season and climate (surrounding tem-
perature), the blood-supply, disease, drugs, the nervous system, etc.

The temperature of a new-born child (37.86° C.) is from 0.1° to 0.3° C.
higher than that of the vagina of the mother; it falls about 1° C. during the
first few hours after birth, and then rises within the next twenty-four hours to
about 37.4° to 37.5° C. The mean temperature of an infant a day or two
old is about 37.4° C. It very slowly sinks until full growth is attained, when
the normal mean temperature of adult life is reached (37.1° C), a standard
which is maintained until about the age of forty-five or fifty, when it declines
until about the age of seventy (36.8° C), and then slowly rises and approaches
in very old people (eighty to ninety years) the temperature of very young
infants' (37.4° C). It is important to observe that during the early weeks of
life the temperature may undergo considerable variations, and that it is readily
affected bv bathing, exposure, crying, pain, sleep, etc., and by many circum-
stances which have little or absolutely no influence upon the temperature of

the adult.

The mean temperature of the female is said to be slightly lower than that

37

578 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of llie niak'. In ob.servatioii.s on childrou Soinnier noted a ditiercnce of 0.05°
C, and Feliling a difference of 0.33° C.

Individuals with vigorous constitutions have a somewhat higher temper-
ature than those who are weaii.

Records obtained by various European investigators indicate that tlie bodily
temperature is subjected to regular diurnal variations. The limits of variation
in health are from 1° to 2° C. The maximum temperature observed is usu-
ally from 5 to 8 p. M. (mean, about 7 p. m.) ; the minimum, from 2 to 6 A. M.
(mean, about 4 A. M.). Carter's ' experiments on rabbits, cats, and dogs show
that rhythmical temperature-changes occur in these animals which agree with
those noted by Jiirgensen in man. This same rhythm is stated to occur during
fasting, so that the ingestion and the digestion of food cannot be claimed to
account for it; moreover, it is prestiiit in fever and not disturbed by muscular
activity and by cold baths. If an individual works at night and sleeps during
the day, thus reversing the prevailing custom, the temperature curve is
reversed, the lowest temperature being noted in the evening and the highest
in the morning.

Insufficient diet causes a lowering of the temperature ; a liberal diet tends
to cause a rise slightly above the normal mean, especially during forced feeding
or when the food is particularly rich in fats and carbohydrates. There is a
rise during digestion which is usually slight, but it may reach 0.2° or 0.3°, the
increase being due chiefly to the activity of the intestinal muscles (see p. 540).
Although considerably more heat is produced during the periods of digestion
than during the intervals, the excess is dissipated almost as rapidly as it is
formed, so that but little heat is permitted to accumulate and thus cause a rise
of temperature. Hot drinks and solids tend to augment, and cold drinks and
solids to lower bodily temperature. In the nursing child Demme found that the
rectal temperature sinks during the first half-hour after taking food, then rises
during the next sixty to ninety minutes to a point from 0.2° to 0.8° C. higher
than the temperature before feeding, and falls again during the next thirty to
sixty minutes.

All conditions which increase metabolic activity are favorable to an increase
of temperature. Thus, during the activity of the brain, glands, muscles, etc.,
more heat is produced than when the tissues are at rest; indeed, so abundant
is heat-production during severe muscular exercise that the temperature of the
body may rise as much as 0.5° to 1.5° C. (1° to 2.7° F.). During sleep the
temperature falls from 0,3° to 0.9° C. or more in young children.

During the summer the mean bodily temperature is from 0.1° to 0.3° C.
hi<rher than durino; the winter. In warm climates it is about 0.5° C. hijjher
than in cold climates, but the difference is not due to race, since it is observed
in individuals who have changed their habitations from one climate to another.
Continued exposure to excessively high or low temperatures is inimical to
life. Exposure in dry air at a temperature of 100° to 130° C. may cause
the bodily temperature to increase as much as 1° to 2° C. within a few minutes,
' Journal of Nervous and Mental Diseases, 1890, vol. xvii. p. 782.

ANIMAL HEAT. 579

and the temperature may rise so rapidly as to cause fatal symptoms within ten
or fifteen minutes. A hot moist air is far more opi)ressive and dangerous than

hot drv air.

Baths exercise a potent influence on bodily temperature, hot baths increasmg
and cold baths decreasing it. The effect of a cold bath is less if it follows a
hot bath. Thus Dill ' found that his morning temperature varied from 33.7°
to 36.6° C, after a hot bath (40°-41° C.) it rose, in one instance, as high as
39.5° C, and after a cold bath it remained at 37° C. When, however, the
hot bath 'was omitted the cold bath reduced the temperature to 35.4° C. Bal-
jakowski ^ has recorded some very interesting results which show that the local
application of heat causes the bodily temperature to sink and the cutaneous
temperature of the part experimented upon to rise. The experiments were
conducted on youug men, whose arms and legs were encased in hot sand at a
temperature of 55° C. When the arm was used the axillary temperature sunk
an average of 0.13° C. during the bath and subsequently 0.24° C, the corre-
sponding" records of average rectal temperature being 0.23° and 0.31° C. In
case of the leg bath the corresponding records were axillary 0.06° and 0.32°
C; and rectal 0.21° and 0.25° C. The cutaneous temperature of the limb
expei-imented upon increased materially, the average rise varying from 0.73°
to 1.20° C, according to the part of the limb. Long-continued severe exter-
nal cold may prove fatal, but this is not necessarily due to the effect on bodily
temperature, for Milne-Edwards ^ has shown that rabbits die within five or six
days when exposed to a temperature of -10° to -15° C, without the bodily
temperature falling more than 1° C.

There is a general relationship between tiie frequency of the heart's beat and
the bodily temperature, especially in fever. Barenspruug noted such a coinci-
dence between the diurnal variations of the pulse and bodily temperature ; and,
in fever, Aiken found that for each increase of 0.55° C. (1° F.) above the mean
normal temperature the pulse-rate was increased about ten beats per minute.
But the variations in the two do not always correspond either quantitively or
qualitatively. Liebermeister found in man that for a rise of each degree from
37° to 42° C. the increase in the pulse-rate was 12.6, 8.6, 8.7, 11.5, and 27.5
beats per minute respectively. Beljakowski's * experiments show that the
bodily temperature mav fall and the pulse-rate rise— in one set of experiments
the rectal temperature "falling on an average 0.23° C. and the pulse increasing
on an average 6.85 beats per minute. After the local hot bath the temperature
remained subnormal, and the heart-beats became less frequent, and finally were
on an average from 2.7 to 3.1 beats per minute less than the normal rate.

:^rore important, however, than the pulse-rate is the effect of the amount
of blood supplied to any given part of the body. The mere lowering or rais-
ing of the arm is sufficient to alter the blood-supply to the part ; thus Romer
found that keeping the arm elevated for five minutes was sufficient to reduce

* British Medical Journal, 1890, vol. i. p. 1136.

2 Vratch, 1889, p. 436 ; Provincial Medical Journal, 1890, p. 113.

3 Cmnptes rendus de la Sac. de Biologic, 1891, vol. 112, pp. 201-205. . ♦ Loc. cit.

580 AX AMERICA iV TEXT- BO OK OF PHYSIOLOGY.

the tempfcrature of" the hand 0.19° C, and that if tlje period was doubled the
fall amounted to 0.38° C. Compression of the veins of the arm may diminish
the tonij)cratnre of the hand as innrh a^ 0.25° to 2.-45° C, while compression
of the brachial artery may eanse a fall of 2.4° within fifteen minutes. A larger
supply of blood to the cutaneous surface increases cutaneous temperature and
tends to decrease internal temperature, while a lessened supply causes the
opposite effects.

In abnormal conditions the temperature may be increased or decreased : in
cholera, diabetes, and in the last stages of insanity, it mav be lowered 6° or
8° C. or even more. In fever it is increased, usually ranging between 37.5°
and 41.5° C. (99.4° and 106.7° F.), but in very rare cases it may reach 44° to
45° C. (111° to 113° F.) just before death. A temperature of 42.5° C.
(108.5° F.) maintained for several hours is almost inevitably fatal. In frogs,
the highest temperature consistent with life for any length of time is below
40° C. ; in birds, from 48° to 50° C, and in dogs, from 43° to 45° C. Ex-
ceptional cases are on record of people having survived extraordinarily high
or low bodily temperature, Riehet having reported one in which the tempera-
ture several times was 46° C. (114.8° F.), while Teale records an axillary tem-
perature of 50° C. (122° F.) in an hysterical (?) woman. Frantzel noted a
temperature of 24.6° C. (76.2° F.) in a drunken man, and Kosiirew a temper-
ture of 26.5° C. (79.7° F.) in a man having a fractured skull.

Bodily temperature may be variously influenced by drugs and other sub-
stances, micro-organisms, etc. Some increase it, others decrease it, others are
without any marked influence, while others exert primary and secondary
actions. Among those which increase bodily temperature are cocain, atropin,
strychnin, brucin, caffein, veratrin, etc., and, as shown by Krehl' and others, a
large number of other organic substances and micro-organisms. Temperature
is decreased by anaesthetics, morphin and other hypnotics, quinin, various
antipyretics, large doses of alcohol, etc.

Among the most important of the conditions which affect bodily tempera-
ture are disturbances of the nervous systetu. Injury or irritation of almost
any part of the nerve-centres and of certain nerves may give rise directlv or
indirectly to alterations of temperature, and there are some parts which are
very sensitive in this respect, especially certain areas of the brain cortex, the
striated bodies, the pons Varolii, the spinal bulb, and the cutaneous nerves.
The results of injury or stimulation of these as well as of other })arts will
be considered later on (p. 600).

Temperature-regulation. — The fact that during life the organism is con-
tinxially producing and losing heat, and that the Ixxlilv temperature of homo-
thermous animal is maintained at an almost uniform standard, notwithstanding
considerable mutations of surrounding temperature, renders it evident that
there exists an important mechanism whereby the regulation of the relations
between heat-production and heat-di.<sipation is effected. It must be evident
that when the variations in heat-production and heat-di.ssipation balance, bodily

■ Archil' fur experimentelle PcUhologie und Pharmakologie^ 1895, vol. 35, pp. 222-268.

ANIJfAL HEAT. 581

temperature must remain unaltered, and that if the clianges in one exceed
tlio.se in the other the temperature rises or falls, depending upon whether more
or less heat is produced than is dissipated. It does not follow that because
luat-production is increased the bodily temperature must similarly be affected,
since hcat-dissi])ation may be increased to the same extent and thus effect a
compensation, 'J'herefore an alteration in heat-production or in heat-dissipation
bv no means implies that the temperature must be affected. Moreover, when
the temperature is increased or diminished the change may be caused by
various alterations in the quantities of heat produced or lost, singly or com-
bined, and the temperature may remain constant even when both processes are
materially affected. Thus, the temperature remains comtant when both heat-
production and heat-dissipation are normal, and when both are increased or
decreased to the same extent. The temperature is increased when heat-pro-
duction is normal and heat-dissipation diminished ; when both heat-production
and heat-dissipation are diminished, but when heat-production is diminished
to a less extent than heat-dissipation ; when heat-production is increased and
heat-dissipation remains normal ; when both heat-production and heat-dissipa-
tion are increased, but when heat-production is increased to a greater extent
than heat-dissipation ; and when heat-production is increased and heat-dissipa-
tion is diminished. The temperature is diminished when heat-production is
normal and heat-dissipation is increased ; when heat-production is diminished
and heat-dissipation remains normal ; when heat-production and heat-dissipa-
tion are diminished, but when heat-production is diminished to a greater extent
than heat-di&sipation ; when heat-production is diminished and heat-dissipa-
tion is increased ; and when both heat-dissipation and heat-production are
increased, but when heat-production is increased to a less extent than heat-
dissipation.

It is generally regarded by clinicians that bodily temperature varies directly
with heat-production — that is, that a rise means increased production, and a
fall diminished production ; but the fallaciousness of such a conclusion must
be apparent. It may, however, be accepted as a fact that in fever, as a rule,
an increase of bodily temperature is a concomitant of increased heat-produc-
tion, and diminished temperature of diminished heat-production; but it must
also be observed that pyrexia, although generally due to increased he^it-
production, may also be due partly or wholly to diminished heat-dissipation.
It is obvious, therefore, that temperature variations simply show that the
balance between heat-production and heat-dissipation is disturbed, without
positively indicating how the processes of heat-production and heat-dissipation
are affected.

The mechanism concerned in the adjustment of the relations between heat-
production and heat-dissipation will be considered under another heading
(p. 602).

B. Income and Expenditure of Heat.

Broadly speaking, the source of animal heat is in the potential energy of
organic food-stuffs — so little relatively being obtained from the heat of warm

582 ^l^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

food and drink and directly from external sources, such as tlie sun's rays, that
these sources may be disregarded. This potential energy of food may ije
converted into Unixi dircdhi or indirectly ; directly, as an immediate result of
chemical decomposition ; and indirectly, by mechanical movements, such as
muscular contraction, the flow of the blood, the friction of the joints, etc.
Abont 90 })er cent, of the heat of the organism results directly from chemical
decompositions, and about 10 per cent, results indirectly from mechanical
movements. The potential energy of the food is transformed into kinetic
energy (heat and work) essentially by processes of oxidation. The energy-
yielding food-stuffs enter the body in the form of proteids, fats, and carbo-
hydrates. The proteid is oxidized into urea, CO2, HjO, and various extrac-
tives ; and the fats and carbohydrates are reduced to CO2 and HgO. Dining
these oxidative processes, by which the potential energy of the molecules is
transformed into kinetic energy, the total amount of energy evolved by the
complete oxidation of a given amount of any substance is the same whether
the processes are carried at once to the final stages, that is, to the final disin-
tegration products, or whether they pass through an indefinite number of
intermediate stages, provided that the final product or products are the same.
In other words, the amount of heat evolved by the oxidation of 1 gram of
proteid into urea, CO2., and HgO is the same when the molecule is oxidized
immediately into these substances as when the decomposition is carried through
a number of intermediate stages. Similarly 1 gram of carbon oxidized into
CO2, or 1 gram of H oxidized into HgO, yields a definite amount of heat,
1 gram of C yielding 8080 calories (see p. 584 for definition of calorie),
and 1 gram of H 34,460 calories; 1 gram of proteid oxidized into CO2
and HgO yields 5778 calories; 1 gram of fat oxidized into CO2 and H2O
yields 9312 calories; and 1 gram of carbohydrate oxidized into COg and HjO
yields 4116 calories (see Potential Energy of Food, p. 302).

Income of Heat. — Since the energy-yielding food-stuffs are essentially
proteids, fats, and carbohydrates, and composed of C, H, O, and N, and since
the products of their disintegration are essentially urea, COj, and HgO, the
amount of energy yielded by the oxidation of the food-stuffs can readily be
determined if we know the quantity and quality of the food and excreta. Since
the energy of the organism is manifested essentially in the form of heat and
work, and as under ordinary circumstances but a fraction of it is manifested as
work, we may in making this estimate, as a matter of convenience, consider
that the total available energy of the food appears in the form of heat.

The income of energy may be estimated by determining — (1) the quantity
of oxygen consumed ; (2) the amounts of C and H that are oxidized in the
body into COj and H2O; (3) the quantity and quality of the food, and the
energy yielded by the oxidation of the same substances outside the body when
they are decompospd into the same residual products as appear in the body ;
(4) the quantity of heat produced, by the aid of a calorimeter, the individual
being kept quiet so that as little as possible of the energy expended appears
as work.

ANIMAL HEAT.

583

The first two methods have fallen into disuse. According to the third
method it is necessary that we know the kind and quantity of food ingested,
the Hnal ,)rodaets of disintegration, and the quantity of energy evolved by the
oxidation of each of the food-stuffs to their nornial residual substances. As tiie
basis of the.e calculations wc have the fact that during the complete oxidation
of any -iven substance a definite amount of energy is given off, and that when
the oxidation is but partial only a portion of energy is evolved, the proportion
bein- in accordance with the stage of oxidation. The complete oxidation of
1 ci^m of proteid yields 5778 calories; of 1 gram of fat, 9312 calor^s; and
of'l gram of carbohvdrate, 4116 calories (see Potential Energy of Food, p
302) If these substmices be completely oxidized in the body, the amount of
enei-v evolved will be the same as though the oxidation occurred outside
of the body, provided that the final products are the same in both cases. As
far as fats and carbohydrates are concerned, we are justified in assuming that
they are completely oxidized in the body into CO, and H,0 ; but the proteids,
a. already pointed out, undergo only partial oxidation, each gram yielding
about one-third of a gram of urea. The results of experiments show tha
each gram of urea contains potential energy equivalent to 2523 calories, and
since each gram of proteid yields one-third of a gram of urea representing
841 calories, each gram of proteid yields to the organism only 49o7 calories.
The available energy from the proteid would, therefore, be equivalent to the
total amount of energy derivable from the complete oxidation of the proteid
minus the amount represented in the urea. With these facts in view it is a
simple matter to determine the total income of cniergy, should the diet be
known Thus, if the diet consists of 120 grams of proteids, 90 grams of fat,
and 330 of carbohydrates, the absolute and available amounts of energy
ingested are— ^^^^^ ^^^^^.^^ calories.

Proteids • • 120 x ^778 693,360

I'T . 90 X 9312 837,080

^ , ,• ; ooA ^ 4116 1,358,280

Carbohydrates ^^"^^ ^ ^^^" '^^ —

2,888,720

Deduct the proteid energy in 40 grams of urea, 40 x 2523= J^m

Total daily heat-production ■ ■ • 2,78/, 800

Thfe is assuming that the entire quantity of proteids, fats, and carbohydrates
is digested, absorbed and ultimately broken down into CO,, H.O, and urea.
Thislssumption, however, is not justified by facts, since we know, for instance,
that more or less food escapes digestion. In practice, therefore, it is necessary
to ascertain from the excreta of the animal (see section on Nutrition) just how
much of the ingested food has been absorbed and completely or partially

destroyed in the body. .

Calorimetric investigations also afford us indirect information as to the
income of heat by showing the quantities of heat produced and dissipated.
Such data are of much value, since it is evident that should the energy of the
body be maintained in a condition of equilibrium from day to day, and should
the energy resulting from the transformation of potential energy be manifested

584 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

solely in the form ot" iieat, it follows that the mean daily heat-production and
income of available cncr»i;:y must balance. lint it caimot be considered that this
balance is maintained at a constant standard from hour to hour, nor from day
to day; on the contrary, the fluctuations are undoubtedly considerable, as is
obvious by the fact that we are continually expending energy and only periodi-
cally (at meal-times) acquiring energy. During fasting there is absolutely no
income of energy, yet the output of heat may be subnormal, normal, or hvi)er-
normal ; on the other hand, if an excess of energy be ingested, as in excessive
eating, it is not by any means implied (hat there is a similar excess in heat-pro-
duction, because some of the food in<iested mav be lost as undiirested food or as
partially oxidized excrementitious matters, or may be stored in the body in the
form of carbohydrate, fat, or proteid ; nor does an excess of heat-pi'oduction
imply an excess of income of energy, because the storcd-up energy may be
drawn upon. (For results of the ealorimetric method see p. 589.) The results
of the various methods are in close accord, and indicate that in the adult the
total income of available energy is about 2,500,000 calories.

Expenditure of Heat. — Assuming that the energy of the organism is
expended in the form of heat, and that the total income of available energy is
2^00,000 calories, it has been estimated by Vierordt that about —

1.8 per cent, is lost in the urine and feces 47,500 calories.

3.5 " " " expired air 84,500 "

7.2 " '-' " evaporation of water from the lungs • 182,120 "

14.5 " " " " " " skin. 364,120

73.0 " " " radiation and conduction from skin 1,791,820 "

2,500,000 calories.

Therefore, about 87.5 per cent, is lost by the skin, 10.7 per cent, by the lungs,
and 1.8 per cent, in the urine and feces.

C. Heat-production and Heat-dissipation.

Calorimetry. — The intensity of heat of any substance is measured by means
of a thermometer or thermopile ; the quantity of heat present is estimated by
the weight, the specific heat, and the mean temperature of the body ; the quan-
tity of heat dissipated is measured by the calorimeter ; and the quiuitity of
heat produced is determined by the quantity dissipated plus any addition of
heat to that of the body or miiuis any that is lost (j). 588). The caloric, or heat
unit, is the (juantity of heat that is necessary to raise the tem])erature of one
gram o\' water 1° C. ; the mechanical unit, or grammcter, is the quantity of
energy required to raise one gram a height of one meter, and is equal to 424.5
calories; a kiloealorie or kilogramdcgvec is equal to 1000 calories, and a hilo-
grammeter to 1000 gramraeters. By specific heat is meant the quantity of heat
required to raise the temperature of any substance 1° C, this quantity varying
considerably for different substances. If water be taken as 1, as a standard of
comjiarison, the specific heat of the animal body may be regarded as being
about 0.8 ; in other words, 0.8 of the quantity of heat will be required to heat
the same weight of the animal body as to heat the water. Knowing the weight,

AXr.UAL ir/'JAT. 585

specific heat, and teinponitiirc of" any siihstaiicc the total quantity of heat stored
in it at a giv-'ii tcniiKM-ature may hv. readily calculated. Thus, if the animal
oxperimcnted uj)()u weii;']! 20 kilos, its specific heat he 0.8, and its temperature
be 39°, the total quantity of heat stored would he 20 X 0.8 X 39° = 62.4 kilo-
g-ramdci^rees. In calorimetric; work the total heat in the organism is seldom
considered, but the specific heat of the organism is of importance in determin-
ing the quantity of heat involved in a change of the animal's temperature. For
instance, should the animal weigh 20 kilograms and its temperatm-e be increased
or decreased 0.2°, the cpiantity of heat added to or taken from the heat of the
body, as the case may be, would be 20X0.8X0.2=3.20 kilogramdegrees.
These calculations are of fundamental importance in studying heat-production
and heat-dissipation.

In making estimates of the dissipation of heat no regard is paid usually to
the quantity lost in the urine and feces, because the error involved is so slight,
but the quantities imparted to the air, both in warming the inspired air and in
eva])orating water from the lungs and skin, represent important percentages.

Calorimetry is spoken of as direct and indirect. The former method is
the direct determination of the amount of heat produced and dissipated ; the
latter is the indirect determination based upon estimates of the quantities of O
absorbed and CO2 eliminated, or upon the amount of potential energy ingested
in the food and probably transformed into kinetic energy within the body
(p. 582).^

Calorimeters of various forms have been employed, some of which have
been devised to study the body as a whole, while others are adapted only for
studying parts, such as a leg or arm. They may be classified as ice, air, and
tvater calorimeters in accordance with the chief medium employed to absorb
the heat. They consist essentially of an insulated jacket of ice, air, or water,
which encloses the animal and serves to absorb the heat. The ice calorimeter
is impracticable for physiological uses because the animal is placed under
such abnormal temperature conditions ; the air calorimeter has many inherent
defects, and until very recent years has found but little acceptance ; the water
calorimeter is the form of apparatus usually employed, having been first used
by Crawford in 1788; it has been materially modified by Despretz and
Dulong and subsequent investigators. The now classical instrument of
Dulong consists of two concentric cases. The animal is placed within the
smaller case, which is submerged in the water contained in the larger case,
this in turn being placed within a large box, between which and the calorime-
ter some non-conducting material such as feathers or wool is packed. Suit-
able openings are made for the proper supply of fresh air and for the agitation
of the water in the calorimeter so that an equalization of the temperature of
the instrument can be obtained. This apparatus has certain serious defects,
however, which render it troublesome for expeditious and accurate work. An
improved form devised by the author ^ which is now in general use meets
every essential requirement for a satisfactory instrument. The apparatus con-
* Reichert: University Medical Magazine, 1890, vol. 2, p. 173.

586

AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

sists of two concentric boxes of sheet metal which are fastened together so that
there is space of about one and a lialf inches between them filled with water
(Fig. 142). The outer box is fifteen inches in height and width, and eighteen

Fig. 142. — Reichert's water calorimeter.

inches in length. An opening (A) nine inches in diameter is made in one end
for the entrance and exit of the animal. It is also perforated with three small
holes in the top corners, and a slit-like opening in the top on one side. Two of
the holes are for the tubes for the entrance and exit of air {EN^ EX), the entrance
tube being carried close to the bottom, while the exit tube extends only to
the top of the box, and is placed in the opposite diagonal corner, thus ensuring
adequate ventilation. In the third hole a thermometer {C T) is inserted,
by means of which the temperature of the calorimeter (jacket of metal and
water) is obtained. The opening in the side is for the insertion of a stirrer (.S),
which is for the purpose of thoroughly mixing the water and thus equalizing
the temperature of both water and metal — in other words, of the calorimeter.
Before using the apparatus the calori metric equivalent mu:^t he deierm'inedj
that is, the amount of heat required to raise the temperature of the in.strument 1°.
This may be obtained indirectly by knowing the different substances used in
the construction of the in.strument, their weights, and their specific heats, and
estimating from these data. It is better, however, to make the determination
by burning a definite amount of absolute alcohol or hydrogen within the instru-
ment, or bv using a sealed vessel of hot water of a known temperature and
allowing it to cool to a definite extent. The process is simple; for instance,
each gram of alcohol or each liter of hydrogen completely oxidized yields a
definite number of calories ; similarly, a definite weight of water cooled a

ANIMAL HEAT. 587

definite number of degrees gives off a definite quantity of heat. The heat thus
generated by the oxidation of the alcoliol or hyth-ogen or given off by the cool-
ing of the water is imparted to the calorimeter and increases its temperature.
Knowing the quantity of heat given to the calorimeter and the increase of
temperature of the instrument, the determination of the ciilori metrical equiva-
lent may be easily made. Thus, 1 gram of alcohol yields in round numbers
9000 calories ; if we burn 10 grams of absolute alcohol, 90,000 calorics will
result ; if the temperature of the calorimeter be increased 1°, the calorimetric
equivalent will be 90,000 calories or 90 kilogramdegrees ; in other words, for
each degree of increase of the temperature of the calorimeter a quantity of
heat equivalent to 90 kilogramdegrees is absorbed.

The heat dissipated by an animal is only in part absorbed by the calori-
meter, another portion being given to the air which passes from the instrument,
and another portion to water which is evaporated from the lungs and skin.
Three estimates, therefore, are necessary — (1) of the heat given to the calori-
meter, (2) of the heat given to the air, and (3) of the heat given off in the
evaporation of water.

The estimate of the heat given to the air necessitates the measurement of
the quaiitity of air supplied to the calorimeter, and of the temperature of the
air on entering and leaving the calorimeter; while the estimate of the heat lost
in evaporating water involves the measurement of samples of the air entering
and leaving the instrument and of the quantities of water in both cases, the
total quantity of water evaporated from the animal being estimated from these
data.

The conduct of such experiments is not attended with any material dif-
ficulties. The water of the calorimeter is stirred for a sufficient length of
time in order to obtain a uniform temperature. The temperature of the
animal is taken and the animal then placed within the animal chamber. The
temperatures of the calorimeter and of the air entering and leaving the instru-
ment, and readings of the three gas-meters are recorded. During the progress
of the experiment air temperatures are recorded at regular intervals of ten or
fifteen minutes and the water stirred for a few seconds each time. At the
conclusion of the experiment there are recorded — the temperature of the calori-
meter, the temperatures of the air entering and leaving the calorimeter, the
quantities of air passing through the three gas-meters, and the temperature of
the animal.

The quantity of heat given to the calorimeter is now determined by multi-
plying the increase of temperature of the instrument by the calorimetric
equivalent. If the rise of temperature be 0.6° C. and the calorimetric equiva-
lent be 90 kilogramdegrees, the quantity of heat imparted to the water jacket
will be 90 X 0.6° = 54 kilogramdegrees.

The quantity of heat imparted to the air is determined by finding first the
corrected volume of the air, then reducing the corrected volume to weight,
then multiplying the weight by the specific heat of air at 0° C, and finally
multiplying by the increase of temperature. The corrected volume may be

588 A A AMERICAN TEXT-BOOK OF PHYSIOLOGY.

V P

uhtuiiicd l)v tlu! lollowing formula: V= , where V is

760 (1 + 0.003665 t)
the reqiiirt'd volume at 0° C and 760 mm. barometric pressure, V the ob-
served volume, P the observed pressure, aud t the observed mean temperature :
760 (1 + 0.003665) is conveniently obtained from standard tables. The errors
incident to changes in barometric pressure and in aqueous tension are so slight
tiiat they are not usually taken into consideration. Assuming that the quan-
tity of air suj)plied amounted to 6000 liters, and that the mean temperature
of the air was 20°, the corrected volume would be, omitting l)arometric

V 6000

pressure and aqueous tension, V = = — 5590 liters

(1 + 0.0036656 t) 1,0733
at 0° C. One litre of dry air at 0° C. weighs 0.001293 kilogram ; therefore,
5590 liters x 0.001293 = 7.228 kilograms. If we assume that the air during
its passage through the calorimeter had its temperature increased 3°, and the
specific heat of air is 0.2377, the quantity of heat imparted to the air must
have been 7.228 X 3 X 0.2377 = 5.152 kilogramdegrees.

The next estimate is of the quantity of lieat lost in the evaporation of
ivater. This is determined by finding the difference between the quantities
of water in the samples of the air passing into aud from the calorimeter, and
estimating from these results the amount of moisture imparted to the total air
leaving the chamber. Assuming that 10 grams of water were thus evaporated,
since each gram requires about 582 calories or 0.582 kilogramdegree, the quan-
tity of heat evolved would be equal to 10 X 0.582 = 5.82 kilogramdegrees.

The total quantity of heat dissipated would therefore be the sum of the
quantities given to the calorimeter, to the air, aud to the \vater evaporated :

Given to tlie calorimeter 54,00U kilogramdegrees.

Given to the air 5,152 "

Lost in evaporating water 5,820 ''

Total heat-dissipation 64,y72 "

The quanttf)/ of heat produced is determined by adding to or subtracting
from the quantity dissipated the amount of heat that may have been gained
or lost by the organism. It is obvious that any difierence between the
quantities of heat dissipated and produced must be represented by an increase
or decrease of the mean temperature of the animal. If the animal's teiupera-
ture reiuains unchanged, the quantity of heat produced is the same as the
quantity lost ; if, however, the animal's temperature increases, less heat is
dissipated than is ])roduced ; if it falls, ince versa. The quantity of licat
involved in a change of body-temperature is determined by the product of
the change in temperature into the animal's weight and specific heat. Assum-
ing that the animal's temperature at the beginning of the experiment was
38.95° C. and at the end 39.32° C, the temperature being increased 0.37° C,
that the animal's weight was 25 kilograms, and that the animal's specific heat
was 0.8, the quantity of heat would be 0.37 X 25 x 0.8 ^- 7.4 kilogramdegrees.

ANIMAL HEAT.

589

The quantity of heat produced would, tlierefore, be the total quantity dissipated
phis tlu> (luantity of heat added to the heat of the organism at the time the
oxperimciit begun ; therefore, the heat-produetion was 04.972 + 7.4 = 72.372
kilograiudegrees. If the animal's temperature had fallen, more heat would
have been dissipated than produeed, beeause the total quantity of heat in the
organism was greater at the beginning than at the end of the experiment;
therefore, the cpiantity of heat represented in the change of temi)erature would
have been deducted from the (piantity of heat dissipated.

While calorimetric experiments do nut generally involve any special diffi-
culties, accurate results can only be ensured by the strict observation of certain
details : (1) The temperatures of the calorimeter and room should be as nearly
as possible alike and kept as far as possible constant. (2) The thermometers
employed should be so sensitive that readings can be made in hundredths of a
degree, and they should respond very quickly, so that rectal temperatures can
be'obtained within three minutes. (3) Rectal temperatures are to be preferred,
the thermometer always being inserted to the same extent and held in the
same position, care being exercised to prevent the burying of the bulb in fecal
matter. (4) The animal during the taking of its temperature nmst on no
account be tied down, but gently held, and all circumstances seduously avoided
that tend to excite the animal. The chief sources of error in the calorime-
try are in failures to obtain accurate temperatures of the calorimeter and of
the animal. In the latter case inaccuracy is to some extent absolutely una-
voidable, chiefly because of normal fluctuations which occur frequently and are
often very marked.

Conditions affecting Heat-produetion.— The quantity of heat produced
must necessarily vary with many circumstances. Estimates of heat-production
in the adult range in round numbers from 2000 to 3000 kilogramdegrees per
diem according to the method and incidental circumstances, llius, according
to—

Scharling 3169 kilogramdegrees

Vogel 2400

Him 3725

Ley den 2160

Hemholtz 2732 "

Rosenthal 2446

Danilesky 3210 "

Ludwig 3192

Ranke 2272 kilogramdegrees

Rubner 2843

Ott 103

per hour during tlie afternoon (weight of
man 87.3 kilograms).

Lichatschew . . • ■ 33.072 to 38.723 kilo-
gramdegrees per kilogram of body-weighl
per diem.'

The chief conditions which affect heat-production are age, sex, constitution,
body-weight and body surface, species, respiratory activity, the condition of
the circulation, internal and external temperature, food, digestion, time of day,
muscular activity, the activity of heat-dissipation, nervous influences, drugs,
abnormal and pathological conditions.

1 The fi-ures bv Ott {New York Medical Journal, 1889, vol. 16, p. 29) and Lichatschew
{Diss. inm,luralis/st. Petersburg, 1893; quoted in Hermann's Jahresberichte der Physiologic,
1893, p. 99) were obtained by means of a water calorimeter.

590 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Yoiinj; animals produce more heat, weight for weiglit, than the mature. Tliis
is owing chiefly to the greater activity of the metabolic processes in the former,
autl iu part to the relatively larger body surface, young animals generally
being smaller than the matured and thus having, in proportion to body-weight,
larger radiating surfaces.

Heat-productiou is more active in the robust than in the weak, other con-
ditions being the same.

The weight of the body is obviously a most important factor in relation to
the quantity of heat produced, especially as regards the weight of the active
tissues iu relation to inactive structures such as bone, sinew, and cartilage.
Two animals of the same weight may produce very different quantities of
heat per diem, other things being equal. Thus, a fleshy animal should
naturally be expected to produce more heat than one Avith very little flesh and
an abundance of fat, which is an inactive heat-producing structure. While,
therefore, the relation of heat-production to body-weight does not seem to be
definite, yet the experiments by Reichert^ and by Carter^ indicate that heat-
production bears, broadly speaking, a direct relation to body-weight.

Heat-production is greater relatively in homotherraous than in poikilother-
mous animals ; it varies materially in intensity in different species, especially in
warm-blooded animals ; and it is closely related to the intensity of respiration.
Moreover, it is probable that each species, and even each individual of the
species, has its own specific thermogenic coefficient, that is, a mean standard of
heat-production for each kilogram of body-weight or for each square centime-
ter of body-surface. The following figures giving the heat-production per
kilogram per hour, compiled by Munk,^ are of interest both as regards species
and size and weight of the animal in relation to heat-production :

Horse 1.3 kilogramdegrees.

Man 1.5

Child (7 kilograms) . . 3.2 "

Dog (30 " ) . . 1.7

Dog (3 " ) . . 3.8

Guinea-pig 7.-5 "

Duck 6.0 kilogramdegrees.

Pigeon 10.1

Rat 11.3

Mouse 19.0

Sparrow 35.5 "

Greenfinch 35.7 "

These figures have an additional interest when compared with the respira-
tory activity of different species (p. 537). The intensity of respiration has a
marked significance both in connection with the species and the individual.
The larger the quantity of oxygen consumed the greater relatively is the
activity of oxidation processes, and, consequently, the more active is heat-pro-
duction (see p. 537). Therefore, all circumstances w'hich affect respiratory
activity tend to affect thermogenesis. The intensity of respiratory activity and
the extent of body-surface in relation to body- weight are closely related (p.
538).

Increased activity of the circulation is favorable to increa.sed heat-produc-

' University Meflical Magazine, 1890, vol. 2, p. 225.

' Journal of Nervom and Menial Diseases, 1890, vol. 17, p. 782.

' Physiologie des Menschen und der Saugethiere, 1892, p. 302.

ANIMAL HEAT. 591

tion, this being duo to several factors: (1) A more abmulant supply of blood
may be accompanied by increased metabolic activity. (2) Increased circulatory
activity is favorable to incn'ascd heat-dissipation by causing a larger supply
of blood to the skin, thus facilitating loss by radiation and indirectly tending to
increase thermogenesis. (3) Increased circulatory activity also excites the respi-
ratory movements and the secretion of sweat, thus increasing heat-loss and in-
directly favoring heat-production. (4) The more active the circulation the
larger the amount of heat produced by the heart and the movement of the
blood. The diurnal fluctuations of the pulse-rate are said to be more or less
closely related to similar changes of body temperature.

A rise of internal temperature (bodily temperature) is favorable to increased
metabolic activity (p. 540) and, therefore, to an increase of heat-production ;
conversely, a fall of bodily temperature reduces heat-production. The influ-
ences of bodily temperature are, as a whole, less important than those of ex-
ternal temperature.

The influences of external temperature are in a measure different upon homo-
thermous and poikilothermous animals. In the former, heat-production is in
inverse relation to the temperature of the surrounding medium, so that the
cooler the ambient temperature the greater the heat-production ; in the latter
heat-production increases with an increase of external temperature, because
with the rise of the latter bodily temperature increases, which in turn increases
metabolic activity (pp. 540, 541). Consequently, in warm-blooded animals heat-
production is greater in cold climates and seasons than in the opposite conditions,
while in cold-blooded animals the opposite is the case. Cold applied to the skin
increases heat-production by reflexly exciting muscular activity (shivering, etc.,
p. 541) ; moderate heat exerts the opposite influence unless the bodily tem-
perature is affected, as shown by the results of studies of respiration (p. 541).
The character of the food is important. Danilewsky^ has estimated that the
following quantities of heat are produced under different diets, etc. :

On a minimum diet 1800 kilogramdegrees.

On a leduced diet (absolute rest) 1989

On a non-nitrogenous diet 2480

On a mixed diet (moderate work) 3210

On an abundant diet (hard work) 3646 "

On an abundant diet (very laborious work) 3780

The influence of the quantity and quality of the diet must be potent when
it is remembered that 1 gram of proteid yields about 4937 calories, 1 gram of
fat about 9312 calories, and 1 gram of carbohydrate about 4116 calories. In
cold climates fats enter very largely into the diet because of the greater loss
of heat and the consequent increased demand for heat-producing substances.

During the periods of digestion more heat is produced than during the in-
tervals, this increase being due chiefly to the muscular activity of the intestinal
walls (p. 540). Langlois' experiments indicate that during digestion heat-
production may be increased 35 to 40 per cent.

I Pfiiigei-'s Archivfiir Physioloffie, 1883, vol. xxx. p. 19a

592 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

It is said that heat-prodiietion undergoes diurnal variations wiiich eorre-
spond with the fluctuations of bodily t^fmijerature, but this is doubtful.

All structures produce more heat during activity than during rest. Heat-
production has been e-tiniated to be from two and a half to three times greater
when awake and resting than when asleep, and from one and a half to three
times more when active than when at rest, in jiroportion to the degree of
activity. During hybernation the absorption of O falls considerably (p. 542),
consequently heat-protluctiou is believed to decline to a like degree.

All circumstances which affect heat-dissipation (p. 601) tend indirectly to
influence heat-production.

The most important of the factors influencing heat-production is the ner-
vous mechanism which controls the heat-producing processes (p. 598).

Various drugs exert more or less potent influences directly or indirectly upon
heat-production. Cocain, strychnin, brucin, and other motor excitants increase
heat-production ; while chloroform, most antipyretics, narcotics generally, bro-
mides, and motor depressants decrease heat-production.

Heat-production is diminished in most forms of anaemia, after severe hem-
orrhage, and in most non-febrile adynamic conditions. It is usually increased
in fevers, especially so in infectious fevers. According to Liebermeister, the
increase in fever is probably about 6 per cent, for each increase of 1° C. of
bodily temperature, so that were the increase of temperature 3° C. the increase
of heat-production would be 18 per cent.

Conditions affecting Heat-dissipation. — The loss of heat from the body
occurs through several channels — in the urine, feces, sweat, and expired air,
and by radiation and conduction from the skin ; hence, all conditions which
affect the loss of heat in the above ways must influence heat-dissipation. The
chief of these are : Age, sex, species, the quantity of subcutaneous fat, the
nature of the surrounding medium, clothing, internal and external tempera-
ture, activity of heat-production, body-surface, the condition of the circulation,
respiration, sweat, activity, radiating coefficient, nervous influences, drugs, and
abnormal conditions.

The young di.ssipate and produce more heat in proportion to body- weight
than the adult, this being due chiefly to the relatively greater metabolic
activity and the larger proportional body-surface (p. 538), and consequent
greater radiation, in the young.

Sex per se does not seem to exert any influence, although the adult human
female, weight for weight and for an equivalent bodily surface, probably dissi-
pates less heat than the male, because of her relative abundance of subcu-
taneous fat, which hinders heat-dis«ipation. No difference so far as sex is
concerned has been noted in the lower animals.

Heat-dissipation varies greatly in different species, owing chiefly to relative
size and respiratory activity, to the nature of the medium in which the animal
lives, and to the character of the bo<ly-covering. Heat-dissipation is more
active in homothermous animals than in poikilothermous animals, because of
the greater activity in the former of heat-production. In amphibia heat-dissi-

ANI^fAL HEAT. 693

pation is greater when the animal is in the water than when exposed to the air
if both water and air be of the same temperature, because water is a better
conductor of heat and conse^piently withdraws heat from the body more
rapidly. The hij^her the temperature of the surroundings the higher the
bodily temperature of cold-blooded animals, consequently the greater are heat-
production and heat-dissipation. In warm-blooded animals the effect o!i botii
heat-production and heat-dissipation is in inverse relation to the surrounding
temperature (unless tiie bodily temperature is affected), external heat decreasing
both heat-dissipation and heat-production, and internal heat increasing both.

Subcutaneous fat is a poor conductor of heat, consequently the greater the
abundance of it the greater the hindrance offered to the dissipation of heat.
The value of fat in this respect is illustrated in water- fowl, which, as a rule,
are far more abundantly supplied with fat than other species ; and by the ex-
ceptional abundance of subcutaneous fat in species of fowl which inhabit very
cold waters. Bathing the skin with grease hinders radiation, and is adopted
by swimmers both to conserve the bodily heat and to protect the skin.

When air and water are of the same temperature, heat-dissipation is greater
when the animal is exposed to the water, because the latter is a better con-
ductor. Heat-loss is greater in dry than in moist air, other things being
equal, because in the former the evaporation of sweat from the body and the
loss of water from the lungs are favored, the vaporization of water affecting
heat-dissipation more decidedly than the moisture of the air. Heat-dissipation
is more active in cold moist air than in cold dry air. Cold air is not favorable
to the vaporization of water, whereas cold moist air has a higher si^ecific heat
than the dry air, and thus tends to carry off heat more rapidly.

The character of the covering of the body is of great importance. This
is illustrated in the changes which occur in the natural covering of animals
during warm and cold seasons, and in the characters of the fur of species
which inhabit very cold or very warm climates. During the winter the fur
is longer and thicker than during the summer. Animals living in cold or hot
climates are supplied with a relatively greater or less abundance of fur or
feathers and subcutaneous fat. Man provides for changes of the seasons by
modifying the quantity and quality of his clothing. In the adaptation of
dress to climate, the conductivity, radiating coefficient, hygroscopic capacity,
porosity, weight, and color of the clothing are important factors. The poorest
conductors, other things being equal, make the warmest clothing; fur and
wool are poor conductors and therefore are adapted especially for cold seasons
and climates, while cotton and linen are good conductors and therefore make
cool clothing. The radiating coefficient depends upon the conductivity of the
material and the character of the radiating surface. The coarser the material
the better the radiating surface, hence the better the conductor and the cooler
the clothing. The hygroscopic character of the clothing is of far more
importance than is generally believed. Articles of clothing having a large
capacity for absorbing and retaining moisture are, other things being equal,
of more value, especially for underwear, than those possessing the o])posite

38

r)04 AN AMERICAN TEXT-BOOK OF I'llYSlOLOQY.

(jiialitv. Woollen goods compared with lliosi; made of cotton not only have
a far greater absorptive capacity but retain moisture for a longer tinu.'. \\'hen
the clothing is of wool people are less apt to catch cold from exjHtsure to
draughts and sudden cold than when it is of linen or cotton, the wool pre-
venting a too rapid evaj)oration of moisture, thus guarding against chilling.
Porosity is a comparatively subsidiary factor. The greater the weight of the
clothing, other things being equal, the more is heat-dissipation hindered. Tiie
color of the outer apparel has a certain influence owing to the relative heat-
absorbing cajiacities, black clothing being warmer than white, etc., hence the
general use of white or light-colored clothing in warm climates and seasons.

A rise of internal temperature (bodily temperature) is favorable to an in-
crease of heat-diasipation, for several reasons: (1) Heat-production tends to
be increased and thus cause an effort of the system to get rid of the excess of
heat. (2) The activity of the circulation is increased, causing a larger amount
of l)lood to be brought to the cutaneous surface where it is subjected to the
influence of the cooler surroundings. (3) Respiratory movements are increased
so that heat-dissipation is favored by the larger amount of air respired and
larger amount of moisture carried off. (4) The temperature of the body is
higher in relation to that of the surroundings and thus heat-dissipation by
radiation and conduction is facilitated. The influences of external tempera-
ture are even more potent in their effects than those of internal temperature,
chiefly because of the much wider range of temperature to which the organism
is subjected. Bodily temperature under ordinary circumstances does not vary
more than 1° to 2° C. during the twenty- four hours, but external temperature
may vary as much as 40° C, or more. External heat tends by exciting cuta-
neous nerves to reflexly diminish heat-production and thus indirectly dimin-
ish heat-dissipation ; but this is to some extent antagonized by a dilatation of
the blood-vessels of the skin, an excitation of respiration, and increase in the
quantity of sweat, all of which tend to increase heat-dissipation, but which
are unable to balance the opposite effects. Cold, on the other hand, accelerates
both heat-dissipation and heat-production. The loss of heat from the body
is increased because of the greater difference in the temperatures of the body
and the surroundings ; but, on the other hand, the cutaneous vessels are con-
tracted, the circulation is less active, and the quantity of sweat is lessened, all
of which are unfavorable to heat-dissipation. Yet while these latter altera-
tions tend to diminish heat-loss, they are not sufficient to compensate for the
increased expenditure by radiation and for the greater loss by respiration.

Circumstances which increase heat-production above the normal tend indi-
rectly to increase heat-dissipation. Other things being equal, the greater the
quantity of heat produced the greater the heat-dissipation, unless the bodily
temperature be below the normal, in which case heat-production may be in-
creased and yet heat-dissipation remain unaffected, or even be diminished, until
sufficient heat has accumulated to bring the bodily temperature up to the
mean standard.

The larger the surface of the body ex])osed to the normally cooler sur-

ANIMAL HEAT.

595

roundings, the greater is the loss of heat. Tlie larger the animal the greater the
body-surface, and thorelbre the greater is heat-dissipation ; l)nt in proportion
to bodv-weight smaller animals have larger body-surfaces, therefore heat-dissi-
pation' is relatively greater, although not absolutely so (see p. 537). The area
of body-surface involved in heat-dissipation is affected by the position of the
individual. Thus, bv bringing the arms and legs in contact with the body
the total surface exposed is lessened. On the other hand, animals which
habitually have their legs in apposition with the trunk have their radiating,
surfaces increased when their legs are extended. For instance, in the rabbit
extension of the legs enormously increases heat-dissipation, so that the bodily
temperature is profoundly affected.

The condition of the vascular system exercises an important influence.
Circumstances that excite the circulation affect heat-dissipation both directly
and indirectly. Thus, heat-loss is directly increased by the excitation of the
respiratory movements, by the increased secretion of sweat, and by the larger
supply and increased temperature of the blood to the skin. Increased activity
of the circulation also increases heat-production, and thus indirectly affects heat-
dissipation. Opposite conditions, of course, lessen heat-dissipation.

The larger the quantity of air respired, other things being equal, the larger
the loss of lieat by this channel. The heat-loss occurs both in warming the
air and in the evaporation of water from the lungs, so that the cooler and
drier the air inspired the larger relatively is the heat-loss. The importance
of respiration as a heat-dissipating factor is illustrated by the fact that about
10.7 per cent, of the total heat-dissipation occurs in this way (see p. 584).

Next in importance to radiation is the amount of ^vater evaporated from
the skin. Each gram of water requires 582 calories to vaporize it, and it is
estimated (p. 584) that 364,120 calories are dissipated in this way, or 14.5
per cent, of the total heat-dissipation. An increase of external temperature
increases the irritability of the sudoriparous glands, thus favoring secretion and
heat-dissipation. The value of sweat, however, as a means of carrying off
heat, is materially affected by the temperature of the air as well as by the
amount of moisture present. ' The higher the temperature and the less the
moisture the more rapidly evaporation occurs, and consequently the greater
the loss of heat ; when air is moist and of high temperature evaporation takes
place relatively slowly, if at all. Therefore, individuals can withstand sub-
jection to dry air of a higher temperature and for a longer period than when
the atmosphere is moist. In the former case sweat is rapidly secreted and
vaporized, and thus a marked rise of internal temperature may be prevented.
James found that a vapor bath at 44.5° C. (112° F.) was insufferable, while
dry air at 80° C. (176° F.) caused little inconvenience. AVhen air is of high
temperature and loaded with moisture we say that it is "sultry," but dry air
of the same temperature is not unpleasant.

I^Iuscular activity increases heat-production, excites the circulation and
respiration, and increases the secretion of sweat, all of which directly or indi-
rectly increase heat-dissipation.

596 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

Tlie .surface of the body as a radiating surface cannot be rejL^anled in the
same light as an indifferent, inanimate surface, such as metal or wood. The
coeffidcnt of radiation (the quantity of heat emitted during a unit of time at a
standard temperature from a given area) in an inanimate body remains fixed,
because the surface itself is virtually unchangeable ; but the coefficient for the
living organism is subject to material alterations. These alterations depend
chiefly (1) upon the actions of tlie pilo-motor mechanism whereby the relation
of the natural covering (hair or feathers in the lower animals) of the body to
the skin is effected ; (2) upon changes in the conductivity of the skin owing to
variations of the blood-supply ; (3) upon the varying thickness of the skin in
different species, in different individuals, and in different parts of the body ;
(4) upon the temperature of the surroundings; (5) upon the extent of the
body-surface exposed ; (6) upon the character of the clothing. When the
arrector pili muscles contract the skin is made tense and the cutaneous blood-
vessels are pressed upon and rendered anaemic, thus lessening the quantity of
fluid in the skin and as a consequence lowering the coefficient of dissipation ;
moreover, in animals whose natural covering is fur or feathers, these fibres
cause an erection of one or the other, as the case may be, and in this way
affect the radiating coefficient. The coefficient is enormously increased by
removing the natural covering, such as the fur of the rabbit, under which cir-
cumstances, even though the animal be subjected to a relatively high external
temperature, heat-dissipation is so enormously increased that death ensues within
two or three days. When one side of the body of a horse was shaved and the
animal subjected to an atmosphere having a temperature of 0° C, the tem-
perature of the skin of the shaven side fell 8° in forty minutes, while the
temperature of the unshaven side fell only 0.5°.

The coefficient is diminished where there is excessive sebaceous secretion,
and where grease is artificially applied, and by an accumulation of subcutaneous
fat ; it is increased by wetting the skin, as by sweat or bathing ; and it is
affected by many other circumstances.

Through the operations of the nervous system heat-dissipation may be
affected directly or indirectly by action upon the heat-dissipating and heat-
producing processes — circulation, respiration, sudorific and sebaceous glands,
and arrector pili muscles.

There are many drugs which directly or indirectly affect heat-dissipation.
Drugs which cause dilatation of the cutaneous vessels tend to increase heat-
dissipation ; conversely, those which cause contraction of the blood-vessels
hinder dissipation. Diaphoretics increase heat-loss essentially by increasing
the amount of sweat. Respiratory excitants increase the loss of heat by means
of the increased volume of air respired. Drugs which increase heat-jiroduction
tend to indirectly increase heat-dissipation.

All pathological states which affect heat-production tend to similarly disturb
heat-dissipation. Conditions of malnutrition favor heat-dissipation by causing
a loss of subcutaneous fat, but this is to a greater or less extent compensated
or by the eufeebleraent of the circulation, respiration, and metabolic processes

ANIMAL HEAT. 597

in general. In fever, both heat-prodnction and heat-dissipation are generally
increased, the fbrnier being afJ'ected more than the latter, so that the bodily-
temperature rises. In some forms of fever the rise of temperature is essentially
due to diminished heat-dissipation.

D. The Heat-mechanism.

The heat-mechanism consists of two fundamental parts, one being concerned
in heat-production, and the other in heat-dissipation. Heat-production is
briefly expressed as tlwrmogenesis ; and heat-dissipation, as fhermolyfiis. The
operations of these mechanisms are so intimately related that fluctuations in the
activity of one are rapidly compensated for by reciprocal changes in the other,
so that under normal conditions heat-production and heat-dissipation so nearly
balance that thd mean bodily temperature is maintained within narrow limits.

The regulation of the relations between heat-production and heat-dissipation
is termed thermotaxis, which regulation may be effected by alterations in either
thermogenesis or thermolysis.

The Mechanisra concerned in Thermogenesis. — The portion of the heat-
raechanism concerned in heat-production consists of (1) thermogenic tissues,
(2) thermogenic nerves, and (3) thermogenic centres.

The Thermogenic Tissues. — Almost if not every tissue of the body may be
regarded as being a heat-producing structure. The very fact that oxidative
processes lie at the bottom of all forms of vital activity, and that heat-produc-
tion is a concomitant of oxidation, leads inevitably to the conclusion that as
long as cells possess life they must produce heat. There are, however, certain
of the bodily structures, especially the skeletal muscles and the glands, which
are exceptionally active as heat-producers. Indeed, in the case of the skeletal
muscles the heat-producing processes are of such a character as to justify the
belief that with them thermogenesis is a specific function, because heat is pro-
duced not merely as an incidental product of activity but as a specific product.
When a muscle contracts, heat is evolved as an incident of the performance of
work, and when it is at rest heat is produced not only as an incident of growth
and repair but as the result of a specific act. This latter is proved by the fact
that when the muscles have been in a state of prolonged rest, when the chemi-
cal changes concerned in growth and in repair of waste are inactive, heat-pro-
duction continues to a marked degree. Moreover, the quantity which is pro-
duced varies with the immediate needs of the economy and bears a reciprocal
relationship to the quantity of heat formed in other structures,' and is regulated
apparently by specific nerve-centres.

When the muscles are contracting less than one-fifth of the energy apj.^ears
as work, and more than four-fifths as heat. The contractions of the heart also
furnish an appreciable percentage of heat as an accompaniment of contraction ;
and considerable heat is formed indirectly by the resistance oifered by the
the blood-vessel walls to the blood current. Indeed, the entire work of the
heart becomes converted into heat, representing from 5 to 10 per cent, of the
^ Riibner : Siizungsberichte d. konigl. Bayer. A kad. der Wissenschaften, 1885, Heft 4.

598 AN AMERICAN TEXT-BOOK OF PHYSIO LOGY.

total heat-})ruduction. The quantity IViniied as by-prodiicts of tlie activity of
various structures during a state of muscular quiet is doubtless small compared
witli the rjuautity produced by the muscles.

The TJicnnofjcnic Nvnrn and Centres. — Heat-production may occur intlc[)cnd-
ently of, but under normal circumstances it is regulated by, the nervous system.
A muscle separated from all nervous influences continues to produce heat, but con-
siderably less than before, and it ceases to respond to the demands of the system
for more or less heat as do muscles with their nerves intact. Injuries to certain
parts of the cerebro-spiual axis affect heat-production in muscles, in some in-
stances causing an increase and in others a decrease ; but these changes do not occur
if the nervous communication between the centres and muscles is destroyed.

Thennogenic Nerves. — Specific • thermogenic nerve-fibres have not as yet
been isolated, although the researches by Kemp^ and Reichert^ indicate that
such fibres exist. In muscles probably two kinds of katabolic processes
go on, one subservient to muscular contraction and the other to heat-produc-
tion. From the fact that there may be two kinds of katabolic processes we
are led to the conclusion that two corresponding sets of nerve-fibres con-
trol them, and it seems probable that the katabolic processes which give rise to
muscular contraction and its accompanying heat-production are due to im-
pulses carried to the muscles by motor nerves, while those specifically con-
cerned in the production of heat are transmitted by nerve-filjres of an entirely
different character, possibly those fibres subserving muscular tone. Upon this
hypothesis the latter fibres might be designated as specific thermogenic fibres —
in other words, they are specifically engaged in conveying impulses from the
nerve-centres to the muscles, bringing about katabolic changes which have for
their especial object the production of heat. According to another hypothesis
both muscular contraction and muscular tone are subserved by the motor nerves,
whether or not contraction results being a question of intensity of the impulses.

Our knowledge of the character of the afferent fibres which carry impulses
that reflexly affect thermogenesis is very unsatisfactory. There can be no
doubt that sensory impulses arise in various parts of the organism, especially in
the skin, which exercise important influences upon the heat-producing pro-
cesses. Thus, cooling the skin reflexly excites heat-production, which cannot
be attributed to indirect influences upon other functions, but whether or not
there exist specific afferent thermogenic fibres is not known. It is })ossible that
the temperature nerves of the skin, the cold and the heat nerves, may be
responsible for reflex excitation or depression of heat-production.

The Thermogenic Centres. — The existence of specific thermogenic centres has
for many years been conceded, but it has only been recently that hypothesis
has given place to fact. The most important results of recent research may be
generalized as follows: (1) That the irritation of the skin by heat or cold is
followed by marked changes in thermogenesis, which effects are to a certain
extent entirely independent of vasomotor and other incidental changes, and
which, therefore, are due in part to an increase of heat-production dependent

» Therapeutic GazeUe, 1889, p. 155. ' Ibid., 1891, p. 151.

ANIMAL HEAT. 599

directly upon eiferent tlierinogenie impulses. (2) That injury or excitation of
certain parts of the brain is followed by an increase of heat-production, (3)
That injury or excitation of certain other parts of the brain is fallowed by
diminished heat-production. (4) That injury of the spinal cord may be fol-
lowed by an increase or decrease of heat-production which cannot be entirely
accounted for by vaso-motor and other attendant alterations. (5) That after
operations upon certain parts of the cerebro-spiual axis there follows an increase
or decrease in the quantity of COj formed, indicating a corresponding effect on
the heat-producing processes.

The results of recent calorimetric work show that there are definite regions
of the cerebro-spinal axis which are apparently specifically concerned in ther-
mogenesis ; that the effects of excitation or destruction of each region are more
or less characteristic ; and that the different regions seem to be so intimately
related to one another as to constitute a co-ordinate mechanism. Certain of these
regions when irritated give rise, as a direct result, to increased thermogenesis,
hence they are of the nature of thermo-accelerator centres ; and others to
diminished thermogenesis, hence are thermo-inhibitory centres. Both kinds of
centres seem to be associated with and to govern a third kind which is dis-
tinguished as the general or automatic thermogenic centres. The mechanism
may be theoretically expressed in this form : The general thermogenic centres
may be regarded as maintaining by virtue of independent activity a fairly con-
stant standard of thermogenesis, and as being influenced to increased activity by
the thermo-accelerator centres and to diminished activity by the thermo-inhib-
itory centres. The finer or smaller variations in thermogenesis are presumably
effected by the general centres, whereas the grosser variations are probably ef-
fected by the influences of the thermo-accelerator and therrao-inhibitory centres.

Specific heat-centres (thermogenic and thermolytic) have by various ob-
servers been held to exist in certain regions of the brain cortex, in the base of
the brain just in front of and beneath the corpus striatum, in the corpus stri-
atum, in the septum lucidum and the tuber ciuereum, in the optic thalamus,
in the corpora quadrigemina, in the pons and medulla oblongata, and in the
spinal cord. Some of these centres have been regarded as being thermogenic
and others as being thermolytic. Many errors in deduction have, however,
been made because of the many inherent difficulties attending experimenta-
tion upon the cerebro-spiual axis, and because almost all the methods used
necessarily involve injury or excitation of contiguous parts. The methods
adopted of studying these various regions have been chiefly destruction or
injury by means of a probe, actual cautery, excision, and the injection of
cauterants ; by transverse incisions across the cerebro-spinal axis so as to sepa-
rate higher from lower portions of the cerebro-spinal axis ; and by excitation
by small punctures, electricity, etc.

In classifying these centres we are governed by the results which follow
excitation and destruction. When irritation or destruction directly affects
thermogenesis, the centre is regarded as being thermogenic, but if heat-dissi-
pation is the process directly affected, the centre is regarded as being thermo-

600 AiX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

lytic. In classifying thermogenic centres we wonld regard the centre as being
a general thermogenic centre if it is capable, after the destruction of other
thermogenic centres, of causing the normal output of heat ; a thermo-acceler-
ator centre is distinguished by the fact that excitation increases thermogenesis,
while destruction does not diminish thermogenesis, unless the centre happens
to be active at the time, and further by the fact that after its destruction the
normal output of heat may continue ; a thermo-inhibitory centre is distinguished
by a decrease of heat-})roduction following stimulation and by the absence of
any permanent effect on thermogenesis when the centre is destroyed. The
general or reflex thermogenic centres are undoubtedly continuously active, the
degree of activity varying according to the immediate demands of the organism
for heat ; while the thermo-accelerator and thermo-inhibitory centres are prob-
ably only intermittently active, coming into play when the general centres are
of themselves unable to effect a sufficiently rapid compensation.

While it must be admitted that our knowledge of the precise locations,
physiological peculiarities, and correlations of the thermogenic centres is by no
means complete, we have at our disposal some most important and significant
data. The general thermogenic centres have been shown by Reichcrt * to be
located in the spinal cord. The thermogenic centres in the brain are either
thermo-accelerator or thermo-inhibitory. Thermo-accelerator centres ]>robably
exist in the caudate nuclei (possibly also in the tuber cinereum and optic
thalami), pons, and medulla oblongata.^

Excitation of any one of these regions is followed by a pronounced rise of
heat-production ; destruction of any one region may or may not be followed
by a decrease of heat-production, and if a decrease does occur it may in most
cases be attributed to incidental causes, such as shock and other attendant
conditions. The centre which is common to the pons and medulla is for the
most part probably located in the latter, but it is not so powerful in its influ-
ences on thermogenesis as the thermo-accelerator centres in the basal regions
of the cerebrum. These cerebral centres are affected by agents which have
little or no effect on the heat centres of the spinal cord. Thermo-inhibitory
centres have been located in the dog in the region of the sulcus cruciatus and
at the junction of the supra-Sylvian and post-Sylvian fissures.^ Irritation
of either of them is followed by a decrease of heat-production, while their
destruction may be followed by a transient increase of heat-production. The
cruciate centre is the more powerful. None of these cerebral centres exercises

^ University Medical Magazine, 1894, vol. v. p. 406.

^Reichert: University Medical 3Iafjnzine, 1894, vol. 6, p. 303. Ott : Journal of Nervous and
Mental Diseases, 1884, vol. 11, p. 141; 1887, vol. 14, p. 154; 1888, vol. 15, p. 85; Therapeutic
Gazette, 1887, p. 592; Fever, Thermotaxia, and Calorimetry, 1889. Aronsohn and Sachs: Pjliiger's
Archiv fiir Physioloc/ie, 1885, vol. 37, p. 232. Girard : Archiv de Phjsiologie nonnale ct patholo-
gique, 1886, vol. 8, p. 281. Baginsky iind Lehmann : Virchou's Archiv fiir Pathnlofjie, 1886, Bd.
106, p. 258. White: Journal of Physiolor/y, 1890, vol. 11, p. 1 ; 1891, vol. 12, p. 233. Baculo:
Centri temici, 1890, 1891, and 1892. Tangl : Pjim/er's Archiv fiir Physiologic, 1895, vol. 68, p. 559.

'Wood: "Ye\eT," Smithsonian Contributions to ivnou;W<7e, 1880, No. 357. 0*-t>; Journal of
Nen-ous and Menial Duieases, 1888.

ANIMAL HEAT. 601

any influence on thermogenesis after section of the spinal cord at its junction
with the niedulhi oblongata.

Theoretically, these centres are associated in this way : The general thermo-
genic centres are in the spinal cord, and while they are perhaps impressionable
to impulses coming to them tlirough various sensory nerves, they are not
apparently in the least influenced by cutiuieous impulses caused by changes iu
external temperature nor by changes of the temperature of the blood. It is
not improbable that these centres are in the anterior cornua of the spinal cord.
The thermo-accelcrator and thermo-inhibitory centres are connected with the
general centres by nerve-tibres, the former influencing the general centres to
increased activity, and the latter to diminished activity. The thermo-accel-
erator and thermo-inhibitory centres seem to be especially affected by cuta-
neous impulses which are generated by changes in external temperature, and
to be influenced by alterations of the temperature of the blood. It is doubtless
through these centres that changes in external and internal temperature are
able to affect the heat-producing processes. Presumably both an increase of
temperature of the blood and cutaneous impulses generated by an increase of
external temperature excite the thermo-inhibitory centres, and thus inhibitory
impulses are sent to the general centres, lessening their activity ; on the other
hand, both a fall of temperature of the blood and cutaneous impulses gener-
ated by cold presumably excite the thermo-accelerator centres and thus cause
impulses to be sent to the general centres, exciting them to greater activity.

The Mechanism concerned in Thermolysis. — The loss of heat by the body
is in a large measure incidental to attendant conditions and is not a reflex
result of the activity of a thermolytic mechanism ; in other words, the loss
occurs essentially by virtue of the same conditions as would cause inanimate
bodies to lose heat. The living homothermous organism differs as regards the
loss of heat from dead matter, chiefly in that the rapidity with which heat-
dissipation occurs is regulated to a material extent by vital processes. The
regulation of the loss of heat is effected by the operations of a complex mech-
anism—that is, one consisting of a number of distinct although correlated parts.
A study of this mechanism, which is designated the thermolytic mechanism,
includes a consideration of all of the processes by which heat is lost, of the
nervous mechanisms which govern thera, and of the conditions which affect
them, but especially of those processes and mechanisms which act reciprocally
in conjunction with the thermogenic mechanism to maintain the mean bodily
temperature. Practically all of the heat lost by the organism occurs by radia-
tion and conduction from the skin, by the evaporation of water from the skm
and lungs, and in warming the food, drink, and inspired air. From these facts we
believe that mechanisms which affect the blood-supply to the skin, the quantity
of sweat secreted, the condition of the surface of the skin, and the quantity of
air inspired must in a large measure regulate thermolysis. For instance, if the
temperature of the organism be materially increased there occur increased activ-
ity of the heart, peripheral vascular dilatation, increased respiratory activity, and
(except in fever) an increase in the secretion of sweat. The increase of the

602 .l.V AMERICAN TEXT- BOOK OF PHYSIOLOGY.

activity of the heart together with the dihitation uf the cutaneous blood-vessels
increases the quantity of blood supplied to the skin ; the cutaneous blood-vessels
are dilated, exposing a larger surface of blood to the cooler external surround-
ings, and thus materially favoring the loss of heat by radiation ; the increase in
the (juantity of sweat is favorable to an increase in the amount of ^vater evaporated,
and thus to a larger loss of heat in this way ; an increase of respiratory activity
means a larger volume of air respired, a greater expenditure of heat in warming
the air and in the evaporation of water from the lungs. In man the pilo-motor
mechanism plays a subsidiary and unimportant part in the regulation of heat-
dissipation, but in some lower animals, as in certain Ijirds, it is of considerable
importance. The thermolytic mechanism therefore includes the cardiac, vaso-
motor, respiratory, sweat, and pilo-motor mechanisms. All these are affected
directly or indirectly by the temperature of the blood and skin. An increase
in the temperature of the blood and skin excites all of them so that changes
are brought about which favor heat-loss. The respiratory movements especially
may be rendered intensely active, and in certain animals to such a marked
degree that they may become more frequent than the heart-beats.

Thennotaxis. — Thermotaxis or heat-regulation is effected by reciprocal
changes in heat-production and heat-dissipation brought about by the inter-
vention of the thermogenic and thermolytic centres, just as the regulation
of arterial pressure is effected by the reciprocal relations of the cardio-
inhibitory and vaso-motor mechanisms. If heat-production is more active
than heat-dissipation, thermolysis is so affected that the heat-loss is increased,
and thus the mean bodily temperature maintained ; if heat-production is sub-
normal, heat-dissipation also falls. Similarly, if heat-dissipation is increased,
the heat-producing })rocesses are excited to greater activity to make up the loss ;
conversely, if heat-dissipation is decreased, heat-production also tends to be
decreased. These reciprocal actions depend essentially or wholly upon the
influence of cutaneous impulses and the temperature of the blood. For
instance, an increase of the temperature of the blood increases the activity
of the thermolytic processes, thus effecting a compensation. If we subject an
animal to a moderately cold atmosphere, as in the winter, heat-dissipation is
increased, but cutaneous impulses are generated which excite the tliermogenic
centres so that heat-production is also increased, and thus the bodily temperature
is maintained practically unaffected. It is only under abnormal conditions or
under conditions of intense muscular activity that this reciprocal relation-
ship is so disturbed that changes in one process are not quickly compensated
for by changes in the other.

Thermotaxis is effected in a large measure reflexly, especially by cutaneous
impulses generated by external cold and heat, b(jth thermogenic anil thermo-
Ivtic processes being affected. Cold ap})lied temporarily, as in the form of a
douche, bath, sponging, etc., causes constriction of the cutaneous capillaries.
This lessens both the quantity and temperature of the blood passing through
the skin, the effect of which tends to decrease the dissipation of heat by radia-
tion and conduction. Moreover, a lessened blood-supply causes the skin to

ANIMAL HEAT, 603

become poorer in fluid, .so tluit tiie conduction of" iioat from the warmer inner
parts is lessened. The conductivity of the skin is further decreased by the
action of the pilo-motor muscles, which when in contraction or in a state of
greater tonicity render the skin tenser and thus j)ress out the blood and tissue
juices. The secretion of sweat is diminished, so that the quantity of heat lost
in the vaporization of water is decreased. On the other hand, heat-dissipation
tends to be materially increased by the greater radiation of heat due to the
greater diiference between the temperature of the body and of the douche, bath,
etc., and the tendency to an increase in this way is much greater than the
opposite tendency depending upon the factors above noted, therefore heat-
dissipation is increased. Bathing the skin with cold water increases heat-loss
by the vaporization of water as well as by conduction.

The excitation of the cutaneous nerves by cold reflexly increases thermo-
genesis, and to such an extent that heat-production may even exceed the
quantity dissipated, thus causing an increase of bodily temperature. This rise,
which is transient, may amount to 0.2° C. or more, and is followed by a re-
action in which the temperature may fall 0.2° C. or more below the normal, and
continue subnormal for some hours ; this fall in turn is succeeded by a supple-
mentary reaction in which the temperature may rise slightly above the normal.

The chief reactions brought about by moderate external cold are constriction
of the cutaneous blood-vessels, a diminution of the quantity of sweat secreted,
increased tonicity of the pilo-motor muscles, and increased tonicity of the
skeletal muscles. The action upon the latter muscles may be so marked as
to cause shivering, which increases respiratory activity (see p. 540) and
presumably similarly increases heat-production.

Moderate external heat causes dilatation of the -cutaneous vessels, excites
the general circulation and thus increases the blood-supply to the skin, excites
respiratory movements and the sweat-glands, but decreases thermogenesis.
Owing to the dilatation of the blood-vessels of the skin and the excitation of
the circulation the temperature and the quantity of the blood supplied to the
skin are increased, so that conditions are caused which are favorable to an
increased loss of heat by radiation. Increased activity of the respiratory
movements means a larger volume of air respired, and consequently a greater
loss of heat in warming the air and in the evaporation of the larger quantity
of water from the lungs. The increase in the quantity of sweat formed also
favors heat-dissipation by means of the larger amount of water evaporated
from the skin. When, however, the external temperature is higher than that
of the body, loss of heat by radiation and conduction cannot occur, so that
heat not only accumulates as a result of the interference with heat-dissipation,
but by absorption.

The chief reactions brought about by moderate external heat are a dilata-
tion of the cutaneous blood-vessels, excitement of the general circulation, an in-
crease in the number of respiratory movements, increase in the amount of sweat,
diminished tonicity of the muscles, and diminished thermogenesis which is prob-
ably due to a lessening of the activity of the chemical changes in the muscles.

604 AN A3fEBICAN TEXT-BOOK OF PHYSIOLOGY.

"Wlien external temperature is excessive and continued, heat-regulation is
rendered impossible : if extreme cold, heat-dissipation takes place more rapidly
than heat-production, so that bodily temperature falls until death results; if
verv hot, heat-dissipation is so interfered with that heat rapidly accumulates
within the organism, causing a continuous rise of tenj})eraturc which finally
causes death.

Abnormal T/icrmoidxis. — By this term is meant the regulation of the heat-
processes under conditions in which the mean bodily temperature is maintained
at a standard above or below the normal, as in i'ever and in animals from
which the hair has been shaved. It is assumed that under normal conditions
the heat-centres are " set/' as it were, for a given temperature of the blood,
and that when the temperature of the blood goes above or below this standard
a compensatory reaction occurs, so that thermogenesis and thermolysis are
properly affected to bring about an adjustment. In fever it may be considered
that the centres are set for a higher temperature than the normal ; the higher
the fever, the higher the adjustment. The centres may be set for subnormal
temperatures, as in the case of a rabbit shaved, whose temperature may remain
2° or 3° below the normal for a week or more. When the cause of the ab-
normal condition disappears, the centres are readjusted to the normal standard.

E. Post-mortem Rise of Temperature.

A rise of temperature after death is not uncommon ; indeed, in case of
violent death of healthy individuals, and after death following convulsions,
a rise in temperature is almost invariable. This increase is due to continued
heat-production and to diminished heat-dissipation. Heat-production after
d(»ath may be due to continued chemical activity in the muscles and other
structures which are not dead but simply in a moribund state. There is, as it
were, a residual metabolic activity which remains in the cells until their tem-
])erature has been reduced to such a standard that the molecular transforma-
tions cease — in other words, until the death of the cells occurs. Consequently,
the higher the temperature of the individual at the time of somatic death (the
cessation of the circulation and respiration), the longer heat-production con-
tinues, because the longer the time required to cool the cells to such a degree
that their chemical processes no longer go on. Heat is also produced during
the development of rigor mortis. The more quickly rigor sets in, and the
more intense it is, the greater is the abundance of heat produced.

The tendency to an increase of bodily temperature is favored by the marked
diminution of heat-dissipation which occurs immediately upon the cessation of
of the circulation and respiration. Therefore, while both heat-production and
heat-dissipation fall at once and enormously at the time of death, heat-dissipa-
tion may be decreased to a more marked degiee than heat-production, so that
heat may accumulate and the bodily temperature rise.

Temperature Sense. — (See Cutaneous Sensibility, in the section on Special
Senses.)

X. CENTRAL NERVOUS SYSTEM.

Introduction.

The Unity of the Central Nervous System. — The human nervou.s system
is formed by a muss of separate but contiguous nerve-cells. As each nerve-
cell is always in close relations with some other nerve-cell, this system differs
from those formed by the bones, muscles, or glands, since these tissues are dis-
tributed through the body in masses more or less isolated. Isolated groups of
nerve-cells do not occur. Indeed a group of nerve-cells disconnected from the
other nerve-tissues of the body, as the muscles or glands are disconnected,
would be without physiological significance. It is desirable, therefore, to
emphasize the fact that by dissection the nervous system is found to be con-
tinuous throughout its entire extent.

Subdivisions Artificial. — When, therefore, the nervous system is described
as formed of a central and a peripheral portion, and the peripheral portion is
further analyzed into its spinal and sympathetic components, the parts distin-
guished are found to have no sharply marked boundaries separating them, but
really to merge one into the other.

The convenience of these subdivisions is undoubted, but the physiological
processes which it is our purpose to study, overstep in so large a measure such
conventional limits, that the picture of events in the central nervous system
would be very incomplete, should they be traced only within such prescribed
anatomical boundaries.

By virtue of its continuity, the nervous system puts into connection all the
other systems of the body. Conforming as it does in shape to the framework
of the body, its branches extend to all parts. These branches form pathways
over which nerve-impulses travel toward the central system — the brain and
spinal cord, enclosed in the cranial cavity and vertebral canal — and in conse-
quence of the impulses that come in, there pass out from the central system
other impulses to the muscles, glands, and blood-vessels.

All incoming impulses must reach the central system. ]\Iost important in
this arrangement is the absence of any device for short-circuiting the incoming
impulses. It is a fact of the greatest significance, that until they have entered
the central system the incoming impulses do not give rise to those outgoing,
and thus all incoming impulses are first brought to the spinal cord and brain,
and the outgoing impulses are there aroused and co-ordinated by them.

By means of the central system there are established reactions in those tis-
sues not directly affected by the variation of the external conditions, and thus

605

606 A^' AMKlilCAX TEXT-BOOK OF PIIYSIOLOUY.

there follows an amount and variety of response in the organism as a whole
out of all proportion to the strength of the physical stimuli employed. Owing
also to the wide connections of the nervous system and the conduction of all
incoming impulses to its central part a measure of harmony is maintained
between the various activities of the several systems composing the hody.
Thus not only the various systems forming the body are in this manner con-
trolled, biu the body as a whole, in relation to all things outside of it and
forming its environment, is even more ]ilainly under the guidance of these
administrative cells.

Gro-wth and Organization. — In this connection, it is fitting to emphasize
a character of the central system which is both unique and highly important.
The phvsiological connections existing between the nerve-elements in youth
are very incomplete and poorly established, more so than in any other system
of the bodv; in the history of the growth of the nervous system, the increase
in weight and change in shape run })arallel with an increase in its organiza-
tion— /. e. in the connections between its constituent cells. This organization
results in better and more numerous physiological pathways which permit the
system, as a whole, not only to do more perfectly at maturity those things
which it could do in some degree at an earlier age, but also, by virtue of its
increased complexity, to do at maturity those things which previously it could
not do at all.

Growth in the case of this system implies, therefore, an increase in com-
plexity such as nowhere else occurs, and since this growth can be modified by
the experience of the individual during the growing period, the importance
of understanding it and its relation to organization is evident.

Phenomena Involving Consciousness. — It is with the nervous system
that the phenomena of consciousness are most closely linked. Strictly, physi-
ologv concerns itself at present with the reactions of the nervous system, which
can be studied without an appeal to consciousness. A moment's consideration
shows, however, that in the physiology of the brain the assistance to be
obtained by passing beyond the limit thus laid down is of more value than
any boundary, and hence, although the field of consciousness is sacred to psy-
chology, physiology should not be deprived of any of the advantages which
come from the privilege of occasional trespass.

Plan of Presentation. — In accordance with these facts, it has seemed best
to first present —

Part I. The physiology of the nerve-cell, considered as a peculiar kind of
tissue-element, endowed with special physiological characters.

Part II. The activities of the simplest groups of these elements. The
phvsiological grouping is of course mainly dependent on the anatomical
arrangement, and, as must always be the case, the activities of one group
modify those of others. Stated in general terms, the problem in this part is
that of the ixdhway of any impulse through the central system.

Part III. The reactions of the system taken as a whole. Here its capa-
bilities as a unit are contrasted with those of the other tissue-systems, and its

CENTRAL NERVOUS SYSTEM.

607

growth, organization, and rhytlims of rest and activity, are more properly
presented as functions of all its parts than as I'unctions of special subdivisions.

PART I.— PHYSIOLOGY OF THP] NERVE-CELL.

A. Anatomical Characteristics of the Nerve-cell.

Form of Nerve-cells. — Morphologically, the mature ncrvc-cell is regarded
as composed of a cell-body, containing a nucleus together witli other modified
inclusions and possessed of one or more outgrowths or branches. Some of
these branches may be very long, such for instance as those which form nerve-
fibres ; other branches are short and differ from the nerve-fibres in their structure.

The terms employed in describing the nerve-elements are as follows : To
the entire mass under the control of a given nucleus and forming both cell-
body and branches, the term nerve-cell is applied. The inclusions within the
cell-body have the usual designations. Nerve-cells differ greatly in the
number' of the branches arising from them. In some cells there appear
to be two nerve-fibres arising from the cell-body, in others only one. For
convenience the description about to be given will apply to the latter group
only. From most cells there arises one principal branch, which when con-
sidered alone is described as a nerve-fibre, but when considered as the out-
growth of the cell-body from which it originates, is called a neuron} Cells
with one neuron are called raononeuric. Cells with two neurons, dineuric.
The neuron, in many cases, has branches, both near its origin from the cell-
body and also along its course. These branches are designated as coUatei-als.
Contrasted with this principal outgrowth are the other branches of the cell,

Fig. 143.— a group of human nerve-cell bodies, drawn to scale ; X 200 diameters : A, cell-body from
the ventral horn of the spinal cord, longitudinal section ; C, the same, transverse section ; B, cell from
the third layer of cerebral cortex ; D, cell from the column of Clarke ; E, cell from the ganglion of the
spinal nerve-root, with neuron : F, "solitary" cell from the dorsal horn of the spinal cord ; G, granule
from the cortex of the cerebellum (modified from Waller, Human Physiology).

which are individually much less extensive and which divide dichotomously
at frequent intervals. From the tree-like form which they thus acquire they
have been designated dcndrons.

The accompanying illustration (Fig. 143) shows the features just described
and also gives some idea of the variations in the size of the cell-bodies as found

» Schafer, Brain, 1893.

608

^l^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

in mail. The nerve-cell body is usually ovoid in shape, although this type is
much modified in many cases. As will be seen from Figure 14o, the diam-
eters of nerve-cells range from 10-100 //,' and in some instances, in the spinal
cord, cells of even larger diameter are found.

The Structure of the Nerve-cell Body. — NissPhas shown that in nerve-
cells hardened in strong alcohol there art; two substances — one whith is not
stained by a basic aniline dye, and the sirond which is. The first forms a frame-
work continuous with the fibrillie of tiie nerve-fibre and enclosing the staiuable
substance in its meshes in small masses or granules. These granules are physio-
logically very sensitive, and the study of them under a variety of conditions has
already revealed changes in the nerve-cells where none had previously been found.
Peculiarities of Nerve-cells. — As compared with the other cells of the
body, the best developed nerve-cells are of large size, but the nucleus, pro-
portionately to the cell-body, is not large, its value decreasing, as a rule, with
the increase in the size of the entire cell. The most striking feature of the
nerve-cell, however, is the great length to which its chief branch, the neuron,
may attain, for in no other tissue does anything like so great a proportion of the
cell-substance occur as a branch. The form of cell represented in Figure 144 is

one in which the neuron shows a very short
stem between the cell-body and its terminal
twigs. In such an instance the entire exten-
sion of the neuron may be less than a milli-
meter. With this are to be contrasted those
forms in which the neuron is very long and
its mass great. What its greatest length
may be is easily determined. Within the
central system there are cells whose neurons
extend from the cerebral cortex to the lumbar
enlargement (60 centimeters), and again in the
peripheral system there are cell-bodies in the
lumbar enlargement of the spinal cord the
neurons of which extend to the skin and
muscles of the foot a distance of 100 centi-
meters. These are the extreme cases, but as
the neurons are distributed to all inter-
mediate points both in the central and pe-
ri])heral system, every interme<liate length
between these and the cells with very short
neurons previously mentioned, is to be
found.
Volume Relations. — Calculation shows that the volume of the cell-body
of a pyramidal cell in the human cerebral cortex having a basal diameter of

1 fi = 0.001 of a millimeter.

" Allgemeiner Zeitschrijt fur Psychialrie, 1896, Bd. Hi. S. 1147. (A condensed statement of pre-
vious work.)

Fig. 144.— a cell with a short neuron
giving off many branches. In such a cell
the neuron is less in volume than the cell-
body. This is the extreme form of the
"central cell" (Ram6n y Cajal). D, den-
drons ; N, neuron.

CENTRAL NERVOUS SYSTEM.

609

16 a, is, when calcuUue.l as a cone, approximately 4266 cubic /i. The neuron
from such a cell would have a diauKter of at U-ast 2 /i, the medullary sheath
being indudi'd. This gives un area for the cross se(;tion of the neuron, of 6.3
squat-e /i. Thus in the case chosen a portion of the neuron 680 /z long would
have a volume ecpial to the cell-body. We may assume this neuron to be
15 centimeters = 150,000 /^ long. Dividing the entire length of the ueuron
by the length of the piece having the volume of the cell, it appears that the
volume of the neuron is 220 times that of the cell-body.

Repeating the same process with a cell from the lumbar enlargement of the
spinal cord, taking a medium cell with a diameter of 46 /i and a volume (calcu-
lated as a sphere) of 50,000 cubic //, a neuron with a diameter of 10 //, and
a length of 100 centimeters, the relation of the volume of the neuron to that
of the cell-body is 1570 to 1.

This estimate of the volume of the neuron includes, in addition to the axis-
cylinder, the enclosing medullary sheath. The volumes of these two portions are
approximately equal, so that either the axis-cylinder or the medullary sheath
exceeds the cell-body in volume about half as many times as does the entire
neuron. It is extremely difficult to estimate the mass of the dendrons. In
some instances, as in the cells of the spinal ganglia (Fig. 147) they are absent,
while in the large cells of the cerebellum— Purkinje's cells— they form a mass
which must be many times greater than that of the cell-body proper. In most
cells, however, the dendrons have at best a mass several times as great as that

of the cell-body.

Size of Nerve-cells in Different Animals.— In discussing the size and
form of cells in man it becomes of interest to determine how far the observa-
tions apply to the lower mammals. The facts are briefly these : It can be said
that the smaller mammals usually have the smaller nerve-cells, but the decrease
in the mass of the nerve-cells is not proportional to the decrease in the mass
of the entire body. For example, Kaiser^ has shown that the cell-bodies
occupying the ventral horn in the cervical enlargement of the spinal cord of
the bat, the rabbit, and the monkey are in many cases as large or larger than
those found in man.

Size of the Neurons in Different Animals.— Though the volume of the
cell-body and the diameter of the associated neuron are approximately similar
in any two animals of different size, as for instance in a bat and in man, it is
also evident that the ueuron could nevertheless not have the length in the bat
that it does in man, and that in this last dimension at least there is a diminu-
tion corresponding to the size of the animal. Nevertheless, the volume of the
entire cells— cell-body plus neuron— still remains iwopoHionately very large in
the smaller mammals.

The bearing of this fact on the comparative physiology of the nervous sys-
tem is evident, for, under these conditions, as the volume of the entire nervous
system is diminished, the number of cell-elements constituting it must also be
1 Die Funktinnen der Ganglienzellen des Halsmarkes, Haag, 1891.

39

610

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

diminished, and thus the structure ol' tliis system in the smaller mummals
becomes numerically simj)liHcd.

Size and Function. — Histology shows us the nerve-cell prolonging itself
into branches often nuich sulxlivided, the dendrons and the neuron. Such a
cell contains a mass of living substances capable of being broken down and
built up chemically, and there is nothing against the inference that the larger
the cell the greater is the (piantity of these living substances, and hence the
larger the amount of stored . energy represented by it. The larger cells are
therefore those capable of setting free the greater amount of energy. The
energy-producing changes are in the greatest measure to be associated with the
cell-body, rather than with any of the branches. Ou the other hand, the
nerve-cells with large cell-bodies, sending out as they do branches which are
more voluminous than those nerve-cells that are small, furnish a greater
amount of material to form the ultimate twigs into which these branches
finally split. From this it follows that in general the large nerve-cells have

more points of connection with the structures
about them, as well as the capacity for the lib-
eration of a greater amount of energy.

Gro-wth of Nerve-cells. — During growth
and development the nerve-cells may present
many changes in appearance (Fig. 145).

The nerve-elements are derived from ger-
minal cells found in the epiblast of the embryo.
Amid the columnar epiblastic elements forming
the medullary tube these spherical cells appear
in man about the third to the fourth week of
fetal life.* They divide rapidly and in such
a way that one daughter-cell continues as the
germinal cell, while the other moves away
from the primitive surface of the body and
becomes without iurther division a young
nerve-cell or neuroblast. The formation of
neuroblasts in man ceases or becomes very
slow and unimportant by the end of the third
month of fetal life.

Two chai-acters of the neuroblast are
worthy of careful consideration. First, there
is good indirect evidence that, in early life at least, and before their branches
have been formed, they are migratory, moving in an amoeboid manner.
This being .so, the perfection with which they arrange themselves in the adult
sy.stem depends on the accuracy with which they respond to those condi-
tions that determine their migration as well as upon the normal character of
these directing influences (mechanical strain;^ chemotaxis or nutritive attrac-

' His: Archiv fiir Anatomie und Physiologie, Anat. Abthlg., 1889.
' His : Unsere Korperfonn, 1874.

Via. 145.— PorUon of developing medul-
lary tube (human) seen in frontal section
X 1100 diameters (His) : (;, germinal cell ;
N, neuroblasts.

CENTRAL NERVOUS SYSTEM. 611

tiou).^ But with so nuuh lil,erty of movement and with directing influences
that are so complicated, the chances for deviation from a fixed arrangement are

mucli enhanced.

Polarization of Neuroblasts.— Moreover, very early in the history of the
neuroblast the point on the cell-body from which the neuron will grow ai)pears
in many cases to be fixed, and the cell is thus physiologically polarized.^ This
polarity being established, the direction in which the neuron first grows is
determ'ined, and where the cells are misplaced this polarization can lead^to
the confusion of arrangement found in the brains of some congenital idiots.^

The volume of either the germinal cell or of the first form of the neuro-
blast was found by His * to be 697 cubic /i in a human fetus (embryo R-length
5.5 millimeters, aged 3 to 3.5 weeks). It has jjreviously been shown that the
volume of a spinal-cord nerve-cell is, taken altogether, 78,500,000 cubic fx,
and that of this the neuron occupies 78,450,000 cubic fx, and the cell-body
50,000 cubic 11. If we take half of this total volume, it gives under the con-
ditions chosen an increase in volume between the neuroblast and the mature

cell of 57,456-fold.

Maturing of the Nerve-ceU.— The maturing of the nerve-cell involves
several changes. First, the outgrowth of the neuron or neurons ; next, the
formation of the dendrons ; and finally, in some cases, the medullation of the
neuron, while simultaneously and with greater or less rapidity the absolute
amount of substance in both cell-body and neuron is being increased, together
with a chemical differentiation of the contents of the cytoplasm and the
nucleus. The time in the life-history of the individual at which these several
events occur is variable, and may be delayed beyond puberty at least, while
the rate at which they occur is different in different cases. Furthermore, many
nerve-cells never develop beyond the first stages of immaturity (Fig. 146).^

Form of the Neuron as a Means of Classification.— Of the various
devices used to classify nerve-cells, the form of the neuron is the most useful.

Physiologically, the nerve-cell is significant as a pathway for the nerve-
impulse. tIic current conception of the change called the nerve-impulse is
that it begins at one point of the cell and travels from there to the other parts ;
one of the other parts is the neuron, and along this the impulse can be shown
to pass. Although it cannot be directly demonstrated, there is reason to think
that primitively all the branches of a cell had similar physiological powers.
Indeed, the nerve-cell body stimulated at any point may be responsive just as
an amoeba is responsive at any portion of its surface. When, however, the
branches are formed they become the channels through which the impulses
pass, and hence assume a special significance without indicating any funda-
mental change in the structure of the cell. Where the cell has well-developed

1 Davenport : Bulletin of the 3/u.seHm of Comparative Zoology, Harvard College, Nov., 1895;
Herbst : Biologviche Centralblatt, 1894, Bd. xiv.

* Mali : Journal of Morphology, 1893, vol. viii.

» Koster: Neurologische Centralblatt, 1889, Bd. viii.

* Archivfiir Anatomie tind Physiologie, 1889.

(312

.l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

brandies we expect an arraii<^ena'nt of thcin such tliat the impulse .shall enter
the cell-body by one branch and leave it by another.

On examining tlie mature nerve-cells of man with this idea in mind, two
types arc found. The first type may be exemplified by tlu! pvraniidal cortical

Fig. 146 — ^-Z), showing the pliylogcnetic development of mature nerve-cells in a series of ver-
tebrates; a-e, the ontogenetic development of growing cells in a typical mammal; in both cases only
pyramidal cells from the cerebrum are .shown; .1, frog; i;, lizard; f'.rat; D.man; a, neuroblast without
dendrons; 6, commencing dendrons ; c, dendrons further developed; d, first ajjpearance of collateral
branches ; e, further development of collaterals and dendrons (from S. Ram6n y Cajal).

cells shown in Figure 146. Plere, from a pyramidal body {D) there arise a
number of dendrou.s, while from the lower portion of the cell the neuron grows
out and branches. In the other type the neuron alone grows out. Its branches

Fig. 147.— Spinal ganglion of an embryo duck ; composed of dineuric nerve-cells (van Gehuchten).

are but two in number and both are medullated. They pass in opposite direc-
tions and in this type there are no dendrons. To understand the arrangement
in these cases, recourse must be had to the facts of development. The second

CENTRAL NERVOUS SYSTEM. 613

type begins its development as :i bipolar cell, a neuron growing from each pole
(Fig. 147). In the adult spinal ganglion of tlie higher mannnuls, however,
no such bii)olar cells are to be found, but only cells having a single neuron
which soon divides into two branches.

Figure 14<S beautifully illustrates the phases of this change as seen in a
sin<:;le section. At first one nciuron arises from each pole of the ovoid cell-
bodv. Later the cell-body occupies a position at the side of the two neurons,
which appear to run into one another. Finally the cell-body is separated from
the two neurons by an intervening stem. The stem has the characters of a
nerve-fibre and from the end of it the original two neurons pass off as branches.

From this mode of development it is jilain that the single stem must be
looked upon as containing a double pathway, although it appears to be in all
ways a single fibre, for on the one hand it contains the path for the incoming
and on the other for the outgoing im-
pulses. Recent investigations have
shown in a striking way that cells
modified in this manner are by no
means limited to the spinal ganglia,
but occur in the cortex of the cerebel-
lum and elsewhere. The study of this

^•t!. j^:^,, U«;r.^c -nri'fVi I'f flio fnllnw Fig. 148.— Dineuric changing into mononeuric

modification brings with it the toUow- ^^^^^ ^^^^ ^^^^ ^^^^^^.^^ ^^^^^.^^ ^^ ^ ^^^.^^^p.

ing suggestion : If the single stem in ing guinea-pig (van Oehuchten).

the modified spinal ganglion-cells must

by virtue of its development contain a double pathway, it is fair to inquire
whether the same may not be true of the other forms of the nerve-cell in which
the neuron also appears to be single. Among the cortical cells the arrange-
ment of the branches is such that, for aught that is known, the stem of the
neuron may functionate in the manner suggested, and contain more than one

pathway.

Classifying the nerve-cells, therefore, in the light of these facts, we find—
(1) The pyramidal type, in which the dendrons and neuron are both well
developed, and in which the greater part of the impulses most probably enter
the cell by way of the dendrons and leave by way of the neuron ; (2) The
spinal ganglion type, in which originally the impulse passes in at one pole of
the cell and out at the other, but in the course of development the hvo neurons
become attached to the cell-body by a single stem, and by inference there must
be in this stem a double pathway. In this special case there are no dendrons.

Growth of Branches.— After the cells have taken on their type form, the
branches still continue to grow, not only in length, but in diameter. In man,
for example, the diameter of the nerve-fibres (neurons) taken from the periph-
eral nerves at birth is 1 .2-2 fx for the smallest, up to 7-8 // for the largest, with
an average of 3-4 ji, while at maturity it is 10-15 // for the larger fibres.^

In the second spinal nerve of the frog, Birge found the fibres ^ to increase

1 Westphal : Neurologische Centralblatt, 1894, No. 2.
'■^ Birge : Archiv fiir Anatomie und Physiologie, 1882.

614 AiX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

in average diameter from 7.6 [jl to 12.6 fi, as the total weight ol' tiie frog
increased from 1.5 to 63.0 grams.

The branch which forms the neuron contains an axis-cylinder surrounded by
a meilullarv sheath. There are two views coiioerniug the constitution of the
axis-cyliuder — one' that tiie axis is composed of slender thread-like fil^rillae
floating in a coagulable plasma, these fibrillae being the conductors of the nerve-
impulses. The opposing view is that advocated by Leydig,^ Nansen,^ and
Schiifer/ to the effect that the axis-cylinder is formed by a spongy framework
in the meshes of which is a semi-fluid plasma. According to this latter view
the plasma is the substance through which the impulses ]>ass, Xeitiier view is
bevond criticism, nor does either of them admit of detailed correlation with the
physiological facts. The conception of the axis-cylinder as composed of fibrillae
appears at first sight to offer an anatomical arrangement for a number of isolated
pathways within a single fibre, but the fibrillae cannot be unbrauched from one
end of their course to the other, since many nerve-fibres near their final distribu-
tion divide a number of times, the diameter of the individual fibrillae remaining
the same; and the combined cross sections of the axis-cylinders in the subdivis-
ions demand, therefore, a far greater number of fibrillar than is contained in the
main stem of the fibre. On the other hand, the conception of the axis-cylinder
as a series of tubes interosculating at very acute angles does away at the start
with any notion of structural isolation of the pathways within the fibres.
This latter view is, however, the better supported histologically.

"When the axis-cylinder increases in diameter, it must, under this view, be
by the formation of more of these tubes, for their size, though variable, is not
directly in proportion to the diameter of the fibre. While the neuron is growing
as a naked axis-cylinder it is usually slightly enlarged at the tip (Cajal), sug-
gesting that it is specially modified at that point. The nutritive exchange on
which the increase of the entire neuron depends appears to take place along
its whole extent, and not to be entirely dependent on material passed from the
cell-body into the neuron.

Medullation. — After the production of its several branches the next step
in the growth of the cell is the formation of the medullary sheath. Not all
neurons have a medullary sheath, nor is any neuron completely niedullated.
In the sympathetic system there is a very large proportion of unmeduUated fibres.
In the central system the number is very large although their mass is small.
Of the significance of the medullary sheath we know nothing. The suggestion
that it acts to insulate the nerve-impulse within a given axis-cylinder has little
or no evidence in its favor. The suggestion that it is nutritive is plausible, but
important differences in the physiological reactions of the two classes of nerve-
fibres have not yet been found.

In studving the effect of stimulation and of changes in temperature on the

^ Kuppfer und Boveri : Abhnndlungen d. k. bayer. Akad. den Wissenschaften, Miinchen, 1885.
2 Zelle und Gewebe, Bonn, 1885.

* The Structure and Combination of the Histological Elements of the Central Nervous System,
Bergen, 1887. * Quain's Anatomy, 10th edition, vol. i. pt. 2, 1891.

CENTRAL NERVOUS SYSTEM. 615

irritability and conductivity oi' nerve-fibres* it was found that certain nerve-
fibres, notably tiie vaso-constrictor fibres and the sweat-fibres in the sciatic nerve
of the cat, when they were subjected to a faradic current continued for several
minutes, lost their irritability, completely or in part, at the point of stimula-
tion. This "stimulation fati<;:ue" is not known to be produced in nerves
which ai-e unquestionably medullated. It does occur where the nerves are
iinmcdullated, but it also occurs where the absence of medullation lias not been
proved, and hence cannot be put forward as a differential character distinguish-
ing these two sorts of nerves. The medullated neurons are in their early history
unmedullated, and only later acquire this sheath, so that medullation might be
taken to represent a final step in the highest development of the nerve-cell. The
fact that certain groups of fibres are not functional till after they are medullated
hardly bears on the question, for the following reason : Until a group of fibres
has established a physiological connection with the tissues which it is to control,
it cannot be expected to influence them, and it has yet to be shown that the
appearance of functional activity and the beginnings of medullation are not
both of them the result of such growth-changes at the distal end of the axis-
cylinder. The changes involved in establishing physiological connections are
those by which the tips of the branches formed by the neuron of one cell come
into such relation with other branches of a second cell or some non-nervous
tissue that the nerve-impulse can pass between them. At the same time the
non-medullated neurons establish connections with the tissues controlled by
them just as well as do those which are to be medullated, but why one goes
on to the acquisition of the sheath and the other remains without it, is not
explained. Neither is it known how far one of these forms may re})lace the
other, although, it is not improbable that the proportions of medullated and
unmedullated fibres in different persons may be very unlike.

Gro-\^h of Medullary Sheath. — Whatever may be the significance of the
medullary sheath it is usually formed before the nerve-element as a whole has
attained its full size. In the peripheral system it depends on the presence of
cells which envelop the axis-cylinder, forming a tube about it. Each ensheath-
ing cell is physiologically controlled by a nucleus which becomes situated about
midwav between its extremities. The cell-substance is largelv transformed into
myelin, and the line of junction between two of these sheathing cells forms a
node of the nerve-fibre. In the sheath of a growing nerve-cell at least two
changes are clearly marked : As the axis increases in diameter the medul-
lary sheath becomes thicker. The change is such that in the peripheral
system the areas of the axis-cylinder and of the medullary sheath as shown
in cross sections remain nearly equal (Fig. 149). On the other hand the length
of the internodal segments tends to increase with an increase in the diameter
of the nerve-fibre, and for nerves of the same diameter it is less in man than
in the lower mammals. In a given fibre the segments are. shorter at the extreme
peripheral end (Key and Retziu.s). In the young fibres, also, they are shorter
and increase in length with age.

' Howell, Budgett, and Leonard: Journal of Physiology, 1894, toI. xvi.

616 AN A mi: RICA N TEXT-BOOK OF PHYSIOLOOY.

A jiliysiological significance attaches to these scgmeuts, because, as Ranvier
long since pointed out, it is at the nodes that various staining reagents most

I'asily reach the axis-cylinder. This sug-
gests that normal nutritive exchanges may
follow the same path and thus short inter-
nodal segments giving rise to many nodes
would represent tlie condition most favor-
able to exchange between the axis and the

1 1... ;i;'.— l,..u,L;ii,i.uii,u ^y;. ami tr!insvi.Tse(,-l) p i- . i •

sections of nerve-fibrcs. The lu-avy border SUrrOUndmg plasma. illUS lar, histologl-

represents the medullary sheath, which be- ^^^ observation showS the more numcrOUS
comes thicker in the larger fibres. Human

sciatic nerve. X 200 diameters (modified from nodcS where the pliysiological proCCSSeS

van Gehuchtcn). ^^.^ presumptivelv most active, and hence

supports the hypothesis suggested. Cases of the interjiolation of new sheath-
ing cells to form additional segments between those originally laid down have
also been described.^

Medullation in Central System. — Concerning the relation of the medul-
lary sheath to the axi.s-cylinder in the central system, our information is less
complete. The elements which give rise to the medullary substance are not
known and the myelin is not enclosed in a primitive sheath. There are no
internodal nuclei regularly placed, yet Porter^ has demonstrated in both the
frog and the rabbit the existence of nodes in fibres taken from the spinal cord.
The conditions which there exist must be further studied before any general
statements concerning the medullary suKstance in the nerve-centres can be ven-
tured, yet it is an important observation, that whereas medullation in the
peripheral system is mainly completed during the first five years of life, the
process continues in the central system, and especially in the cerebral cortex,
to beyond the thirtieth year.

AVhatever views may be held concerning the capacities of a medullated fibre,
it is to be remembered that the medullary sheath does not cover the first part
of the neuron on its emergence from the cell-body, nor are ultimate branches
of the neuron medullated in the region of their final distribution.

The acquisition of this sheath occurs in response to a i)hysiological change
that appears at the same time along the entire length of the fibre. The pro-
cess, therefore, is not a progressive one, but practically simultaneous.

What has just been said applies to the main stem of the neuron. As shown
in Figure 146, the neuron often has branches near its origin, and according to
the ob.^ervations of Flechsig^ these may become medullated. Concerning the
time of the medidlation of these branches there are no direct observations, but
if it is controlled by the same conditions which appear to control the process in
the main stem, then, as the branches form their physiological connections later
than the main stem, it would follow that their medullation should also occur
later, and the studies on the progressive medullation of the cerebral cortex
favor such a view.

1 Yignal : Archives de Physiologic, 1883. * Quarterly Journal Microscopical Science, 1890.
' Archivfiir Anatomie und Physiologie, 1889.

CJ:.\ til 1 L XI'JR VO T \S S YSTEM.

617

Changes in the Cytoplasm, — While the nerve-cell is passing from the
immature to the inatiirc form, inorcasino; in mass and in the number of its
branches, as well as aecjuiring its medullary sheath, it is also undergoing vari-
ous ehemical changes. The chromatic substance in the cytoplasm becomes
more abundant at maturity and the pigment-granules increase in <|uantity.'

Old Age of Nerve-cells. — But the nerve-cell, though possessing, in most
cases, a life-history co-extensive with that of the entire body, eventually exhibits
regressive changes. These changes of old age consist, in some measure, in a
reversal of those jirocesses most evident during active growth. The cell-body,
together with the nucleus and its subdivisions, becomes smaller, the chromatic
substance diniinishes, the jiigment increases, the cytoplasm exhibits vacuoles, the

C D

Fig. 150.— Toshow the changes in nerve-cells due to age: A, spinal ganglion-cells of a still-born male
child ; B, spinal ganglion-cells of a man dying at ninety-two years ; n, nuclei. In the old man the cells
are not large, the cytoplasm is pigmented, the nucleus is small, and the nucleolus much shrunken or
absent. Both sections taken from the first cervical ganglion, X 250 diameters ; C, nerve-cells from the
antennary ganglion of a honey-bee, just emerged in the perfect form ; D, cells from the same locality of an
aged honey-bee. In Cthe large nucleus (black) is surrounded by a thin layer of cytoplasm; in D the
nucleus is stellate, and the cell-substance contains large vacuoles with shreds of cytoplasm (Hodge).

dendrons atrophy, and the neurons also probably diminish in mass. In some
instances the entire cell is absorbed. Some of these facts are illustrated by the
observations of Hodge ^ on the spinal ganglion-cells of an old man of ninety-
two years as compared with those of a new-born child (see Fig. 150). The

^ Vas : Archiv filr mikroskopische Anatomic, 1892.
' Journal of Physiology, 1894, vol. xvii.

618 AiX AMEBICAN TEXT-BOOK OF PHYSIOLOGY.

changes in the outline of the nucleus are also to be noted, as well as the
decrease in their volume. The figures for the decrease in the volume of the
nucleus are given in the following table, showing the ])rin('ij)al differences
observed on comparing the s[)inal ganglion-cells (first cervical ganglion) from
a child at birth with those from a man dying from old age at ninety-two years
(Hodge) :

Child at birth ; male. Old man.

Volnine of nucleus 100 per cent. 64.2 per cent.

Nucleoli visible o.'i " " 5 " "

Deep pigmentation 0 " " 67 " «

Slight i)igmentation 0 " " 33 " "

Analogous changes were found by this investigator in the antennary gan-
glia of old honey-bees as compared with the corresponding ganglia taken from
those which had ju.st emerged in the perfect form. These are also shown in
Figure 150.

Since Nvith the chemical and morphological variations which occur during the
entire growth-cycle there must go variations in the physiological powers, we
are led therefore to anticipate in old age a correlation, on the one hand, between
the decrease in the quantity of functional substance in the cyto|)lasm and a
decrease in the energy-producing power of the cells, and, on the other, between
the absorption of the cell-branches and a limitation in the extent of the mflu-
ence exerci.sed by a given cell. Both of which defects are characteristic of the
nervous system during old age.

B. The Nerve-impulse ■within a Single Nerve-cell.

The Nerve-impulse. — Xerve-cells form the pathways along which nerve-
impuLses travel. As introductory, therefore, to the study of the composite
pathways in the central system, comprising as they do several elements
arranged in series, it becomes important to study the behavior of the nerve-
impulse within the limits of a single cell-element.

Experimentally it is found that the nerve-impulse is revealed by a wave of
molecular change in the form of an electrical variation which passes along the
nerve-fibre in both directions from the point of stimulation. Under normal
conditions the intensity of the electrical change does not vary in transit, but
it does change with changes in the strength of the initial stimulus. It moves
in the peripheral nerves of the frog in the form of a wave some 18 rcillime-
ters in length, at the mean rate of 30 meters per second, and this rate can be
somewhat retarded by cooling the nerves, and accelerated by warming them.
In mammals, the rate in the peripheral nerves has been found by Helm-
holtz and Baxt to be 3-1 meters per second. The nerve-impulse can be
aroused at any point on a nerve-fibre provided a sufficient length of fibre be
subjected to stimulation. Mechanical, thermal, chemical, and electrical stimuli
may be used to arouse it, but just how the impulse thus .started differs from
that normally passing along the fibres as a consequence of changes in the cell-
bodies of Avhich these fibres arc outgrowths is not known. It appears, how-

CENTRAL NERVOUS SYSTEM. 619

ever, that tlie impulses roused by artificial stimuli are usually accompanied by
a much stron<j;er electrical variation than accompanies the normal impulses.

In the peripheral system the nerve-impulse, when once started within a
fibre, is confined to that track and does not difiiise to other fibres running par-
allel with it in the same biuidie. In other words, throughout this portion of
its course the conduction of the impulses is isolated.

The above-mentioned facts have been observed on the peripheral nerves,
and these morphologically are but parts of the medullated neurons, the cell-
bodies of which are located either in the central system proper or in the spinal
or sympathetic ganglia.

The observations apply therefore to but one portion of the nerve-cell, and
our present purpose is to determine how far it is possible to extend them so
that they apply to the entire nerve-cell, noting at the same time the modifica-
tions introduced by this extension.

Conditions Surrounding- the Extension of the Nerve-impulse. —
Owing to the small size of nerve-cell bodies, there are of course very few
instances in which a single nerve-cell, or part of such a cell, has been the
object of direct physiological experiment.

Groups of elements are usually employed like those represented in the
groups of neurons forming the various peripheral nerves, and w4iere these
have common functions, the inference may be made from the changes in the
mass to changes in the constituent units. This method can be used without
serious error, and it is possible, therefore, to speak of events occurring in the
individual elements, although the experiments were made upon masses of
them.

Direction of the Nerve-impulse. — In the case of a given nerve-cell, the
impulses which we usuall}' consider pass in one direction only. For instance,
along the ventral nerve-roots of the spinal cord the impulses pass from the
cord to the periphery, while in the dorsal roots, so far as they take origin
from the cells of the spinal ganglia, these impulses travel in the opposite
direction. At the same time experiment has shown that if a nerve-trunk be
stimulated at a given point, then the nerve-impulse can be demonstrated as
passing away from the point of stimulation in both directions.

We are therefore led to inquire what limits are set to the passage of im-
pulses in a direction opposite to the usual one. The narrowest limits, it
appears, are those of the single cell in which the impulse has originated. The
experimental observations are as follows : When the fibres forming tli^ ven-
tral root of the spinal cord are stimulated electrically, and the cross section of
the cord, somewhat cephalad to the level at which the root joins it, is explored
with an electrometer, there is not found any evidence of nerve-impulses pass-
ing cephalad in the substance of the cord. The arrangement of the cells in
the cord is such, however, that the cell-bodies which give origin to the fibres
forming the ventral root are physiologically connected with fibres running
toward them from every portion of the cord, and under normal conditions
these fibres convey impulses to them. The experiment shows that when, under

620

^^Y AMEniCAN TEXT-BOOK OF PHYSIOLOGY.

the ooiulitions named, an ini])ul.se enters the ecll-budy bv way of the ventral
root-fibre to wliieli it gives origin, it does not pass out of tliis cell-budy into
tlie other elements of the cord causing an electric change detectable as a nega-
tive variation. It appeal's, therefore, that the connection between the fibres
of the cord and the cell-bodies in question is such that though impulses
readily pass from the former to the latter, they do not jms.s in tiie reverse
direction, thus showing that in this instance the cell-boundary sets a limit to
the reversed impulse.*

With the elements forming the dorsal spinal root, the case is at first glance
apparently different, though in reality it is the same. These elements are

those having the cell-body located in the spinal
ganglion. The cells are essentially dineuric
(Fig. 148) ; one neuron extends from the
point of division toward the periphery, and
the other enters the spinal cord to distribute
itself as a fibre coursing longitudinally for some
distance within it (see Fig. 151). The normal
direction of the eftective impulses is from the
periphery toward the cord, and Avithin the cord
they are delivered to other elements which cany
them in all directions. It is therefore to be ex-
pected that the stimulation of the dorsal root-
fibres would give rise to impulses })assing in both
directions in the dorsal columns of the cord.
When, however, the dorsail columns of the cord
are electrically stimulated in across section made
just above the level of the entrance of a dorsal
root, then it is found that the electrical varia-
tion is to be detected in the nerve-fibres on the
distal side of the spinal ganglion. These im-
pulses have therefore passed in a direction the
reverse of that usually taken. The fibres which
are stimulated in this instance in the cross sec-
tion of the cord are, however, outgrowths of the
spinal ganglion-cells, and thus, although the
stimulation of the cord does give rise to an im-
pulse in the peripheral nerve, nevertheless the
impulse is continually within the limits of one
cell-element. The question of whether the re-
versed impidse can traverse the cell-body is
here answered in the affirmative, for these cells
are virtually dineuric, and everything jioints to the passage of the impulse
through the cell-body in passing from one neuron to the other. There is,
however, no evidence that the stimulation of the dorsal columns of the cord
^ Gotch and Horsley : Proceedings of the Royal Society, 1888.

Fig. lol.— a longituditml section
of the cord to show the branching of
incoming root-fihres in dorsal col-
umns. At the left are three /> R
root-fibres, each of which forms two
princii)al branches. These give off
at right angles other branches, col-
laterals, Col, which terminate in
brushes. C C, central cells, whose
neurons give off similar collaterals
(Ram6n y Cajal).

CENTRA Fj nervous SYSTEM. 621

produces outgoing impulses in the dorsal nerve-roots except when the stiinuhis
is applied to the neurons whieli ai'c outgrowths of tiie (;ells of the dorsal ganglia.

Arrangement in the Central System. — As will be shown later on, there
is reason to picture tiic passage of the uerve-inipulse through the central
system as accomplished by a series of relays in which each cell-body is roused
to discharge its own impulse as the consequence of an impidse received from
some other cell.

When therefore an impulse is brought by one neuron to a cell-body, and
passed on by way of it to another neuron which is a part of the stimulated cell,
there is no escape from the conclusion that, if in this case the cell-body is
physiologically significant, it rather originates the impulse which traverses
the second neuron than acts merely as the conductor for it.

This is suggested by the changes caused in the cell-body as the result of
stimulating it. At the same time there is an appreciable delay (0.036 second)
in the passage of the nerve-impulse through the cell-body in the case of those
cells which form the spinal ganglion.'

Double Pathways. — If the view is correct, that in passing through the
spinal ganglion the impulse enters the cell-body, then the nerve-impulse passes
to and fro along the common stem which joins the cell-body with the two
neurons {vide Fig. 148). In such a case, the impulse going toward the cell
must travel either through the entire stem, or through a part of it only. This
stem is conceived as homologous with the bases of the two neurons which
originally arose from the dineuric cell, thus morphologically representing a
double pathway, although in the mature cell there is, from the histological
side, absolutely no trace of this duplicity.

The same arrangement must exist in the case of cells like those represented
in Figure 152, in which the neuron arises from the base of a dendron at some

Fig. 152.— Showing the relations between the terminal branches of the dendrons (D) and of the
neurons [N') of the optic fibres where they come together in the superficial layer of the optic lobe of
the chick ; also showing the origin of the neuron (iV) from a dendron (van Gehuchten).

distance from the cell-body, and in which nerve-impulses arriving over the
dendron and leaving by the neuron must follow the portion of the cell-branch
which is common to both, passing along it first in one direction and then in
the other. It appears not improbable, therefore, that some outgrowths of the
cell-body which morphologically are simple, really contain more than one
physiological pathway.

^ Gad and Joseph : Archiv fur Anatomie und Physiologic, 1889,

622 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Significance of Shape. — Since tlie outgoing nerve-impulses pass along
the efferent cell-branches to their tijw, it follows that if the impulses are
destined to leave the cell limits they will do so at the extremities of the
branches. This leads to the question how far the j)ossession of branches is
necessary to the functional activity of a nerve-cell either for the reception or
transmission of an impulse. Since it has been pointed out that the spinal cord
of the newt and fish* is capable of conduotiug impulses even before the den-
drons of the cells composing it are developed, it follows that the transmission
of impulses is in some way dependent on the condition of the cell-wall inde-
pendent of cell-branches. This modification of the cell-wall may exist at
points where there are no branches, or during this early period be a general
property of the wall and only later become the peculiar property of that por-
tion Avhich forms the tips of the branches. But not only the ciipacity to
receive, but also the capacity to deliver impulses is a function of the ends of
the branches, and the cell-wall at these points must therefore be peculiarly
modified with a still further differentiation determining the direction in which
the impulses may pass. If, therefore, the mature cell is thus arranged, its
shape and the number of its branches have a meaning. Each dendron repre-
sents at least one pathway by which impulses reach the cell-body. If, then,
there are many dendrons, the cell-body is subject to a more complicated series
of stimuli than if the branches are few. It will be ■ remembered that the
young nerve-cell has no dendrons, that the first branch to be formed is the
neuron, and that the completion of the full numl^er of dendrons is a slow
process. The j)athways formed by the dendrons are, therefore, continually
increasing up to maturity.

Effect of Impulses. — The impulses which arrive at the cell-body produce
there chemical changes. These changes when they reach a given volume and
intensity cause a nerve-impulse which leaves the cell-body by way of the
neuron. If the nerve-impulse is, as we a.ssume, dependent on the chemical
changes occurring in the cytoplasm, then the nerve-impulse must vary accord-
ing to these changes, which in turn can hardly be similar when the incoming
impulses that arouse them arrive along different dendrons.

Concerning the modifications in the nerve-impulse as de|)endent on the
cell-body, there are thus far known only the variations in the intensity of the
negative variation, this being greater with the stronger stimulus. When the
nerve-impulses leave a cell-b(xly after momentary stimulation, they depend not
upon a single event but a series of events, varying slightly for the different
groups of cells. Experiments showing the multiple character of the impulses
aroused within the central sy.stem have been made by Gotch and Hoi"sley.*
When the motor cortex of a monkey was stimulated (Fig. 153) by means of
the faradic current, the muscles which by this means were made to respond
showed a long tonic contraction followe<^l by a series of shorter clonic ones
(Fig. 154, D). When the spinal cord had been cut across, the cortex was

• His: Archiv fur Anatomie und PhynoloyU, 1890.

* Proceedings of the Royal Society, London, 1888.

CENTRAL NERVOUS SYSTEM.

623

again stiinulalcd and tlio changes in the fibres
of the cord which convey the impulses from
tlie cortex to the spinal centres were investigated
by means of the capillary electrometer. By this
means a curve (Fig. 154, D) was obtained as a
record of the negative variations passing along
these fibres. This latter curve corresponds
with the record for the muscular contraction
and hence the relation between the two series
of events is evident. It appears, therefore,
that the cortical cells after the cessation of the
stimulus still continue to discharge in a rhyth-
mical manner. The attempt was also made
to determine the rhythmic character of the
negative variations in the motor nerve-trunk
between the cord and the contracting muscle,
but the changes there present, though sufficient
to cause contractions of the muscle, were not
strong enough to be recorded by a delicate
capillary electrometer. This result suggests
that the impulses sent out from the spinal cord
by the normal discharge of the motor nerve-
cells in it may differ from the impulses artifi-
cially aroused in the lesser intensity of the
electrical changes that accompany them. The
rate at which the nerve-cells discharge, as
shown by the number of impulses which pro-
duce tetanus of a muscle indirectly excited,
either by artificial stimulation of the nerve-
elements in animals or by voluntary impulses

in man, is about

Mercury.

,'SuIjjhHric acid 10 fc.

Microscope.

^i

ten per second. It
appears thatat least
the cortical cells
and those of the
spinal cord have
the same rate of
discharge, and that
this rate is the same
in some mammals
(dogs, cats, rabbits,
and monkeys) as in

man. Hence a tendency to discharge about ten times a second may be assumed

as characteristic of the mammalian nerve-cell.^

' Scbiifer and Horeley: Journal of Physiology, 1885, vol. vii. Schiifer: Ibid.

I Mercuri/.

Fig. 153.— Schema illustrating the experiment for determining the num-
ber of separate nerve-impulses passing down the spinal cord upon stimula-
tion of the cortex (from experiments on the monkey ; Horsley) : E, E, elec-
trodes, intended to be on the " leg area." Wliere the cord is interrupted one
non-polarizable electrode is placed over the cut end of the pyramidal fibres
going to the lumbar enlargement ; the other, on the side of the cord. These
lead to the capillary electrometer, in which the column of mercury moves
each time an impulse passes.

624 AX AMEllTCAN TEXT-BOOK OF PJIYSfOLOGY.

Points at which the Nerve-impulse can be Aroused. — It appears pro-
bable that the excitation oi" any part of a nerve-cell is capable of producing

D

I Excitation.

I 1 Sec. I

E.rcilutioii.

I I I I I I I I I ^ ■'''«•. I

Fig. 15-1.— From a photographic record of the movements of the coliiinn of mercury in a capillary
electrometer (Gotch and llorsley). The arrow shows the direction in which the record is to be read.
The upper curve (B) shows the period of excitation by the interrupted current ; this is followed by a series
of waves in the record showing a number of separate impulses sent down from the cortex after electrical
stimulation has ceased. In the lower curve the exciting electrodes were a|)plied to the white matter
directly, the corte.v having been removed. The record shows that in this case no impulses pass after the
stimulation has ceased.

a nerve-impulse, Miicther the stimulus be applied at the tips of the dendrons
or to the neuron in its course.

There is, however, no indisputable evidence that within the central nervous
system the cell-bodies of nerve-cells can be made to discharge by the direct
application of electrical or other artificial stimuli to them, for there is no
locality suited for such isolated stimulation. In every place where such cell-
bodies are found they always lie more or less imbedded in the terminals of
neurons that have originated elsewhere, and hence present methods are not
fitted to decide whether the impulse is aroused in these cases indirectly by the
stimulation of the terminals or directly by the passage of the stimulus through
the cell-body alone. That artificial stimuli do in some way arouse the cell-
bodies to discharge is amply shown by the fact that when the cortex is stimu-
lated under the conditions just mentioned, the impulses continue to come from
the cortex after the stimulus itself has ceased to act.

If after such a reaction the cortical layer containing tlie cell-bodies be cut
away, exposing the cut ends of the fibres which have originated from them,
and the stimulus be again applied, an impulse is to be detected in these fibres
so long as the stimulation is continued, but the impulses cease when the
stimulus stops. This diiference in the time-relations and the form of the
impulses according to the presence or absence of the cortical layer is taken as
an indication that in the first instance the cell-bodies were stimulated, but it
still leaves the question of directness of the stimulation undecided.

Probably every nerve-element in all its parts is to some degree irritable,
and the reports to the effect that the cell-bodies cannot be directly stimulated
are not supported by satisfactory proof that no nerve-impulses passed from the
point to which the stimulus was applied.

Irritability and Conductivity. — In general, parts of the system which are
irritable are also conductive, but there are special cases in which the irrita-
bility of the nerve-fibre can be distinctly separated from its conductivity, the
latter being present while the former is absent.

It is an old observation that on stripping down the phrenic nerve by com-

CENTRAL NERVOUS SYSTEM. 625

pressing it between the tluimb and forefinger and sliding these along the
nerve, ti contraction of the diaphragm is cansed. The part of the nerve thns
stinndated is soon exhausted. If, now, the same operation is repeated on a
portion of the nerve lying nearer the spinal cord, contraction of the diaphragm
again follows. This result was originally used to support the theory of a
nerve-fluid, and wius held to demonstrate that after the nerve-tubes in the
portion of the trunk compressed had been emptied so that no reaction followed
further pressure, then if the pressure were applied still nearer the cord the
fluid from that part of the nerve could be driven forward and a contraction
of the diaphragm would result. The notion of a nerve-fluid in the sense in
which that terra was used by the earlier physiologists has long since been
abandoned, but for our purpose the experiment is important as showing that
irritability and conductivity do not under such treatment disappear at the
same time, but that the fibres remain conductive after they cease to be irrita-
ble, as is shown by the flict that the peripheral part of the nerve, though irre-
sponsive, still permits the impulses aroused nearer the cord to pass through it.

It has been also shown ^ that in young regenerating motor fibres it often
happens that while no response is to be obtained by the direct stinndation of
the regenerated peripheral portion, yet the stimulation of the central and fully
grown portion does cause a contraction of the muscles controlled by these
fibres. In this case the newly formed fibres can conduct an impulse which
gives rise to a contraction, although such an impulse cannot be aroused by
directly stimulating them.

In the case of the cell-body certain conditions must be present in order
that an impulse sufficient to cause an evident response shall be aroused.
There is certainly no evidence that stimuli which for one reason or another
do not cause such responses are without any effect whatever. At the same
time all cases in which there may be marked delay in the response occur
where the impulse passes from one cell to another, and hence the question can
always be raised as to the exact point at which delay occurs.

Number of Stimuli necessary to Elicit a Response. — In an isolated
portion of a nerve-cell, like a nerve-fibre for instance, a single stimulus
is followed by a single nerve-impulse ; on the other hand, the studies which
have been made to determine the number of weak stimuli necessary to dis-
charge a series of cell-elements indicate that there is a summation of stimuli,
i. e. the discharge does not follow until a series of stimuli has been given.
These experiments have been made for the most part with reflex frogs, and
they indicate that with very weak stimuli that can be individualized, like
mechanical impacts or single induction shocks, a given reaction can be obtained
with remarkable regularity after a given number of stimuli, while the intervals
between the single shocks may be varied within comparatively wide limits
without modifying the number required.^

^ Howell and Hiiber: Journal of Physiolocpj, 1892, vol. xiii.

* Ward : Archiv fiir Analomie und Physiologie, 1880 ; Stirling : Arbeiten aiis der physiologischen
Anstalt in Leipzig, 1874.
40

t)26

A^" AMERICAN TEXT-BOOK OF PHYSIOLOGY.

WhetlicT, liowever, the delay in tlie response is due to the failure of the
cytoplasm oi' the reeeiviiig cell to discharge until i-cpcatcd itupulses liave
reached it, or whether the inoditieation of the cell which causes the delay is
a process taking place at the point where the inipulse passes over from the
branches of one cell to those of another, is not directly determined by the
experiments. The indirect evidence is, however, entirely in favor of the view
that the delay which is notable in the arousal of a reflex response occurs at
the point where the impulse i)asses from one cell to another.

0. The Nutrition of the Nerve-cell.

The metabolic processes within the nerve-cell are continuous, and the
chemical changes there taking place involve not only those prerequisite to the

enlargement of the cell during
J>»f^^^^^^_ growth, but also those leading

1^ A to the formation of such sub-

stances as by their breaking
down release the energy that
appeal's in the nerve-impulse.
The passage of the nerve-
impulses probably alters the
osmotic powers of the cell-
wall toward the surrounding
j)lasnia, and this of course is'
fundamental to the nutritive
exchange. It follows, there-
fore, that the passage of nerve-
impulses is one factor deter-
mining the nutrition of these
cells.

Cell-body. — Histologically
we look uj)on the cell-bodies
as the part in which the most
active changes occur, since the
network of blood-vessels is
most dense about these, indi-
cating that the metabolic pro-
cesses are here most active '
(Fig. 155).

Chemical Changes. — For
the direct micro-chemical de-
termination of special sub-
stances within the nerve-cells there are but few methods, though some phos-
phorus-bearing substances (nuclein.s) can be demonstrated,^ and the occurrence

^ Shimamura: Neurologische Centrdlhlatt, 1894, Bd. xiii.

^ Lilienfeld und Monti: Zeitschrift fiir physiologiache Chemie, 1892, Bd. xvii.

Fig. 155.— Frontal sections through the human mid-brain
at A, level of the anterior quadrigeminum ; J!, level of the
posterior quadrigeminum (Shimam)ira). On the left side the
Vjlood-vessels have been injected ; on the riglit the gray mat-
ter is indicated by the heavy lines. It apjiears by this that
the blood-vessels are most abundant in the gray matter.

CENTRAL NERVOUS SYSTEM.

627

of chemical changes due to activity and to age are very evident. The nature
of these latter changes is quite unknown. Tiiere is general consensus that
the alkalinity of the nerve-tissues is decreased during activity, and this decrease
in alkalinity may amount at times to a positively acid reaction.' This change,
too, is better suj)ported by the observations made where the cell-bodies are
numerous, than by those made where the fibres are alone present.

Trpphic Influences. — W'lien a nerve-cell is not kept active by the passage
of nerve-impulses through it, it usually atrophies and may degenerate. The
reason for this appears to lie in the fact that the loss of those changes
which accompany the nerve-impulses decreases the vigor of the nutritive
exchange with the result of causing a steady diminution in the volume of the
cell or even its disintegration. Such changes are found, for instance, in the
nerves after the amputation of the limb to which they were supplied.^

The result of an amputation is that portions of the neurons originating from
cell-bodies located either in the ventral horns of the spinal cord, or in the
cells of the spinal ganglion, are removed. In the latter case the normal
pathway for the incoming impulses is interrupted at its peripheral end, and in
the former the last part of the pathway by which the impulse is delivered at
the periphery is destroyed (see Fig. 156).

Fig. 156.— Cross section of the spinal cord of the chick, X 100 diameters (van Gehuchten) : D, dorsal
surface ; V, ventral surface ; d. r, dorsal root ; v. r, ventral root ; g, spinal ganglion. On the left the arrows
indicate the direction of the larger number of impulses in the dorsal and ventral roots respectively. The
small arrow on the right dorsal root calls attention to the fact that some neurons arising in the ventral
plate emerge through the dorsal root and convey impulses in the direction indicated.

The disturbance caused in the two sets of cells is, however, not the same.
In the case of the cells of the spinal ganglion the chief pathway by which they
are stimulated under normal conditions, is so far mutilated that only a com-
paratively small number of impulses passes over them. That some do pass,
is indicated by the sensations apparently coming from the lost limbs — sensa-
tions which are often very vivid and minutely localized.^

^ Gscheidlen : Archiv fur die gesammte Physiologie, 1874, Bd. viii.

^ Grigoriew : Zeitschrift fur Heilkunde, 1894, Bd. xv.

* Weir-Mitchell : Injuries of Nenes, Philadelphia, 1872.

628 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Oil analyzing th6 condition thus established by an amputation it is seen
that the cells located in the spinal cord are deprived by such an operation of
one principal group of incoming impulses, namely those which arrive through
the dorsal root-fibres that are most closely associated with them ; but at the
same time there remain many other ways in which these same cells are nor-
mally stimulated. The efferent pathway from these cells is incomplete, and
the impulses which must pass along the stumps are inefficient. That im-
pulses do pass along the stumps of the efferent roots is beyond question, since,
when the distal portion of an efferent nerve is cut off the cell can be shown
to still discharge through the portion of the fibres connected with the cell-
bodies. Moreover, the muscles of any stump tend to execute the associated
contraction w'hicli they normally perform, thus showing that the group of
cells is fully innervated, although its discharge is without mechanical signifi-
cance, and finally there is always a tendency to the regeneration of the cut
fibre which indicates activity through its entire length.

It is therefore not improbable that after amputation' impulses do pass down
even those fibres which end without physiological connections. It is explica-
ble from this that in the case named the spinal ganglion cells should be more
affected than those of the spinal cord. Further, since the efferent cells of the
leg are more commonly innervated bilaterally than are those of the arm, we
might expect the efferent cells in the cervical region to be more readily affected
by an amputation.

Wherever in the central system a group of fibres forms the chief pathway
for the impulses arriving at a given group of cells, then the destruction of
these afferent fibres brings about the more or less complete atrophy of the
cells with which they are secondarily associated, and this effect is the more
marked the younger the animal at the time of injury. Examples of this
relation are found in the " nuclei " of the sensory cranial nerves.

Thus the activity of a given cell has the value of contributing to the
strength of its own nutritive processes, and different cell-elements, so far as
they are physiologically united, stand in a nutritive or trophic relation to one
another such that the cell receiving impulses is in some measure dependent for
its nutrition on the cell which delivers the impulses to it.

Fatigue. — It is a familiar fact that living tissues may be fatigued. In
the nervous system the signs of fatigue are both physiological and histological,
but it is to the latter changes only that attention will be here directed.

Not only is the food-supply to the nerve-cells, as represented by the quality
and quantity of the plasma, variable, but the cells themselves are subject to
wide variations in their power to use the surrounding substances.

When in a nerve-trunk containing both afferent and efferent spinal root-
fibres passing to a limb, the afferent fibres are stimulated by a faradic current
applied intermittently, changes in the cell-bodies in the spinal ganglion are to
be observed (Hodge).

When this experiment is made on a cat, and, after death, the sections
from the stimulated are compared with those from the corresponding but

CENTRAL NERVOUS SYSTEM.

629

unstimulated spinal ganglion, a picture like that represented by Figure 157 is
obtained.*

The sections indiciitc that the cytoi)lasm together with the enclosed nucleus
and nucleolus as well as the nuclei of the enclosing capsule of the cell, have

Fig 157.-TWO sections, A and B, from the first thoracic spinal ganglion of a cat. B is from the gan-
glion which had been electrically stimulated through its nerve for five hours. A, from the correspond-
ing resting ganglion. The shrinkage of the structures connected with the stimulated cells is the most
marked general change, n, nucleus ; n. s, nucleus of the capsule ; v, vacuole ; X 500 diameters (Hodge).

all suffered change by this treatment. The stimulus was applied for only
fifteen seconds of each minute, the remaining forty-five seconds being given to
rest. In this way the cells here figured had been stimulated over a period of
five hours. The nuclei of the sheath are flattened, the cytoplasm somewhat
shrunken and vacuolated. With osmic acid the nuclei of the stimulated cells
stain more darkly and the cytoplasm less darkly than in a resting cell. The
nucleus is shrunken and crenated, and the nucleolus is also diminished in size.
In the first experiments the attempt was made to demonstrate a measurable
change within the nerve cell-bodies as the result of stimulation. Assuming the
nuclei of these cells to be approximately spherical, and calculating their vol-
ume as spheres, the shrinkage amounted to that shown in the following table :
1 Hodge : Journal of Morphology, 1892.

630

l.V AMIJBICAX TEXT-BOOK O/ I'l I VSIOLOGY.

2\ihk sJtou-iiKj the Ikcreaac in the \'oluinc of the Nadeua of iSthaulated iSpuial
Ganc/lion-cells of Cats. Stimulation for fifteen seconds alternating with
rest for forty-Jive seconds (Hodge).

stimulation cont

mied

^hriukaKc in the volume of the nuclei

for-

of thf .stiinuluted cells.

1 hour

22 per cent.

2.5 hours

21 " "

5

24 " "

10

44 " "

This table further shows that the shrinkage is greater, the greater the time
during which the stiinuhis was applied. There is thus established not only
the fact of a change in tiie cell, but al.'^o a connection between the amount of
this change and the length of time during which the stimulus was allowed to
act. The results when expressed by a curve yield the following :

Per

cent.

100

\\

•

90

\\
"\\

80

\^ \

^.^

* — V

\

^

70

60

-

\

\^

50

1 1

\^

1 1

1

1

L_

2i

10 IIV

23

29

Fig. 158.— The broken line indicates the volume of the nuclei of the spinal ganglion-cells of a cat
after stimulation for the times indicated. The solid line indicates the volume of the nuclei, first after
severe stimulation for five hours, and then in other cats, also stimulated for five hours, but subsequently
allowed to rest for different periods of time. The period of rest is found by subtracting five hours from
the time at which the record is made. After twenty-four hours of rest the nucleus is seen to have
regained its normal volume (Hodge).

Table to show Influence of Rest.

Right brachial plexus of each Cat stimulated in the same manner for five hours,
to rest for a variable time after the stimulation had been stopped.

Cat allowed

Nuclei.

Cat, 17
Cat, 16
Cat, 21
Cat, 19
Cat, 18
Cat, 7

Rest.
0 hours.

6.5 hours.

{

12 hours. <.

18 hours. <

24 hours. <,
Normal.

Mean diameter of nuclei in m.

16.40 Left, normal.

12.93 Riglit. stimulated.

16.70 Left, normal.

\o.0U Right, stimulated.

16.34 Left, normal.

14.73 Right, stimulated.

17.08 Left, normal.

16.03 Right, stimulated.

17.01 Left, normal.

17.11 Right, stimulated.
( 114.20 Left.
\ 1 14. 54 Right.

Shrinkage.

I 48.8%
} 26%
} 26%
j 18%
[ +2%
+ 6.9%

Cells.

Mean diam-
eter in ft..

f 57.

\ 52.

j 56

I 54

f 55

1 51

f 56

1 55

Whether these changes could be considered similar to the normal physi-

CENTRAL NERVOUS SYSTEM.

631

ological variations (1(|mii(1((1 on \vli»'tli< r it was possible to demonstrate recov-
ery from them. This was accomplished in the followin*^ manner.

Under fixed conditions a cat was stimulated in the usual way and the
amount of shrinkage in the nuclei of the spinal
gangliou-cells was determined. This was found to
be almost oO per cent. Four other cats were
similarly treated and then allowed various periods
(six and a half, twelve, seventeen, and twenty-four
hours) in which to recover. The results appear in
Figure 158 and the table on page 030.

The effects of stimulation described were found
not only in the nerve-cells of cats, but also in tluxse
of frogs which had been stimulated in a similar
manner.

Having thus shown that the change was physio-
logical in the sense that it was one from which the
cells could recover, it remained to be shown that
the features of the change were discernible in the
living cell, and were not caused secondarily by the
actions of the reagents employed in preparing the
sections.

For the study of the living cell, frogs were
chosen, and the cells of the sympathetic ganglia
examined. In these experiments cells from dif-
ferent frogs were prepared under two different
microscopes and kept alive in the same way by irri-
gation with a nutrient fluid. In one case, however,
the cell was stimulated by electricity, while in the
other no stimulation was applied. During the time
of the experiment the cell which was not stimulated
remained unchanged, while the stimulated cell went
through the series of changes exhibited in Figure
159.^

So far as the main features are concerned the
shrinkage and crenulation of the nucleus was essen-
tially similar to that found in the nuclei of the
spinal ganglion cells of cats. These results demon-
strated therefore the natural character of those
changes in the nerve-cells which had been found
after treatment with histological reagents.

It followed that if these changes were really
significant of normal processes they should be found
in the nerve-cells of those animals which show
well-marked periods of activity, alternating with periods of rest

^ Hodge: Journal of Morphology, 1892, vol. vii.

Fig. 159. — Showing the changes
in the form of the nucleus result-
ing from the direct electrical
stimulation of the living sym-
pathatic nerve-cell of a frog.
The hour of observation is given
within each outline. The experi-
ment lasted six hours and forty-
nine minutes. A control cell
treated during this time in the
same manner, except that it
was not stimulated, showed no
changes (Hodge).

To deter-

632

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

mine this, birds and bees were examined, one set of preparations being made
from animals which were killed at the beginnin<r of the day, after a night of
rest, and the other froni those killed at the end of the day, after a period of
activity. Similar changes were fonnd in the cells of the spinal ganglia of
l^'.nglisli sparrows, of the cerebrnm of pigeons and cerebellum of swallows, and
of the antennary lobes of bees (see Fig. 160).

^ ■•?#Pii■y^^•■•X)C^;■o■

^•-f?^\•• ■';:•■■■ i=^*;.'".'v5.' ■

Fia. 160.— Spinal ganglion-pclls from English sparrows, to show the daily variation in the appearance
of the cells due to normal activity : A, appciirance of cells at the end of an active day : B, appearance of
cells in the morning after a night's rest. The cytoplasm is filled witli clear lenticular masses which are
much more evident in the rested cells than in those fatigued (Hodge).

A study of these figures shows the cells to be turgid with large round
nuclei, at the beginning of the day after a night of rest, and on the other
hand that they are vacuolated and shrunken and with altered nuclei at the
end of an active period. These observations therefore justify the conclusions
drawn from the apjiearauces following direct stimulation.

Other observers ' have obtained similar results. The motor cells of the
spinal cord and cells of the retina (dogs, INIann) have been added to the list
of those showing changes. After a short period of stimulation of the sympa-
thetic cells of the rabbit, both Vas and Mann have found a preliminary swell-
ing of the cell, and the same has been noted by Mann in the case of retinal
cells in the dog.

The application of these ob.servations to changes in the human nervous
system has thus far been made only in a casual way, but enough has been
already observed to make certain that the results are applicable.

It will be noted that the changes described follow variations in the amount
of stimulation, the nutrient conditions represented by the surrounding plasma
remaining nearly constant. This latter, however, may undergo alteration, and
recent observations show that in various forms of poisoning by inorganic sub-

* Vas: Archiv fiir mikroskopische Anatomie, 1892; Mann: Journal of Anatomy and Physiology,
1894.

CENTRAL NERVOUS SYSTEM. 633

stances or iu zymotic diseases, the nervous system and especially the cell-bodies
are aflected early and in a profound manner.*

With the establishment of these facts conccrnintj^ the cell-body the question
at once arises whether the nerve-fibres are in a like manner altered as a result
of their activity.

The matter has been tested in this way : In a cat or dog a nerve-trunk was
stimulated by a measured induction current, and the contraction of the muscle
controlled by it, recorded. The physiological connection between the nerve and
muscle was then interrupted by the giving of curare and the nerve was tcta-
nized.^ The stimulation of the nerve-trunk was continued in some cases for
five hours. On the complete disappearance of the curare effects, a stimulus
similar to that employed in the first instance was found to produce muscular
contraction, thus showing that the continuous stimulation of the nerve-trunk
during this interval had not seriously diminished its power to transmit the
nerve impulses aroused in it.

Histological changes have also been souo;ht for in the nerve-fibres after
prolonged stimulation, but thus far they have not been demonstrated. Chemi-
cal changes in the nerve-fibres, if present, must be extremely small, and the
thermal variations which occur amount to less than 0.0005° C, or, in other
words, are not demonstrable.^ Histological and chemical changes due to
activity have therefore been seen in the cell-bodies alone.

Degeneration and Regeneration of Nerve-elements. — All parts of a
nerve-cell are under the control of that portion of the cell-body which con-
tains the nucleus; in this respect the nerve-tissues are similar to other tissues
which have been studied, and iu which the nucleated portion of the cell is
found to be the more important. It was shown by Waller^ that a nerve-
fibre belonging to the peripheral nerves when separated from the cell of which
it was an outgrowth soon degenerated from the point of section to its final
distribution. The process is often designated as Walleriau degeneration.
According to recent studies on this subject,^ this degenerative change occurs
practically simultaneously along the entire length of the portion cut off. The
changes following the section consist in a fragmentation of the axis-cylinder
followed by its disappearance, enlargement and multiplication of the nuclei
of the medullary sheath, and absorption of the medullary substance, so that
in the course of the fibres there is left at the completion of the process the
primitive sheaths together with the sheath-nuclei. In the early stages of this
process the medullary sheath, moreover, undergoes some changes, the result of
which is that it stains more deeply with osmic acid, and hence appears very
black in comparison with the normal fibres about it (Marchi).

Degeneration of Non-meduUated Fibres. — Concerning the progress of

'Schaflfer: Ungarisehes Archiv filr Mediein, 189^ ; Pandi: Ibid., 1894; Popoff: Virchovfs
Archiv, 1894; Tschistowitsch : Petersburger medicinische Wochenschrift, 1895.

* Bowditch : Archiv fur Anatomie und Physiologic, 1890.
' Stewart : Journal of Physiology, 1891, vol. xii.

* Nouvelle methode anaiomique pour investigation du Systhne nerveux, Bonn, 1851.
^ Howell and Huber : Journal of Physiology, 1892, vol. xiii.

634

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

degenerative changes in the non-nieihilluted fibres iuformatiou is scanty.
Bowditch and Warren^ observed that when the sciatic nerve of the cat was
sectioned, degeneration of the motor and vaso-constrictor fibres in the periph-
eral portion went on at about the same rate. Stimulation of the peripheral
part of the nerve gave a vaso-dilator reaction after the vaso-constrictor reac-
tion had entirely disappeared, suggesting that the constrictor fibres degenerate
more rapidly than do the dilators, although it is not improbable that tlie
dilator fibres in this location really belong to the medullated class (Howell).
After five dayS no vaso-motor reaction at all could be obtained. In a recent
study by Tuckett^ of the degeneration of the non-medullated fibres contained
in the branches springing from the superior cervical ganglion, it is stated that
the degeneration as traced by histological and physiological methods is com-
plete within thirty to forty hours after section of the fibres, and that the
degenerative changes involve only the core of the fibres, the outside sheath
and nuclei being unaffected.

Degeneration in the Central System. — In the central system, the distal
portion of the fibres separated from the cell-body degenerate as at the periph-
ery, and this reaction has therefore formed a means by which to study the
architecture of the central system. The details of the process are, however,
not well understood.

So far, then, as the principal outgrowth of the nerve-cell is concerned, it is
found to be always under the nutritive control of the cell-body from which it
springs. The changes which take place when the spinal roots are cut will serve
to illustrate this control (see Fig. 161). Section of the dorsal root at the distal

Fig. 161.— Schema of a cross section of the spinal cord, showing the dorsal and ventral roots and the
points at which they may be interrupted : D R, dorsal root ; V R, ventral root ; G, ganglion : M, muscle ;
S, skin ; 1, lesion between ganglion and cord ; 2, lesion between muscles and cord; 3, lesion between skin
and ganglion ; 4, combination of 2 and 3.

side of the spinal ganglion at 3 causes a degeneration of all the fibres which
form the dorsal nerve-root distal to the ganglion. Section of the dorsal root
at 1 causes degeneration, central to the section, of those nerves which are out-
growths from the cell-bodies of the spinal ganglion. Section of the ventral
root at 2 causes a degeneration distal to the point of section in those fibres
which form the ventral root and which arise from the cells within the spinal
cord. In each case, therefore, the degeneration occurs ou one side only of the
section, and that is the side away from the cell-body.

' Journal of Physiology, 1885, vol. vii. ^ TuckeU: Journal of Physiology, 1896, vol. xix.

CENTUM. NERVOUS SYSTEM. 035

It is sometiinos stated that degeneration takes place in the direction of the
uerve-inipulse. In a general way this is trne, since the impulses usually
travel from the cell-body along the neuron. In the case of the fibres arising
from the cells of the spinal ganglion it is not true, since the section at the
distal side of the ganglion causes degeneration away from the spinal cord,'
while that on the })roximal side of the ganglion causes degeneration toward
the spinal cord ; yet in both neurons the impulse is in the same direction —
namely, always toward the cord.

The distal portions of the nerve may be regenerated, or, under other con-
ditions, the remainder of the neuron together with the cell-body from which
it springs may atrophy, and this latter process may result in even the complete
destruction of the nucleated ))()rti()n.

Degeneration of Nucleated Portion. — In any case the internodal seg-
ment of the peripheral nerve-fibre which has been directly injured by the
section degenerates centrally as far as the next node of Ranvier. Whether
beyond this point any marked change is to occur depends on several circum-
stances. When regeneration is prevented, the younger the animals on which
the operation has been made the more marked are the involutionary changes.
These consist, first, in a stoppage of growth-processes in the elements affected ;
second, in a simple atrophy. Such, for example, are the changes taking place
in the cells of the spinal cord after the amputation of a limb. Sometimes also
true degeneration follows. That these effects may be very plain in man, the
amputation should be one near the trunk — i. e. involving a great number of
nerve-fibres, and be of long standing — i. e. more than one year.^

It was discovered by von Gudden ^ that when nerves in young animals
are pulled away from their attachment with the central system, they most fre-
quently break just at the point where they emerge from the cord or brain axis.
When an efferent nerve is thus broken, in animals just born or very young,
the remaining portion — i. e. the cell-bodies with so much of their neurons as
lie within the central system — atrophies to complete disappearance. The cause
of this complete disappearance in the case of very young animals thus injured,
seems to lie in the intense struggle for nutriment among the nerve-elements
themselves. Thus young cells meeting with injury are unable to compete
with those about them for nourishment, and so perish. The bearing of such
a fact is very direct. If in man there is reason to think that an injury was
suffered during fetal life, there is a possibility that the injury may not only
have prevented the further development of the cells involved, but may also
have caused the complete destruction of some of them, in which case, of
course, the architecture of the region is necessarily abnormal.

Such complete disappearance as the result of early injury has not been
shown for cells which lie entirely within the central system, or for those form-
ing the spinal ganglia. In the case of those central cells which form the
sensory nuclei, like the sensory nucleus of the fifth nerve, or of the vagus,

^ Grigoriew : Zeitschrift fur Heilkunde, 1894, Bd. xv.
* Archiv fur Psychiatrie, 1870, Bd. ii.

636 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

pullin<2; out tlie nerve-trunk causes only tin atr()])hy of the central cells, and
not their complete disappearance.^

Regeneration. — When the two ends of the sectioned nerve are brought
together under favorable conditions, the peripheral portion of the trunk may
be regenerated. This occurs in the following steps as described bv Howell
and Huber.^

While the fragmentation and absorption of the myelin in the distal portion
of the cut nerves is going on, the protoplasm in the neighborhood of the
sheath-nuclei tends to increase. These enlarged masses of protoplasm then
apjiear as a thread of substance within the old nerve-sheath. A new sheath
is, however, soon formed on the jn-otoplasniic thread, and the whole consti-
tutes an "embryonic fibre." Tiie embryonic fibres lying on one side of the
cut unite with those on the other, union taking })lace in the intervening cica-
tricial tissue. Next the myelin appears in isolated drops, usually near the
nuclei, and these subsequently unite to form a continuous tube, the formation
of the myelin proceeding centrifugally from the wound. Then follows the
outgrowth of the new axis-cylinder slightly behind the organization of the
myelin into the tubular form.

It must not be forgotten that the last act, the formation of the axis-cylin-
der, is the important event, and while the whole process of repair may require
many months, the rate at which the axis-cylinder, when started, grows out
from the central end may be comparatively rapid. If this explanation be
correct, namely that the axis-eylinder is an outgrowth from the central end,
then the regeneration of the neuron is in so far but a repetition of the events
by which it was originally formed. The development of the medullary sheath
in its relation to the axis is, however, different in the two cases. When first
regenerated, the fibres resemble normal young fibres in being small, but
whether they later attain the size of those which they replace has not been
shown. Moreover, it appears that the two functions of irritability and con-
ductivity do not both return at the same time. The newly formed fibres are
capable of conduction before they become sufficiently irritable to respond to
artificial stimuli directly applied to them. In the first stages of irritability,
also, the young fibres responded more readily to slight mechanical stimuli
than to induction shocks — a differentiation in reaction which serves to suggest
the complexity of the changes involved in the re-formation of the fibres.

Regeneration of this sort which is found in the peripheral system is not
knoA^ to occur in the central system, although in many ways the conditions
of such regeneration seem there most favorable. This fact also has its ai)pli-
cation in the use of the method of degeneration for determining architectural
relationships ; for when once caused to degenerate, the bundles of fibres thus
altered can be tracked through the central system without fear that new growth-
changes will obscure them.

The dorsal spinal root degenerates when the section is made between the

' Forel : Festschrift zur von Ndgeli und von Kollikcr, Zurich, 1891.
^ Journal of Physiology, 1892, vol. xiii.

CENTRAL NERVOUS SYSTEM. 637

cord and the spinal ganglion. Study of its develo[)Mic'nt has shown that in
the first instance the spinal ganglion becomes connected with the cord by the
outgrowth from the cells of tlie ganglion of those fibres which form tiie dorsal
root. It would follow that as the cells of the spinal ganglion can regenerate
the fibres which pass toward the periphery, they should also be able to regen-
erate those which form the dorsal root, but as yet there have not been reported
any cases where a dorsal root has been thus re-formed.

That the regeneration is due to an outgrowth of the central stump has
been clearly shown by Huber,' who iuserted a bone tube between the two ends
of the sciatic nerve of the dog, and obtained regeneration of the nerve with
a return of function although the initial interval between the two parts of the
nerve was more than three centimeters. The rate of growth from the central
end has been specially studied by Vanlair.^ In the facial nerve of the rabbit,
function was restored in eight months after section, and in the pneumogastric
and ischiadic nerves of the dog in about eleven months. In the latter case,
this gives an average rate of growth of about 1 millimeter a day. In the
scar-tissue between the two parts of the nerve the rate is not more than 0.25
millimeter a day, and hence the return of function tends to be delayed by any
increase in the distance between the cut ends of the nerve. It appears also
that the return of the cutaneous sensibility is more rapid than the return of
motion (Howell and Huber).

On testing the capacity of the sciatic nerve for repeated regeneration
Vanlair found that in a dog, when it was cut a second time, it not only regen-
erated but did so more rapidly than in the first case.

Much interest has always attached to the exact course taken by the regen-
erating fibres. They appear in a general way to be guided by the old sheaths
of the peripheral portion. But the peripheral nerves contain both afferent and
efferent fibres, and it would appear most probable that in the process of re-for-
mation these should undergo much rearrangement. Since the peripheral por-
tion of the nerve acts as a guide to the growing fibres, the experiment has
been tried of cross-suturing. Thus Howell and Huber ^ having cut both the
median and ulnar nerves in dogs, sutured the central end of one nerve to the
peripheral end of the other, and obtained reunion with extensive return of
sensation and movement, and without iuco-ordi nation to be attributed to the
unusual arrangement of the nerve-fibres. Such a rearrangement without
inco-ordination is not easy to explain in view of the association of certain
functions, such as the control of a given set of muscles, with a special cell-
group in the cord. The most remarkable observation, however, on the regen-
eration of nerve-trunks has recently been reported by Langley.* The pre-
ganglionic nerve going to the superior cervical ganglion of the cat is composed
of fibres with several functions. These fibres are derived frt)m the first
thoracic nerve, which mainly controls those cells in the ganglion that are

^ Journal of Morphology, 1895, vol. xi.

* Archiv de Fkysiologie normale et pathologique, 1894.

^ Loc. cit. * Journal of Physiology, 1895, vol. xviii.

638 AN AMJ'JRICAN TEXT-BOOK OF PHYSIOLOGY.

connec'tod witli the pupil and (lie nictitating membrane ; from the second
thoracic nerve, wiiich is mainly associated with the cells controlling the
blood-vessels of the car and in a less measure the nictitating membrane; from
the third thoracic, which connects with a few cells which control the ])upil ;
from the fourth thoracic, which connects mainly with cells controlling the
erection of the hairs on the face and neck ; from the fifth thoracic, which cou-
uects with the cells controlling the vessels of the car, and also the hairs of the
face aud neck ; and from the sixth and seventh thoracic, supplying hairs only.
When the pre-ganglionic fibres were cut, therefore, and allowed to regenerate,
various things might happen. The newly-formed fibres might grow past the
ganglion, or they might form novel connections with the cells there contained,
or finally, they might repeat the original connections. As a matter of fact,
the last arrangement is the one accomplished, and in the case of the cat used
in this experiment, stimulation of the nerve-roots above mentioned gave after
regeneration the reactions characteristic for the several roots. It would ap-
pear, therefore, that in some way each group of the regenerating pre-gangli-
onic fibres had selected those cells which they had originally controlled.

The reg-eneration which has thus far been described has been that of the
non-nucleated neuron by that portion of a nerve-cell which was nucleated.
The regenerated portion always lies in the peripheral nervous system. Con-
cerning the regeneration of the dendrous there are no observations.

The possibility of the formation of entirely new cell-elements in the pro-
cess of repair remains to be mentioned. When the central system is injured
it sometimes happens that mature nerve-cells there ]>resent show in their
nuclei those changes which are characteristic of nuclei about to divide, but
division does not take place ^ either in the nuclei or in the cell-bodies. In
mammals there is no convincing record of the formation of new nerve-cells
in the central nervous system of the mature animal. In some lower verte-
brates (lizards) regeneration of the spinal cord has been reported, and in the
newt such regeneration has been obtained in the retina, but the result in both
cases ap})ears to be due rather to the enlargement of embryonic cells still
remaining in these regions than to an exhibition in the mature cells of powers
absent from the corresponding cells of the mammalia. At various times and
in several places the idea has been advanced that . in the peripheral nervous
system at least there was in progress a continuous process of degeneration and
regeneration, as though this portion of the system was being continually reno-
vated. What is knoM'n of the fixity of the central system and of the relation
between the central system and that of the periphery, very strongly supports
the idea that change in one would necessitate change in the other, and for
central changes of this sort the evidence has never been advanced. To be
sure, slow srrowth-chamz-es occur in the central svstcm until after the thirtieth
year, but the additions which are thus made result from the enlargement of
nerve-cells tTiere present as structural units from a very early age, and such

* Sanarelli : " I processi riparativi nel Cervello e nel Cervelleto," R. Accademia del Lincei,
1891.

CENTRAL NERVOUS SYSTEM. 639

repair as is nuulo ofciirs in ihc peripheral system only, wliile a cell once
(l:uii:ii:;ed by injury to its nucleated portion is not to he replaeed.

PART II.— THE PHYSIOLOGY OF GROUPS OF NERVE-CELLS.

A. Organization and Architecture of the Central Nervous

System.
The reactions of groups of associated nerve-cells have usually furnished
the largest mass of facts presented under the title of the physiology of the
central nervous system. When it was recognized that the nerves formed
pathways by which the sensory surfaces of the body were put into connection
with the central system, and also the pathways by which this system was in
turn rendered capable of controlling the tissues of expression, it became at
once important to determine over what nerves the impulses arrived at the
central organ, how they travelled through that organ, and by what other
nerves they were again delivered at the periphery.

Both anatomical and physiological research have been directed to this end.
The arrangement of these paths as found in the adult human nervous system
is our principal object ; at the same time it should not be forgotten that the
reactions of simpler mammalian systems have furnished the greater number of
facts, and if the pitfalls surrounding the assumption that the reactions found
in the nervous system of a rabbit or monkey hold true in all detail for that
of man can be avoided, no danger and much gain will follow from the use of
the facts of comparative physiology.

Physiological Unity of the Central Nervous System. — So far as its
physiology is concerned, the nervous system of any mammal must be regarded
as a unit. Custom, however, sanctions a division into a central and peripheral
nervous system. The central system is usually taken as that enclosed within
the bony cavities of the cranium and vertebral canal, excluding the dorsal
root-ganglia ; the peripheral, that formed by the spinal and cranial nerves and
the ganglia associated with them. Neither of these parts has an independent
significance, and furthermore the central system is largely penetrated by nerve-
fibres from the dorsal spinal roots, fibres which have an origin outside of those
cells which form the walls of the medullary tube and constitute the central
system in the strict morphological sense. On the other hand, the retina, which
is in large measure morphologically a i)art of the medullary system, is, as a
rule, not counted as belonging to this system, but is put down as a peripheral
sense-organ. These facts are here mentioned solely to emphasize the point that
gross anatomy has found convenient certain methods of division which, if
strictly followed, confuse the morphological relations. Yet, for many purposes,
the subdivision into central and peripheral portions is advantageous.

General Arrangement of the Central Nervous System. — The general
architecture of the central system is best understood by means of schemas
(Figs. 162 and 163). As the typical arrangement is found in the spinal cord,
a cross section through this part will most readily express the facts.

640

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

The dorsal root-fibres among the spinal and cranial nerves, together with
their homologues in the retina and tiie olfactory region, are the only channels for
the entrance of impulses into
the central system. Once having
arrived there, the impulses cause
other cells to discharge, and these
in turn still others, through an
indefinite series. The original
impulse may thus arouse many
other impulses within the system,
antl these spread until some of
them reach cell-bodies which give
rise to efferent fibres and which
discharge awav from the central
system. The efferent fibres pass
out mainly by the ventral roots, but
in part by the lateral (when pre-
sent) or by the dorsal roots (Fig.
163). Such efferent fibres end
either directly in striated muscle
tissue, or in the neighborhood

D.G

DP y-^

Fig. 162.— Schema of the arrangement of the
human spinal cord ^s seen in cross section ; for
clearness the afferent fibres arc shown on the
left side only, efferent and central cells on the
right side only (von Lenhossek) : D. li, dorsal
root; V. i?, ventral root; D. P, direct pyramidal
fibres ; C. P, crossed pyramidal fibres ; (', direct
cerebellar tract ; A. Z,, antero-lateral tract: D. C,
dorsal columns. The various classes of cell-
bodies are indicated by the manner of draw-
ing.

Fig. 163.— Schema of the distribution of the
efferent fibres of the spinal roots. A, afferent
fibres in the dorsal root only ; E, E, efferent fibres
in both dorsal and ventral roots. In the ventral
root one group of efferent fibres goes to .V, the
striped muscles ; another group to ganglion cells,
S, forming a single sympathetic ganglion, or to S',
cells located in more than one sympathetic gan-
glion, but all connected with one efferent fibre by
means of its collaterals ; P, peripheral plexuses
into which the neurons of some sympathetic cells
run.

of ganglia (sympathetic ganglia). The fibres from the ganglia, in turn,
very often connect with a peripheral plexus, such as the double plexus of
Meissner and Auerbach, or the plexuses about the blood-vessels.

The evidence for the foregoing statements is briefly the following : The

CENTRAL NERVOUS SYSTEM. 641

experiments and observations of Sir Cliarles Bell (1811) and Majeudie (1822)
showed that sensation followed the stimulation of the central ends only of the
dorsal nerve-roots, and that direct contractions of the skeletal nniscles occurred
only when the peripheral portions of the ventral and lateral roots were stim-
ulated.

It had previously been shown by Hales and Whytt (1768) that even
though both roots were intact, destruction of the spinal cord prevented the
excitation of the dorsal roots from causing a reflex response, and hence the
cord was to be regarded as forming part of the pathway. Moreover, it had
been shown by the earlier investigators, before Bell, that the excitation of the
ventral roots produced a response. Brown-Sequard ' showed that section of
the (last six thoracic and first two lumbar) dorsal roots caused (in guinea-pig,
rabbit, and dog) a vascular dilatation and a rise of 1° to 3° C. in the hind
limbs. Strieker showed that stimulation of the peripheral ends of the cut
dorsal nerves caused a rise in the temperature of the foot ; and Morat showed
that stimulation of the peripheral end of a cut dorsal root produced vaso-
dilatation. The studies in the degeneration of the nerve-fibres^ siiow a small
group in the dorsal root which, upon section of the root between the ganglion
and cord, degenerates toward the periphery and remains intact toward the
cord — a behavior which is precisely opposite to that which occurs in the case
of the fibres taking origin from the spinal ganglion-cells.

Finally, van Gehuchteu and others have shown, that in histological prep-
arations (chick), these fibres can be traced through the ganglion itself (see Fig.
163). In the dorsal roots of the lumbar region of the monkey, Sherring-
ton ^ was unable to find any efferent fibres. The connection of some of the
ventral roots with sympathetic ganglia was established by Budge (1851), and
physiological as well as histological observations show that the further con-
nection of these ganglion-cells with the elements which they ultimately control
is in many instances by way of the peripheral plexuses.

Classification of Nerve-elements. — In accordance with this arrangement
of the nervous system, the elements which compose it fall into three groups :
(1) The afferent cells, those whose function it is to convey impulses due to
external stimuli from the periphery, including the muscles and joints, to the
central system. The expression " external stimuli " is in this case intended to
include also such stimuli as act within the tissues of the body, for example,
those acting on tendons and muscles, and affecting the afferent nerves which
terminate in them. (2) The central cells, those the neurons of which never
leave the central system, and the function of which is to distribute within this
system the impulses which have there been received. (2) The efferent cells,
or those the neurons of which pass outside of the central system, and which
carry impulses to the periphery. In this last group, again, two minor divisions
may be made, namely, («) the efferent elements the cell-bodies of which lie

' Gazette medicale de Paris, 1856.

' Gad and Joseph : Archivfur Atiatomie und Physiologie, 1889.
^ Journal of Physiology, 1895, vol. xvii.
41

642 .l.V AMKRirAX TEXT-BOOK OF PlTYSlOJ.OCiY.

within the central system, as is the case with those giving rise to the ventral
root< ; ili) tliose forming tlic periphoral ganglia entirely outside of the central
svstem — the sympathetic ganglia and tiie more <jr less solitary cells which tidce
part in the formation of the peripheral plexuses.

Relative Development of Different Parts. — The bulk of the three sub-
divisions which have been named is by no means equal. The central .system
is far more massive than the afferent and efferent, taken together, but the
relation cannot be stated with any exactness, since the ma.ss of the peripheral
system is not definitely known. The afferent and efferent groups are, how-
ever, about equal in weight, so that the comparatively small ma.ss of either of
them, taken alone, is apparent. When in addition to this disproportion it is fur-
ther recalled that in both the groups last named the number of cell-elements
is small as compared with the number which compose the central .«y.stem, the
disproportion is still further emphasized. That the central or distributive
division of the nervous .system is thus the most important is indicated also by
the fact that, in tiie vertebrate series, as the complexity of the entire nervous
system increases, the proportional development of the group of central ele-
ments is mo.st marked.

Moreover, if we take the areas of the cross sections of the various spinal
and cranial nerve-trunks as a measure, it is found that the areas for the afferent
are greater than those for the efferent elements, and that the area of afferent
nerves increases from the cord toward the encephalon.

Organization. — During early fetal life all the cells are isolated from each
other. Either they are without branches as in the earliest state, or the branches,
although formed, have not come into such relations with the neighboring ele-
ments that nerve-impulses are able to pass by way of them. The series of
changes by which the elements are put into the most perfect physiological
connection which they will ultimately attain may be designated as orf/anization.

This change is dependent on two structural conditions — («) the number of
the dendritic branches, and of the terminal and collateral branches of the
neurons, and (6) the relations in which these dendrons and terminal and col-
lateral branches stand to one another.

In the case of cells like tho.se of the cortex, it is to be seen from the
instructive figure of Cajal (see p. 612), that in the vertebrate series the cor-
tical cells tend to possess more branches the higher the animal stands in the
.series, i. e. the more complicated and adaptable its reactions. Further, the
same figure .shows that in the development of the individual cells it passes
from a condition in which it has few to that in which it has many branches.
Certainly the disposition of the cell-substance in the form of branches in-
creases the surface thus exposetl, and, assuming that the nutrition of the cell
takes place over this surface generally, they increa.se its nutritive capacity.
There is, however, another and more important standpoint from which they
may l)e regarded. Cajal has sugge.sted that the dendrons are the pathways
by which impulses enter the cells. If this is true, then the number of den-
drons characteristic of any group of cells may Ije taken as an index of the

CENTRAL NERVOUS SYSTEM.

643

variety of incoming impulses to wliicli they are subject. In the case of the
afferent, central, and efferent groups of cells, the following can be stated:
Unless the l)raneh whicii passes toward the ])eriphery from the cells of the
spinal ganglia be considered as homologous with the dendrons — because it car-
ries incoming impulses — tiiese cells are without dendrons but possess two
neurons. In either case they are subject to but one group of impulses — those,
namely, which enter the cell over the peripheral neuron. The central neuron
ramifies widely within the central system.

Among the central cells we have the greatest variety of arrangement, the
dendrons being insignificant in certain cells of the dorsal horns of the gray
matter, and abundant in the large pyramidal cells of the cortex ; or again, the
granules of the cerebellar cortex with few dendrons may be contrasted with the
large cells of Purkiuje having many — these being taken merely as examples.

Finally, the bodies of efferent calls are characteristically supplied with a
large number of dendrons — again an arrangement which fits with the physio-
logical demands, as they must react to many stimuli though they discharge
but one way and with but one sort of effect.

Connections between Cells. — In determining the connection between
cells, the fact that the neuron is the outgrowth of a cell-body and that each
cell is an independent morphological unit forms the point of departure. Under
these circumstances the question of the connection between cells takes the
more explicit form of the question whether cell-branches become continuous
by secondary union. In mammals, man included, there is no good histo-
logical evidence that such secondary
union occurs in the central system,
A close apj)roximation of the parts
of two nerve-cells is alone to be
seen. The means by which the cells
are brought close together are not
always the same. If the branching
of the neurons in the neighborhood of
the dendrons of the large pyramidal
cells is subject to the interpretation
that the impulses act across the small
intervals that separate these two struc-
tures, then, when it is found that the
neurons in some cases end in an en-
closing basket or frame about the
bodies of the cells of Purkinje, it
would be correct to infer that the ac-
tion took place between the terminals
of the neuron and the bodij of the cell
which they surround. If this infer-
ence is correct, then the dendrons are not necessarily the sole pathways for the
impulses which affect a given cell (see Fig. 164).

Fig. 164.— Showing at the lower edge of the figure
a series of basket-like terminations of neurons
which surround the bodies of the great cells of
Purkinje in the cortex of the cerebellum (Ram6n
y Cajal) : C, cell-body ; N, neurons ; B, basket-like
terminations arising from cell C, and enclosing the
cells of Purkinje.

644

AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

Theories of the Passage of the Nerve-impulse. — Accej)tiug the view
tliat the nervous system is composed of discontinuous l)ut closely apju'oxi-
mated cell-elements, it remains to explain how impulses arising within the
limits of one element are able to influence others.

As an hypothesis, this may be assumed as dependent on chemical changes
set up at the tips of the terminals and affecting the surrounding substance,
which, thus affected, acts to stimulate the neighboring dendrons. As this is
only an hypothesis, it may be left with the statement that it seems to fit in
large measure the group of facts which it is necessary to explain.

The structural changes which permit the stimulation of one element to
affect another are com})leted slowly, and, as we shall later see, these changes
continue in some parts of the human nervous system up to middle life.

From what has just been stated it follows that the nervous system of the
immature person is quite a different thing from that of one mature, since in
the former it is more schematic, more simple, the details of the pathways not
having been as yet filled out. Moreover, considering the slow and minute
manuer in which the central system is organized by the growth of the cell-
branches, it is the last ]>lace where there should be expected structural uni-
formity in the details of arrangement.

B. The Physiological Anatomy of the Nervous System.

It follows from what has already been stated concerning the relations of
cell-elements, that the impulse which enters the central system along a given
dorsal neuron is bound to be first delivered to those cells in the neighborhood
of which the branches of the neuron terminate.

Therefore, in determining the course that the impulses take, the determina-
tion of the mode in which the dorsal root-fibres are distributed is the first step.

Fig. 165.— Schema of the humau spinal cord : D. R, dorsal root, right side ; Col, collaterals from the
dorsal root- fibres; Z). C, dorsal columns ; P, crossed pyramid ; P", direct pyramid ; C, direct cerebellar
tract; A, antero-lateral tract. ^

Afferent Roots. — The manner of this termination is shown in Figures 151
and 165.

Here the afferent neuron having entered into the cord is seen to divide, and

CENTRAL NERVOUS SYSTEM. 645

send one branch caudad, while the otlier [)a.s.ses ceplialad (Fig. 151). The
length of these branches is dillicult of determination, but it ai)|)ears that the
one passing eephahid is probably the longer as a rule, and tliat it may extend
over nearly the entire length of the cord. By means of collaterals, these main
branches are connected with cells witliin the cord, probably both efferent and
central. Through the central cells arranged in series, pathways are formed
by which the incoming impulses may produce an effect at parts of the system
remote from the point of entrance, as well as pass almost directly to the effer-
ent cells in the neighborhood where they enter.

Of these afferent roots there are thirty-one on either side, and for each
dorsal root there is a corresponding ventral one. Due allowance being made
for components which liavc failed to develop, the cranial nerves can be
homologized with them. Considering, then, the longitudinal extension of
the cord, it falls into a .series of segments marked on each side by a pair of
spinal nerves.

Sag-mentation. — The segmentation thus indicated is most evidently
marked by the arrangement of the efferent or ventral spinal nerves. The
studies on the relations between the efferent nerve-fibres and the cell-bodies
which o-ive orig-in to them indicate that the latter are located at the same level
in the cord as that at which the fibres springing from them emerge. This
permits us to infer that the cells of origin for any ventral root tend to concen-
trate in the segment from which that root springs.

The afferent nerve-fibres have in part at least a somewhat extended course
through the cord, and are less strictly limited to the segment with which they
make their superficial connections. At the same time, a number of central
cells belong to each segment, and must be more closely connected with the
dorsal and ventral nerves with which they are immediately associated, than
with any others. Nevertheless the human spinal cord shows but poorly
the segmental disposition of the elements in it wdien compared with that
of lower vertebrates, like the snakes for example, in which the concentra-
tion of the nerve-cells about the region of emergence of the roots is more
evident.

Bilateral Symmetry. — The body being in the main bilaterally symmet-
rical, it is to be expected that the nervous system which controls it will be
constructed in the same manner. Such is, indeed, the case. Architecturally
this symmetry is not perfect, since each cell on one side is not exactly bal-
anced by a corresponding cell on the opposite side, but the number of cells
in corresponding regions is approximately the same, and for physiological
purposes the bilateral symmetry, is quite complete. Yet this arraugeAient is
not without exception.

Dorsal and Ventral Plates. — In the human fetus the shape of the me-
dullary tube, — the tube from which, later, the brain and spinal cord are
developed — is shown in cross section in Figure 166.

Sl'io-ht indentations on either side of the tube are here evident on the inner
wall. They divide each side of the tube into a dorsal and ventral portion.

{)46

.l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Ti^d.r

anil His' has followed these two portions, with a gn^ove dividing thera
througii the entire length of the tube. The dorsal plate {d.p) he designates
as the /'7//</c//>/a/^' (literally, wing-plate), and the ventral plate (u. p.) as the
Grundplatte (literally, foundation-plate). The interest attaehing to these sub-
divisions resides iu the fact that the parts of the
tube thus marked off are loci for cells having
well-marked and different physiological func-
tions. The incoming neurons arriving from
the cells of the spinal ganglia are limited in
the distribution of the main branches to the
dorsal plate, and the cell-bodies which give
rise to the efferent fibres are to be found in the
ventral plate only. The central cells are pres-
ent in both plates, though grouped in the local-
ity where the two plates come together, and
being rather more abundant in the dorsal one.
The collaterals of the afferent fibres are distrib-
uted to both plates. There is thus in the cord
a general arrangement whereby the central cells
are located between the afferent neuron and the
efferent cell-bodies. Far more important than
this, however, is the relation which becomes evi-
dent as we pass cephalad — namely, that the cerebellum, quadrigemina, and
almost the entire mass of the basal ganglia, together with the hemispheres,
are the homologues of the dorsal plates, and contain central cells only (Fig.
167).

Fig. 1G6.— Cross section in the cer-
vical region of a fetal human spinal
cord at the sixth week; X 50 diameters
(Kolliker) : c, central canal ; a, a,
groove separating the two plates ; d.p,
dorsal plate ; v.p, ventral plate, in
which alone are located nerve-cells
the neurons of which leave the central
system ; d.r, dorsal root ; v.r, ventral
root.

Fig. 167.— Schema showing the encephalon and cord ; the unshaded portion is that derived from the
dorsal plate ; the shaded that from the ventral (from Minot) : C, cerebrum ; Cb, cerebellum ; F, foramen
of Monro; /, infundibulum ; .V, bulb; 0, olfactory lobe; P, pons; Q, quadrigemina; Sp.c, spinal cord;
III, third ventricle ; IV, fourth ventricle.

1 His : Abhandlungen d. maXh.-phya. Clause d. kiinigl. Sdcfus. Geeellschafl dcr Wissemcha/Un,
1889.

CENTIiAL NERVOUS SYSTEM.

647

///

There arc then to We expeeted from tlu-se cells, ioniiiiig as they do the
great bulk of the central system, reactions of the same order as those occurring
amony; the eentral cells of the cord.

Decussation.— All through the central system neurons pa.ss from one
lateral half to the other, witness for example the arrangements of the optic
chiasma, the eallosum, the decussation of the
pyramidal fibres and the ventral commissure
in the cord itself. It is to be noted, however,
that the bulk of the commissures is small as
comj)ared with the masses which they connect.
So far as known, the neurons of the dorsal roots
that have entered the dorsal colunni of the cord
on one side of the middle line do not cross, by
their main stems at least, to the other side. As
regards the efferent cells, it appears that the
neurons of some of these do cross in the ventral
commissure, but in the instances above given,
and in the case of the greater number of fibres
belonging to the ventral commissure, the ueurons
concerned are the outgrowths of central cells
(Fig. 168). In the case of the central cells
the decussation may be effected by the entire
neuron or by a principal branch from it. Such
is the arrangement in the case of certain cortical
cells which send one branch to the eallosum
(Cajal). Besides these connections between
parts lying symmetrically on either side of
the middle line, there are of course dorso-ven-
tral connections, but the neurons by which this
is effected do not run in bundles and are there-
fore less obvious and probably less important.

Fig. 168.— Illustrating the partial
and complete decussation of the
fibres of the third and fourth cranial
nerves, and the absence of decussa-
tion in the, case of the sixth: ///,
root of the third cranial nerve; IV,
of the fourth ; VI, of the sixth.

O. Pathway op the Impulses.

Conditions of Stimulation. — In speaking of the nerve-impulses we regard
them as always initially arou.sed at the periphery, using this last term in a
wide sen.se. The conditions necessary for this arousal are an external stimulus,
acting on an irritable nerve-end. While life exists, stimulation of varying
intensity is always going on, aird hence there is no moment at which the
nervous system is not stimulated and no moment at which the effectiveness
of this stimulus is not varied. The response to this continuous and ever-
varying stimulation is not neces.sarily observable, but occasionally the variation
in the stimuli is so wide that an evident reaction follows.

Though the foregoing statements suggest that the chief variable is that
represented by the stimulus, the strength of which changes, yet as a matter of

648 AN AMERICAN TEXT- BOOK OE PHYSIOLOGY.

fact the variations in the j)iiy.si()l()gic'al (cheniica!) condition of tlio nerve-cells
arc eqnally important, and neither factor can be studied independently.

The term central stimulation is sometimes employed. For example, the
spasmodic movements of the young child, when there is no change noticeable
in the external stinndi acting upon it, are sometimes attributed to this cause;
but these, although doubtless due to central changes, altering the irritability
of the cells, are most properly classed with the reactions which follow the
external stimulus. The misconceptions here to be avoided are those of sup-
posing that the nervous system is at any time unstimulated, and that the
evident responses follow a change of the external stimulus only.

Strength of Stimulus and Strength of Response. — AVhere the im})ulse
does not traverse more than one nerve-element, there is a direct relation be-
tween the strength of the stimulus and the strength of the response. The
negative variation in the isolated nerve increases with the intensity of the
stimulus which is sent through it. The same is true for submaximal stimuli
a}>plied to the nerve when the nerve is still attached to a muscle, and the
height of the muscular contraction is measured.

When, however, the impulse in one cell-element is used to arouse an impulse
in another, as in all experiments where the nerve-cells are arranged in a physio-
logical series, the strength of the impulse from the second is less easy to pre-
dict. This is explained as due to variations in the ease with which the impulse
in one element stimulates the next, and also to the variations in the second
cell of those conditions which determine the intensity with which it may
discharge.

When an impulse has once entered the central system the arrangement
of the pathways involves the distribution of it to a larger and larger number
of elements. This may be illustrated by Figure 169.

At the same time that the impulse is thus distributed it tends to die out.
If, as we assume, it is a wave of molecular change that passes along the neuron,
then when the neuron divides the energy in the main stem is distributed to
the mass of substance which forms the branches, and if the mass of these,
as is usually the case, is greater than that of the main stem, then the energy
in any branch will be less than in the main stem.

In the case of some of the cells about Avhich the branches of the neuron
end the impulse will not be adequate to cause in them a discharge, although
it may still produce a certain amount of chemical change in them. The
impulse thus tends to disappear within the system, by producing in j)art chem-
ical changes strong enough to cause a discharge, and in part similar changes
of a less intensity.

Diffusion of Central Impulses. — Thus the general result of sending an
impulse into the central system is that it tends to be distributed and at the
same time to become weaker. Finally, by one or more of the central paths it
reaches an efferent cell which is in a condition to discharge so as to produce
an evident reaction.

If the previous description has been correct, two very important events

CENTRAL NERVOUS SYSTEM.

649

occur: in the first place, the impulse reaches a far greater number of cells
than evidently discharge, an.l in the second, the pathway followed by the nn-

( ^

FIG 169 -schema to show how, by means of the collaterals and the central cells, several Paths are
openTo aS impure coming in over A,A, also showing how an impulse may arrive at a gjven part of a
efferent ceU by more than one pathway among the central cells : C,C, CC . C C , neurons
cells the bodies of which are located in other segments ; E, efferent cell.

pulses which do produce the discharge is by no means the only pathway over
which the impulses can or do travel. u • i

The most convenient illustration of this process of diffusion can be obtained
by a study of the knee-kick or knee-jerk as it is more commonly called.
The reaction in question consists in a contraction of extensor muscles of the
knee in consequence of a blow on the tendon just below the knee-pan. As
a result of this contraction, the leg is extended, and a kick of greater or less
extent is made from the knee joint. Very careful studies of the conditions
controlling this response have been made by a number of mvest.gators
notably Westphal,^ Lombard,^ Bowditch and Warren,^ Weir-Mitchell,

1 Archiv filr Psychiatrk, 1875.
» Joumd of Physiology, 1890.

2 American Journal of Psychology, 1887.
* Philadelphia Medical News, Feb., 1886.

650

AK AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 170.— Record of the knee-kick of a tk'ineiited
patient. The knee wa.s tapped at regular intervals of
five seconds. While the patient was asleep and all
about was quiet, no response was obtained ; after such
an irresponsive period the sound of some one walking
on the floor below caused at ^ a series of kicks which
gradually diminished ; the same at B. At C two taps
with a pencil and a distant locomotive-whistle produced
a longer series. The arrow indicates the direction in
which the record is to be read (Noyes).

Noyes.^ It is fouiul tlmt under given conditions, the variations in the
extent of the kick can be referred to variations in the excitability of tliat
portion of the spinal, cord from which the fibres controlling the muscles take

their origin, namely, the second,
third, and fourth lumbar seg-
ments.

In the same individual under
constant conditions and for short
periods of time, the knee-kick
may be fairly constant in its ex-
tent, but the normal extent for
different individuals may vary
widely, all the way from those
cases in which this reaction is nor-
mally absent to those in which it is
normally very large. In the same
individual there are also variations
from day to day, variations com-
parable for in.stance to those in the
condition of athletes whose capacity
for performing a given feat is, as
we know, by no means constant.
Experimentally the most marked variation which is observed in the extent
of the knee-kick occurs when the patient passes from the waking to the
sleeping state, or vice versa. The regulated blow of a hammer automatically
released, and striking the same point of the tendon, will produce little or no
reaction when the patient is asleep, whereas in full wakefulness the reaction
may be very evident. Figures 170, 171 illustrate such variations.

Attention was first directed to this peculiar reaction for the reason that in
some degree it could be used to test the physiological condition of the spinal
cord, it being found that the knee-kick M'as usually abolished in those condi-
tions in which the lumbar portion of the cord is damaged or its connections
with the higher centres interrupted, whereas it was much exaggerated in those
conditions in which disturbance in the higher centres tended to cause excessive
stimulation of the cord. As soon, however, as the reaction was studied with
greater care in normal persons, it became evident that the condition of this
part of the spinal cord was subject to remarkable ^uctuations, and that these
fluctuations depended in a measure on circumstances which coidd be controlled.
For example, there are here given (Fig. 171) six records showing respectively
the increase in the extent of the knee-kick after the subject was suddenly
awakened; on repeating Browning's Poem, "How they brought the good
news from Ghent to Aix ; " as the result of talking ; in consequence of the
crying of a child in the next room ; and immediately after swallowing. The
point here insisted upon and for which illustration is sought by the accom-
' American Journal of Fsycholoyy, 1892.

CENTRAL NERVOUS SYSTEM.

651

panying figures, is simply this : that an extra stimulus caused by the condi-
tions just enumerated and sent into the central system, often at one very def-

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Fig. 171.— a series of small figures showing various reinforcements of the knee-kick (Lombard); curves
constructed from the original records. Numbers at the left indicate the height of kick in millimeters : A,
subject asleep, when the curve is lowest; * reinforcement after being called; B, first part of curve low;
* reinforcement in the knee-kick on repeating Browning's poem, "How they brought the good news from
Ghent to Aix." C, * reinforcement as the result of talking ; D, * reinforcement due to itching of the ear;
E, * reinforcement due to the crying of a child in the next room ; F, * reinforcement due to swallowing.

inite point, does not limit its influence to that immediate portion of the system,
but in all these cases the nerve-cells located iu that portion of the spinal

052 AK AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cord which controls the knee-kick are so modified that the extent of the
kick is noticeably altered.

There is little doubt that if" there were a means of measuring other motor
reactions and testing their variability as determined by variations in the
incoming stimuli, results concordant with these just given could be obtained.
Thev illustrate a fundamental condition in the reactions of the central system
— namely, that every stimulus which falls upon it alters its responsiveness, and
that it is continually in a state of tension due to the effect of many stimuli
which we often fail to recognize. If we follow strictly the anatomical inter-
pretation, it appears, as a consequence of these observations, that any nerve-
impulse arriving over the afferent pathways can and does affect to a varying
degree all the efferent cell-elements, that there must be a pathway for the
nerve-impulses from some of the terminals of each afferent fibre to the neigh-
borhood of each cell giving rise to efferent impulses.

Variations in Diffusibility. — The degree to which any set of incoming
impulses modifies the responsiveness of the central system depends in the
first instance on the physiological connections of the fibres by which they
travel, and in the second, on the particular condition in which the central
cells happen to be found. As to the first point, we should expect the afferent
nerves with the widest central connections, such as the olfactory, optic, and
auditory nerves, to be the most efficient in this respect, and this is the case.
Concerning the second, it is observed, for example, that by means of drugs it
is possible to alter the diffusibility of incoming stimuli to an enormous extent.
Strychnin and drugs with a similar physiological action have this as one of
their effects.

Influence of Strychnin. — The experimental study of strychnin-poisoning
shows the following relations: A frog poisoned by the injection of this drug
is easily thrown into tetanus whether the brain is intact or has been removed
previous to the injection. The drug is found to have accumulated in the sub-
stance of the spinal cord.' The peculiar change wrought in the nervous sys-
tem is such that a slight stimulus will cause an extended and prolonged tetanic
contraction of the skeletal muscles, i. e. the diffusion of impulses within the
cord is very wide and efficient to an unusual degree. The direct application
of strychnin to the spinal cord has been carefully studied by Houghton and
Muirhead.^ AVhen the strychnin solution was applied locally to the brachial
enlargement of the spinal cord of a brainless frog, a subsequent stimulation of
the skin of the arms produced tetanic contractions of the arms, and later, after
the poison had acted for a time, of the entire trunk and legs. On the other
hand, stimulation of the legs in such a case produced a slight reflex or none
at all. Since in order to cause contraction of the leg muscles the efferent cells
controlling the muscles of the leg must be discharged — and in the one case
Avhen the stimulus was applied to the arm region these cells discharged so as
to cause a tetanic spasm, while in the other, wdien the stimulus was applied to
the legs, they discharged only slightly — the alteration in the cord produced by
1 Lovett : Journal of Physiology, 1888, vol. ix. * The Medical News, June 1, 1895.

CENTRAL NERVOUS SYSTEM. 653

the drug must affect some other group thau these efferent cells. Since, more-
over, a tetanus of the legs could be caused by the stimulation of the skin of
the arm, the application of the drug being to the brachial enlargement only,
it appears that the central cells, or those conducting the impulses entering by
the dorsal root-fibres in the brachial region to the nuclei of the lumbar en-
largement, arc probably affected ; and further, that it is the bodies of these
cells on which the drug must act, since they alone were in the locality at
which the drug was applied. The application of the drug to the dorsal root-
ganglia and to the nerve-roots between the ganglia and the cord proved to
be without effect, so that the two parts which can possibly be influenced are
the terminations of the sensory afferent nerves within the cord and the bodies
of the central cells with which these terminations are associated. But whether
the change is in both these structures or only in one cannot now be determined.

The diffusion of impulses in the central system depends anatomically not
only on the amount of branching among the neurons of the individual cen-
tral cells, but also on the association of many cells together so as to accomplish
this wide distribution of the impulses. In the case of the afferent elements,
as we have seen, the diffusion depends on the branching of the neurons
alone.

Peripheral Diffusion. — Turning next to the efferent system, we find the
conditions for diffusion dependent on the arrangement of several cells in
series. When a group of efferent cells discharges, we know from the arrange-
ment of the ventral roots that the impulses leave the cord mainly along the
fibres which comprise these roots, but where the lateral root is present they
may also pass out over it, as well as over the few efferent fibres found in the
dorsal roots. These neurons carrying the outgoing impulses have two desti-
nations : (1) The voluntary or striped muscle-fibres ; (2) the sympathetic
nerve-cells, grouped in masses to form the vagrant ganglia (see Fig. 163).

In the case of those neurons passing to the voluntary muscles, the impulses
are distributed to the muscle-fibres to which the final branches of the neuron
extend, but there is no evidence that in these localities the impulses, having
entered a given muscle-cell, necessarily pass beyond the limits of that cell by
conduction through the muscle-substance. It thus happens that one part of
a large muscle can be innervated by one bundle of fibres and another part by
a different bundle, or that the same parts of a muscle may be innervated
by fibres which reach it through more than one ventral nerve-root, and also
that with a given stimulus the strength with which a muscle contracts depends
on the proportion of the neurons stimulated, and therefore on the proportion
of the muscle-fibres thrown into contraction.^

When the impulses are thus sent out there is in the case of motor nerves no
diffusion, the effect being limited to the peripheral distribution of the efferent
nerve-elements by way of which the impulses leave the central system. The
fibres going to the voluntary muscles form, however, but one portion, which

^ Gad : " Ueber einige Beziehungen zwischen Nerv, Muskel, und Centrum," Wiirzburger Fest-
fchrift, 1882.

654 A\ AMF.RKAN TEXT-BOOK OF PHYSIOLOGY.

lias just been indicated as gnnij) 1. The connections of the remaining group
(2) are still to be examined.

Sympathetic System. — Associated with the efferent neurons of the cerebro-
spinal system, and with these alone, is the series of vagrant ganglia and also
of peripheral plexuses containing ganglion-cells, which taken together form
the sympathetic system.' This system is composed of nerve-cells always mono-
neuric but sometimes with and sometimes without well-marked dendrons.
The cells are more or less grouped in ganglia, and these ganglia interpolated
between the efferent neurons of the spinal nerve-roots on the one hand and
the peripheral plexuses or secreting cells on the other. The number of cells
in the ganglia is greater than tiie number of spinal neurons going to them,
and hence their interpolation in the course of the ventral fibres increases the
number of pathways toward the periphery, as is shown in Figure 103. In
speaking of the fibres concerned it is desirable to distinguish l)etween the
pre-ganglionic, or those originating in the medullary centres and ])assing to
the ganglia, and the post-gangl ionic fibi'cs, or those originating in the cells
of the ganglia and passing to the peripiiery.

Following the histological observations of Ga.skell ' and the jjhysiological
studies of Langley,^ previously quoted, an outline of the relations of the sym-
pathetic cells, based on those found in the cat, is briefly as follows :

Pre-ganglionic fibres, i. e. those growing out of cell-bodies located in the
cord, arise from the first thoracic to the fourth or fifth lumbar, and from these
segments only (Gaskell). The fibres are medullated. Langley's experiments
indicate that no sympathetic cell sends a branch to any other sympathetic cell.
It has been shown that the pre-ganglionic fibres are interrupted in the ganglia.
The post-ganglionic fil)i-es are in part medullated, though sometimes medulla-
tion occurs only at intervals, but in the main they are gray or unmedullated.

The cerebro-spinal neurons end in the ganglia in such a manner that the
branches of the pre-ganglionic neuron are distributed to a number of the
ganglion cell-bodies, and these cells in turn send their neurons either directly
to the peripheral structures controlled by the sympathetic elements or to the
plexuses such as are found in the intestine and about the blood-vessels.

The same pre-ganglionic fibre may have connections with several cells in
one ganglion, or, by means of collaterals, connect with one or more cells in a
series of ganglia (Langlcy).

Manner of Diffusion. — It has been found that while the cells in a sympa-
thetic; ganglion are so arranged that one ])re-ganglionic fii)re may be in con-
nection with a group of cells, and thus the impulses which pa.ss out of the
ganglion be more numerous than those which entered it, yet the several r/roiips
of cells within tlie ganglion are not connected. In the peripheral plexuses
there appears to be a different arrangement.^

' Gaskell: Journal of Physiolofjy, 188o, vol. vii. ; von Kolliker: "Ueber die feinere Anat-
omie und die physiologische liedeutung des syinpathisclieii Nervensystems," Verhandlungen
Oeselischnfl deidscher Naturforscher und Aerzte, 194, Allgenieiner Theil, 1894.

^ Langley : "A Short Account of the Sympathetic System," Physiological Congress, Berne, 1895.

^ Berkeley : Anatomischer Anzeiger, 1892.

CENTIiAL XKliVorS SYSTEM. 055

It has been observed upon stimulation of the branches of the coeliac plexus
in the (lou;, tliat the several branches, thonj^h unlike in size, bring about nearly
the same ([uantitative reaction, in the constriction of the veins, from which we
infer tliat tliounh enterin-i- the peripheral plexus by diiferent channels, the
impulses find their way to the same elements at the end, owing to a multi-
plicity of i)athways within the plexus.'

Experiments with strychnin on the more proximal sympathetic ganglia do
not show anv increased (liifusibility following the apjdication of the drug, but
on the other hand, Langley and Dickinson Miave shown that nicotin apjjlied
to various sympathetic ganglia of the cat produces a condition whereby elec-
trical stimulation below the ganglion, which in the normal animal is followed
bv dilatation of the pupil, is without effect. Since the application of the drug
to the nerve-fibres on either side of the ganglion is ineffective, when at the
same time the application to the ganglion itself is effective, it is inferred that
tlie drug acts by altering some peculiar relation existing within the ganglion,
and the relation which is assumed to be thus modified is that between the
fibres terminating in the ganglion and the cells which they there control.
The relation between the post-gauglionic fibres and the peripheral plexuses is
not interrupted by nicotin, and hence is different from that between the pre-
ijanglionic fibres and the cell-bodies which they control.

Evidence for Continuous Outgoing Impulses. — Under normal condi-
tions, striped and unstriped muscular tissues are always in a condition of
slight contraction. When the nerves controlling any such set of muscles are
cut, or their central connections injured, the muscles at first relax.

If a frog, rendered reflex by the removal of the brain, the cord remaining
intact, be huug up vertically, it is fouud that the legs are slightly flexed at
the hip and knee. If now the sciatic nerve be cut upon one side, the leg on
the side of the section hangs the straighter, indicating that the muscles have
relaxed a little as the result of the section of the nerve ; if, in the same animal,
the smaller arteries in the web of the foot be examined both before and after
the section, it is found that after the section they have increased in diameter.
Conversely, artificial stimulation of the peripheral stump causes a contraction
of the vessels, but it is not possible in so rough a way to imitate the tonic con-
traction of the skeletal muscles.

It is inferred from these experiments that normally there pass from the
central system along some of the nerve-fibres impulses which tend to keep the
muscles in a state of slight contraction. Destruction of the entire cord abolishes
all outgoing impulses, and produces a complete relaxation of these muscles.

Though the intensity of these outgoing impulses is normally always small,
yet it is subject to significant variations. The diflerence between the tone of
the muscles of an athlete in prime condition and those of a patient recovering
from a prolonged and exhausting illness is easily recognized, and this differ-
ence is in a large measure due to the difference in the intensity of the impulses

• Mall : Archivfiir Anatomie und Physiologic, 1892.

* Proceedings of the Royal Society, 1889, vol. xlvi.

656 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

passing out of the cord. Among tlie insane, too, the variations in this tonic
condition follow in a marked way the nutritive changes in the central system,
and both facial and bodily expression have a value as an index of the strength
and variability of those impulses on which the tone of the skeletal muscles
depends. Indeed, so wide in the insane is the variation thus brought about,
that when the expressions of the same individual at one time in a phase of
mental exaltation and at another in that of mental depression are com-
pared, it appears hardly j)ossible that they can be those of the same person.

This continuous outflow of impulses from the central system is indicated
also by the continuous changes within glands, and the variations in these
metabolic processes according to the activities of the central system.

Rigor Mortis. — Even in the very act of dying, the influence of these im-
pulses can be again traced. The death of the central nerve-tissues being ex-
pressed as a chemical change, causes impulses to pass down the efferent nervesj
and these impulses modify those chemical changes which, in the muscles of a
frog's leg for examjjle, lead to rigor mortis. It thus ha[)pens that a frog sud-
denly killed and then left until the onset of rigor, will under ordinary condi-
tions show this at about the same time in both legs. If, however, the sciatic
nerve on one side be cut immediately after the death of the animal, the begin-
ning of rigor in that leg is much delayed ; thus showing that the nervous con-
nection is an important factor in modifying the time of this occurrence
(Hermann).

Summary. — In their most general form the activities of the nervous sys-
tem can therefore be pictured as follows : The peripheral termini of the sensory
or afferent nerves are isolated and there pass into the central system at least
as many distinct impulses as there are nerves that have been stimulated. The
point of entrance of these impulses is in each case the point at which the affer-
ent nerve connects with the cerebro-spinal system, and these points taken all
together form a corresponding projection of the sensory surfaces upon the cen-
tral system. Once entered into the central system and transmitted to the cen-
tral cells by the collaterals and terminals of the afferent fibre, such an incom-
ing impulse has open to it many pathways among the central cells, and by these
pathways it can reach any group of efferent cells. That all the pathways by
which it can travel are traversed by it, and that all the efferent cells are in
some measure affected, is very probable. Both the diffusion and the response
are, however, subject to wide modifications.

The evident response which we commonly regard as the reaction to any
stimulus, arises from a more or less localized group of efferent cells and
emerges as a series of impulses which pass by the efferent nerves either to find
a comparatively limited expression in the contractions of the voluntary muscles
or enter into the series of ganglia and plexuses forming the sympathetic system
to be distributed in a diffuse manner to the unstriped muscles and the secret-
ing tissues.

In brief, then, the impulses enter the cerebro-spinal system according to
the fixed anatomical relation of the afferent nerves. They leave this system

CENTRA L NERVOUS SYSTEM. 657

according to similar auatoinical restrict ions imposed by tlie arrangement of the
efferent cells, and along the etierent pathway they are directed by isolated
fibres either to the voluntary muscles, or by means of other fibres to the
ganglia of the sympathetic. In this latter subdivision the arrangement is
for diffusion from the proximal to the distal members of the series, and here
the area of tissue finally atlected is large as compared with the part of the
efferent system from which the outgoing impulse may have started. Yet
the point at which the most significant diffusion of the impulses occurs is the
central system.

The afferent elements being single cells only, the amount of diffusion which
may occur is limited to the branches of this one group of elements alone.
The efferent subdivision of the nervous system, so far as it connects with
skeletal muscles, represents a single element, but so far as it is connected with
the sympathetic system there are at least two elements arranged in series. The
arrangement of the central system, however, is but an elaboration of this latter
in so far as the number of elements involved may be increased above two.
Any incoming impulse entering the central system at any point tends to be
diffused over a large portion of the central cells and by them to all the
efferent elements, but the path between the point of the arriving impulse and
that at which the evident discharge originates in the efferent cells is variable.
The permeability of the central system is therefore inconstant, and probably
this inconstancy depends on the one hand on the ease with which the incoming
impulses are transferred to it and from it, as well as the ease with which they
pass among the elements constituting this subdivision itself. The chief prob-
lem in the physiology of the central system is, therefore, to determine how
the nerve-impulses find their way among the central cells and at what point
they pass over to the efferent cells so as to cause an evident response.

D. Reflex Action.

The simplest and most constant of the co-ordinated reactions of the nerv-
ous system are reflex. The term involves the idea that the response is not
accompanied by consciousness, and is dependent on anatomical conditions in
the central system which are only in a slight degree subject to physiological
modifications. This view of reflex activities is in a large measure justified by
the facts, but at the same time it must be held subject to many modifications,
and it is not possible to make a hard and fast line between reflex and voluntary
reactions.

The principal features of a reflex act may be illustrated by following a
typical experiment.

Typical Reflex Response. — If the central nervous system of a frog be
severed at the bulb, so as to separate from the spinal cord all of the portions
of the central system above it, the animal is for a time in a condition of col-
lapse. If, after twelve hours or more, such a frog be suspended by the lip, it
will remain motionless, the fore legs extended and the hind limbs pendent,
though very -slightly flexed. If such a frog were dissected down to the nervous

42

058 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY^

system, tlicre would be f'oiuul the following arrangement: Aifcrciit lil)i-('.s run-
ning from the .skin, muscles, and tendons, and forming the dorsal nerve-root
with its ganglion. The central mass of the cord in which these roots end, each
root marking the middle of a segment. From each segment of the cord go
the ventral root-tibres passing to the muscles lying beneath the skin to which
the sensory nerves are distributed, as well as to the ganglia of the sympa-
thetic system. The mechanism demanded for a reflex response is au afferent
j)ath leading to the cord ; cells in the cord by which the incoming impulses
shall be distributeil ; and a third set of efferent elements to carry the outgoing
impulses. It is important to consider in detail what occurs in each portion
of this reflex arc.

In a frog thus prepared, stimulation of the skin in any part supi)lie(l by
the sensory nerves originating from the spinal cord causes a contraction of
some muscles.

Influence of Location of Stimulus. — The muscles which thus contract
tend to be those innervated from the same segments of the cord that receive
the sensory nerves that have been stimulated. Thus stimulation of the skin
of the breast causes movements of the fore limbs, and stimulation of the rump
or legs corresponding movements of the hind limbs. It is noticeable, how-
ever, that wherever the stimulus is applied, the hind limbs have a tendency
to move at the same time that the muscles most directly concerned contract.

Segmental Reactions. — In attempting to explain this associated contrac-
tion of the leg muscles, it must be remembered that the hind limbs are, par
e.vcellence, the motile extremities of the frog, and therefore all general move-
ments involve their use. We infer from this, moreover, that the arrangement
in the spinal cord of the frog is not such that the sensory impulses coming
into any segment tend to rouse exclusively the muscles innervated by that
segment, bijt that these incoming impulses are diffused in the cord unevenly
and in such a way as to easily involve the segments controlling the legs. As
reflex co-ordinating centres, therefore, the several segments of the cord have
not an equal value.

When the stimulus is applied on one side of the median plane, the re-
sponses first appear in the muscles of the same side, and if the stimulus is
slight they may appear on that side only. The incoming impulses are there-
fore first and most effectively distributed to the efferent cells located on the
same side of the cord as that on which these impulses enter. Such a state-
ment is most true, however, when the stimulus enters the cord at the level
Avhere the nerves to the limbs are given off. At other levels the diffusion to
the limb centres may take place more readily than to the cells in the opposite
half of the same segment. When the muscles of the side opposite contract
it is found that those there contracting correspond to the group of muscles
giving the initial response. The diffiision then tends to be across the cord
and to involve the cells located at the same level as that at which the
incoming impulses enter it.

There is some reason to think that the i)ath by which the diffusion takes

CENTRAL NERVOUS SYSTEM. 659

place is not the shortest one between the two groups of cells, but a path in
which the actual crossinj^ of the inipulsfs occurs t(jwar(l the cephalic end of the
cord, so that tiicy must pass up the cord on one side and down on the other.

Strength of Stimulus. — In a reflex response the strength of the stimulus
intlncnccs the extent to which the muscles are contracted ; the number of
muscles taking part in the contraction, and the length of time during which
the coutraetion continues. That the strength of the stimulus influences the
extent to which the contraction of a given group of muscles takes place is
easily shown when, for example, tlie toe of a reflex frog which has been sus-
pended is stimulated by pinching it or dipping it in dilute acid. In this case,
if the stimulus be slight, the leg is but slightly raised, whereas if the stimulus
be strong it is drawn up high. In the same way by altering the stimulus the
muscles which enter into the contraction may be only those controlling the
joints of the foot, whereas, with stronger stimuli, those for the knee and hip
are successively aflTected, thereby involving a nuich larger number of muscles.
Here, too, we infer a spread of the incoming impulses which is orderly, since
the several joints of the limb are moved in regulai sequence.

The responses which are thus obtained are not spasmodic, but are contrac-
tions of muscles in regular series, giving the appearance of a carefully co-
ordinated movement — a movement that is modified in accordance both with
the strength of the stimulus and its point of application. Moreover, such a
movement may occur not only once but a number of times, the leg being
alternately flexed and extended during an interval of several seconds, although
the stimulus is simple and of much shorter duration.

Continuance of Response. — The continuance of the response after the
stimulus has been withdrawn must be of course the result of a long-continued
chemical change at some point in the pathway of the impulse, and it appears
probable by analogy with the results obtained from the direct stimulation of
the central cortex, that in these cases the stimulating changes are taking place
in the central cells.

Latent Period. — It has been observed that in the case of a reflex frog an
interval of varying length elapses between the application of a stimulus and
the appearance of a reaction. The modifications of the interval according to
variations in the stimulus have been carefully studied. When dilute acid is
used as a stimulus, this latent interval decreases as the strength of the acid is
increased. When separate electrical or mechanical stimuli are employed, the
reaction tends to occur after a giv€f)i number of stimuli have been applied,
although the time intervals l)etween the individual stimuli may be varied
within wide limits. The experimental evidence for electrical stimuli shows
that the time intervals may range between 0.05 second and 0.4 second,^ while
the number of stimuli required to produce a response remains practically con-
stant.

Summation of Stimuli. — A single stimulus very rarely if ever calls
forth a reaction if the time during which it acts is very short, and hence there
* Ward : Arehiv fiir Analomie und Physiologie (Physiol. Abthl.), 1880.

660 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

has deveU)|K(l tlio idea of tlie sumuiatioii of stiimili, implying at some |)art of
the pathway a piling np of the effects of the separately inefiicieut stimuli to
a point at whicli they ultimately become effective.

The details of the changes involved in this summation and the place at
whicii the changes occur are both obscure, but it would seem most probable
that summation is an exj>ression of changes in the relations between the final
twigs of the aliei'ent elements and the cell-bodies of the central or efferent
elements, which permit the better passage of the impulse from one element to
the other, for the evidence strongly indicates that the course of the impulse can
be interrupted at these junctions. The foregoing paragraphs are concerned,
therefore, with changes occurring in the afferent portion of the patliway.

Next to be considered is the amount of central nervous matter which must
be present in tlie frog's spinal cord in order that the reactions can take place.

Reactions from Fractions of the Cord. — U the construction of the cord
was strictly segmental in the sense that each segment contained the associated
nerves for a given band of skin and muscle, there should be no disturbance on
dividing the cord into its anatomical segments, and practically, among the
invertebrates, where the ganglionic chain is thus arranged, the single segments
can perform alone all the reactions of which they are capable under normal
conditions. In such invertebrates the only change effected by the combination
of the segments is that of co-ordinating in time and in intensity the reactions
of the series. If, on the other hand, the segments of the cord were more or
less dependent upon one another, and not physiologically equivalent, modifica-
tions of various degrees would arise according to the segments isolated. It has
been found that the spinal cord of the frog may under special conditions be
reduced to three segments and reactions still be obtained.

During the breeding season the male frog by means of his fore legs clasps
the female vigorously and often for days. If at this season there is cut out
from the male the region of the shoulder girdle bearing the fore limbs together
with the connected skin and muscles and the three upper segments of the
spinal cord, then an irritation of the skin will cause a reflex clasping move-
ment similar to that characteristic for the normal male at this season.^

The Efferent Impulses. — Incessantly the efferent impulses pass out from
the cord to the muscles and glands. With each fresh afferent imjndse those
which go out are modified in strength and in their order, but just how they
shall be co-ordinated is de])endent on so many and such delicate conditions that
even in the simplest case the results are to be predicted only in a general way.

The attempt to determine the spread of the impulse in the cord by deter-
mining the order in M'hich the various muscles of the thigh and leg contracted
in response to thermal stimuli was made by Lombard.^ In a reflex frog the
tendons of the leg and thigh muscles were exposed at the knee, and each
attached to a writing rod in so ingenious a manner that simultaneous records
of fifteen muscles could sometimes be obtained. The stimulus was a metal

' (ioltz : Crntrcdblatt fiir die medicinische Wi.fucnscha/ten, 1865.
* Archiv fur Aiiutomie mid Physiologic^ 1885.

CENTRAL NERVOUS SYSTEM. 661

tube filled with warm water at 47° to 61° C'., \\\\\v\\ was applied to the skiu.
Uuder these conditions it was remarkable that a continuous stinudus was
often followed, not by a single contraction of the muscles, but by a scries of
contractions, suggesting that in the central system the cells are roused to a
discharge and then ai'c for a time concerned with the preparation for sending
out new impulses, and that during this latter period the muscles were relaxed.

Aj)parently a high degree of uniformity in the conditions was obtained in
these experiments, but at the same time the reactions were far from uniform,
in either the latent time of contraction or the order in which the contrac-
tion of the several muscles followed, although certain muscles tended to con-
tract first, and certain series of contractions to reappear. The co-ordination
of the contractions is therefore variable in time, even under these condi-
tions. These variations are probably due either to the fact that the impulses
are not distributed in the centre in the same manner on each occasion, or if
they are thus distributed, the central and efferent cells vary from moment
to moment in their responsiveness. That these cells should so vary is easy
to comprehend, lor all the cell-elements in such a reflex frog are slowly dying.
In this process they are undergoing a destructive chemical change, and with
these destructive changes are generated weak impulses sufficient to cause their
physiological status continually to vary, thus modifying the effects of any
special set of incoming impulses acting upon them.

It is not to be overlooked also that the dissection of the muscles tested,
and the removal of the skiu about them, deprived the spinal cord of the
incoming impulses due to the stretching of the skiu by the swelling of the
contracting muscles and disturbed the order and intensity of such sensory im-
pulses as come in from the tendons and the muscles themselves. However
much these impulses may add to the regularity of the muscular responses, as
apparently they do, in the case of an intact leg, these experiments indicate
that the regularity thus obtained is dependent rather on the constancy of the
incoming stinudi than on any fixed arrangement in the nerve-centres them-
selves. It is thus evident that the discharge of one efferent cell is not neces-
sary in order that another efferent cell may discharge, but that each dis-
charging cell stands at the end of a physiological pathway and may react
independently.

Purposeful Character of Responses. — When the muscular responses of
a reflex frog to a dermal stimulus are studied, they are seen to have a purpose-
ful character, in that they are often directed to the removal of the irritation.
This is demonstrated by placing upon the skin on one side of the rump a
small square of paper moistened with dilute acid. As a result the foot of the
same side is raised and the attempt made to brush the paper away ; if the first
attempt fails, it may be several times repeated. When the irritation has been
removed, the frog usually becomes quiet. If the leg of the same side be held
fast after the application of the stimulus, or if the first movements fail to
brush away the acid paper, then the leg of the opposite side may be contracted
and appropriate movements be made by it. Emphasis has been laid by various

662 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

physiolotjists upon reactions of this sort as sliowin^ a capability of choice on
tlie part of the sj)inal cord, tiius grantinj^ to the cord psychical poxv-ers.
Against such a view it must be urged that the movements of the leg on the
side opposite to the stimulus do not occur until after the muscles of the leg
on the same side have responded. When these responses are inefficient be-
cause the leg is prevented from moving or because they fail to remove
the stimulus, the prime fact remains that the stimulus continues to act and
the diffusion of the impulses in the cord goes on, involving in either case
the nerve-cells controlling the muscles of the opposite leg. The adjustment
of the reaction of the leg, on whichever side it occurs, is, however, far from
precise ; and although the movements of the leg, when the stimulus is applied
far up on the rump, differ from those which follow the application of the
stimulus to the lower part of the thigh, yet in either case they are very wide,
and in both cases the foot is brushed across a large part of both the rump and
\eg. Considering, therefore, the rather general character of these movements,
and the fact that the movement of the opposite leg only follows after a con-
tinued stimulus to the leg of the same side has produced an ineffective response,
it is best to explain the result by the diffusion of the im])ulses within the cord,
leaving quite to one side the psychical element. Such reflex actions are in a
high degree predictable, but in reality this has little significance, since there is
but one general movement that a frog in such a condition can make, whether
the stimulus be applied to the toes or the rump — namely, the flexion of the
leg — so that under these circumstances the prediction of the kind of movement
is a simple matter. The extent of the contraction is related to the intensity
of the stimulus, and is in turn dependent on the excitability of the central
system, which can be increased or diminished in various ways. The modifi-
cation of the reaction as dependent on the location of the stimulus can be in a
measure predicted, but the modification is wanting in precision just in so far
as the movements themselves are wanting in this quality.

Periodic Reflexes. — Not all reflexes are to be obtained from the same
animal with equal intensity at different times. In genei-al, frogs in the spring-
time and in early summer, after reviving from their winter sleep, are highly
irregular in their reflex responses — so irregular that students are advised not to
attempt the study of these reactions at this season. On the other hand, it is
during the spring that the mating occurs, and during this period the male
clasps the female and exhibits the peculiar reflex which has already been
described. Comparable with this variation in the frog must be the changes
which occur in the spinal cords of migratory birds which both in the spring
and in the fall are capable of such extended flights, or in the svstem of hiber-
nating mammals and all animals exhibiting extensive periodic variations in
their habits of life.

General Applicability of these Resiilts. — There are manv reptiles and
fishes in which the arrangement of the S])inal cord is more simple than that in the
frog ; such are the animals in which the actions of locomotion are verv uniform,
and in which these locomotory actions represent the principal responses of the

CENTRAL NERVOUS SYSTEM. 663

muscles whatever the stiniuhis. In these cases small segments of the body
will perform the hx'oiiiotor reactions when the segments of the spinal cord
belonging to thcin are intact (Stciner).^ Tarchanow has shown tliat l)eheaded
ducks can still swim and tly in a co-ordinated manner, and among mammals
(dog and rabbit) Goltz and others have demonstrated that if the lumbar region
be separated from the rest of the cord by a cut and the animal allowed to
recover from tiie operation, it will with proper care live for many months,
and not only are the legs responsive to stimulation of the skin, but the reflexes
of defecation and urination are easily induced by slight extra stimulation. An
instructive reaction occurs when such animal is held up so that the hind legs
hang free. When thus held the legs slowly extend by their own weight and
then are flexed together. The reaction becomes rhythmic and may continue
for a long time. It is assumed in this case that the .stretching of the skin and
tendons due to the weight of the pendent legs acts as the stinmlus, and in con-
sequence the legs are flexed. This act in turn removes the stimulus, and as a
result they extend again, to be once more stimulated and drawn up.

In man, as a rule, death rapidly follows the complete separation of any
portion of the cord from the rest of the central system, especially if the sep-
aration be sudden, as in the case of a wound. But Gerhardt^ has recorded
the retention of the reflexes in the case of compression of the cord by a tumor,
the case having been under observation for four and a half years ; and Hitzig '
a case in which a total separation between the last cervical and first thoracic
segments had been survived for as long as seven years. The principal reac-
tion to be observed in such cases is a contraction of the limb muscles in
response to stimulation of the skin, such as a drawing up of the legs when
the soles of the feet are tickled. No elaborate reflexes are, however, retained
in connection with the muscles of locomotion. In the normal individual
reflexes involving striped muscles are found in the tendon reflexes, of which
the knee-kick is an example, in winking, and the whole series of reflex modi-
fications of respiration, such as coughing, sneezing, and the like.

The activities of the alimentary tract are examples of reflex actions in-
volving the peristaltic contraction of unstriped muscles in deglutition, defe-
cation, and similar peristaltic movements in other hollow viscera. So, too,
micturition, the cremaster reflex, emission, and vaginal peristalsis and the
reactions of parturition are to be classed here. Moreover, the entire vascular
system is controlled in this manner, the contraction and distention of the
small arteries being in a large measure in response to stimuli originating at a
distance ; while as a third group we have the glands, the activity of which is
almost entirely reflex.

It thus appears that the reflex responses, namely, simple reactions unac-
companied by consciousness, are in man mainly given by the unstriped mus-
cle-tissue and by glands, and only in a minor degree by the striped muscles.
Moreover, while the typical reflex is a reaction over which we cannot exercise

' Die Functionen des Centralnervensystems der Fuiche, Braunscliweig, 1888.

» Neurobgische Centrcdblait, 1894, S. 502. ' Loc. cU.

I)u4 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

direct control, the normal individual has some power over many of" these
reactions ; for example, the impulse to micturition or defecation can be thus
delayed, respiration arrested, and in some instances, so remote a reaction as
the beat of the heart either accelerated or slowed at will.

It is of interest to note that many reflexes which in the young are not
controlled, as micturition for instance, become so gradually — a change most
j)robal)ly dependent on the growth of neurons from the ce})halic centres into
the cord, thus subjecting the cord-cells to a new set of impulses which modify
their reactions. That such is the case is indicated by the fact that extreme
fright or anaesthetics which diminish the activities of the higher centres often
cause these reactions to take place involuntarily. Other reflexes are present
in early life, but disappear later; such are the sucking reflex of an infant, and
the remarkable clinging power of the hands, by which a young child is
enabled to hang from a bar, thus supporting the weight of its entire body,
often for several minutes. This last capacity soon begins to wane, and usually
disappears by the second month of life (Robinson, Nineteenth Century, 1891).

The Nervous Background. — We return now to the conditions which
modify the spread of the imj)ulses within the central system, when this
system is represented by the spinal cord of a reflex frog. Admittedly, there
is here j)resent but a fraction of the central system. It lias been shown that
all incoming impulses tend to spread over a large part of the central system.
In a reflex frog, therefore, the cord is cut ofiF from the remote effects of
impulses which normally enter the system by way of cells located in the por-
tion removed. Moreover, in the complete nervous system, the incoming
impulses tend to be transmitted to the cephalic end, and in some measure
give rise to impulses returning within the central system and afi'ecting the
efferent cells. In a fragment of the central system like the cord, such im-
pulses taken up by the central cells must pass so far as the neurons are intact,
but as these end at the level of the section, such impulses are lost, in the
physiological sense, at that point.

The fact, therefore, that the experiments with sj)inal reflexes are conducted
on a portion of the central system has two im])ortant j)hysiological conse-
quences. In the first place, there are w^anting incoming imjndses, direct or
indirect, from the portion removed ; on the other hand, through the section
of the afferent neurons, in their course w-ithin the central system, there is a
direct diminution in the number of the pathways by which the impulses arriv-
ing at the cord may be there distributed. It is most probable that in the frog,
at least, the reduction of the central mass does not so much diminish the num-
ber of pathways by whi(!h the impulses may be immediately distributed by way
of the afferent and central elements, as it diminishes the number of impulses
wdiich by way of the portion removed arrive at the efferent cells and modify
their responsiveness.

The modification of the responsive cells under more than one impulse is
well illustrated by an experiment of Exner :' A rabbit was so prepared that an
' Arckiv fiir die gesammte Physiologic, Bd. xxvii.

CENTRAL NERVOUS SYSTEM.

665

electric stimulus could We uppliiil to the cerebral cortex at a j)()int the excita-
tion ot" wliifli caused colitractiou of certain muscles of the foot. One of these
muscles was attached to a lever so that its contraction could be recorded, and
a second electrode a})})lied to the skin of the foot overlying the muscle. The
discharging efferent cells in the cord were in this case subject to impulses from
two directions, one from the cortex and one from the skin of the foot. With
a current of given strength stimulation of the cortex alone caused a contrac-
tion of the muscle, and stimulation of the skin of the foot alone, a similar
contraction. When both were stimulated simultaneously, the extent of the
contraction was greater than when either was stimulated alone. If now the
strength of the stimulus applied to the skin was so reduced that, alone, it was
inefficient, then a stimulus from the cortex, which produced a reaction, as
indicated by the first cortical stimulus in Figure 172 (^1, a), put the efferent

Moremeiil of pmr.

'

stimulation of cortex.

»"'

A

»"

JJ; b' " paw.

^h

Time in .feanids.

i L_r-

"\_A

\_\

\_\ ^_r

rAHHrlrirlrViiirii

Fig. 172.— To show the reinforcing influence of stimuli applied to the cerebral cortex and to the skin
of the paw, on tlie movements of the paw of a rabbit (Exner). The arrows indicate the direction in
which the curves are to be read. In curve A the cortical stimulus at a causes a movement of the paw.
Dermal stimulus, within a second, at b causes a movement of the paw. Cortical stimulus at a' causes a
movement of the paw. Dermal stimulus several seconds later at b' is ineffective. In curve B dermal
stimulus at b is ineffective. The cortical stimulus at a several seconds later is also ineffective. The
dermal stimulus at b' is ineffective, but if followed within 0.13 second by a cortical stimulus at a' a move-
ment of the paw occurs.

cells in such a condition that the stimulus from the skin {A,b) Figure 172,
applied within 0.6 second, produced a second contraction of the muscle,
although, alone, the stimulus from the skin had proved inefficient. Here the
first efficient stimulus from the cortex had rendered the discharging cell, for a
short period of time, more excitable. In the same figure the record shows that
if a longer interval, here more than three seconds, be allowed to elapse, then
the second stimulus from the skin remains inefficient. A similar relation be-
tween the two incoming impulses is also found to hold, when the stimulus
from the skin is made to precede. The curve B, Fig. 172, shows the results
when both stimuli are inefficient. In this the stimuli {b and a) produce no
effect when given several seconds apart, but when they occur within a short
interval (6' and a') — in this case 0.13 second — a contraction of the muscle
follows. These various experiments, taken together, show in a beautiful way
that in the cases chosen the two sets of impulses tend to reinforce each other,
whether they are efficient or inefficient, and without regard to the order iu
which they come.

This relation between the discharging cell and those by way of which it is
stimulated can be illustrated in still another way. It was observed by Jen-
drassik ^ that when a patient was being tested for the height of his knee-kick,
^ DeiUsches ArcMv fUr hlinische Mcdicin, Bd. xxxiii.

6GG

.l.y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a voluntary muscular contraction, or an extra sensory stimulus occurrini; about
the same time that the tendon was struck, had the eil'ecf of" increasing the height
of the kick. This was studied in detail by Bowditch and Warren/ and they
were able with great exactness to measure the interval between the contraction
of the muscle used for reinforcement and the time at which the tendon was
struck. The curve shown iu Fig. 173 represents the results of these experi-

40-

30-

2D-

10-

0

10-

20-

30-

.V .1/

\

\.
'\

! \

ir

Xnrinal.

Time.

OrOZ" 0.4"

OJ"

lor

1.7-

FiG. 173.— Showing in millimeters the amount by which the " reinforced " knee-kick varied from the
normal, the level of which is represented by the horizontal line at 0, " normal." The lime intervals
elapsing between the clenching of the hand (which constituted the reinforcement) and the tap on the
tendon are marked below. The reinforcement is greatest when the two events are nearly simultaneous.
At an interval of 0.4" it amounts to nothing: during the next 0.6" the height of the kick is actually
diminished the longer the interval, after which the negative reinforcement tends to di.sappear; and
■when 1.7" is allowed to elapse the height of the kick ceases to be affected by the clenching of the hand
(Bowditch and Warren).

ments. It indicates that in general the closer together these two stimuli occur,
the greater the reinforcement. At an interval of 0.4 second no effect is pro-
duced by the muscular contraction. Increasing the interval only very slightly
has, however, the effect of greatly diminishing the height of the knee-kick —
i. e. decreasint; the strength of the discharge of the efferent cells — and this
effect is not lost until the interval is increased to 1.7 second, when the volun-
tary muscular contraction ceases to modify the response. A given efferent cell
is thus modified in its discharge according to the several stimuli that act upon it.
Effects of Disuse. — Studies on inactivity show that a certain amount of
exercise in any given cell is necessary for its proper nutrition, and if the exci-
tation fall below the point which causes this, the responsiveness of the cell is
diminished.

For example, a strychnized reflex frog on being dipped into a solution of
cocaine loses iu so large a measure its irritability that its responsiveness falls
far below that of a normal frog.^ In this case the central system is deprived
by the action of the cocaine of the impulses which even in the absence of any
special form of irritation normally arrive from the .>^kin, and the abolition of
these impulses causes a diminution iu central responsiveuess. Effects which

^Journal of Physiology, 1890, vol. xi.

* PoulssoD : Archil' J'iir Palholofjie und eiperimenielle Pharmakologie, 1885, Bd. xivi.

CENTRAL NERVOUS SYSTEM. 667

cau tluis be accomplished in a few seconds by cutting off the afferent impulses
from the skin may of course follow any slow diminution in these impulses,
althougii all such slow changes are nuu-h more likely to be accompanied by
some sort of compensation whereby other alferent impulses in a measure take
the place of those which have been sup})resse(l. The loss of these impulses
which rouse the cells to activity is usually a more important condition than
direct nutritive change, and must for this reasou always be kept in view.

Inhibition. — On the other hand, let one leg of a reflex frog be stimulated
in the usual manner by pinching or by acid, and then the experiment repeated,
while the other leg is lightly pinched at the same time, and it will be found
that either the latent period preceding the response is increased or, with the
strength of stimulus employed, the reaction does not occur. This is an ex-
ample of inhibition which can be caused by the simultaneous excitement of a
nerve-cell in several ways.

To obtain inhibition there nuist be at least two pathways by which impulses
reach a given cell, and the two stimuli must tend to excite different reactions.
When they tend to excite the same reaction a reinforcement follows. The inhi-
bition, therefore, is connected with the effect of these two sets of impulses upon
the responding cell, and that is always associated with the fact that as the two
paths end in different relations to the cell, the impulses must enter it at differ-
ent points, and hence in the first instance tend to act on different portions of
the cell-contents.

Though at the present time it is not possible to give a theory of inhibition
that will be general and satisftictory, there is enough known to indicate that
this effect, when developed in the central nervous system, is not produced by
a special set of nerve-fibres, but is the result of the action of several incom-
ing impulses, arriving by different paths, on the responsiveness of a given
cell.

E. Voluntary Actions.

On attempting to distinguish between a voluntary and reflex act from the
physiological standpoint, we find the chief difference to be that the voluntary
act is not predictable, because, according to the capabilities of the animal, it
may be more variable in form than is the reflex response, and also because,^
instead of occurring within a short interval after the stimulus, as does the
reflex, the voluntary response may be delayed even for years. For example,
we read in a book some statement that makes us desire to question the author.
The question is a response to the stimulus given by the printed page, and it
may be carried out by writing a letter within a few hours, or delayed until a
meeting with the author years hence. During this interval, and in the absence
of the author, the reaction which will take the form of a question remains
incomplete, while his presence is sufficient to set in motion the train of stimuli
which shall cause it. Moreover, consciousness enters as an element into such
reactions, and there is present a mental image of the act to be accomplished,
together with some remembrance of its execution.

61)8

.l^y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

For the most complex vuluiitiiry reactious tlic entire central .sy.stem is
necessary, aud especially the cortex of the cerebral hemispheres, while it has

already been shown that the impulses
which cause reflex actions can make
their circuit in a very limited portion
of the spinal cord. In the case of vol-,
untary reactions the impulses take a
longer pathway and involve a larger
number of nerve-elements, since from
the point at which they enter the sys-
tem they must pass to the cephalic end.
At the same time, in a voluntary reac-
tion a greater number of impulses com-
bine to modify the discharge from the
efferent cells.

Tracts in the Central System. —
How this result is accomplished has
been studied both in mammals and in
man. Histology shows us the fibres of
the dorsal root entering the cord and
sending one branch cephalad and the
other caudad, both branches giving off
collaterals (Fig. 174). In man and the
higher mammals the dorsal root-fibres
enter the cord in three groups — a me-
dian group, an intermediate group of
large fibres, and a lateral group of
very fine fibres, the bundle of Lissauer.
When the dorsal root is sectioned be-
tween the ganglion and the cord, all
these fibres degenerate.
The degeneration extends in the doreal columns down the cord two or
three centimeters from the level of the section, and also up the cord as far as
the nuclei of the dorsal columns, located at the commencement of the bulb.
If the section is made near the caudal end, the degeneration may in conse-
quence run through the entire length of the cord. Moreover, it occurs only
on the side of the cord to which the sectioned nerves belong. Take, for
example, the area of degeneration caused by the section in a dog of the dorsal
roots on the left side between the sixth lumbar and second sacral nerves.
The degeneration in the lower lumbar region is represented in Figure 175, A,
in the upper lumbar region in B, and in the thoracic in C. On passing
cephalad the area of degeneration becomes smaller. This is interpreted to
mean that all along, between the caudal and cephalic limits, fibres are given
off from the main bundle to the intermediate segments of the cord. Here is
evidence of an arrangement that is always to be kept in view. Though a

Fig. 174. — Schema showing pathway of the sen-
sory impulses. On the left side 8, S' represent
afferent spinal nerve-fibres ; C, an afferent cranial
nerve-fibre. This fibre in each case terminates
near a central cell, the neuron of which crosses
the middle line and ends in the opposite hemi-
sphere (van Gehuchten).

CENTRAL NERVOUS SYSTEM. 669

number of fibres among those degenerating after section of the dorsal roots
may run tlie longer course, the larger portion run a short or an intermediate
course, and are therefore distributed at different points between tlie termini.
Injury to the dorsal roots at different levels shows, moreover, that the fibres

Fig. 175.— Sections showing the degeneration in the dorsal columns of the dog's spinal cord when the
dorsal roots from the sixth lumbar to the second sacral have been cut on the left side (Singer) : A, level
of the sixth lumbar; B, level of the fourth lumbar; C, level of the sixth thoracic. Degenerated area in
black.

from a given level which run the length of the dorsal columns do not mingle
indiscriminately with those from other levels, but form a bundle, and that
this bundle in the cephalic part of the cord tends to lie nearer the middle line
the more caudad the level from which it arises.

From these relations it is evident that comparatively few of the dorsal
root-fibres run the entire length of the dorsal columns. If, then, it is remem-
bered that in describing the arrangements of the cord emphasis is usually
placed on the very short pathways formed in part by collaterals and con-
cerned in the simpler reflexes, and on the longest pathways concerned in the
voluntary reactions, as two extremes between which are to be found a more or
less complete series of intermediate arrangements, the unevenness of the pre-
sentation can be corrected.

Since these fibres in the dorsal columns of the cord degenerate on destruc-
tion of the dorsal roots, it is inferred that they must be morphologically con-
tinuous with certain fibres in the roots, and, since the dorsal roots are aflFerent
pathways, they too must form part of the afferent pathway in the cord.

It is of course a portion only of the afferent pathway that is thus formed,
for both the intermediate and lateral groups of root-fibres enter the gray
matter of the dorsal horn, and must there come into physiological connection
with otlier nerve-cells both central and efferent. The fact that the connection
is only physiological accounts for the arrest of the Wallerian degeneration at
these points after section of the dorsal roots.

The continuation of the paths for the afferent impulses must therefore be
formed by the neurons of the central cells with which the dorsal root-fibres
connect.

Degeneration after Hemisection of Cord. — Upon heraisection of the
cord involving one lateral half the ascending fibres which degenerate appear
in the dorsal columns, in the dorso-lateral a.scending tract, and in the ventro-
lateral ascending tract. The number of degenerated fibres is large on the side
of the lesion, but on the opposite side there are also degenerated fibres in all

(JTo AN AMERICAN TEXT-BOOR' OF J'HVSIOLOGY.

these localities, although thoy aiv hy no means so imiiiorous. It is interred
that all the fibres which thus degenerate form paths for the aflPerent impulses.

The impulses which come in over a dorsal root on one side can therefore
find their way cephalad either hy the direct continuations of the dorsal root-
fibres running in the dorsal column of the same side, or bv wav of central
cells in the lateral column of the same side of the cord, and also to a less
degree in the lateral and dorsal columns of the opposite side.

The tracts which undergo Wallerian degeneration after this treatment
inelude. therefore, those formed by the neurons arising from central cells.
These cells have their cell-bodies arranged in a column running the length
of the cord. In the neighborhood of this column some of the dorsal root-
fii)res terminate. In the bulb we are familiar with such groups of cells, well
marked as the " nuclei of the sensory nerves," and these cells in the cord,
though far less clearly segregated, are the homologues of those in the bulb.
If this is granted, then the fibres which are continued from these central cell-
groups, whether in the cord or bulb, are also homologous.

Corroborative of what has been said on the subject of afferent pathwavs in
the cord are the results of Pellizzi.^ He studied dogs, making use of the
method of Marchi, whereby the nerve-sheaths of fibres beginning to degen-
erate or the nutrition of which is disturbed give a characteristic reaction ; he
found, after heraisection of the cord, the same lesions that have been described
above, with the addition that the changes could also be followed in some of
the fibres of the ventral roots. More significant, however, is the fact that
section of the lumbar and sacral dorsal roots, without direct injury to the
cord, gave rise to modifications of the medullary sheaths, detectable by the
method of Marchi, in all the localities just named.

A distinction must be made at this point. Wallerian degeneration in the
central system means eventual de.struction of the severed fibre. The method
of Marchi shows a characteristic change in fibres entering upon this degen-
eration, but this method also shows changes in the sheaths of elements which
are only physiologically connected with those about to undergo Wallerian
degeneration, but which themselves are, as a "rule, not ultimately destroyed.
Under the usual conditions of experiment Wallerian degeneration is confined
within the morphological limits of a single cell-element, but the physiological
changes in the cells overstep this limit, as shown by Marchi's reaction. It is
proper to add, also, that Wallerian degeneration may under some conditions
extend to a group of nerve-cells only j)hysiologically connected with those
suffering the initial injury.

Physiological Observations on Afferent Path-ways. — Making use of
the fact that strong stimulation (jf the sensory fibres, such as those in the
sciatic nerve, causes a rise in blood-pressure, Woroschiloff''^ sought to block
the passage of the impulses causing this reaction by section of the cord in
different ways in the upper lumbar region of the rabbit. It appears that in

' Archives Ilaliennes de Biologie, 1895, Bd. xxiv.

^ Berichte der math.-phys. Clause d. k. Gesellsch. d. Wissen. zu Leipzig, 1874.

CENTRAL NERVOUS SYSTEM. 671

this animal the reaction was most diminishccl — that is, stimulation of the
sciatic produced least rise in the blood-pressure — when the lateral columns of
the cord had been cut through ; and that the effect of section of the lateral
column on the side opposite to that on which the stimulus was applied was
greater than that following section of the column on the same side. These
experiments are open to the criticism that tiie results are proved only for a
very limited set of conditions, and hence it would be unwise to make any
broad inference from them ; yet at the same time they form a very definite
part of the evidence which directs our attention to the lateral columns of
the cord as a principal afferent pathway.

The phvsiological observations of Gotch and Horsley ' indicate that when
in a monkey a dorsal root is stimulated electrically, then 80 per cent, of the
impulses pass cephalad on the same side of the cord, while the remainder cross.
Of the 20 per cent, that cross, some 15 per cent, pass up in the dorsal columns.
The dorso-ventral median longitudinal section of the cord in the monkey
(sixth lumbar segment) - shows an ascending degeneration in a small part of
the dorsal area of the direct cerebellar tracts and of the ventro-lateral tracts,
as well as in the columns of Goll. This would indicate that the section had
cut fibres which crossed the middle line and ran cephalad in these localities.

These investigations all point to the several tracts most closely connected
with the dorsal nerve-roots as the paths for the sensory impulses. The experi-
mental results, taken together, are by no means accordant, but not necessarily
mutually exclusive : confusion must, therefore, not be permitted to enter here
through any unwarranted attempt to combine observations which should really
be kept apart, and the failure of which to harmonize is in large degree an ex-
pression of the physiological complexity of the cord.

Osawa ^ found that when the cord in a dog was hemisected (in the upper
lumbar or lower thoracic region) the animal showed for the most part no per-
manent disturbance of sensation or motion.

If the cord is first hemisected on one side, and later on the other side, the
second hemisection being made a short distance above or below the first, sen-
sation and motion persist behind the section, although they are somewhat
damaged. After three hemisections, alternating and at different levels, there
still remained a trace of co-ordinated movement possible to the hind legs,
although the sensibility of the parts could not be clearly demonstrated. The
path thus marked out for any afferent impulses is certainly a tortuous one.
These observations were followed by a number of others, the most important
of which in this connection are the following :

Section of all parts of the cord except the two lateral columns (in the lower
thoracic region, Fig. 176) was without influence on the sensibility or move-
ments of the hind legs. After section of the entire cord, with the exception of
the dorsal and ventral columns and the intervening gray matter, sensation was

^ Croonian Lectures, Philosophical Transactions Royal Society, 1891.

^ Griinbaum : Journal of Physiology, 1894, vol. xvi.

' Untersuchungen Uber die Leitiingsbahnen im Riickenmark des Hundes, Strassburg, 1882.

672

AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

nearly destroyed, while the voluntary niovemeuts of the leg were but slightly
disturbed (Fig, 177), After section of the entire cord, with the exception of
the dorsal columns, both sensation and motion were lost (Fig, 178),

Fig, 176.— Outline of the
spinal cord of a dog;
the shaded portion indi-
cates the extent of the
lesion. The lateral col-
umns of the cord are in-
tact (Osawa).

Fig. 177.— Outline of the spi-
nal cord of a dop; the shaded
portion indicates the extent
of the lesion. The dorsal and
ventral columns, together
with the intermediate gray
matter, are intact (Osawa).

Fig. 178.— Outline of the spi-
nal cord of a dog; the shaded
portion indicates the extent
of the lesion. The dorsal
columns alone are intact
(Osawa).

Here are a number of very striking results. It is to be noted that the
lateral columns of the cord form the important pathway for all the impulses
which influence sensation and motion caudad to the section, but, at the same
time, section of them causes a marked diminution of sensation alone. On the
other hand, the preservation of the dorsal columns alone does not preserve
sensation.

It will be understood, of course, that the motion in question is executed
by muscles lying caudad to the section and is co-ordinated with that of the
structures lying in front of it. Similarly sensation was inferred from move-
ments executed in front of the level of the section and caused by stimulation
behind it.

A double hemisection of the spinal cord as described above seems to involve
an interruption of all the long pathways. Yet the nervous impulses pass
such a block in both directions. Probably within the central system as
elsewhere the amount of information conveyed is not directly dependent on
the number of nerve-fibres stimulated. In general, a very small number —
those brought into action by pulling out a single hair — are as efficient in
co-ordinating our re.spon.ses as would be the stimulation of a thousand times
the number. Such being the ca.se, it is not impossible that although after the
sections of the cord both the number and intensity of the impulses that pass
the point of section may be diminished, yet they may still remain sufficient to
modify the reactions of the caudal portion of the cord, which is in no very
great degree dependent on such modifying impulses. That the impulses may
pass along a cord twice hemisected on opposite sides demands the aid of the
gray matter, and we at once refer to the short fibre-tracts as the pathway.

It is a drawback to such a view that physiologists have not been accustomed
to lay much weight on the connections established by these short tracts, but
from the anatomical side there is no inherent difficulty in accounting for many

CENTRAL NERVOUS SYSTEM. 673

reactions by means of them. It is evident that, so far as the dog is copcerned,
the long and preferred pathways in the spinal cord are by no means the only
pathways, and, though probably the human cord offers fewer possible alter-
natives, the arrangeuR'ut is j)resumi)tively according to the same plan.

Specific Nerves. — In order to analyze the afferent pathways still further,
we next inquire whether among the dorsal nerve-roots which pass between the
cord and periphery there are separate nerve-fibres for eacli of the modes of
sensation represented by pressure, heat, cold, pain, and the nmscle-sensation.
The data available for determination of this question are not of the best, but
are still of some value.

The number of dorsal root nerve-fibres on both sides was found (in a
woman twenty-six years of age) by Stilling to be approximately 500,000,
which is probably an underestimate.^ The area of the skin in a man of 62
kilograms (136 pounds), and twenty-six years of age, was found by Meeh
to be 1,900,000 square millimeters.^ Taking three-fifths of the number of
the dorsal root-fibres (300,000) as the portion going to the skin, the other
two-fifths going to the muscles and joints, there is evidently one nerve-fibre
to innervate, on the average, about 6 square millimeters of skin.

It is recognized that dermal innervation is extremely unequal, as the experi-
ments on tactile discrimination and the like all indicate. The average distri-
bution which has just been suggested must therefore be subject to local modi-
fications that are very wide. Moreover, Woischwillo ^ has determined that in
man the skin of the arm is three times better supplied with sensory nerves
than that of the leg. In both arm and leg the relative abundance of the
sensory nerves increases toward the extremity of the limb. This increase is
specially marked in the leg. Assuming, however, one nerve-fibre to 6 square
millimeters to be the average relation, it becomes a serious matter to postulate
separate groups of fibres for each mode of dermal sensation, since each time
a new set of fibres is admitted the area of the skin innervated by any one
fibre with a given function is thereby increased.

The histological evidence for the area of skin innervated by a single sen-
sory fibre has still to be gathered, but in the mean time physiological observa-
tions indicate that the area controlled by a single fibre cannot be indefinitely
extended, and the suggestion of a new category of nerve-fibres needs very
ample evidence to make it plausible. This being the case, there is good reason
to limit the number of categories of nerve-fibres.

In every case the fibres carrying the impulses which come from the skin
arise as outgrowths of the spinal ganglion-cells. Trophic nerves as a special
category are not recognized, nor reflex nerves, the functions attributed to the
latter being now explained by the collaterals of the afferent fibres. At pres-
ent it is sometimes maintained that there must be special nerves for pain, pres-

^ Stilling : Neue Untersuchungen iiber den Bau des Riickenmarks, Cassel, 1859.
^ Zeitschrift fiir Biologie, 1879, Bd. xv.

* " Ueber das VerhJiltniss des Kalibers der Nerven zur Haul und den Muskeln des
Menschen," Inaug. Diss. (Russian), 1883, vide Centralblatt fiir Nervenheilkunde, 1883, Bd. vi.
43

674 AN AMKRHWN TEXT-JiOOK OF Pll YSIOIJXI Y.

sure, lioat, and cold. Tlie evidence foe lliose of pressure and heat and cold i.s
the most satisfactory.

Pain. — Upon severe stimulation of the skin or muscles the noi-mal person
exj)eriences a distinct sensation of j)ain. There is, however, threat variation
in the intensity of this sensation when the same stimulus is ai)plied to dill'erent
pereons.

If we include abnormal persons, it is found that while in a few cases com-
plete absence of painful sensations has been noted — the other sensations
remaining normal — there are at the other end of the scale those cases in which
pain is produced by many stimuli, wdiich would not have this effect on persons
in ordinary health. The capability of a given stiniulus to ]iroduce pain is
therefore subject to w'ide variations according to the general condition of the
subject.^ The same stimulus has different effects in a given individual accord-
ing to several circumstances. Peripheral irritation, such as an inflammatory
process in the skin, greatly increases the intensity of the pain caused by the
stimulation of the nerves supplying the locality. Continued stimulation of
the sensory nerves of the muscles and viscera has the same effect.^ Local
anaesthetics, such as cocaine, may reduce the sensibility to zero, and the same
follows the general anaesthesia produced by chloroform, ether, nitrous oxide,
morphia, and similar drugs. Painful sensations are distinct and powerful
only Avhen the stimulus is applied to general sensory nerve-trunks — /. e. those
mediating cutaneous, muscular, and visceral sensibility — while the nerves
which mediate the special sensations of light, sound, taste, and smell do not
give pain even on excessive stimulation.

Limiting our observation, therefore, to the nerves of cutaneous sensibility,
it is found that the sensations of pressure, heat, and cold may all be present to
a normal degree, and yet increasing the stimulus be without effect in causing
any painful sensations whatever. This would represent a condition of com-
plete analgesia. Moreover, the capacity of the skin to cause abnormal painful
sensations upon the adequate stimulation of each of these groups of nerves
may be associated (in lesions of the central system) with any one group alone,
the abnormal pain-sensations thus produced being either those of excess or
deficiency.

We advance the hypothesis, therefore, that each of these three sensations,
if pushed to excess, is usually accompanied by pain of gradually increasing
intensity. Therefore it is most probable that these nerves when slightly
stimulated mediate their proper sensations, but when this stimulus is pushed
to excess they can give rise to j)ain also, and that in the last instance this sen-
sation of })ain may prove exclusive of any other. If this view^ is correct it
appears improbable that special pain-nerves exist.

As various experiments show, increasing either the strength of the periph-
eral stimulus, the number of fibres to which it is applied, or the irritability of
the terminals of the fibres, will assist in arousing palnftd sensations. In the

' Strong: P.v/cholofjirnl Rei-ieu', 1895, vol. ii. No. 4.

^ Gad uiid Goldscheider : Zcituclirift fiir klinischc Mcdicin, Bd. xx.

CENTRAL NERVOUS SYSTEM. 675

last analysis the pljysiological condition for pain is excessive stimulation,
which by all analogy must mean excessive discharge within the central system.
The changes following this discharge into the central system are not such as
lead to co-ordinatt'd muscular responses, but to convulsive reactions of a very
irregular character. Where this process takes place in the central system we
do not know, because we can only determine the existence of this sensation
when conscious. As to normal analgesia, it must be looked upon as depend-
ent on a condition in which excessive stimulation cannot be produced ; and we
find this condition normally present in the case of the nerves of special sense.

Ilcturning now to the arrangements by which the several dermal sensations
are mediated, the hypothesis may be entertained that one peripheral twig
of a dermal nerve may be modified for thermal and another for mechanical
stimulation, and, though they run by way of the same ganglion-cell, may yet
find a different distribution in the centre, and thus lead to different sensations.

Since in the pathological cases the one sort of sensibility may be lost while
the others remain, it has been inferred that there were separate fibres for the
conveyance of each sort of sensation. This idea was expressed in the law of
the specific energies of nerves as formulated by Johannes Miiller, who jwinted
out that in many cases the same nerve might be stimulated in any way, me-
chanically, electrically, or chemically, as well as in the normal physiological
manner, and that in all cases the mode of the response was the same — a sen-
sation of light or taste or contact, as the case might be. Hence it was argued
that the mode of the sensation was independent of the kind of stimulus, but
dependent on the nature of the central cells, among which the afferent fibres
terminated. It will be seen, however, that this argument does not touch the
character of the nerve-impulses in any two sets of nerves, and we have no
observations by which to decide whether the nerve-impulses passing along
the optic nerve-fibres are, for example, similar or dissimilar to those which
pass along the auditory fibres.

If the nerve-impulses are always all alike, there seems no escape from the
inference that separate nerve-fibres convey the different sorts of impulses to the
cord. At the same time, it is just possible that the nature of the impulses and
of the resultant sensation is, in the nerves of cutaneous sensibility, determined
by the form of the peripheral stimulus, and that, as a consequence, different
branches of the same nerve-fibres may be conceived of as susceptible to differ-
ent forms of stimulation, and thus the two different sensations follow from the
partial stimulation of the same nerve-fibres.

Pathway of Impulses in the Spinal Cord. — The question arises how
these impulses are distributed among the afferent tracts which are recognized
in the cord, and whether these tracts form special paths for the impulses that
rouse the several sensations of pressure, temperature (heat and cold), and pain.
Since it is necessary to know the sensations of the subie(!t, this problem can be,
in some ways, best studied in man. Here, owing to wounds or disease, it may
so happen that some of these sensations are lost or greatly diminished, and it
is to be determined whether this loss is constantly associated with the inter-

676 .l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

ruptiou of defiuite tracts. Unfortunately, however, the material- for such a
study is very meagre.

The weight of evidence indicates that the result of a lesion in one lateral-
half of the spinal cord in man and in the higher animals is followed by a loss
or impairment of motion on the same side, and a loss of sensation which is
greatest on the side opposite to the lesion. As just cited, there are cases in
dogs where the damage caused by the hemisection is apparently transient,
and no permanent loss can be demonstrated, but in man the loss of function
tends to be far more persistent.

On the basis of a case ^ in which the lateral column of the cord and the
gray matter of both horns on the same side was the seat of damage, and in
which there was a total loss of pain on the opposite side of the body without
impairment of tactile sensibility, it may be inferred that the pain-impulses
cross soon after entering the cord, and pass cephalad by some path lying within
the damaged area. A second case ^ is recorded in which a stab- wound divided
all of one-half of the cord plus the dorsal column of the other half. There
was here a loss of sensibility to pain on the side opposite the lesion, together
Nvith the loss of tactile sensibility on both sides, pointing, therefore, to the
dorsal columns as the paths for the tactile impulses.

The observations of Turner^ on monkeys, in which hemisection of the cord
had been made in the lumbar and thoracic regions indicate that all sensory
impulses cross immediately after entering the cord, yet section in the cervical
region showed that the impulses roused by touching the skin pass in part on
the same side of the cord as the section, the other sensory impulses being,
however, completely crossed.

On the other hand, from his work on hemisection of the dorsal cord of
the monkey at different levels,* Mott found the disturbance of sensibility of all
forms mainly on the side of the section. The evidence for the path of the
cutaneous impulses is therefore contradictory.

In addition to the cutaneous impulses there are the sensory impulses from
the viscera, muscles and tendons, which find their path cephalad probably along
the direct cerebellar tract as well by the other pathways conducting cephalad.
After hemisection of the cord the " muscular " sensations are usually lost on
the side of the section.

Since, then, the dorsal and lateral columns of the cord appear to contain
the chief afferent paths for the sensory impulses, the next step in following
the pathway is to find the terminations of these tracts.

The long tracts in the dorsal columns are connected with the nuclei of
those columns (nuclei of GoH and of Burdach) on the same side. The cells
of these nuclei send their neurons cephalad ; in part they decussate in the
sensory crossing and contribute to the formation of the lemniscus, by way of
which they pass either directly to the cerebral cortex or reach this only after

^ Gowers : Clinuxd Society's Transactions, 1878, vol. xi.

* Miiller : Beitrage zur pathologische Anatomic und Physiologic des Rilckenmarkcs, Leipzig, 1871.

' Brain, 1891. * Mott: Journal of Physiology, 1891, vol. xvii.

CENTRAL NKin'OrS SySTEAf.

677

interruption in the thalamus.' Fig. 179, a.s will be observed, shows no fibres
running directly to the cortex without interruption in the thalamus. It will

f'ortex.

luternitclear fibre. .-

j' Nucleus
< of dorsal
{^columns.

Fig. 179.— To illustrate the pathway of a sensory impulse arriving at the nuclei of the dorsal columns
" d" or the gray matter of the pons and bulb " c." The impulse is represented as passing over to a new
element "a" in the thalamic nuclei, and from thence to the cortex. In the other direction the cortex
is shown as connected with the thalamic cells by the neuron b'; only the fibres arising from the nuclei
of the dorsal columns cross the middle line "meson" (von Monakow).

be noted that these fibres of the dorsal columns are physiologically joined with
the contralateral thalamus and hemisphere. In part, however, the neurons from
the dorsal nuclei enter the cerebellum by the inferior peduncle of the same side.
The ascending fibres in the lateral columns of the cord pa.-s to the cerebellar
hemisphere of the same side by way of the inferior peduncle of the cerebel-
lum, and, although the paths out of the cerebellum are not clearly marked,
the general relation of the hemispheres of the cerebellum to that of the cere-
brum is a cro.ssed one. Some of the fibres by which this crossed connection
is accomplished pass from the cerebral hemisphere along the crus of the same
side to the olivary body, and thence by way of the arcuate fibres of the pons
and the middle peduncle to the opposite cerebellar hemisphere.

It is with the " motor " region of the cerebral hemisphere that this con-
nection of the cerebellum appears to be most marked. If this really repr<^
^ von Monakow : Archiv fur Psychiatrie und Nervenkrankheiten, 1895, Bd. xxvii.

678

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

sents the path for the sensory impulses finding their way by the antero-lateral
tract, then the impulses are finally delivered to the hemisphere on the same
side of the system as that on which they enter.

The direct cerebellar tracts pass by the way of the restifoiin body to the

A
N.D.S. ST.MI'D.D.

T.Af! ' ST.MED.S. ^'-'M''- ^^4— — ^ T.A.D.

VIII.R.P.S.
(ATE.)-"

VIII.R.P.D.

N.D.S.
T.A.8. \ FiT.MED.R.

N.D.D.

C.R.^

Fig. 180.— Sections of the bulb of a rabbit after lesion of the cochlear portion of the eighth nerve
(Onufrowicz) : A, section at the level of the posterior root of the eighth nerve ; H, section at the level of
the accessory ganglion of tlie eighth nerve. In the designations the final S^ " left " and tlie final D —
" right." C.R, restiforme ; N.D, dorsal nucleus ; 1', pyramids ; St. Med, strite mcdullares ; r..l, tubcrculum
acusticum (atrophied on the left side) ; Gl.Ac, accessory ganglion (atrophied on the left side) ; VIII.R.P,
posterior root of the eighth nerve (atrophied on the left side): VIII.R.A, anteriorrootof the eighth nerve ;
VII.G, knee of the- seventh nerve ; VII. K, nucleus of the seventh nerve ; V, root of the fifth nerve.

middle lobe of the cerebellum, mainiy on the same side ; from here, by way
of the superior peduncle, there is a crossed connection with the more cephalic
cell-masses.

On passing up the axis the sensory cranial nerves appear. Those which
depart most from the type of the dorsal spinal nerves are the eighth or audi-

CENTUAL NERVOUS SYSTEM. 679

tory, the second or optic, and the first or olfactory ; and these require special
comment.

Eighth Nerve, Heainng. — The eightli nerve goes to the ear. The gau-
gliou-eells appear in two groups, the accessory ganglion Gl.Ac. and the spiral
ganglion of the cochlea. This latter is definitely associated with the cochlear
braneii of the autlitory nerve which has to do with the organ of Corti. The
other branch of the auditory nerve, the vestibular, is associated with the semi-
circular canals, the functions of which are not auditory, but concerned with the
maintenance of equilibrium (see Fig. 180).

The branch for the semicircular canals and that for the cochlea have dif-
ferent central connections.^ The auditory fibres proper arising from the cells
of the spiral ganglion in the cochlea and from those of the anterior auditory
nucleus [Gl. ac), first connect with the cells of the tuberculum acusticura
{T.A.), and are thence continued by the striae acusticse {St. med.) into the
lemniscus of the opposite side ; through this with the posterior quadrigemi-
nuni and the internal geniculate body of that side, probably the thalamus also,
and thence by the internal capsule toward its occipital end, with the cortex
of the more occipital portions of the first and second temporal convolutions.

This path is indicated by comparative anatomy (Spitzka), by experimental
degeneration practised on animals (von Monakow), and by pathological observa-
tions on man where the pathway has become injured or diseased in one of its
parts.

By the two latter forms of evidence it appears that the portion of the cere-
bral cortex is also associated with the lateral nucleus of the thalamus of the
same side, for injury to the cortex causes atrophy of this part of the
thalamus.

Second Nerve, Optic. — As has long been recognized, the optic nerve, so
called, is a cerebral tract morphologically equivalent to such tracts as connect
any portion of the cerebral cortex with a primary centre, the retina being in
part the representative of the cerebrum, and the pulvinares, the quadrigemina,
and genieulata externa being the primary centres.

At the chiasma where the two optic nerves come together their fibres inter-
mingle, and then emerge as the optic tracts, which contain not only the fibres
connected with the retina, but others added from the superposed parts of the
brain.

In the higher mammals it was shown by von Gudden ^ tiiat in the chiasma
the majority of tlje fibres forming one optic nerve pass to the tract of the
opposite side, but that a portion of the fibres remain in the tract of the same
side.

This was inferred because removal of one optic bulb caused in young
rabbits a degeneration in the associated optic nerve and also in both optic
tracts — most marked, however, in the tract of the side opposite to the lesion.

^ Onufrowicz : " Exper. Beitrag zur Kenntniss des centralen Urspriinges des Nervus acus-
ticus," Inaug. Diss., 1885.

^ von Gudden : Gesammelle und hinterlassene Abhandlangen, Wiesbaden, 1889.

680

AN AMERirAA TEXT- HOOK OF PIIYSIOhOQY.

Conversely, the section of one optic tract causes a degeneration in both optic
nerves, the nerve of tlio side opposite to the lesion being most affected, and a
smaller degeneration a])pearing in the nerve of the same side (see Fig. 181).

Pig. 181— Illustrating the relations of the afferent fibres in the optic nerve. The crossed fibres are
indicated by solid lines, the uncrossed fibres by broken lines : A', nasal side of the right eye ; T, temporal
side of the same ; G. E, geniculutum externum : P, pulvinar ; C Q, quadrigeminum antcrius.

It appears from this that in the higher mammals an optic tract is composed
of fibres from both optic nerves, but mainly of fibres from the nerve of the
opposite side. In the fish, amphibia, reptiles, and birds — except the owls' —
as well as in the lower mammals (mouse and guinea-pig, for example) the
decussation appears to be complete.^ For the partial decussation in the owls
the evidence is physiological. This distribution of the optic fibres was asso-

' Ferrier : The. Croonian Lectures on Cerebral Localization, London, 1890, p. 70.
' Singer und Miinzer: Denkschriflen der math.-naturuiss. Classe der kais. Akademie der Wissen-
achaften, 1888, Ed. Iv.

CENTRAL NERVOUS SYSTEM. 681

ciated by von Guddon with the position of the eyes in tlic head. The extreme
lateral position of the eyes as it occurs in the lower nminnials permits of but
little combination of the two visual.fields ; whereas the position in man, in a
frontal plane, permits a combination of the fiehls to a much greater degree. It
was in accordance with this principle that partial decussation of these nerves
was anticipated by von Guddeu in the owl, although the histological evidence
for it was not obtained by him.

In man the evidence from degeneration in the optic nerve j)oints to the
presence of a crossed and an uncrossed bundle of fibres in each optic nerve,
the uncrosse<l being much the smaller of the two bundles. The contrary view
of complete decussation has been maintained by Michel.^ Tlie central ends
of the afterent optic fibres forming an optic tract are distributed between the
anterior quadrigemimim, the geniculatum externum, and the ])ulvinar of the
same side. By central cells located in these latter structures tlie pathway is
continued to the occipital cortex of the hemisphere of the same side, by the
fibres passing in the occipital end of the internal capsule and forming the
optic radiation. It must be remembered, however, that between the cortex
and the primary centres, and again between these centres and the bulb, there
are pathways conducting //-o?/! the cortex to the primary centres, and also from
the primary centres to the retina.*

As the result of partial decussation it will be seen that the relations of the
two bulbs to the cortex is this: The nasal or crossed bundle of the contra-
lateral bulb and the temporal or uncrossed bundle of the bulb of the same
side come together in the optic tract of one side, and are associated with the
occipital lobe of that side. Hence it would appear that hemianopsia or
blindness in the corresponding halves of the two eyes following a lesion
of the optic pathway anywhere behind the chiasma would be, in some
measure, explained by this anatomical arrangement. If strictly interpreted
an approximately equal number of fibres would be expected for each half
of the retina. Such, however, has not been established as the relation be-
tween the areas of the bundles. It is to be added, nevertheless, that ana-
tomical arrangements such as decussations are probably open to wide indi-
vidual variations, and hence that many more observations are required before
we can say what is the usual relation between these two bundles.

With a view to determining the exact location of the cortical centres in
man many observations have been made. The cuneus and immediately sur-
rounding parts of the cortex are those most concerned. Heuschen^ indicates
the calcarine fissure and its immediate neighborhood as the most important
locality. Observations on the arrest in the development of the cortex due to
early blindness following destruction of the bulb in the case of the blind deaf-
mute Laura Bridgman show the entire cuneus to be the central and funda-
mental portion, while the associated portions extend some distance on to the

' Kolliker's Festschrift, Wiirzburg, 1887.

* von Monakow : Archivf. Psychiatrie, 1890, Bd. xx. H. 3.

' Experimentelle und pathologiscke Untersuchungen iiber der Gehirn, Upsala, 1890-92.

682 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

convex surface of the hciui.spliei'e.^ Ferrier^ from the .study of monkeys em-
phasizes the importance of the cortex of the angular gyrus ; l»ut these various
results must ultimately be harmonized through studies of degeneration in man
and the monkeys which will show the relative values of the several parts, all
of which are in some degree involved.

First Nerve. — Comparative anatomy indicates that the parts of the en-
cephalon mediating the .sense of smell are most clo.sely connected with the
cerebral hemispheres, in the sen.se that phylogenetically the first development
of the hemispheres was in connection with the central terminations of the
olfactory tracts.^ It happens in man, however, that although the cerebral hem-
ispheres are proportionately much more massive than in the lower mammals,
yet the olfactory bulbs and tracts are at the same time but poorly developed.
The pathway of the olfactory impulses is from the olfactory area in the nose
to the olfactory bulb of the same side, thence via the olfactory tract to its
termination in front of the anterior perforated space, one branch of the tract
passing directly into the substance of the gyrus fornicatus at this point, and
the other going into the more lateral portion represented in man by the tem-
poral end of the gyrus hippocampi. The cortical areas, together with the
olfactory lobe and tract, form the rhiuencephalon of the comparative anat-
omists. It has been shown, nevertheless, by Hill ^ that in anosraic mammals
the fascia dentata alone varies with the development of the olfactory apparatus.
The experimental pathological evidence is very meagre in relation to these
nerves, but, on the other hand, the anatomical evidence is of the best.

The brief sketches of the pathways for incoming impulses indicate that
with the exception of those coming by the olfactory tract, they arrive ulti-
mately at the cerebral cortex over the fibres forming the internal capsule,
most, if not all, passing by way of the thalamus. In the cerebral cortex are
found the terminal branches of the last cell-groups furnishing neurons which
conduct toward the cerebrum, and these are arranged in several layers corre-
sponding to the various strata of fibres which the cortex always shows.

F. Localization of Cell-groups in the Cerebral Cortex.

The foregoing .section has brought to light the fact that groups of incom-
ing impulses find their way to the cerebral cortex. The path to the cerebrum
is best developed in the higher animals. In any case, the impulse in order to
produce evident responses must finally escape from the central .sy.stera into the
tissues controlled, and using the reactions of the expressive tissues as a guide,
it is our present purpose to trace the impulses in those cases in which the cor-
tex forms part of the path. We turn, therefore, to the study of those parts
of the cerebral cortex the direct stimulation of which produces impulses that
pass to cell-groups lying more or less caudad in the central system.

' Donaldson : American Journal of Psychology, 1892, vol. iv. No. 4.
- The Croonian Lectures on Cerebral Localization, London, 1890.

* Sir William Turner: Journal of Anatomy, 1890; Edinger: Anatomische Anzeiger, 1893.

* Philosophical Transactions of the Royal Society, 1893, vol. clxxxiv.

CENTRAL NERVOUS SYSTEM.

683

Earlier Observations. — It wiis demonstrated by Fritsch and Hitzig in
1870 ' that if a constant current was applied to the surface of the dog's brain,
it was possible by interrupting it to obtain movements of the limbs and face
when the electrodes were placed on certain parts of the cerebral cortex, and
the reaction varied according to the place of stimulation, a constant rela-
tion subsisting between the two. From this time on, active investigations
of the relations thus suggested have been pursued, both by stimulating small
areas in the cortex of various aiiinials, including the monkey and man, and
by the removal of various parts of the cerebral hemispheres and cortex,
together with the study of the effects of pathological lesions in man. The
results following removal of parts are complicated by the transitory effects
of the lesion, and can best be treated by themselves later on. The results
following the stimidation of the cortex are the simplest, and will next be
described.

Stimulation of Cortex. — The common method of experiment is to apply
the faradic current by means of fine but blunt electrodes, the ends of which
are but two or three millimeters apart, to the exposed surface of the cerebral
hemispheres, the pia being undisturbed. Rabbits, dogs, and monkeys have
been the animals most commonly studied.

If the current be slight, its application for one or more seconds causes a
response in the shape of movements of muscles, which are thrown into co-
ordinated contraction. The contraction continues for some time after the
stimulus has been removed. When the stimulus is very strong, instead of a
limited and co-ordinated response, there may be a widespread contraction of
many muscles, resembling an epileptic convulsion. This, however, occurs
more commonly in the lower than in the higher mammals. On the other
hand, the irritability of the cortex is easily reduced, so that it becomes irre-
sponsive, and often immediately after the first exposure of the brain there is a
time during which a response cannot be obtained.

Turning to the areas of the cortex which are occupied by the extension of

Fig. 182.— Lateral view of a human hemisphere. The cortical visual area on this aspect is shaded ( V).

the pathways from the special sense-organs, it is found that the visual area
alone exhibits any elaboration when examined by the method of stimulation.

^Arehiv fur Anatomie und Physiologic, 1870.

684

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 183.— Mesial view of a human hemisphere. The corti-
cal visual area is shaded, )',• cortical area for smell, S.

To be sure, Ferrier' very early pointed out tliat stimulation of the other sen-
sory areas causes movements. It was by means of the movements tiius ob-
tained that he sought to localize the sensory centres, assuming that the move-
ments were in response to sensations caused by the irritation of the cortex.
As the result of stimulation of a sensory area tlie muscles of the sense

organ itself or those immediately
associated with it respond (see Figs.
182, 183).

Shiifer^has shown in the mon-
key that the dorsal portion of the
visual area is associated with the
upper portion of the retina, the
eye being turned downward as the
result of stimulating this portion.
This is interpreted as a movement
of the eye intended to bring a
stimulus falling on the upper part of the retina into the centre of the field of
vision. When the stimulus is applied to the ventral portion of the area a
corresponding upward movement of the eye occurs, and the corresponding
relation holds for the stimulation of the lateral and mesial portions of the
area. These movements occur in both eyes, although the stimulus is applied
to one lobe only, and hence the two retinal fields appear to be superposed in
the visual cortex of each hemisj)here.

The experiments on the stimulation of the other sensory areas show, in
the first place, that these areas contain cells the stimulation of which causes
the contraction of certain mu.scles immediately associated with the organ of
sense, and, in the second place, that while each of the areas is pre-eminently
concerned with the reception of impulses from a particular sense-organ, yet
no one of them is exclusively sensory.

Deferring for a moment the other evidence by which the sensory charac-
ters have been established, and also the arrangements within the cortex by
which any group of muscles can be made to respond to stimuli arriving at any
sensory area, we shall follow out the distribution of those cortical cells the
stimulation of which causes contractions of the skeletal muscles.

The results here presented were obtained from the electrical stimulation of
the monkey's brain by Beevor and Horsley^ (see Figs. 184, 185). These
experimenters explored the exposed surface of the hemisphere with the elec-
trodes, moving them two millimeters at a time, and at each point noting the
muscle-group first thrown into contraction.

As the result of many observations on the monkey, it is possible to map out
the cerebral cortex in the following way : The surface of the hemispheres is
divided into regions (motor and sensory regions), which are the largest sub-

' The Functions of the Brain, 1876.

* Proceedings of the Royal Society, London, 1888, vol. xliii.

^Philosophical Transactions of the Royal Society, 1888-90.

CENTRAL NERVOUS SYSTEM.

(J85

Fig. 184.— Brain of the macaque monkey, showing the sensory and motor areas. In the sensory region
the name of the sensation is over the locality most closely associated with the corresponding sense-organ ;
in the motor region the name of the part is written over the portion of the cortex which controls it. The
upper figure gives a lateral view of the hemisphere, and the lower a dorsal view (Beevor and Horsley).

divisions. These are subdivided into areas for the muscle-groups belonging
to different members of the body — arms, head, trunk, etc., or those areas

PoF.

Fig. 185.— Mesial surface of the brain (monkey). The localization of motor functions is indicated
along the shaded portion of the marginal gyrus. The location of the visual area is indicated at the tip of
the occipital lobe, and the location of the olfactory area at the tip of the temporal (Horsley).

(J8G ^liV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

witliiu M'liicli all the impulses from a given seuse-orgau reach the cortex.
The areas in turu may be marked off into centres, formed by the groups of
cells which, for example, control the smaller masses of muscle belonging to a
given segment of a limb, or in the visual area are represented by those cells
especially connected with one part of the retina. There is thus a motor region
the stimulation of which gives rise to the more evident bodily movements.
AVithin this are several subdivisions, the stimulation of one of which is fol-
lowed by movements of groups of muscles — for instance, those controlling the
arm — and within such an area in turu come the smaller centres, or those
the stimulation of which is first followed by movements at one joint only.

Another method of studying the cortex is to regard the character of the
movement obtained by stimulating a single area, as that of the arm. Figure

Fig. 186.— Showing in the arm-area (monkey's brain) the localization of movements having
different characters (after Horsley).

186 shows that stimulation of the upper arm-area gives rise in the first in-
stance to movements of extension, whereas the lower arm-area yields those of
flexion. This basis of subdivision is, however, not so useful as the analysis
into centres. As the smallest subdivisions, the centres are most convenient
for further study.

If a vertical incision be carried around such a centre so as to isolate it from
the other parts of the cortex, the characteristic reactions still follow the stimu-
lation of it, indicating that tiie special effect can be produced l)y the passage
of impulses from the point of stimulation toward the infracortical structures.
If, in addition, a cut be made below the cortex and parallel with its surface,
then stimulation of the cortex above this section is ineffective, thus indicating
that the impulses pass from the cortex directly into the substance of the hem-
isphere along certain nerve-tracts, which by this operation were sectioned.
Further, if the bit of cortex thus separated from the underlying white sub-
stance be removed and the faradic current be applied to the white substance
beneath, a reaction of the same type and involving the same muscles can be
obtained, although it differs from that to be gotten from the cortex it.self, in

CENTRAL NERVOUS SYSTEM.

687

the fii*st place by being less co-ordinated, in the second by continuing only so
long as the stimulus lasts, and in the third place by giving rise to less intense
electrical changes connected witii the passing impulse.

These facts, taken together, lead to the conclusion that when the cortex is
stimulated the impulses concerned in producing the muscular contractions
traverse cell-bodies at the ])oint of stimulation, and are transmitted thence
through the underlying fibres. We shall see later that this direct course
probably does not represent the sole pathway for these impulses.

Secondary Degeneration. — The course of these impulses is next inferred
from the relation between the removal of different parts of the cortex and
the consequent secondary degenerations throughout the length of the central
nervous system. When the part of the cortex removed is taken from the
motor area, then the degeneration occurs in the internal capsule and in the

Fig. 187.— Schema of the projection fibres within the brain (Starr) ; lateral view of the internal cap-
sule : A, tract from the frontal gyri to the pons nuclei, and so to the cerebellum ; B, motor tract ; C, sen-
sory tract for touch (separated from B for the sake of clearness in the schema) ; D, visual tract ; E, audi-
tory tract; F, G, E, superior, middle, and inferior cerebellar peduncles ; J, fibres between the auditory
nucleus and the inferior quadrigeminal body : K, motor decussation in the bulb ; Vt, fourth ventricle.
The numerals refer to the cranial nerves. The sensory radiations are seen to be massed toward the
occipital end of the hemisphere.

callosum. The path of the fibres forming outgrowths of the cortical cells
can be followed thence through the crusta and pyramids to the spinal cord.
After removal of the motor region of one cerebral hemisphere the degeu-

688 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

eration is niainlv in the internal capsule and erusta of the same side, though
bv wav of fibres crossing in the callosuni it may be traced on the other side also.
At the decussation of the pyramids the fibres occupying the internal capsule
of the same side as the lesion, for the most part cross the middle line (see Fig.
187). The portion which remains uncrossed passes as the direct pyramidal
tract of the ventral columns in man, while the crossed bundle, which is much
the larger, lies in the dorso-lateral field of the lateral column, forming the
crossed pyramidal tract. This, however, is only the principal, but not the com-
plete, distribution of the degenerated fibres.

The direct pyramidal tracts disappear in the cervical region, .having entered
the substance of the cord by way of the ventral commissure, and probably
having there undergone decussation. The crossed pyramidal tract shows the
greatest diminution in area after passing caudad of the cervical and lumbar
enlargements, and hence it is inferred that the pyramidal fibres largely
terminate in these regions of the cord. Most important, however, is the
observation of Sherrington,^ that even with a unilateral cortical lesion degen-
eration occurs in both crossed pyramidal tracts, and that at the level of the
two enlargements the degenerations in the crossed pyramidal tract on the same
side as the lesion is larger than above or below these enlargements, thus
showing a local increase in the degenerated fibres running on this side.
Sherrington's first explanation of this bilateral degeneration in the pyramidal
tracts was based on the assumption that fibres which had once crossed at the
decussation of the pyramids recrossed at lower levels. If, however, such
were the case, the recrossiug would carry a number of the degenerated fibres
across the middle line, and decrease by so many the fibres in the opposite
half. The diminution of the fibres in number on the first side of the cord
does not warrant this inference : Sherrington therefore put forward the view
that the pyramidal fibres recrossing in the cord are derived in large part from
a division of the pyramidal fibres into two branches, one of which may cross
to the opposite side of the cord, while the other continues its first course;
such dividing fibres he designates as "geraiual fibres," the number of which
is by no means small.

The observations of Sherrijigton were made on monkeys (Macacus) and
dogs, and probably tiie arrangements of these fibres in man is similar. The
observations are particularly significant as giving an anatomical basis for the
control of the movements in both halves of tiie body from each cerebral
hemisphere.

The continuous degeneration, coupled with the histological evidence for
the absence of intervening nerve-cells, indicates that the cell-bodies in the cortex
have neurons that extend all the way to the cell-grou})s of the spinal cord,
even as far as the sacral region. The neurons of one group of these cortical
cells pass, however, to the cell-groups in the cervical enlargement, while those
from others pass to the groups in the lumbar enlargement. It thus happens
that if the spinal cord be cut across in the middle of the thoracic region, and
1 Journal of Physiology, 1889, vol. x.

CENTRAL NERVOUS SYSTEM. 689

then the lef]:;-area (see Fig. 153) be stimulated, an electrometer applied to the
cut end of the cord will show the passage of nerve impulses, because the
electrometer is applied to a tract of fibres on their way to the lumbar enlarge-
ment, and the fibres originate in cortical cells within the region stinmlated.
When, however, the cortical stimulus is made in the arm-area, the electrometer
being applied as before, no electric change occurs, for the neurons of the cells
in the arm terminate in the part of the cord containing the cell-groups which
control the muscles of the arm, and these all lie cephalad to the point of
section of the cord. It is evident, therefore, that the arrangement is a com-
paratively simple one — namely, an extension of the neurons of the several
groups of cortical cells from the different areas for the leg, arm, face, etc., to
the axial cell-groups which control the muscles of these parts, and which
are situated in the cord. Sherrington reports ^ a degeneration of some fibres
as far as the lumbar enlargement even when the lesion is confined to the
cortical area for the arm. Assuming .the correctness of this observation, it is
to be harmonized with the preceding statements to the effect that stimulation
of the arm-area does not produce an electrical variation in an electrometer
applied to the crossed pyramidal tracts in the mid-thoracic region by the fact
that the number of these long fibres is small.

The cortical cells in the motor region belong to the group of central cells
— i. e. their neurons never leave the central system — and hence they are
engaged in distributing impulses within it. To the axial cell-groups in the
cord they bring impulses, and therefore from the standpoint of these latter
may be considered as afferent, whereas, owing to the fact that they carry
impulses away from the cortex, they are sometimes called efferent. Confusion
can be avoided, however, by refraining from either term. Just how these two
sets, the cortical and the cord elements, are related still requires to be worked
out. The number of fibres in the pyramidal tracts indicates that there cer-
tainly is not one fibre for each cell in the axial cell-groups, because the num-
ber of pyramidal fibres is very much less than is the number of cells which
they control. This discrepancy is in some measure relieved by the formation
of " geminal " fibres already described. Moreover, the branching of the pyr-
amidal fibres near their termination is very probable, and the most plausible
view at present is that each pyramidal fibre by means of its collaterals comes
into physiological connection with a considerable number of efferent cells, and
probably the cells controlled by any one fibre at its terminus form more or less
compact groups.

Mapping of the Cortex. — Having sketched the relations of the pyramidal
cells forming the motor region of the cerebral cortex to the parts lying below,
it will be important to study the arrangement, size, subdivisions, and com-
parativ^e anatomy of this region, and then to examine the relation of it to the
other parts of the cortex. The observations here quoted are those on the
monkey only.

On glancing at Figure 184 it is evident, first, that the areas for the head
^ Journal of Physiology, 1869, vol. x.
44

690

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and i'acc :n-e widely separated from
each otlier — that tlie ann-area lies her
tweeu them, and that the area for the
trunk, though less.soiiematieall y plaeed,
is located between the arm and leg.
This arranjreujent is more typically
represented on the mesial (Fij^. 18o)
than on the conv-ex surface of the
hemisphere.

The muscle-groups M'hen enumer-
ated cephalo-caudad being those for
the head, arm, trunk, and legs, the
serial order of the cortical areas is
thus in correspondence with the order
of the muscle-groups which they con-
trol.

The Size of the Cortical Areas. —
Evidently there is no direct relation
between the extent of a cortical area
and the mass of muscles which it con-
trols; certaiidy in man the mass of
muscles in the leg is five times greater
than that in the arm, and this many
times greater than that in the face and
head ; yet it is for the last area that
the greatest cortical extension is found.
Mass of muscle and extent of cortical
area do not therefore go together.

When the movements effected by
the muscles in these several areas are
considered, we find that such move-
ments become more complex and more
accurate as we apj)roach the head, and
it therefore accords with the facts to
consider the extension of the motor
areas as correlated with the refinement
of the movements which they control —
a relation which may be expressed ana-
tomically as an increase in the number
of cortical cells controlling the related
cel]-grou])s in the cord.

Subdivision of Areas. — The areas
which have been described are further subdivided, the subdivisions in the arm-
area being the clearest. Here it is found that the stimulation of the upper
part of the arm-area gives rise to movements which start at the shoulder,

Fig. 188.— Horizontal section of the Iniinan cere-
brum, showing the internal capsule on the left
side: F, frontal region; G, knee of the cup.siile ;
JVC, NC, caudate nucleus ; NL, lenticular nucleus ;
O, occipital lobe : TO, thalamus ; X, X, lateral ven-
tricle. In the internal capsule the letters indicate
the probable position of tlie bundles of fibres which
upon stimulation give rise to movements of the
parts named or which convey special sets of in-
coming impulses; E, eyes; //, head; 7, tongue; M,
mouth ; /-, shoulder; li. elbow ; D, digits ; A, abdo-
men; P. hip; A", knee; f, toes; .S temporo-occip-
ital tract ; OC, fibres to the occipital lobe ; OP, optic
radiation (based on Horsley).

CEXTI!. 1 /. NKR VO US SYSTEM.

G91

while stimulation at the lower part of this area gives rise to movements first
involvino; the fingers, and especially the thumb. The centres from which
these several reactions may he obtained occupy, as Fi<j;ure 184 shows, narrow
fields across the cortex in a fr(»nt()-(K('i[)it:il direction. Moreover, the centre
for the most proximal joint of the arm is farthest removed from that fin* the
most distal, while (ho intermediate joints are represented by their several cen-
tres lying in reoujar order between these two. A similar arrangement appears
in the subdivisions of the leg, and in the face-area as well.

Interpreting these facts in the terms of nerve-cells and their arrangement,
it appears that in the shoulder centre the neurons of the cortical cells that dis-
charge downward pass predominantly to the efferent cell-groups which in the
spinal cord directly control the muscles of the shoulder, and that a similar
arrangement obtains for the other centres in this region with the correspond-
ing cell-groups in the cord. The stimulation of the different portions of the
internal capsule where it is composed of bundles of fibres coming from the
motor region shows (observations on orang-utang) that the fibres running to
the several lower centres are here aggregated, and are ranged in the same
order as the cortical centres themselves (see Fig. 188).

Separateness of Areas and Centres. — As we ascend in the mammalian
series there is an increase in the perfection with which cells forming the sev-
eral centres are segregated, though the areas in the different forms tend to
hold the same relative positions.*

Figures 189, 190 give the localizations recently obtained in the rabbit's
brain by stimulation (Mann). The various areas occupy a large propoi'tion

of the cortex, and in some cases come
very close together, so that they are
not easily separated by experiment.

Fig. 189.— Rabbit's brain, dorsal view. The
areas indicated are those the stimulation of which
causes a movement of the parts named (Mann).

Fig. 190.— Rabbit's brain, lateral view. The
areas indicated are those the stimulation of which
causes a movement of the parts named (Mann).

In the lower monkeys {Macacus sinicus) these cell-groups are segregated,
so that those associated with the cervical portion of the cord and forming the
arm-area are much more together, and quite separate from those associated
with the lumbar region, leg-area. In the orang-utaug,^ and to a greater
extent in man, a further separation occurs, so that they come to be surrounded

* Mann: Journal of Anatomy and Phyxiolof/y, 189o, vol. xxx.

* Beevor and Horsley : Proceedings of the Royal Society of London, 1890-91, vol. xlviii.

692

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 191. — Lateral view of the left hemisphere of an orang-utang, showing the motor area about
the central fissure (Beevor and Horsley).

by parts of the cortex from which no response can be obtained upon direct
stimulation (see Fig. 191).

Fig. 192.— Lateral view of a left human hemisphere, showing the motor areas in man. The schema
is based on the observations on the monkey, on pathological records, human, and on direct experiments
on man. It is to be remembered that in the human brain the excitable localities are surrounded by
rather extensive areas not directly excitable (Dana).

Fig. 193.— Mesial view of a human hemisphere, showing motor areas. Formed in the
same way as Figure 192.

By a few direct experiments and by many pathological observations some-
thing is known of the motor centres in the human cerebral cortex. When

CENTRAL NERVOUS SYSTEM,

693

the results are plotted they give a distribution such as is shown in Figure 1 92.
At the same time all such figures are largely compiled from results obtained
ou the monkey. It is here seen that the two central gyri are the principal
seat of these areas, and that it is ouly along the great longitudinal fissure divid-
ing the hemisjMiores that the motor areas extend beyond this limit in a cephalo-
caudad tlirection. Perhaps the relation most wortiiy of remark is the com-
paratively small fraction of the cortex concerned with the direct control of the
spinal cord cells. The motor areas in man are elaborated, not so much by
the increase in the number of the cells controlling the lower centres, as by an
increase in the number of those cells under the influence of which these areas
react. The relation of the areas in a frontal section is shown iu Figure 194.

Fig. 194.— Frontal section of the human cerebrum on the left side. The fibres forming the internal

capsule ( ), the callosum ( ), and the anterior commissure (. — .— . — .—) have been

indicated. T, cortical area for the trunk ; L, cortical area for the leg ; A, cortical area for the arm ; F,
cortical area for the face ; A, anterior commissure ; C, callosum ; CO, optic chiasma ; NC, caudate nucleus ;
NL, lenticular nucleus ; R, fornix ; TO, thalamus ; X, lateral ventricle.

Sensory and Motor Regions. — If an attempt is made to unify the con-
struction of the entire cortex by bringing the motor and sensory areas under
a common law, it must be based on the fact that the system of neurons bring-
ing impulses to the motor region forms part of the aiferent pathways from the
skin and muscles. To Munk ^ is due the credit of having from the first looked
upon the responsive cortex as marked off into areas within which certain groups
of afferent fibres terminated, so that apart from the sensory areas named from
the special senses, he calls the area which controls the skeletal muscles the
" Fuhlsphare," on the assumption that in it end the fibres bringing in impulses
* Ueher der Functionen der GrosshiiTirinde, 1881.

G94 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

from tlie skin and nnisclcs. It has been supjgested, to be sure, that separate
localities were the seat lor the dernial and nuisenhir sensations. Ferrier' in-
dicated the limbic lobe, especially the hii)i)ocampal gyrus, wliile Horslev and
Schafer' argued for the gyrus foruicatus. At present the weight of evidence
is iu favor of the location of the centres for dermal and muscular sensations
in the same area as that from which the muscles of the trunk and limbs can
be made to contract.^ Botii in monkeys and in man defects in sensation are
not permanent after limited lesions of the cortex, but, as suggested by Mott,
the wide distribution of the incoming impulses would explain this result.

Thus the entire portion of the cortex to which a definite function can be
assigned must be looked upon as made up of fibres which bring ini[)ulses into
it and cell-bodies which by their discharge send impulses to other divisions of
the central system as well as to other parts of the cortex itself All parts of
the cortex having assigned functions give rise on stimulation to movements,
but in the case of the movements aroused by the stimulation of the sensory
areas, so called, they involve the contractions of only those muscles controlling
the external sense-organ, as the eyeball, external ear, tongue, and nostrils, and,
though physiologically important, and in the case of the eye at least reaching
a high degree of refinement, they are quantitatively very insignificant as com-
pared with the responses to be obtained from stimulating the " motor region,"
from whicii contractions of the larger skeletal muscles are obtained. Hence
the significance of the usual terms " sensory " and " motor " in describing the
respective regions.

Multiple Control from the Cortex. — It has been found that stimulation
of the cortex in the region of the frontal lobes marked "eye" (Fig. 184) was
followed by movements of the eye. Schafer * has shown that very precise
movements of the eye also follow the stimulation of the temporal and
various parts of the occipital cortex. Since the efferent fibres which control
the muscles concerned start from the cell-groups of the third, fourth, and
sixth cranial nerves, it w'ould appear most probable that in both parts of the
cortex there are located cells the neurons of which pass to those groups and
are capable of exciting them. An alternative hypothesis — namely, that the
impulses M'hich produced the movements when the occipital region was
stimulated, travelled first to tiie cortical cells in the frontal lobe and thence
by way of them to the efferent cell-groups — was at one time considered, for
the latent period of contraction of these muscles was less by several hun-
dredths of a second when the stimulus was applied in the frontal region than
M'hen applied elsewhere. The experiments of Schafer show, however, that
when the occipital and frontal lobes are separated from one another by a sec-
tion severing all the association fibres, still the reactions can be obtained by
stimulation in the former locality, — showing that the connections of the two

> Tht Functions of the Brain, 1876.

* Philosophical Transactions of the Royal Society, 1888, vol. cxxix.

* Mott : Journal of Physiology, 1894, vol. xv.

* Proceedings of the Royal Society, 1888, vol. xliii.

CENT HAL xi:nvoj\'^ SYSTE^^. 695

cortical areas witli the cell-o;r()nps coiitrolliiifr the muscle.s of the eye are
iiulepeiuh'nt of" eaeh other.

This instance of the ilireet control of the same axial c-ell-groiips from dif-
ferent areas of the cortex is analogous to the control of efferent cell-groups in
the spinal cord, either by impulses coming down from the cerebrum or by
those entering the cord directly through the dorsal roots, and the instance
here cited is typical of a general arrangement.

Cortical Control Crossed. — Where the stimulation of the cerebral cortex
causes a response on one side only, that response is on the side opposite to the
stimulated hemisphere. It sometimes happens, however, that two groups of
symmetrically placed muscles both respond to the stimulus applied to one
hemisphere only, but these cases: — the conjugate movements of the eyes;
movements of the jaw muscles or those of the larynx, — always depend on the
response of muscles which are naturally contracted together.

This reaction depends on the arrangement of the fibres in the cord, since
in lower mammals (dog and rabbit, for example) it is not seriously disturbed
by the removal of one hemisphere.

Course of Impulses Leaving- the Cortex. — In the higher mammals, as
w^ell as in man, it is by way of the pyramidal fibres that impulses travel from
the cortex to the cell-groups of the axis. The pyramidal tracts by definition
form in part of their course the bundles of fibres lying on the ventral aspect
of the bulb, caudad to the pons, ventrad to the trapezium, and between the
olivary bodies. According to Spitzka,^ these are absent in the case of the
elephant and porpoise. It has been pointed out, too, that removal of a hemi-
sphere causes in the dog and most rodents a degeneration of other parts of
the cord (dorsal columns) than those occupied by the pyramidal tracts in man.^
The fibres passing from the cortex to the efferent cell-groups in the cord do
not, therefore, hold exactly the same position in various mammals.

Size of Pyramidal Tracts. — It has been clearly shown that if the cross
sections of the cords of the dog, monkey, and man be drawn of the same size,
the pyramidal fibres being indicated, then the area of this bundle is propor-
tionately greatest in man and least in the dog, the monkey being intermediate
in this respect. The relations thus indicated are evident — namely, that the
number of fibres controlling the cell-groups in man is the largest, and is much
larger than that in the lower animals.

• The relative areas of the pyramidal tract, the area of the entire cord being
taken as 100 per cent, at corresponding levels, are given by v. Lenhossek ^ for
the following animals :

Mouse 1.14 per cent.

Guinea-pig 3.0

Rabbit 0.3

Cat 7.76 «

Man 11.87 "

^ Journal of Comparative Medicine and Surgery, 1886, vol. vii.

^ von Lenhossek : Anatomischer Anzeiger, 1889.

^ Diefeiner Bau des Nervensystems im Lichte neuester Forschunyen, Basel, 1893.

69()

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

This relation is to be carefiiUy noted, for with it is correlated the degree
of the disturbances in the reactions of the entire nervous system following
removal of parts of tiie encephalon, the effect being slight when the encephalou
is connected with the cord by a small number of Hbres, and serious when the
connection is by many fibres, as in the case of man and the highest mammals.

G. Pathways within the Hemispheres.

If the guiding idea of the })atliway of the nervous impulse through the
central system had been rigidly followed, the association tracts in the cerebral
hemispheres would have come up for discussion immediately after the descrip-
tion of the afferent pathways. The knowledge of the arrangement in the
cerebral cortex which has been obtained from the stimulation of it is, how-
ever, so much less complicated than that obtained by other methods of inves-
tigation that the observations on this head were made introductorv to the
whole matter of localization, although in so doing the strict sequence of the
presentation was interrupted and the emphasis put on the cell-groups which
discharge from the cortex to the lower centres.

Determination of Sensory Areas. — The determination of the sensory
areas in man has been through the study of brains modified by destructive
lesions or congenital defects.

The cortical centre for smell, inferred from comparative anatomy and
physiology to be at the tip of the temporal lobe and closely connected with

the hippocampal gyrus and the
uncus, has been similarly located
in man on the basis of pathologi-
cal observations ; but the evidence
is indirect and incomplete (see
Fig. 195). Concerning the loca-
tion of taste sensations even less
is known. Both of these senses,
it must be remembered, are insig-
nificant in man, and hence their
central locations have not been
studied with great care.

On the other hand, the cortical
areas for hearing and sight have
been located with much more precision and certainty.

Damage to the first and second temporal gyri in man causes deafness in
the opposite ear, and concordantly conditions of the ear wdiich early in life
lead to deafness and deaf-mutism are accompanied by a lack of development
in these gyi'i.^ Destruction of these temporal gyri on one side always causes
deafness in the opposite ear, but there has not yet been reported a case of com-
plete deafness due to a double cortical lesion alone.

* Donaldson : American Jownul of Psychology, 1891.

Fig. 195.— Lateral view of a human hemisphere. The
cortical area for smell is shaded (S ) ; the cortical area
for hearing is shaded ( II).

CENTRAL NERVOUS SYSTEM. 697

lu the case of the visual areas in man there is tiie same sort of evidence,
but somewhat more exact. Tlie destruction of the area represented by the
cuueus and the surrounding cortex (see Figures 182 and 183) always injures
vision, and the faihirc of the eyes to grow arrests the deveh)pment of this
portion of the hemisphere.'

Hemianopsia. — It is found, moreover, that injury to tlie visual area in one
hemisphere })roduces usually a hemianopsia or partial defect of vision in both
retinas. The homonymous halves are aifected on the same side as the lesion,
and the dividing line is usually vertical. The clinical })icture corresponds to
a semi-decussation of the optic tract and the representation of the homon-
ymous halves of each retina in both hemispheres. At the same time the rela-
tion is much more complicated than at first sight appears, for the point of
most acute vision is often unaffected in such cases ; and for this peculiarity we
have no anatomical explanation.^

In neither vision nor hearing do we find in man any subcortical cell-groups
capable of acting as centres ; that is, after the removal of the appropriate cor-
tical region the corresponding sensations and reactions to the stimuli which
arouse these sensations are completely and permanently lost.

From these facts, therefore, it appears that the impulses which give rise to
visual and auditory sensations are delivered in certain parts of the cerebral
cortex, and unless they arrive there the appropriate sensations are absent.

Association Fibres. — Common experience shows us that we can volun-
tarily contract any group of muscles in response to any form of stimulus —
dermal, gustatory, olfactory, auditory, or visual. When, therefore, the hand
is extended in response to a visual stimulus, the nerve-impulses pass first to
the visual region, and then are transferred to the cortical cells controlling the
muscles of the hand. This connection is accomplished through the so-called
association fibres of the cortex. These fibres are formally described as those
which put into connection different parts of one lateral half of any subdivis-
ion of the central system (see Fig. 196).

The bundles which are thus shown in the cerebral hemisphere must be
looked upon as typical of the arrangement throughout the entire cortex, and,
further, the arrangement in the cortex is typical of that in other parts of
the central system. Anatomy would suggest, and pathology bears out the
suggestion, that it is by these tracts that the impulses travel from one area
to another.

Aphasia. — The development of the ideas bearing on this subject has been
slow. After the publication of the great work of Gall and Spurzheim (1810-
19) on the brain, some pathologists (Bouillaud, 1825; Dax, 1836), especially
in France, were in search of evidence touching the doctrine of the localization
of function. At the same time the subject of phrenology, as put forward by
Grail and Spurzheim, was not in good repute, and anything which looked that
way, even in a slight degree, was generally scouted. Broca, however, pub-

' Donaldson : American Journal of Psychology, 1892, vol. iv.
* Noyes: New York Medical Record, 1891.

698 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

lished (18G1) the iinjxjrtant ubservatiou that when the most ventral or the
thirtl frontal convolution in tlie left hemisphere (often designated Broca's con-
vulutiou) was thrown out of function, the power of expression by spoken
words was lost, and hence the name of " speech-centre " has been applied to
this convolution.

Since this discovery, which links the nourohitjy of the first part of the

Fig. 196.— Lateral view of a human hemisphere, showing the bundles of association fibres (Starr):
A, A, between adjacent gj'ri ; B, between frontal and occipital areas ; C, between frontal and temporal
areas, cingulum ; D, between frontal and temporal areas, fasciculus uncinatus ; E, between occipital and
temporal areas, fasciculus longitudinalis inferior; C, X, caudate nucleus; O, T, optic thalamus.

century with that of to-day, and also forms a fundamental observation in the
modern doctrine of cerebral physiology, many steps have been taken.

It was early observed that although in such cases the capacity for spoken
language was lost, nevertheless the muscles which were used in the act of
phonation were by no means paralyzed. This relation is due probably to the
fact that the speech-centre of Broca does not contain cells which connect
directly with the lower nuclei controlling the mu.scles of phonation.

The interesting observation was also made that in the ordinary person
the mu.scles could not be controlled for ])houation from the right hemisphere.
Thus the symmetrical portion of the right hemisphere has not the same physi-
ological value.

Besides this lesion, which involves the cortex frontad to the motor region
proper, numerous other lesions — namely, those which involve the tracts run-
ning between the areas of special sensation (vision and hearing, for example),
and the motor or expressive region — produce corresponding results (see Fig.
197).

An individual in whom the association tracts between the visual and motor
areas have been interrupted can, for instance, see an object presented to him in

CENTRAL NERVOUS SYSTEM.

699

H

Fig. 197.— Lateral view of a human hemisphere ; cor-
tical area V, damage to which produces "mind-blind-
ness;" cortical area H, damage to which produces
" mind-deafness ; " cortical area S, damage to which
causes the loss of audible speech ; cortical area W, dam-
age to which abolishes the power of writing.

the sense that he gets :i visiuil impres.sion, but because of the interruption of
the association fibres the object is not recognized, and the impulses reaching this
sensory area elicit no response
from the jnuscles, the motor
areas for which are located else-
where.

Of these connections between
sensory and motor areas a suffi-
cient number have been studied
to suggest that the typical ar-
rangement of the cells in the
cerebral cortex is the following :
The afferent impulses ai'e dis-
tributed in the sensory cortical
areas among several classes of
cells. Some of these, through
their neurons, form association
tracts by which the impulses are
transferred from the sensory to
the motor regions. Concerning

the exact manner in which the impulses arrive at these associating cells, or
concerning the layer in the cortex which represents them, information is
meagre, but the observations on the distribution of the fibres in the cortex
suggest that the short association tracts must be at the level of the superficial
fibre-layers, while the longer tracts extend far below the cortex, and would
most naturally be associated with the deepest layers of cells.^ Upon attempt-
ing to carry out this arrangement to anything like the completeness demanded
by the physiological reactions, it is necessary to postulate the existence of such
pathways between each sensory and each motor area, and thus there must be a
pathway extending from every sensory to every motor area. This arrange-
ment is of course to be pictured as modified in several ways.

In the first place, the connection between a given motor and a given sen-
sory area is by no means proportionate in the several instances. The connec-
tion, for example, between the visual area and the motor area for the arm is
probably represented by more nerve-elements, and these better organized, than
the connection between the gustatory area and that for the movements of the

leg.

When, therefore, it is said that such connections exist, it must be added
always that the nexus is different for the several regions concerned, and, what
is more, that in man, at least, it is different for the two hemispheres.

The Relative Functions of the Two Hemispheres. — "When the subject
is right-handed, it appears that in man injury to the left cerebral hemisphere
is more productive of disturbance than injury to the right hemisphere. At
the same time, lesion of the left hemisphere is far more frequent than that of

^ Andriezen : Brain, 1894.

700 AiY AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the right. So far as can bo judged from experiments ou man, tlie higher
sense-organs, the eye and the ear, are more perfect, physiologically, on the right
side. Since the connection of the sense-organs is largely with the cortex of the
contralateral hemisphere, this nieans tliat the impulses going mainly to the left
hemisphere are better differentiated than those going to the right. For these
impulses to reach a motor area in the same hemisphere would ap|)ear to be
easier than to reach the corresponding area on the opposite side, and it is thus
possible to see how, on the basis of the slightly better sense-organs of the right
side, the left-brained man might have been developed. The observations of
Flechsig' on the pyramidal tracts also show that this tract, before mcdullation
at least, may be unevenly developed on two sides of the cord, and the ease of
control may thus be rendered unequal — a condition which must be dominant
in the determination of the side of the body which shall be exercised.

Doubtless there are other factors concerned, and, moreover, it has yet to be
demonstrated that the sense-organs of the left side are superior in persons left-
handed. Nor has the inequality of the crossed pyramidal tracts in the adult
been established wath reference to these questions. Be this as it may, the
lesions which cause aphasia or apraxia (inability to determine the meaning and
use of objects) arc predominantly in the left hemisphere in persons who are
right-handed, while there is some evidence that the right hemisphere is more
important in left-handed persons.

In the adult, damage to one hemisphere is usually followed by a permanent
loss of function, but this loss may be transient when the lesion occurs in the
very young subject, so that during the growing period the sound hemisphere
can in a measure take up the function of the one that has been injured.

Assuming this general plan for the arrangement of the cortex to be correct,
it is evident that a given cell, the neuron of which forms part of the pyrami-
dal tract, must in the human cortex be subject to a large series of impulses
coming to it over as many paths. Schematically, it would be as represented
in Figure 198.

The discharging cell may be destroyed ; then, of course, the muscles con-
trolled by it become more or less paralyzed. The discharging cell may, how-
ever, remain intact, but the pathways by which impulses arrive at it be dam-
aged. This is the type of lesion which produces symptoms of aphasia. When
an interruption of associative pathways occurs some one or more of these tracts
is broken, and hence this discharging cell does not receive a stimulus adequate
to cause a response.

The physiological simplicity of the elements in any part of the central sys-
tem, either when different portions of the system from the same animal or
when the corresponding portions of different animals are compared, depends
on the number of paths by which the impulses are brought to the discharging
cells.

Composite Character of Incoming Impulses. — To these conclusions
based on the anatomy are to be added others suggested by clinical observa-
' Leilungsbahnen im Qehim und Rikkenmark, 1876.

CENTRAL NERVOUS SYSTEM.

701

tious. That a patient suttering from a lesion between the visual and motor
areas may be able to recognize an object and to indicate its use, it is sometimes
necessary that the object shall apjieal to several senses. For example, the
name and use of a knife, when seen alone, may not be recalled, but when it is

rtotoi-T'

Fig. 198.— Schema showing in a purely formal manner the different sort of afferent impulses which may
influence the discharge of a cortical cell.

taken into the hand — that is, when the dermal and muscular sensations are
added to the visual one — the response is made, though, acting alone, any one
set of sensations is inadequate to produce this result.

Just where the block occurs in such a case it is not possible to say with
exactness, but the lesion lies, as a rule, between the sensory and motor areas
concerned, and by the damage to the pathway, it is assumed that one or more
groups of impulses are so reduced in intensity that they are alone insufficient
to })roduce a reaction ; and therefore it is only when the impulses from several
sides are combined that a response can be obtained.

Variations in Association. — It is a familiar fact that individuals differ
in no small degree in the acuteness of their senses — i. e. in the power to dis-
criminate small diiferences, and this, too, when the sense-organs are normal.
Further, the powers of those best endowed are by no means to be attained by
others, however conscientious their training. Moreover, the central sensory
pathways differ widely. The inference is fair, therefore, that those who think
in terms of visual images, as compared with those who think in auditory
terms, do so by virtue of the fact that in the former case the central cells con-

702 .l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cenicd iu vision arc distinctly the bctlvr oPiranizod, wliilr in the latter ease it
is those concerned in hearinL;:.

In the same way, tlie power ot" expression varies iu an etjually marked
degree, and the capacity for the expression of" ideas by means of the hand iu
writing is by no means necessarily equal to the power of expression by means
of spoken words. In the former case we have the results of the play of im-
pulses from the several sensory centres on the motor area for the hand, and
this is reinforced by the sight of that which has been written, whereas in the
latter case impulses from these same sensory centres play upon the area wiiich
controls the muscles of phonation, and the reaction is reinforced by the sound
of the words uttered. Of course in the case of a defective, like a blind-deaf-
mute, the expression of thought is by movements of the fingers, and this is rein-
forced by the tactile and muscular sensations which follow these movements.

It is not by any means to be expected that the anatomical connections
which render such reactions possible will be equally perfect for the different
sensori-motor combinations or the same combinations in different persons, and
hence the powers of the individual will be modified by the perfection of
these paths in the several cases. From this it also follows that' the same
lesion as grossly determined will not produce identical results in the two per-
sons, for it will not efRnit the damage of structural elements which are strictly
comparable.

Path-w^ays through Gray Matter. — Moreover, what is true of the spinal
cord is also probably true of the cortex — viz. that while the long tracts are
the usual and preferred pathways between centres, shorter tracts formed by a
large series of cells often serve as the pathway, and impulses may under some
conditions find their way from one part of the cortex to another by way of
these more complex tracts.

Latent Areas. — It has been plain from an examination of the foregoing
figures, as well as from the descriptions, that there must be a large portion of
the cortex which, so far as has been observed, may be called latent. These
regions, which include nearly the entire ventral surface of the hemispheres, a
large part of the mesial surface, and on the dorsal and lateral aspects a large
portion of the frontal and temporal lobes, certainly require a word.

The various forms of investigation yield negative results. The speech-
centre is, strictly speaking, neither a motor nor a sensory portion of the cortex,
and yet when it is damaged the function of speech is disturbed. We have
come to look upon the speech-centre as containing cells by way of which im-
pulses pass to the centres controlling the muscles of phonation. This relation
su2:s:ests that the rest of the cortex called latent mav act in a similar manner,
and that by way of it pass impulses which modify the discharge of the motor
areas proper. From any one portion of the latent area, however, the connec-
tions are not massive enough to permit of impulses which will cause a contrac-
tion, and hence these impulses coming from one locality to a discharging cell
form only a fraction of the impulses which control it ; and for this reason the
significance of these parts fails to be clearly evident upon direct experiment.

CENTRAL NERVOUS SYSTEM. 703

The corlex of" tlio froiilal lohcs has some connections with the nuclei of the
pons, and so with the cerehelhnn. The more recent experiinents on tlie func-
tions of this region are by Bianchi ^ and Grosglil<,^ the former on monkeys
and dogs and the latter on dogs alone.

These experimenters found that the removal of one frontal lobe is com-
paratively insignificant in its effects, while when both are removed the change
is profound. On removing the frontal lobe on one side only there is no dis-
turbance of vision, hearing, intelligence, or character. There do occur both
sensory and motor disturbances, but these are for the most part transient. On
the side o])posite to the lesion there is in the limbs a blunting of all sensations
and some paresis. Moreover, there is a hyperaesthesia combined with a paresis
of the muscles of the neck and trunk which move these parts away from the
side of the lesion.

These several effects of the operation tend to pass off, and if then the
remaining frontal lobe be removed from a dog or monkey, not only do the
symptoms just described appear on the other side of the body, but still more
fundamental changes occur. A ceaseless wandering to and fro, such as Goltz"*
observed in those dogs in which the anterior half of the brain had been
removed, characterizes the animals ; curiosity, affection, sexual feeling, pleasure,
memory, and the capacity to learn are at the same time abolished, and the
expressions of the animal are those of fear and excessive irritability. That,
therefore, the frontal lobes play an important role in the total reactions of the
central system is amply evident, but this by no means justifies the conclusion
that they are the seat of the intelligence.

H. Comparative Physiology of the Central Nervous System.

For the better comprehension of the conditions found in man and the
monkey, it will be of importance to briefly review the comparative physiology
of the central nervous system in vertebrates below the monkey. This system
in the lower vertebrates is usually composed of a very much smaller number
of cells than is found in that of man, and also cephalization, or the massing
of the elements toward the head and in connection with the principal sense-
organs, has gone on to a far less extent.

It must not be thought, however, because it is the custom to emphasize
the reflex activities of the lower vertebrates, and to show that these reflexes
can be carried out even by fractions of the spinal cord alone, that therefore
the spinal cord is particularly well developed in them. Comparative anatomy
shows in the lower vertebrates a simplicity in the structure of the cord quite
comparable with that found in the brain, and as we ascend the vertebrate
series both parts of the central system increase in complexity. In this increase,
however, the cephalic division takes the lead, and further, by means of the
fibre-tracts, the cell-groups in the cord are more and more brought under the

' Archives Italiennes de Biologie, 1895, t. xii.
' Archivfiir Anatomie und Physiologie, 1895.
' Ueber die Verrichtangen des Grosshinis, 1881.

704 ^iV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

influence of" the special sense-organs which connect with the encephalon. The
physiological reactions of the higher vertebrates are especially modified hy this
latter arrangement. It is therefore true that the cord, as well as the brain, is,
in man, more complicated anatomically than in any of the lower forms, and
this in spite of the fact that the independent reactions of the human cord are
so imperfect.

One result of this concentration of the nerve-elements toward the head,
and the dependence of the rest of the system on the encc]>halon, is, as we shall
see, that the cephalic division becomes thereby a more necessary portion of the
pathway for the incoming impulses, and, conversely, as cephalization fails to
take place the several parts of the system remain more independent.

Reactions of Portions of Spinal Cord. — When an amphioxus is cut
into two pieces and then put back in the water, a slight dermal stimulus
causes in both of them locomotory movements, such as are made by the
entire animal.

When a shark (Scyllium canicula) is beheaded the torso swims in a co-ordi-
nated manner when returned to the water. Separation of the cord from the
brain does not deprive a ray {Torpedo oculata) of the pow'er of perfect loco-
motion. The same is true of the ganoid fish. In the case of the cyclostome
fish (Petromyzon) the beheaded trunk is, in the water, inactive, and, on gentle
mechanical stinnilation it makes inco-ordinated responses, but, put in a bath
formed by a 3 per cent, solution of picro-sulphuric acid, locomotion under the
influence of this strong and extensive dermal stimulus is completely performed.
In the case of the eel the responsiveness even to the picro-sulphuric acid bath
is evident in the caudal part of the body alone. In the bony fish this power
in the spinal cord has not been observed.^

In these experiments the central system is represented by the entire spinal
cord with the associated nerves, or by some fraction of it, but so simple, con-
stant, and independent are the reactions of the cord under normal conditions
that a strong stimulus is able to elicit the characteristic responses from even a
fragment of the system. The higher we ascend in the vertebrate series the
less evident do the independent powers of the cord become.

For the determination of the functions of the several parts of the nervous
svstem it is possible to employ in animals the method of removal as well as
the method of stimulation. The doctrine of localization was at one time
crudely expressed by the statement that a cortical centre was one the stimula-
tion of which produced a given reaction, and the removal of which abolished
this same reaction. Goltz* soon showed that in the dog the removal of even
an entire hemisphere did not cause a ]iaralysis of the muscles on the opposite
side of the body, although others had shown that a stinmlation of certain por-
tions of the cortex of the hemisphere would cause these muscles to contract.
It was argued, therefore — and quite rightly — that the cortical centres of the
dog did not completely answer to the definition.

^ Steiner : Die Functionen des Centralnervensystems und ihre Phylogenese, 2te Ablh., " Die
Fische," 1888. ^ Ueber die Verficklungen des Grosshims, 1881.

CENTRAL NERVOUS SYSTEM. 705

From the experimental work of the strict localizationists like Hitzig/
Munk,^ and Fcrricr,^ and t'roni the work of tiiose who, like GoUz^ and Loeb/
denied a strict localization in the cerebral hemispheres, several important points
of view have been developed.

In the first instance, anatomy indicates that in the central system there are
but few localities which consist only of one set of cell-bodies, together with
the fibres coming to these bodies and going from them. Almost every part
has both more than one set of connections with other parts and also fibres
passing through it or by way of it to other localities. Hence in removing any
part of the hemispheres, for instance, not only are groups of cell-bodies taken
away, but a number of extra pathways are interrupted at the same time, and
thus the damage extends beyond the limits of the part removed. Moreover,
when any portion of the central system has been removed there is a greater or
less amount of disturbance of function following immediately after the opera-
tion ; but this disturbance partially passes away. There are thus " temporary "
as contrasted with "permanent" effects of the lesion, and these require to be
sharply distinguished, because it is the permanent loss which is alone sig-
nificant in these experiments. Finally, it has been made clear that neither the
relative nor the absolute value of any division of the central system is fixed,
but depends on the degree to which cephalization has progressed, or, to use the
more common measure, the grade of the animal in the zoological series, both
expressions signifying an increase in the connections between the cerebrum

Fig. 199.— Schema of the encephalon of a bony fish— embryonic (Edinger). The vertical black line
marks off the structures in front of the thalamus.

and the lower centres. The age of the animal on which the operation has
been made is also of no small importance in this respect. These relations
can be illustrated by reference to several experiments.

Removal of Cerebral Hemispheres. — If from a bony fish the cerebral

' TTntersuchungen iiber das Gehirn, Berlin, 1874.

* Ueber die Functionen der Grosshirnrinde, Berlin, 1881.
' The Functions of the Brain, London, 1876.

* Ueber die Ven-ichtungen des Grosshim.% Bonn, 1881.

* Arch. fUr die gesammle Physiologic, Bde. 33 u. 34, 1884.
45

70G

AN AMERICAN TEXT-HOOK OF PII YSIOLOC Y.

liemisphert's (inclii(liii«; the coi-jjora striata as well as the iiiajitlc) be removed,
the animal apparently suffers little ineonveniencc". The movements are undis-
turbed ; sueh fish play together in the usual manner, discriminate between a
worm and a bit of sti'ing, and among a series of colored wafers to which they
rise, always select the red ones first.' In these fish the eye is the controlling
sense-organ, and, as will be recognized (see Fig, 199), the operation has by no
means damaged the primary centres of vision.

Quite different is the result when the cerebrum is removed from a shark.^
Tn this case, although the eyes are intact, the animal is reduced to comj)lete
quiescence ; yet on the whole, the nervous system of the shark is rather less
well organized and more simple than that of the bony fish. The astonishing
effect produced is explained by a second experiment (see Fig. 200). If the

Fig. 'JOO.— Schema of the cncephalon of a cartilaginous fish (Edinger). The vertical lilack line marks
oif the striatum and pars olfactorius, which lie in front of the thalamus.

olfactory tract be severed on one side, no marked disturbance in the reactions
of the shark is to be noticed ; when, however, both tracts are severed, the
shark acts as though deprived of its cerebrum. From this it appears that
the removal of the principal sense-organ, that of smell, is the real key to the
reactions, and that the responsiveness of the fish is reduced in the first instance,
becau.se in this case it has been deprived of the impulses coming through the
principal organs of sense, and in the second the removal of the cerebrum is
mainly important because the cerebrum contains the pathway for the impulses
from the olfactory bulbs to the cell-groups which control the cord.

Passing next to the amphibia as represented by the frog, there are seveml
series of observations on the physiological value of the divisions of the central
system. Schrader'^ finds the following: Removal of the cerebral hemispheres
only^ the optic thalami being uninjured, does not abolish the spontaneous activ-
ity of the frog. It jumps on the land or swims in the water, and changes from
one to the other without special stimulation. It hibernates like a normal frog,
retains its sexual instincts, and can feed by catching passing insect.s, such as flies

' Steiner : Die Funclionen der Centralnervensystems, 1888. ^ Steiner, loc nt.

' Archiv fur die gesammte Physiologic, 1887, Bd. xli.

CENTRAL A Eli VO US SYSTEM.

707

(see Fig. 201). A frog without its hemispheres is therefore capable of doing
several things apparently in a spontaneous way. Such frogs balance themselves

ii \

Fir; '^01 -Frog-s brain; the parts in dotted outline have been removed: A, brain intact; B, cerebral
hemispheres removed; C, cerebral hemispheres and thalami removed ; i), cerebellum removed; £, two
sections through the optic lobes ; F, two sections through the right half of the bulb (Sterner).

when the support on which they rest is slowly turned, moving forward or back-
ward as the case demands in order to" maintain their equilibrium. In doing

708 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

this the frog tends first to move the liead in the direction opposite to the motion
of the support, and then to follow with movements of the body. If the optic
thalanii are removed (Fig. 201, C), the power of balancing is lost, because,
although the movements of the head still occur, those of the body are abolished.
A frog thus operated on and deprived of the hemispheres and thalami exhibits
the lack of spontaneity which is usually described as following the loss of the
hemispheres alone, but which is not a necessary consequence of this operation,
as the preceding experiments show.

A frog possessed of the mid-brain and the parts behind it (Fig. 201, C)
will croak when stroked on the back. When the optic lobes have been
removed this reaction becomes more difficult to obtain, but it is not necessarily
abolished, neither is the characteristic fling of the legs in swimming. At the
same time, a frog with its optic lobes can direct both its jumping and swim-
ming movements according to light stimuli acting through the eye, jumping
around and over obstacles which form a shadow in its path, and climbing out
of the swimming tank on the lighter side. This power is lost when the optic
lobes have been removed.

"When the anterior end of the bulb (pars commissuralis — Stieda) has been
also Removed, then the frog becomes incessantly active, creeping about, and not
coming to rest until he has run himself into some corner. Schrader found such
frogs capable of clambering over the edge of a box 18 centimeters high. They
are at a loss when the edge of the box has been finally attained, and vainly
reach into space from this position. In the water they swim " dog-fashion,"
and only upon special stimulation do they make a spring.

If more of the bulb is removed, the bearing of the frog departs more and
more from the normal, and is only temporarily regained in response to strong
stimulation ; nevertheless, co-ordinated movements can be obtained when the
bulb down to the calamus scriptorius has been removed, and only when the
movements of the arms are directly affected by the damage of the upper end
of the cord does the inco-ordination become constant.

A section through the optic lobes at a (Fig. 201, E) puts the frog in a con-
dition similar to that following the isolated removal of the lobes, while a sec-
tion at b has the curious effect of causing the animal to move backward upon
stimulation of the toes.

When the small ridge which forms the cerebellum in the frog has been
removed, a slight tremor of the leg-muscles and a loss of precision in jumping
are the only defects noted (Fig. 201, D). These results hold for symmetrictil
removal of the divisions of the encephalon. When the removal is unsymmet-
rical in the inter-brain, mid-brain, or bulb (Fig. 201, F, a and h), there is
more or less tendency to forced positions or forced movements.

As a rule, action is most vigorous on the side of the body associated with
the greater quantity of nerve-tissue. This relation appears as a natural result
of the greater effectiveness of the incoming impulses when entering a larger
group of central cells. Indeed, the removal of the different portions of the
central system in the frog is accompanied l)y a progressive loss in responsive-

CENTRAL NERVOUS SYSTEM. 709

ness, stronger and stronger stimuli being recjuired lo induce a reaction, Tliis
holds true down to the anterior end of" the bulh, the removal of wliicli, on the
contrary, sets free the lower centres, so that the frog becomes incessantly active.
Just how this release is effected is not easy to explain, but further removal is
again followed by the loss of responsiveness.

Passing next to the bird, as represented by the pigeon, the observations of
Schrader are the most instructive.^ The removal of the hemispheres from the
bird (see Fig. 202) involves taking away the mantle and the basal ganglia, the

Fig. 202.— Schema of the encephalon of a bird (Edinger). The oblique black line marks off the
structures in front of the thalamus.

chiasma and the optic nerves being left intact. For the first few days after
operation the bird is in a sleep-like condition. Next the sleep becomes broken
into shorter and shorter periods, and then the bird begins walking about the
room. From the beginning its movements are directed by vision; slight
obstacles it surmounts by flying up to them, larger ones it goes around. In
climbing its movements are co-ordinated by the sense of touch, and the normal
position of the body is maintained with vigor. The birds which walk about
by day remain quiet and asleep during the night. In flying from a high
place the operated pigeon selects the point where it will alight, and prefers a
perch or similar object to the floor.

A reaction to sound is expressed by a start at a sudden noise, like the
explosion of a percussion cap.

Pigeons without the cerebrum do not eat voluntarily, though the presence
of the frontal portions of the hemispheres is sufficient to preserve the reaction.

In a young hawk slight damage to the frontal lobes abolished for the time
the use of the feet in the handling of food, and thus abolished in this way the
power of feeding as well as that of standing.

With the loss of the cerebrum the pigeon does not lose responsiveness to
the objects of the outer world, but they all have an equal value. The bird is
^ Archiv fur die gesammte Physiologie, 1888, Bd. xliv.

710 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

neither attracted nor repelled, save in so far as the selection of the points toward
which it will fly is an example of attraction. Sexual and maternal reactions
both disappear, and neither fear nor desire is evident.

In ascendini; the mammalian series the removal of the cerebrum becomes a
matter of increasing difficulty. The reasons for this are several, and reside in
the increasing size of the blood-vessels and the nutritive complications depend-
ent on the increase in the mass of the cerebrum, as well as in the greater physi-
ological importance of this division. Goltz ' has been able by repeated ope-
rations to remove the entire cerebrum of a dog, and still to keep the animal
alive and under observation for eighteen months, at the end of which time the
animal, though in good health, was killed for further examination. This dog
was blind, though he blinked when a bull's-eye lantern was suddenly flashed
in his face. He could be awakened by a loud sound, and when awake re-
sjionded to such sounds when intense by shaking the head or ears. This
would not, however, be complete proof that he could hear. The sense of taste
was so far present that meat soaked in quinine was rejected after tasting.
Tactile stimuli and those involving the muscle sense, as in the case when the
animal M'as lifted, caused him to struggle and to bite in the direction of the
irritiition. These reactions were modified according to the locality of the stim-
ulus. The power to make movements expressive of pain was still present.

On the motor side the dog was capable of such highly complicated acts as
walking, standing, and eating, and in these operations was guided by the muscle
sense and that of contact. The sexual instincts were lost, but the animal was
excessively active, and became more and more excited when ready to defecate
or when hungry.

The examination of the brain showed that all parts in front of the mid-
brain had been removed or Avere degenerated, so that the defects were due to a
removal of rather more than the cerebrum j^roper.

Emotions, feelings, conscious sensations, or the capacity to learn were entirely
wanting in this dog, and its reactions were those of a very elaborate machine.

If we compare, now, the effects of the removal of the cerebral hemisphere
in the bony fish, the pigeon, and the dog, we see that the results of the operation
are progressively more disturbing as we pass up the series. In the higher
animals the effects are more often fatal, the disturbance immediately following
is much more severe, the return of function slower, and the permanent loss
greater. As a partial exception to the above statements is the observation that
af^er operation the general health of pigeons always declines, and it is not
possible to keep them alive more than about six weeks. On the contrary, a
dog could be kept in good health for some eighteen months ; but there is this
difference, that the removal in the case of the dog was made by several suc-
cessive operations.

By removal of the cerebrum the higher animal tends to lose just those
capacities which best serve' to distinguish it from the lower forms. When,
therefore, the inquiry is made why the results gotten in the dog are not obtaiu-
' Arehiv fiir die gesammle Physiologie, Bd. xli.

CENTRAL NERVOUS SYSTEM. 711

able in monkey or man, tliero arc several replies. In the first place, no sueii
extensive experiments have been made on monkeys of the right age and nnder
ecjnally favorable eonditions. If a matnn; animal is taken, the secondary
degenerations are so massive that they certainly cause great disturbance iu the
remaining part of the system. This is not equivalent to an assertion that the
same results could be obtained in the monkey by more extensive experiments,
but a suggestion of one difference behind the results thus far reported. There
is no reason for assuming any deep-seated difference in the arrangement of the
central system of the highest mammals as compared with that in the lower.
Indeed, in some human microcephalic idiots the })roportion of sound and
functional tissue in the encephalon is less than one-iburth that found in a
normal person, yet, on the other hand, no normal adult could lose anything
like that amount of tissue which is out of function in these microcephalic brains
and at the same time live.

The central system, therefore, even in man, is to be looked upon as possessed
of some power to adapt itself when portions have been lost, but this is most
evident when the defect begins early and develops slowly.

Keeping the cerebrum still in view, it is possible to go into further detail.
In forms below the monkey the loss of portions of the cerebral cortex from the
motor area is accompanied by a greater or less paralysis of the muscles repre-
sented. This, however, is an initial symptom only, and gradually disappears,
though not always with the same completeness. In man, of course, the tend-
ency to recover is least.

The anatomical relations behind this difference are the followina : The
efferent cells iu the ventral horns are dominated principally by two sets of
impulses, those arriving directly over the dorsal roots of that segment in which
they are located, and those coming over the long paths by way of the cerebral
cortex- and pyramidal tracts. In the lower mammals this second pathway is
insignificant, and when interrupted, therefore, the disturbance in the control of
the ventral-horn cells is but slight. Passing up the series, however, this path-
way tends to become more and more massive and important, as the figures pre-
viously given show (see p. 695), until in man and the monkey a damage of it
such as is effected by injury to the cortex causes a high degree of paresis if not
permanent paralysis, because by this injury a greater proportion of the impulses
is thus cut off from the efferent cells.

It has previously been shown that the cortical areas do not vary accord-
ing to the mass of the muscles which they control. Experiments also show
that it is the fore limbs which are most disturbed in their reactions when the
lesion involves the cortical centres for both fore and hind limbs, and this falls
under the law that the more highly adaptable movements {i. e. those of the fore
limb as contrasted with the hind limb) are most under the control of the cortex.
If the examination be restricted to the fore limb alone, it is found that the
finger and hand movements or those of the more distal segments are in turn
the ones most disturbed. Thus, in the limbs, the more distal groups of mus-
cles are those best controlled from the cortex. It follows, then, that for the

712 AX amp:rican text- hook of physiology.

arm, paralysis of shoulder movements as the result of cortieal lesion is least
eomj)lcte, while as we travel toward the extremity of the arm the liabilitv to
disturl)anee of its function as the result of cortical injury increases steadily.

Turniiiu', now, to the "sensory" areas of the cortex, the principles under-
lying- their physiological significance and connections appear to be similar.
The lower the animal in the vertebrate series the more probable that its reac-
tions can be controlled by the atterent impulses which have not passed through
the cerebral cortex.

, None of the senses except vision can be analyzed sufficiently to bring out
the signiHcancf of subdivisions of the cortical area ; hence the illustrations are
taken from that sense alone.

It has already been shown that without cerebral hemispheres a bony fish can
distinguish the colors of wafers thrown on the water and discriminate between
a bit of string and a worm. In the same case a frog is able to direct its move-
ments and to catch flies — i. e. to detect objects in motion and react to them
normally. A pigeon can direct its movements in some measure, and even select
a special object as a perch, but it is not able to respond to the sight of food or
its fellows or those objects which might be supposed to excite the bird to
flight. In the dog the vision which remains permits only the response of
blinking when the eye is stimulated by the flash of a bull's-eye lantern.
The progressive diminution in the response which follows visual stimuli
in these animals is open to the interpretation that the path by which the
impulses may pass over to the cells forming the primary centres interme-
diate bet\Aeen the sense-organ and the cortex is progressively diminished.
Thus the impulses arriving at the primary optic centres are in a less and
less degree reflected toward the cord, as the pathway to the cortex becomes
more permeable. When therefore, the cortex has been removed the reac-
tions taking place by way of it are disturbed in proportion to their normal
importance.

In the first instance, when the reflexion occurs in the primary centres, the
incoming impulses are distributed toward the cord by paths not known,
while in the second, they pass from the cortex along the pyramidal tracts.

In the cortex subdivisions of the visual area have been made by Munk.*
He found that the more anterior ])ortions of the visual area were associated
with the superior parts of the retina, and the more posterior portions with the
inferior, while the area in one hemisphere corresponded with the nasal portion
of the contralateral retina, and to a less degree M'ith the temporal portion of the
retina of the same side. The determination of these relations wns made by
the removal of parts of the visual area (dogs) and the subsequent examination
of the field of vision. It apj)ears, therefore, that the incoming imjndscs from
certain parts of the retina are delivered at definite points in the cortex, and
that when the j)aths are interrupted in the dog or higher mammals these
impulses are blocked. By stinndatioii, it will be remembered, Schiifer deter-
mined similar relations in the monkey.

' XJiher die Functionen der Grosshirnrinde, Herlin, 1881.

CENTUM. NERVOUS SYSTEM. 713

Before leaving the eerebrul heinisplieies, lueiilion ol'tlie (iict should be made
that still other functions, control of the sphincter ani (Fig. 189), secretion of
saliva, and micturition can be roused by the stimulation of the cortex in the
appropriate region — namely, in the region where the muscles and glands con-
cerned might be expected to have representation if they followed the general
law of arrangement. Changes in the production and elimination of heat from
the body follow interference with the motor region of the cerebrum, and the
removal of portions of the ctn-tex in this region is followed by a rise in the
temperature of the muscles aifected.

In the encophalon, the cerebrum, and especially its outer surface, is the por-
tion the functions of which have been studied. The significance of the other
portions of the encephalon can be far less well determined. The disturbances
caused by the section and stimulation of tiie callosum have been studied by
Koranyi ^ and by Schafer ^ and Mott. It was found that comjilete section
of the corpus callosum was not followed by any perceptible loss of function.
On the other hand, stimulation of the uninjured callosum from above gave
symmetrical bilateral movements, while if the cortex on one side was removed
stimulation of the callosum gave unilateral movements on the side controlled
by the uninjured hemisphere. These results seem to corroborate the conclu-
sion derived froni histological work to the effect that the system of the callo-
sum is composed only of commissural fibres and that it sends no fibres directly
into the internal capsule of either side. Concerning the corpora striata and
the optic thalami very little is known. In the case of the corpora striata injury
causes in man no permanent defect of sensation or motion, although both forms
of disturbance may at the outset be present in the case of acute lesions. Lesions
of the corpora striata cause a rise in temperature.^ Following a puncture of one
corpus striatum there occurs in rabbits a rise amounting to some 3° C. : it
begins a few minutes after the operation and may last a week, but the temper-
ature tends to return to the normal. The most striking feature in these exper-
iments is the very wide effects produced by an extremely small wound, like the
puncture of a probe.

In the cases where lesion of the striatum on one side causes in man a rise of
temperature it appears mainly on the side of the body opposite the lesion.*
A vaso-motor dilatation occurs over the parts of the body where the temper-
ature is high.

In less degree a rise of temperature follows injury of the optic thalamus —
at least such is the result of experiments on rabbits — but the effect of the lesion
is never so marked as in the case of the striatum. Owing to the disproportion
between the area of the lesion and the extent of the effects, it is difficult to con-
ceive of the anatomical relations which permit the reaction. It is of interest
to note, however, that similar relations hold for the vaso-motor centre in the

* Archiv fur die gesammte Physiolor/ie, Bd. xlvii. ^ Bram, 1890.

' Aronsohn und Sachs: Archiv filr die gesammte Physiologie, 1885, Bd. xxxvii. ; Richet:
Compt. rend, de I' Acad, des Sciences, 1884 ; Ott : Brain, 1889, vol. xi,

* Kaiser; Neurologische Centralblatt, No. 10, 1895.

714 ^liV' AMERICAN TEXT-BOOK OF PHYSIOLOGY.

bull), in which case tlie vessels siippiyinir a great area are controlled by a small
grou{) of cells.

The difficulty of an anatomical explanation is increased by the fact ' that
Ott enumerates in animals six heat-centres : 1. The cruciate, about the Rolandic
fissure; 2. The Sylvian, at the junction of the supra- and post-Sylvian fis-
sures; 3. The caudate nucleus; 4. The tissues about the striatum ; o. A point
between the striatum and the thalamus, near the median line; 6. The anterior
mesial end of the thalanuis.

The only other division of the encephalon, the functions of which can j)roj>-
erly be described apart, is the ccrcbelhim. This portion is among vertebrates
almost as variable in its development as the mantle of the cerebral hemispheres,
and in many fish and mammals is asymmetrical in its gross structure.

The recent work on this subdivision has been carried out in the first instance
by Luciani,^ and later by RusselP and by Ferrier.*

The cerebellum is not concerned with psychical functions. The removal
of it does not cause permanently either paralysis or anaesthesia, but the imme-
diate effects of an extensive injury are a paresis and analgesia as well as anaes-
thesia mainly in the hind legs, and in consequence a high degree of inco-
ordination in locomotion. A distinct series of symptoms, however, follows
injury to this organ, and these are modified according to the locality and
nature of the lesion. Removal of one half (cerebellar hemisphere plus half
the vermis) of the cerebellum in the dog causes a deviation outward and
downward of the optic bulb on the opposite side, a proptosis of the bulbs on
both sides, nystagmus and contracture of the muscles of the neck on the
side of the lesion, and an increase of the tendon reflexes in the limbs. lu
walking the dog wheels toward the side opposite to the lesion, and tends to fall
torrard the side of the lesion.

The symptoms are chiefly unilateral, and, caudad from the cerebellum, are
on the side of the lesion. The symptoms are less severe when only one hemis-
phere, instead of an entire half of the cerebellum, has been removed. The
existing symptoms are not intensified by the removal of the remaining half.
The permanent condition of the muscles after operation is expressed by an
atoiiia, or lack of tonus, in the resting muscles ; an asthenia, or loss of strength,
which was measured by Luciani, and was most marked in the hind leg; an
astasia, or a lack of steadiness in the muscles during action ; and finally an
ataxia, or a want of orderly sequence, in the contractions of a muscle-
group. The general expression of these symptoms is a twist of the trunk,
the concavity being toward the operated side, combined with a disorderly gait.
At the same time there is no demonstrable permanent disturbance of tactile
or muscular sensibility.

Though the two halves of the cerebellum are united by strong commissural
fibres, the complete division of the organ in the middle line is followed by a
disturbance of the gait which is only transitory. Hence it is inferred that the

^ Ott : loc. cit. ^ Archives Italiennes de Bioloijic, 1891-92. xvi.

^ Philosophical Transactioru Royal Society, 1894. * Brain, 1893, vol. xvi.

CENTRAL NERVOUS SYSTEM. 715

connections of the cercbelluin are mainly \vill> the same side of the bull) and
spinal cord. Cephalad of the eerebellum the coimection, however, is a crossed
one, each cerebellar hemisphere beinir associated with tlu; (contralateral cerebral
hemisphere. Throughout these connections, both cephalad and candad t(. the
cerebellum itself, it appears that there is always a double pathway, and the
eerebellum not only sends impulses to, but receives them from, the regions with
which it is associated.

One eifcct of removal of one half of the cerebellum is to increase the respon-
siveness of the cortex of the contralateral cerebral hemisphere to electrical sthn-
nlation, therebv making it possible with a weaker stimulus to obtain a reaction
which could be obtained from the other hemisphere only by a stronger one.
When an irritative lesion is made, instead of a merely destructive one, the rota-
tion and foiling are away from the side of the lesion instead of toward it.

The experiments altogether show the cerebellum to be closely associated with
the proper contraction of the muscles, and this is so directly connected with the
maintenance of equilibrium that it is not surprising to find that stimulation or
removal of the cerebellar cortex, besides producing nystagmus, may give rise
to deviations of the eyes similar to those found on injury to the semicircular
canals or stimulation of their nerves in fishes.^

PART III.-PHYSIOLOGY OF THE NERVOUS SYSTEM
TAKEN AS A WHOLE.

A. Weight of the Brain and Spinal Cord.
In attributing a value to the mass of the nervous system we assume that
the elements which compose it possess potential energy. This energy varies
for any given element in accordance with a number of conditions, but for the
moment it will be sufficient to point out that if the mass of the entire system
is sio-nificant the masses of its respective subdivisions are also significant, as
showing in some measure the relative physiological importance of the several

parts. , . . ,

Changes Dependent upon Age.— That the mass of the system varies with
acre is a matter of common observation. The changes which occur m the mass,
atthou-h they are specially evident, are not the only changes which take place ;
for with the change in mass go hand in hand changes in the relations which
the elements bear to one another, and which result in making the organization
of the svstem different at the different periods of life. Moreover, the special-
ization of the nerve-elements, in the mammals at least, has been carried to such
a point that they are utterly dependent for their full activity on the nutritive
system and the character and amount of the nutrient plasma is a circum-
stance of prime importance. Any variation in this factor serves to com-
pletely alter the activities of the system, be it never so well organized, and

' Lee: Journal of Phydology, 1893, vol. xv. ; 1894, vol. xvii.

716 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

therefore the discussion of the general powers of the nervous system for per-
formance must never leave this factor unconsidered.

Constituents of the Central System. — Calculation shows that the cell-
bodies probably contribute less than 10 per cent, of the entire weight of the
central system, so that the remainder must be made up of neurons and other
tissues.

In the central system there are present, besides the nerve-elements proper,
the sustentacular tissues and the nutritive vessels — the channels for blood and
lymph. Just what fraction of the total w^eight of the central system is thus
represented has not been exactly determined, but it must be nearly equal to
that of the nerve cell-bodies alone.

The weight of the brain is the weight of these several constituents.

Of course a brain congested with blood would weigh more than one from
which the blood had been largely withdrawn, but there is no way of controlling
this condition directly. Previous to weighing, the brain is sometimes sub-
divided and even cut into large sections, in which case of course much of the
blood and lymph has the opportunity to drain away. In some cases too the
brain is weighed without, and in others with, the pia.

'Weight of the Pia and Fluid. — Broca's table for the weight of the pia in
males is as follows : ^

20-30 years 45 grams.

31^0 •' 50 "

60 '■ 60 "

The cast of the ventricles, as made by Welcker, displaces 26 cubic centi-
meters of water, so that the fluid filling these cavities would Aveigh a trifle
over 26 grams.

Percentag-e ofWater. — In man the percentage of water in the gray matter
of the cerebrum is 81.8 per cent., and in the -white matter 70 per cent.'

Specific Gravity. — According to calculation, the specific gravity of the
entire encephalon is 1036.3 in the male and 1036.0 in the female. Ober-
steiner' found the specific gravity of the cortex to gradually increase from
frontal to the occipital lobe. It was further found that while the outermost
layer of the cortex had a specific gravity of 1028, that of the middle layers
was 1034 and of the deepest layers 1036, thus indicating a progressive increase
from the most suj)erficial to the deepest layers — an increase to be associated
with the larger proportion of medullated fibres in the deeper layers.

"Weight of the Encephalon and Spinal Cord. — As a result of the pre-
ceding statement it follows that when the weight of any portion of the nerv-
ous system is taken, the final record represents, in addition to the weight of
the nerve-tissues proper, that of the supporting and nutritive tissues, together
with the enclosed blood and lymph. It is, however, assumed that under
normal conditions the relation between the nervous and non-nervous tissues is

' Broca, quoted bv Topinard : Elements d" Anthropologic ghi^nle, 1885.

* Halliburton : Journal of Physiology, 1894. » Centralblatt fur Nenenheilkunde, 1894.

CENTRAL NERVOUS SYSTEM.

717

maily a constant one, and tliat tlio results of diiforent weighings are therefore
comparable among tlieinselves.

Interpretations of Weight.— Assuming as the simplest case that the nuin-
ber of the nerve-elements e<)mi)osing a given portion of the central system is
constant, then differences in the weight of these portions in^ diU'erent individ-
uals imply variations in the size of the component cells. The signifieance of
variations in the size of the nerve-elements must be, primarily, that the larger
the cells, and especially the larger the cell-bodies, the greater the mass of cell-
substance ready at any moment to undergo chemical change leading to the
release of energy. On the other hand, if the number of elements is variable,
an increase in the number must, in view of the law of isolated conduction,
also provide a larger number of conducting pathways. Whether this increase
in the number of pathways shall further add to the complication of the sys-
tem depends on the localities at which it occurs. Bearing these facts in mind,
we may turn to the records of the weight of the encephalon.

-Weight of the Encephalon.— The encephalon is that portion of the cen-
tral nervous system contained within the skull. The accompanying diagram

Fig 203 -Showing the principal divisions of the encephalon made for the study of its weight : 1,
hemisphere seen from the side, fissuration according to Eberstaller; 2, mid-brain, region of the quad-
rigemina; 3, pons; 4, cerebellum, or hind-brain; 5, bulb, or after-brain. Divisions 2, 3 and 5, taken
together, form what is designated the " stem " in the tables of Boyd (modified from Quain s Anatomy).

(Fig. 203) shows the encephalon, together with one manner of subdividing it.
Its weight has usually been taken while it was still covered by the pia, but
after altowing the fluids to drain away for five minutes or more. As has
been stated, sometimes drainage has been fjicilitated by cutting into the brain ;
hence, when the brain-weight records by any observer are to be discussed, the
first question concerns the method according to which the brains were exam-
ined, for the weights may be either with or without the pia and with or with-
out drainage.

IS

.liV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

The anthropologists classify the encephala according to weight in tl)o fol-
lowing manner :

Tlic Xomendaiure of the Encephalon according to Weight. Weight in Grama

{Topinard).

Classes. Males. Females.

Macrocephalic From lit2o-1701 From 1743-1501

Large " 1700-1451 " 1500-1351

Medium " 1450-1251 " 1350-1151

Small " 1250-1001 " 1150- 901

Microcephalic " 1000- 300 " 900- 283

The brain-weight in the majority of persons falls within the group of
medium brains, and average figures are obtained by combining the individual
records in which all variations from the medium occur. Of course races of
small size, like the small people of India or the Pygmies of Africa, would not
be expected to possess encephala equal in weights to those of the larger races of
Europe. Any set of average figures, therefore, should be based as nearly as
possible on observations made on a homogeneous population. "Within the
limits of a given race there are several conditions which determine differences
in brain-weight, namely, sex, age, stature, and body-weight.

From the observations by Dr. Boyd on the weight of the brain in England
the following table has been compiled :

Table shoving the Weight of the Encephalon and its Subdivisions in Sane
Persons, the Records being arranged according to Sex, Age, and Stature
(from 3IarshaWs tables based on Boyd's records).^

Males.

Females.

m

bo
<

a
o

"3

o

S

S

0)

o

5

1
1

■

S
35

a

TO

S
s

1

1

i

3

1-4

£

c
"3

1

1
<

Stature 175 cm. and upward.

Stature 163 cm. and upward.

20-40

1409 . 1232 149

28

23

134 I 1108 1 1265

20-40

41-70

1363 1192 144

27

23

131 1055 1209

41-70

71-90

1330 1 1167 ' 137
Stature 172-167 cm.

26

24 a

130 1 1012 1 1166
Stature 160-155 cm.

71-90

20-40

1360 1188 1 144

28

26 s

137 s 1055

1218

20-40

41-70

1335 1164 144

27

268

131 1055

12128

41-70

71-90

1305 1135 1 1428

28 as

24

128 969 8

1121

71-90

Stature 164 cm. and under.

Stature 152 cm. and under.

20-40

1331 1168 1 138

25

24 s

130 1 1045

1199

20-40

41-70

1297 1123 ! 139 a

25

25a8

129 1051 a

1205 a

41-70

71-90

1251

1095

131

25

25 as

123

974

1122

71-90

The method of weighing the brain used by Dr. Boyd ^ was as follows : The
skull-cap being removed and the pia being intact, the hemispheres were sliced

' a indicates that a record considered according to age is too large; ••< indicates that a record
considered according to stature is too large.

^ PltUomphirdl Tranmdiom of the Iioy(d Society, London, 1860 ; see also Marshall : Journal of
Anatomy and Physiology, 1892.

CENTRAL NERVOUS SYSTEM. 719

away by horizontal sections as far <l()\\ii as tiic tentorium. The parts of the
hemispheres still rcmainino; were then removed by a sec-tion passinfr in front of
the qiiadrigemina. The cerebellum was next separated from the stem, this
latter being represented by the quadrigemina, the pons, and the bulb. Each
hemisphere, the cerebellum, and the stem were then weighed separately.

Between the twentieth year and old age there are here represented the average
encephalic weights, arranged in two main groups according to sex, and then in
large horizontal groups according to stature, those of a given stature being sub-
divided according to age. This record is typical of what has been found by
other observers and may be discussed without further evidence.

If groups of similar ages and corresponding statures are compared accord-
ing to sex, it is at once seen that the male possesses the heavier encephalon, and
that all the subdivisions of it are likewise heavier.

When individuals of the same sex and falling within the same age-limits
are compared according to stature, those having the greater stature are found to
have the greater brain-weight, though in the case of the subdivisions of the
encephalon, and especially among the females, there are some irregularities, but
these would probably disappear could the number of observations be increased.
Finally, within the groups of those having the same stature, but different ages,
the weight decreases with advancing age. The middle group, forty-one to
seventy years of age, is in one way unfortunate, because, while the brain is
probably still growing (see curve of growth. Fig. 204), during the first third
of that period, and is nearly stationary (males especially) during the second, it
begins to diminish so rapidly during the last third that the average weight is
lower for the cases between sixty-one and seventy years than for the twenty
years between forty-one and sixty years. Between seventy-one and ninety
years the involutionary changes in the central system are most marked, and
the decrease in weight during this period is clearly indicated.

Body--weight. — As regards the relations between the weight of the central
system and the weight of the body the case is not so clear. In the first place,
the presence of fat at maturity disturbs the results, because the nervous system
cannot be expected to vary with changes in the quantity of an inactive tissue
representing stored food-stuff merely. The taller individuals have a larger
cranial capacity than the shorter, and hence the variation of brain with body-
mass can only be made fairly when persons of the same stature, but of dif-
ferent body-weights, shall have been carefully compared.

If under these circumstances it shall appear that the bulkier individuals
have the heavier nervous system, then the excess in their favor can be fairly
correlated with the excess of the active tissues.

Before suggesting an explanation of these variations according to age, sex,
and stature, it is to be noted that they occur in other mammals as well as in
man. As regards the difference in the Aveight of the encephalon due to sex, it
has been shown to obtain among the apes,^ the mate having the heavier brain •
and from the general relation of size according to sex among the mammalia,
^ Keith; Journal of Anatomy and Physiology, 1895.

720 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

where the male as a rule has the greater body-weight, it is to l)e aiitit-ipated that
a similar difference in \\\v weight of the brain will be shown in other groups.

Among individuals of the same sj)ec'ies, but of different races or of different
lengths and weights, the law holds good that the larger races have the heavier
brains, as do the larger and heavier individuals. Here, as in the case of man,
it is always assumed that the differences in body-weight are mainly correlated
with the active tissues like muscle, and not with fat. As to the loss of the
brain in weight after maturity, observations on animals are scanty, but point
to decrease in weight toward the natural close of life.

Interpretation of Brain-weight. — In the absence of fuller data the
explanation of the series of differences just mentioned is, in a very high degree,
tentative. The loss of weight in advanced years appears to be due to a gen-
eral atrophy of the nerve-elements. The greater brain-weight associated with
greater stature appears to depend on the variations in the size of the elements
rather than in their number, and, so far as can be seen, the distinction accord-
ing to sex is susceptible of a similar explanation.

The fact that the difference in brain-weight between the two sexes more
probably depends upon a difference in the size of individual elements than
upon a difference in the number of these elements is strongly suggested by
the following considerations: The microcephalic brains, constituting one group
which always appears in long series of records, belong to individuals whose
intelligence is very limited or to those to whom the functions necessary to mere
existence are just possible. In this latter class we have presumptively arrived
at a brain in which the functional elements are reduced to the lowest number
compatible with life.

Subjoined is a table giving the average weights of microcephalic brains for
the two sexes, the observations being divided into three groups. In each of the
groups taken the average weight for the females is less than that for the males :

Tlie Weight of the Brain in Microcephalics {condensed from Marchand)}

Group. 241-600 grams. 501-800 grams. 801-1015 grams.

Males 349 651 954

Females 299 621 912

When the weight for the two sexes is here compared, it is seen that the
average for the female is the closer to the lower limit in each group. As by
hypothesis we are dealing with the least po.ssible number of elements in either
sex and as there is no reason to assume that this minimum number is materi-
ally different for the two sexes, the inference is plausible that in these cases
the difference in weight is in a large measure due to the difference in the size
of the constituent elements. If this holds for the lower limit of the series, it
is of course also probable that it holds throughout the entire series as well.

As compared with the average brain, those of either sex forming the groups
heavier than the average owe their greater weight more often to an increase in
the size of the constituent elements than to an increase in their number. On

* Marchand: Nova Acta der Kaiserl. Carol. Deutseh. Akad. der Naturforscher, HaWe, 1890.

CENTRAL NERVOUS SYSTEM. 721

the oth«- luUKl, in those gro,.ps'posse..sing the smallest weight not only the si.e
but more probably also the n„,nber, of elements may be r«h,ee,l below ha
f, „Kl in nLn,al persons. These statements are of eon,-., to ho aPl'l-d "■ the
' n, to n,en,llers of the sao,e race. We know ,h:,, the i-™™=''« »^
Laller nervous systems than that of man have a far s.nall.r .nnnU.r of ne>^e-

"'nr;;;:X:wJ't'i::'t- the wiOer variations in the nuntWr of eeUs .»n,posing the
nervous system in n,a,> ocrur among the different raees, and that here, as we 1
rimong the mieroeephalies, in which development has been early arrested,
difforenoes in the number of cells are most marked. . , , f

W^^hts of Different Portions.-A study of the proport.onal w.tghts of
theTevell subdivisions of the encephalon aeeording to the sex stature, and
a« 4 OS that there is verv little difference caused by vanattons ,n these co, -
d^;^ This too, so far as it goes, suggests that the absolute we.ght ts depend-
en mther on variations in the si.e than in the number of the elements, sntee
rl"* nilL variation in number would be less probable than a harmontons

^•"tll y::ironr„e„t.-It is not to be -P-^ .Hat ^he ^e^j'^^^^^^^^

brain aM.on<. the least-tavored classes in any eommunity will be the same as

^ of thos^ who, during the yea. of growth, are -«<;; " -"^ "r^l

All extensive series of observations which we pos.sess relate to he lea.t ta^or«l

• Tm -es and hence it is not improbable that the figures in the foregoing

TbTe :^d; e b^^ on data obta'ined mainly at the Marylebone workhouse

Tn Lo'uJon are decidedly below those which would be obtained ft-om 1. mo^

<-,rt„n^te classes in the same eommunity. We have a list of biain-«eignts

i 1 tn iTthe r cords for a number of men of acknowledged emtnence,

nd IsT or othet. who attained recognition as able persons wnthout be.ng

::lptionally remarkable. It shows the men i,, this list to have bn.ns on the

nvprao-e heavier than the usual hospital subject .^ . , , i

C:mpaHson of the brain-weights of eminent men with the weights taken
frotn Z ksses used to furnish the standard has been made by Manonvrter.
The tible on p ^e 722 gives the brain-weights occurring among etn.nen men
Jompati "th those fomKl among Parisians of the lower classes, these latter
bZ subdivided ac«>rding to stature (Manouvrier). The flgnr^ expre^ the
number of brains in each group of 100 that would fall w.tlun the bmtts of
wpio-ht oDDO^ite to which the entries stand.

^t^.. wide range in the weights given in these ^tables b«t at the same
time their average is high as compared with the figures of Bo>d and other
c^b^erve," Sinel even those who at. undoubtedly disttngutshed presen
br^hiwei^hts havin. a wide range, and since any long series of observations
wo"u ™th a faFr number of eases of high brain-weight without any
rggiiol of superior mental ability, it is ,vident that tl^ 5^ ■-■-|

anrunnsnal mental capability are by - "-"^X l^w ve^ M;bT 'L
sion in harmony with common observation. ^ hether, However, n ^
1 Donaldson : The Growth of the Brain, 1895.

46

•22

AA"^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Aveight is to be con.sidered more frequent among men of tlistinetion eannot be
determined until there is available a large number of records obtained, not
from the less-favored social classes, but from j)ersons accounted as successful
merchants, bankers, and members pf the learned j)rofessions.

Weight of the Encephaion.
in Grams.

Parisians
of Broca.

Adult.

168 cm.

Parisians

of Tall

stature.

171-185 cm.

Eminent Men.

1st Series.

2d SeriPR Series 1 and
idberies. scombined.

900-1000

0.6

0.6

7.1

23.3

31.5

23.8

9.6

3.5

3.5
15.5
27.5
34.6
15.5

3.4

ii.i

17.8

33,3

24.5

2.2

2.2

2.2

6.7

1001-1100

1101-1200

2.9 1.2

2.9 7.5

17.2 17.5

48.5 40.0

22.8 23.8

5.7 3.3

. . 1.6

. . 1.3

. . 3.8

1201-1300

1301-1400

1401-1500

15(»l-lti00

11)01-1700

1701-1800

1801-1900

1901-2000

2001 and more

Total

100

100

100

100 100

Brain-weight of Criminals. — The observations of Manouvrier have
shown that among French murderers the brain-weight is similar to that of the
individuals usually examined in the Parisian ho.spitals. In the same manner,
the observations on the brain- weight among the insane indicate, according to
the records of Boyd and others, that the insane as a class (the microcephalics
being of course excluded) are not characterized by a special brain-weight.
AYhen, however, the insane are grouped according to the special diseases from
which they have snifered, it is evident that those in which the brain was con-
gested at death exhibit the higher weight, while those in which the pathological
processes caused destructive changes exhibit a low^ weight. The differences in
these cases are rather the results of disease than the cause of it.

Brain-weights of Different Races. — Concerning the weights of the brain
in different races there are no extensive observations which have been made
directly on the brain itself. Davi.s^ has, however, determined the cranial capaci-
ties of a series of skulls belonging to different races, and the brain-weights as
calculated from these are as follows :

Races.

European

Oceanic

American

Asiatic . .

African

Australian

Males.

«

1

O

299

210

52

124

53

24

1364—1212
1369—1192
1338—1209
1397—1155
l.fl6— 1165
1414—1027

1340
1293
1282

1278
1268
1190

1180
1185
1164
1171
1187
1089

Females.

1099—1278
1139—1239
1087-1263
1042—1276
1100—1220
966—1194

94
95
31
86
60
11

' Journal of the Academy of Natural Science, Philadelphia, 1869.

CENTRAL NERVOUS SYSTEM. 723

This, as will be seen, gives the largest brain-weights to the western Europeans,
but for a proper interpretation of the results there are needed at least the data
concerning stature and ag(! of the cases studied, both of which are here lacking.

Weight of Spinal Cord. — Comparatively few observations are available
for the spinal cord : Mies^ found that in adults it weighed 24 to 33.3 grams,
with an average weight of 26.27 grams : this for the cord deprived of the
nerve-roots, but covered by the pia. The variations due to sex and stature
have not been determined. It seems probable', however, that the cord, like
the brain, will be found lighter in females and in short persons: Mies states
that its decrease in old age is proportionately less than that of the brain.

Bilateral Symmetry as determined by the Balances. — The central
nervous system in its larger features is bilaterally symmetrical. In detail,
however, there are many deviations. The question at once arises whether
these variations are normally wide enough to permit us to attach to them a
distinct' physiological value. While, morphologically, bilateral symmetry is
expressed in the arrangement of the central system, common experience and
clinical observations show that most persons are physiologically one-sided, and
the two sets of facts are apparently out of harmony, provided an anatomical
basis is sought for the physiological reactions. The facts bearing on this ques-
tion are the following :

The two cerebral hemispheres in man are found to weigh within a gram of
one another in about one-third of the cases recorded (Franceschi). Larger
differences, when found, are not distinctly in favor of either hemisphere, accord-
ing to the observations of this same author. The results of those observers
who have found one side constantly heavier are discordant.

In individual cases, of course, wide differences between the weight of the two
hemispheres may occur, but these are clearly abnormal.

Asymmetry Otherwise Determined. — Other asymmetry has not been
detected by the balances. The human cerebellum has not been studied in
reference to its bilateral symmetry, but in cats Krohn ^ found the molecular
layer thinner on the right side, and the same is true in the case of the sheep.
In both these animals the middle lobe (vermis) is, however, asymmetri-
cal, being twisted to the right, and it is just possible that the thickness of
the molecular layer may be associated with this arrangement. Flechsig's
observations on the asymmetry of the pyramidal tracts have already been
noted.

In connection with these anatomical results it is to be noted that the blood-
supply to the anterior portions of the left hemisphere is through the left
carotid, which appears mechanically fitted to furnish a more direct supply than
does the right ; and, bearing in mind the dominant influence of nutritive con-
ditions for nervous response, this arrangement may yet prove to be significant.

The few data which are available on the asyinmetrv of the central system
do not therefore give us a basis sufficient to explain the asymmetry of function.

^ Neurol Off isehe Centralblati, 1893.

'' Krohn : Journal of Nervous and Mental Disease, 1892.

"24

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

B. Growth-changes.

The characters of the brain and cord thus far described have been those
found for the most part in tlie adult. Between birth and the natural end of
life, however, great changes take place, and, as it is necessary to consider the
functions of the central system at all times in its history, the importance of
knowing the direction in which the growth-changes are probably occurring is
obvious.

Growth of Brain. — The weight of the brain from birth to the twenty-fifth
year is given below (Vierordt ').

Inc7'ease in Brain-weight with Age — Encephalon Weighed Entire witli Pia

{compiled by H. Vierordt).

Males.

Females.

Age.

No. of Cases.

Brain.

Brain.

No. of Cases.

0 months

1 year

2 years

3 "

4 "

5 "

6 "

7 "

8 "

9 "

10 "

11 "

12 "

13 "

14 "

15 "

16 "

17 "

18 "

19 "

20 "

21 "

22 "

23 "

24 "

25 "

36

17

27

19

19

16

10

14

4

3

8

7

5

8

12

3

7

15

18

21

14

29

26

22

30

25

381
945
1025
1108
1330
1263
1359
1348
1377
1425
1408
1360
1416

1487
1289

1490
1435
1-109
1421
1397
1445
1412
1348
1397
1424
14.31

384
872
961
1040
1139
1221
1265
1296
1150
1243
1284
1238
1245
1256
134i>
1238
1273
1237
1325
1234
1228
1320
1283
1278
1249
1224

38

11

28

23

13

19

10

8

9

1

4

1

2

3

5

8

15

18

21

15

33

31

16

26

33

33

Total number of cases, 415.

Total number of cases, 424.

From the same figures the first part of the accompanying curve (Fig. 204)
has been formed.

The curve beyond the twenty-fifth year is continued on the basis of the
observations by Bischoff,^ and for comparison the curve representing the
encephalic Aveights of a series of eminent men, forty-five in number, is drawn
in a dotted line, the averages for decennial periods being alone plotted.

These records exhibit the fact that at birth the weight of the brain is about
one-third of that which it will attain at maturity. The increase is very rapid
during the first year, and vigorous for the first seven or eight years, after which
it becomes comparatively slow. The maximum weight is indicated in the

^ Archiv fiir Anatomie und Physiologie, 1890. * Himgewicht des Menschen, Bonn, 1880.

CENTRAL NERVOUS SYSTEM.

725

Fig 2(M.-Curves for each sex, showing the weight of the brain according to age. For the first
twentv-five years the curve is formed from annual averages based on the figures of H. Vierordt; from
twenty-five years on the curves are formed from decennial averages based on the observations of
Bischoff. All the data are from observations on the less fortunate classes. The dotted curve for emi-
nent men is formed from decennial averages based on forty-five observations.

fifth decade (males), fourth (females), although there is a premaximum in the
middle of the second decade (at thirteen and fifteen years for males and four-
teen vears for females), in which the too early and too vigorous growth of the

•20

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cncoplialon aj>i)cars to be an important factor in tho cause of death ; hence the
larger brain-weight Ibimd at autopsies during those years. W'iiile, in general,
the individual may be supposed to follow in the development of his eneej)halon
the course here indicated by the curve, this premaximal increase must be ex-
ccj)ted tor the reasons given.

It appears probable, from varions lines of research,' that individuals differ
widely in the length of time during Mhich the brain enlarges, and also in the
time at which the atrophic changes due to old age become evident. The curve
for the brain-weight of eminent men also points in this direction. In this
latter group the atrophy of old age does not become evident until the sixtieth
year. To explain this, it must be remembered, as ha.s been previously stated,
that the records of the weight of the brain, such as those here quoted from
Boyd, Bischoff, and Vierordt, are all based on hospital autopsies made in
densely-settled communities, and that the social status of the individuals there
examined was that of a class least vigorous and least favorably situated. It is
not surprising, therefore, that when compared with the group of eminent men,
both vigorous and, as a rule, more favorably situated, not only should the
average weight be greater in this group, but, what is more important, growth
should continue for a longer time and the period of senile atrophy be deferred.

If, as appears probable, these differences depend on the favorable or unfa-
vorable conditions existing during growth, then it will be evident that the
average man is possessed of a nervous system which probably grows for a
longer time and resists decay to a later age than the figures of Bischoff or
of Boyd would suggest.

"Weight of Brain at Birth. — The older records gave the male child the
heavier brain at birth, while the newer records, like those of Vierordt and
others, give the reverse. Be this as it may, the weight at birth is seen to be
nearly alike in the two sexes, and the difference in w^eight becomes distinct and
increases during the period of most active growth up to maturity, from which
time to the end of life this difference between the sexes remains nearly constant.

The proportional weights of the different parts according to the method of
subdivision practised by Boyd are here shown. The figures indicate the per-
centage values of the parts of the encephalon :

Weight of the Encephalon and its Parts at Different Ages {Boyd).

Males.

No. of Casea.

Age.

Cerebrum.

Cerebellum.

Stem.

45

New-born.

92.4

5.8

1.60

22

7 to 14 years.

87.8

10.3

1.61

99

30 " 40 "

87.3

10.6

1.98

95

70 " 80 "

I

87.0

"EMAI.E-S.

10.7

2.09

45

New-born.

9-2.1

6.2

1.50

18

7 to 14 veara.

87.9

10.5

1.50

80

.30 " 40 "

87.0

10.8

2.01

128

70 " 80 "

86.9

10.9

2.15

* Gallon : Hereditary Oeniuf, 1884; Venn: Nature, 1890.

CEJSTUAL NERVOUS SYSTEM. 727

Tlio table iiulu'iites a i>n.i)<)iti<)iial relation al birth, and probably lor a
short time alter, dittereiit froiu that (bund at inaliirity, but this very early
approximates that tbund in the adidl.

Relation between Growth of Body and Encephalon.— When the eurve
of growth Ibr the entire body is compared with that Tor the growth of the
encephalon, it is (piite evident that the growth is more rapid in the central
nervous system than jn the body at large, and that it is almost completed in
the former at tlie end of the eighth year, whereas the body has reached but
one-third of the weight which it will attain at maturity.

A causal relation between a well-developed central system and the subse-
quent growth of the entire body is thus suggested, aud also it is evident that
conditions which influence growth will at any time find the body on the one
liand, and the central system on the other, at quite different phases in their
development.

The long-continued growth of the body brings it about that the central
system, which at birth may form 12 per cent, of the total weight of the indi-
vidual, is at maturity about 2 per cent, or less. For this change in proportion
the increase of the muscular system is mainly responsible.

Further, the much smaller mass of the muscular system in the female is
the chief cause of the higher percentage value of the central system in the •
female— a relation which has been much emphasized, but which is really not
significant, since in both sexes this high percentage value of the central system
is most developed at birth, and becomes steadily less marked as maturity is

approached.

Increase in the Number of Functional Nerve-elements.— Having
thus briefly indicated the facts of growth so far as they can be detected by
the balances, it still remains to mention the series of changes which may be
studied by other means, such as micrometric measurements or enumeration.
The results obtained by these methods are somewhat complex and must be
treated with great care. Human embryology indicates that after the third
mouth of fetal life the number of cells in the central system is not increased.
With the cessation in the production of new cells the only remaining means
of increase in size is by enlargement of those cells already present.

How this occurs is well indicated by the accompanying table (page 728),
which shows the change in the size of cell-bodies in a given locality in man.

All vertebrates are not similar in respect to the manner of this change.
Birge^ has shown that in frogs there is a gradual increase in the number of
the fibres forming the ventral and dorsal spinal roots, and that this goes on at
the rate of about fifty additional fibres in the ventral roots and seventy in the
dorsal, for each gram added to the total weight of the frog. The increase was
still apparent in a frog weighing one hundred and twelve grams. In the case
of the ventral root-fibres it was also determined that the cells of origin in the
ventral horns of the spinal cord increased in number in a similar manner.
Here is exemplified an instance of long-continued enlargement of the nervous
1 Birge: Archivfur Anaiamie und Pkysiolocjie, Supplem., 1882.

728

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

system by tlie regular developiuuiit ol" iiiiinuturc cells, a inetliod of" growth
most marked probably in those animals which increase in size so long as they
live.

Volumes of the Largest Cell-bodies in the Ventral Horn of the Cervical Cord of

Man [based on Kaiser* s records of the mean diameters).

The volume TOOjW^ in tlie fetus of four weeks, is taken from His, and the figures represent
multiples of that volume.

Fetus

Child at birth
Boy at fifteen years
Man, adult ....

It is believed that in this case the new cells and new fibres are not, strictly
sjieaking, new morphological elements, but are the result of developmental
changes taking place in the cells present in the system from an early period.

A distinction is thus to be made between cell-elements which, because they
are not developed, are therefore not a part of the system already physiologi-
cally active, and those cells already organized together and which are fully
functional. When, therefore, it is said that the cells of origin for the ventral
root-fibres increase in number, the increase refers to the latter group, and not
to the total number of elements of both kinds present in the cord. In other
^vords, the number of cells appears to increase because the number of devel-
oped cells become greater.

On the other hand, Schiller ^ counted the number of nerve-fibres in the
oculo-motor nerves of cats, and found but a very slight difference in this num-
ber between birth and maturity. So far, then, as this nerve is concerned, it is
found in the cat to be nearly complete at the time of birth.

In man there are very few observations on the increase in the number of
functional nerve-cells with age. Kaiser,^ as is shown in the accompanying
table, found in man increasing numbers of large nerve-cells in the ventral
horns of the spinal cord at the ages named :

Number of Developed Cells in the Cervical Enlargement of Man ai
Different Ages (Kaiser).

Age. Number of Nerve-cells.

Fetus, 16 weeks 50,500

" 32 " 118,330

New-born child 104,270

Boy, fifteen years 211,800

Male, adult 221,200

' Schiller: Compter rendus de P Academic dcs Sciences, Paris, 1889.
* Die Functionen der Gangliemellen des Halsmarkes, Haag, 1891.

CENTRAL NERVOUS SYSTEM.

729

Here, as in the frog, the apparent increase must be looked upon as due to
the gradual development of elements present from an early date.

Increase in the Fibres of the Cortex. — The area of the cerebral cortex
(see Fig. 205) varies according to several conditions, but in general the more
voluminous the cerebral hemispheres the greater its extent. That which cov-
ers the walls of the sulci has in man about twice the extent of that directly
exposed on the surface of the hemispheres.

Fig. 205.— Diagram illustrating the extent of the cerebral cortex. The outer square {E) shows a sur-
face approximately ^V of 2352 sq. cm. in extent ; the inner square (A) has two-thirds of this area, and is
the proportion of the cortex sunken in the fissures. 2352 sq. cm. is approximately the area of the entire
cortex in a male brain weighing 1360 grams.

In the cortex of the human cerebral hemispheres it has been shown by
Vulpius' that the number of fibres in the different layers is greater at the
thirty-third year than at earlier periods, and in old age the number is again
decreased. At exactly what age decrease sets in is not to be determined from
these observations. They show, simply, that in general the number of fibres
was less at seventy-nine years than at thirty-three years.

In a similar way Kaes^ has compared the development of the thickness of
the cortical fibre-layers in a youth of eighteen years as contrasted with a man
of thirty-eight years, and found them thicker in the latter.

The relation of the cell-bodies in the cerebral cortex at different ages is
illustrated by Figure 206.

Significance of Medullation. — Two sorts of nerve-fibres are described —
those with and those without a medullary sheath. Both have the power of
isolated conduction, but in the peripheral system the non-medullated fibres are
found in connection with the sympathetic system, where less specialized func-
tions are carried on, and also in a large but varying degree in the central sys-

^ Vulpins: Archivfur Psychiatric und Nervenkrankheiten, 1892.
^ Neurologische CkntralblaU, 1891.

730

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tern. The wider significance of" this difference in medullatiou is at the
moment quite obscure.

The first suggestion, tliat absence of the medullary sheath is an immature
condition which persists in various parts of the nervous system, brings us at

ol

D

Fig. 206.— To show in the developing human cortex the increase in the number and size of the
mature ceU-bodies, as well as the separation of them from one another (Vignal) : A, fetus of twenty-
eight weeks; JS, fetus of thirty-two weeks: C, child at birth; A man at maturity; I-V, layers of the
cortex according to the enumeration of Meynert.

once to the question of the physiological difference thus implied but not
explained.

It is known that the central system is at birth very imperfectly medullated,
and the growth of these medullary sheaths must form a large part of the total
increase in its bulk. In the mature fibre the axis-cylinder and the medullary
sheath have nearly equal volumes, and therefore approximately equal weights.
The medullated fibres form probably not less than 90 per cent, of the total

CENTRAL NERVOUS SYSTEM.

731

weight of tlie norvo-tissiies composing the encephaloii, and of this one-half
would he medullary substance.

Increase in the Mass of Nerve-cells. — The amount of this increase under
various conditions has ali'cady l)een discussed, and heen found to range between
zero and fifty-thousand-fold.

Number of Cells. — A conservative estimate of the number of cells in the
entire central system is 3,000,000,000. Giving each cell of this number a vol-
ume of at least 700//' (His' measurements give 697;/'), then this entire number
could easily be placed in 2.25 cu.cm. We assume that about three-quarters
of the total volume of the central system is nerve-tissue proper, while
the remaining quarter is composed of the supporting tissues and blood-
vessels.

Volume of Central System. — The volume of the entire system contain-
ing cells of the number and size chosen, as well as the supporting tissues, would
then, on the supposition made, be about 3 cu.cm., which is approximately that
found in the human fetus at the end of the twelfth week (see Fig. 207). The
enlargement occurring between this time and maturity is that between 3 cu.cm.
and 1340 cu.cm., the latter figure being the volume of the encephalon and cord,

Maturity

/

Birth

/

/

/Fet''B

A

/ 1

12 wks.

/

/

Fig. 207.— Cubes illustrating the relative volumes of the central nervous system at the twelfth week
of fetal life, at birth, and at maturity. The cubes as shown have exactly one-eighth of their true
volumes.

weighing 1386 grams (encephalon 1360 grams, and spinal cord 26 grams),
and having together a specific gravity of 1036. This change demands an
average enlargement in the nerve-elements of four hundred and forty-
seven-fold, which, it is seen, is well within the limits of that found for
a cortical cell of medium size which had enlarged six hundred and sixty
times (pages 608, 609).

732

AN AMERICAN TEXT- BO OK OF PHYSIOLOGY.

Estimates of the Volume of the Central No'vous St/stem. Encephalon and Spinal

Cord at Different Ages.

Three-quarters of this volume is assumed to represent the nerve-elements i)roper. For the
first two records I am indebted to Professor F. P. Mall. The third is estimated.

Subject.

Fetus

((

((
Child

•Man .

Age.

2 weeks.

4 "
12 "
At birth.

Adult.

Weight.

Grams.

Volume of Nervous SyBtem—
Encephalon and Cord.

Vol.,
cu.cm.

% of this in
cu.cm.

381-f4

385

1360+26

1386

0.04
0.2
3.0
376

1340

0.03
0.15
2.25

282

1005

From the foregoing facts, together with those bearing on the cell-elements,
it is possible to get some conception of the growth-processes in the central
system, and to see how they are due to an enlargement of the nerve-elements
which have been formed at a very early stage in the life-history of the
individual. In such enlargements the chief inci-ease is due to the formation
of the neurons, and in them, in turn, about half the substance is represented
by the medullary sheaths.

In all probability these sheaths are no exception to the rule according to
which all parts of the body are variable, not only in their absolute but also in
their relative size, and therefore it is possible that the quantitative variation in
this constituent is a very important factor in modifying the weight of the cen-
tral system.

Change in Specific Gravity with Age. — During fetal life and at birth the
specific gravity of the nerve-tissues is low, but becomes higher at maturity.
This change is correlated in some measure with the development of the medul-
lary substance.

For the gross physical changes which have thus been indicated as occurring
during growth an explanation is to be found in the changes affecting the con-
stituent elements, and these have been set forth when describing the growth
of the individual cells.

C. Organization and Nutrition of the Central Nervous

System.

What is here meant by organization may be easily illustrated. When, for
example, by later growth new tissue is added to the liver or the skin is in-
creased in area or a muscle enlarged, there is caused by the addition of new
substance a change in the powers of these tissues, which is mainly quantitative.
The larger organ exhibits the same capabilities that the smaller organ exhibited,
but does so in a greater degree.

In the central nervous system, on the other hand, it appears that with

CENTRAL NERVOUS SYSTEM. 733

growth the system becomes capable of new reactions iu the sense that its
various responses are controlled and directed by a larger number of incoming
impulses, and thus the number, complexity, and refinement of the reactions
is iucreaseil, and in this sense it really attains new powers.

AVith the change in the age of the central system there occurs from
birth to matnritv, if we may ju(l<r(' from general reactions, an increase in
this organization which is maintained during the prime of life, and then
in old age this breaks down, at first gradually, and later rapidly. It
becomes important, therefore, to examine the manner in which this organ-
ization is accomplished.

Organization in the Central System. — When first formed the cells com-
posing the central system are completely separated from one another. In the
mature nervous system the impulses, as has been pointed out, probably travel
for the most part from the neurons of one unit to the dendrons of another.
From the original position in which the young cells, the neuroblasts, are
produced, they plainly migrate, and often these migrations involve groups of
cells, as in the case of those forming the olivary bodies (His).

For organization the most important changes, however, are those affecting
the branches, both dendrons and neuron. During growth both of these in-
crease in the length of their main stem and of their respective branches. In
picturing the approach of two elements within the central system the process
is usually described as that of the outgrowth of the neuron toward the den-
drons or bodies of those cells which are destined to receive the impulse, but it
must by no means be forgotten that the dendrons are also growing, and the
question of the approximation of the branches of these latter to those of the
neurons depends on their own activities as well.

The conditions modifying this process are, however, obscure. It is evident
that medullation outside of the central system is not necessary to the functional
activity of a fibre, and therefore probably in the central system unmeduUatetl
fibres are also in many cases functional. Whatever may be the relation of
the establishment of new pathways to the acquisition of medullary sheaths by
the neuron and its branches, it is also clear that all fibres which when mature
are medullated begin as unmedullated fibres, that the increase in medullation
throughout the central system is an index of the increase in organization. A
consideration of the facts of growth iu the layers of the cortex, for instance,
will show them to be open to this interpretation.

Applying these ideas concerning organization to the three classes of cells,
afferent, central, and efferent, composing the nervous system, we find the fol-
lowing : In the central system the afferent cells contribute to organization by
the multiplication of the collaterals. At the periphery the division of the
branches of the neuron increases the number of opportunities for excitation
which such an element offers. These cells are without dendrons. Among
the central cells all possible modes of growth are contributory; that is,
the branches of both kinds add directly to the complexity of the central
pathways. On the other hand, the efferent grouj) contributes to this com.-

734 AX AMERICAN TEXT- HOOK OF PHYSIOLOGY.

plcxity almost solelv by the furination of dcndroiis, the collaterals which come
from the neurons of these cells forming but an insignificant contribution. Not
onlv, tiierefore, is organization in large ])art dependent on changes in the cen-
tral cells bv reason of their numerical preponderance, l)ut also by reason of the
fact that to them a multiplication of pathways both by elaboration of the
neurons and the dendrons is alone possible.

Defective Development. — In view of these facts, defective development
in the nervous system may depend on failure in one or more of these several
processes by which the system is organized, and it should be possible to correlate
defective development involving mainly one set of elements with a distinct
clinical picture. The results of defective development are not merely an
absence of certain powers, but in some measure a diminution in the strength
and range of thos(; that remain.

Laboratory Animals. — The bearing of these facts on the conception which
we form of the nervous systems of those animals commonly employed for
laboratory experiments may be here mentioned. The frog, pigeon, rabbit,
cat, and dog form a series in which the total mass of the central system
increases from the beginning to the end of the series.

The number of cells in the largest system, that of the dog, is many times
greater than that in the smallest, the frog, and it is probable that the others are
in this respect intermediate. Organization is apparently more rapidly completed
and more nearly simultaneous throughout the entire system in forms like the
froo; and pigeon, and also in these latter the organization is least elaborate at the
cephalic end. While the educability of the nervous system of the dog may
depend on several conditions, the comparative slowness of organization is
undoubtedly one of them, and a very important one. Where the organ-
ization is early established it is found that the parts organized have a
greater independence than under the reverse conditions. In selecting an
animal, therefore, on which to make a series of experiments, these several
facts must be kept in view, for the choice is by no means a matter of
indifference.

Blood-supply. — For the general distribution of the blood-vessels in rela-
tion to the gross subdivision of the brain the student is referred to the works
on anatomy. The finest network of vessels is, however, to be found where
the cell-bodies are most densely congregated, and indeed the distinction
between the masses of gray and white matter in the central system is as
clearly marked by the relative closeness of the capillary network as in any
other way. One result of this relation between the blood-supply and tiie cell-
bodies which form the gray matter is a general arrangement of the vessels along
the radii of the larger subdivisions of the brain, as the cerebral hemispheres
and the cerebellum.

The conditions which control the circulation within the cranium and spinal
canal are not exactly the same at all periods of life, but the variations occur
in minor points only.

The general conditions are the following : The evidence, physiological and

CENTRAL NERVOUS SYSTEM. 735

histological, is against the existence of vaso-motor nerves in the vessels of the
pia or of the enccphalon and cord (see Circnlation).'

The circulation in these regions, therefore, is not modified by any rcjicx varia-
tions in the calibre of the vessels. The authors just cited do not find any evi-
dence for a local control of the arterioles whereby the products of nerve-cell
activity cause an increase iu the diameter of the vessels affected by these sub-
stances. The reactions of the central vessels are broadly those of a system of
elastic tubes in a closed cavity. As a result, it is found that the quantity
of blood in the central system is subject to very slight variations only. A rise
in the arterial pressure causes a more rapid flow of the blood through the
encephalon. It also causes a rise in the venous j)ressure, and with this a
corresponding rise in the intracranial pressure, the last two varying in the
same sense and to the same extent.

The flow through the central system is subject to the influence of gravity,
and takes place the. more readily the more the resistance is diminished.^ The
principal controlling mechanism is in the splanchnic area. According to the
condition of the vessels in this area the intracranial blood-pressure varies.

It is to be noted in passing that when a person lying on a table is balanced
on a transverse axis, this axis is about 8.77 centimeters to the cephalic side of
the line which joins the heads of the femurs.^ This leaves, of course, the
splanchnic area mainly on tiie cephalic side of this axis, and hence any inflow
of blood from the extremities would tend to make the head end of the person
thus balanced dip down. This dip will occur even when the splanchnic area
alone is filled, and hence the dipping as such would not necessarily indicate an
increase in the quantity of blood in the encephalon.

In the adult the cranial cavity is almost rigidly closed. There is an oppor-
tunity for the escape of a small quantity of fluid through the foramen magnum
into the vertebral canal. When, as the result of increased arterial pressure,
the brain has increased so as to drive out the subdural fluid, the brain is forced
against the walls of the cranium and blocks the outflow into the spinal canal.
In the same way it has been found that if a mass displacing from 2-3 cu.cra.
be introduced into the subdural space of a dog the brain will adjust itself with-
out rise of intracranial pressure. If in this case the volume of the mass intro-
duced is increased, there follows a rise of intracranial pressure, and this rise in
every instance tends to impede the circulation through the brain. While the
fontanelles are open the brain normally pulsates, and we recognize in its varia-
tions in volume all the different variations in blood-pressure with which we are
familiar. The pulsation of the brain is doubtless an important aid to the
movements of the fluids within and hence tends to facilitate nutrition during
the earlier periods of growth.

In pathological cases where the cranial wall has been destroyed, there is
a similar variation in volume to be observ^ed in the adult, and it is possible

' Bayliss, Hill, and Gulland : Journal of Physiology, 1895, vol. xviii.

' Hill : Jownal nf Phyniolof/y, 1895, vol. xviii.

* W. und Ed. Weber: Mechanik der menschlichen Gehwerkzewje, 1836.

736 JN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

that the beneficial effects which in .so many instances follow trc})hinin<^ of the
sknll may depend upon this mechanical release. Of course in cases with a
defective skull-wall an increase in arterial pressure causes a more decided
increase in the volume of blood in the brain ; this, however, is much more
marked than it would be under ordinary conditions, and is not to be regarded
as the main effect, which is an increase in the quantity of the blood passed
through the central system in a unit of time. Mosso ^ has found the tempera-
ture of the blood coming from the brain (dogs) slightly higher than tiiat of
the rectum and of the arterial blood. The differences are very small, but
he draws the conclusion that the metabolic processes in the brain are suffi-
ciently intense to raise the temperature of the blood passing through it.

As against the intensity of the metabolism in the central system, it has
been observed that blood taken from the torcular Herophili of the dog was
intermediate between arterial blood and that taken from the femoral vein, thus
indicating that the arterial exchange was less intense in the brain than in the
muscles of the leg. The following is a condensed statement of the figures :

Percentages of Oxygen and Carbonic Acid in various Samples of Dogs'

Blood {Hiliy

. r CO . • 1 1 ^ CO., 37.64 per cent.

Average of 52 arterial samples ■, ^ „ „, „

t. O 18.25 "

Average of 42 torcular samples 1r»* iq'^q «

A r OQ <• 1 • f CO2 45.75 "

Average of 28 femoral vein 1 rk « Q/I «

The absolute quantity of blood in the brain and cord is certainly small ;
if we nuiy judge from the observations on animals, it is not more than 1 per
cent, of the entire blood in the body. It is to be remembered, however, that
the cell-bodies, which alone are well supplied with blood, probably represent
less than one-tenth of the entire encephalic mass.

With general rise and fall of pressure elsewhere there is a rise and fall of
pressure within the central system. During the first phases of mental activity
blood is withdrawn from the limbs ; the blood thus withdrawn can be shown
to pass toward the trunk, for when a pei-son lying on a horizontal table sup-
ported at the centre on a transverse knife-edge is just balanced, then increased
activity of the cerebral centres causes the head end to dip down (Mosso), and
if the skull wall is defective the brain is seen to swell.

In the latter stages of fatigue the blood-supj)ly to the nerve-centres dimin-
ishes owing to a decrease in force of the heart-beat and the tonicity of the
splanchnic vessels, .so that the brain in birds exhau.sted by a long flight has
been found by Mosso to be in a high degree anaemic. There is much rea.sou to
think that in man a similar reaction occurs.

The study of the cerebral circulation in the case of those in whom the
skull-wall is at some point deficient shows a bulging of the skin over the open-
ing into the cranial cavity as a result of mental effort or emotion. In the

^ Die Temperatur des Gehims, 1894, Leipzig. * Journal of Physiology, vol. xviii., 1895.

CENTRAL NERVOUS SYSTEM.

737

nonnal adult this bultring cannot of course occur to anything like such an
extent, and the s|)ace for the arterial blood must he gained in the first instance
by driving- out the blood from the venous simises within the erauimn and
througli the removal of the subduial Ihiid.

Influence of Glands. — In the growth of the nervous system it is not only
the quantity, but the })eeuliar qualities, of the blood that are important, and
among the various glauds the activity of which is necessary for the growth
of the nervous, as well as the other systems, and also needed for its full
maintenance, the thyroid appears as very important. In sporadic cretinism,
associated as it is with atrophy of the thyroid, the feeding of sheep's thyroids
has produced remarkable growth-changes in all parts of the body — the nervous
system included.

At the same time, experimental extirpation of the thyroid is followed by de-
structive changes in the central system, caused by disturbances in its nutrition.

Starvation. — In starving animals the nervous system loses but very little
in weight.' This small loss is most striking, and would seem to be best
explained on the assumption that the other tissues are used to keep up the
central system, which, when even slightly reduced in weight, ceases to act.

Fatig-ue. — The histological basis of fatigue, as expressed by the changes
in the individual cells, has already been discussed. The fatigue of the
system as a whole is but the expression of fatigue in large numbers of its
elements, but the manner in which the changes show themselves is somewhat
complicated.

When the attempt is made to raise a weight by the voluntary contractions
of the muscles of the index finger at regular intervals, say once a second, it is
found that if the weight be heavy the power of the finger decreases, and the

lllililll I I I lllllllll III! I II I I I

Fig. 208.— a record of the extent of the flexions of the forefinger lifting a weight at regular intervals.
The light lines are those for the voluntary contractions; the heavy lines, those for contractions follow-
ing the direct stimulation of the flexor muscles by electricity. In the former there are periods, in the
latter none. The arrow shows the direction in which the record is to be read (Lombard).

weight soon ceases to be lifted as high as at first. Finally, a point is reached
when the voluntary effort produces little or no elevation of the weight. If,
however, despite this failure, the effort is still made at regular intervals, it
occurs in some persons that this power returns gradually, and a few seconds
later the contractions are very nearly as high as at the beginning of the ex-
periment (Mosso). This phenomenon may repeat itself many times, giving a
record formed by groups of contractions most extensive near the centre of
* Voit : Zeitschrift fur Biolofjie, Bd. xxx., 1894.
47

738

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

each grouji, these latter being separateil by jwrtions of tlie curve in whieh the
contractions are very small or \vanting(see Fig. 208). (See General Physiology
of Nerve and ^rusclc, p. 120.)

Daily Rhythms. — Within the cycle of the astronomiciil day the progress
of events leading to fatigue is not a steady one. Lombard ' found that if the
cajiacity for voluntary effoi-t was measured by the amount of work which could
be done by voluntarily contracting the flexor muscles of the index finger before
the first failure to respond to a voluntary stimulus appeared, then the curve

Fig. 209.— Showing at each hour of the day and night how many centimeters a weight of 3000 grams
could be raised by repeated voluntary contractions of the forefinger before fatigue set in. The curve is
highest at 10 to 11 a. m. and 10 to 11 p. .m. ; lowest, 3 to 4 p. m. and 3 to 4 a. m. Circle with dot, observation
made just after taking food; sqiiare with dot, smoking; *, work done eight minutes after drinking 15
cubic centimeters of whisky (Lombard;.

expressing this capacity for voluntary work throughout the day was repre-
sented as in Fig. 209. Briefly, the curve shows two maxima, at 10 p. m. and
10 A. M., with two minima midway between them. In general the immediate
effect of taking food i.s to increa.se the work done by the subject. Alcohol has
the same effect, while smoking produces a decrease.

Further, from day to day this capacity for w(jrk was influenced by a num-
ber of external conditions — temperature, barometric pressure, etc.

Time taken in Central Processes. — All processes in the nervous system
take time, and are for the most part easy to measure. The rate of the nerve-
impulse has already been given. It has also been noted that in passing through
the body of a spinal ganglion-cell the impulse suffers some delay. When,
' Journal of Physiology, vol. xiii., 1892.

CENTRAL NERVOUS SYSTEM. 739

however, it passes fVoiu uiic clement t<t anotlier the delay is even more marked,
and it is [)lansil)le to assume that this detention oc(.'urs at the juncture of the
elemcuts. Thus in those parts of" the central system where the cell-eleraents
and also the cell-junctions are most numerous, the time taken is longest.

0.5 S^ec.

^

Fig. 210.— To show the rate at wliich impulses pass through the nervous system of a frog. At the
extreme left the vertical has the value of 0.5 second and the other verticals arc compared with it; thus
between the cerebrum and the optic lobe requires about 0.25 second ; between the bulb and the lumbar
enlargement a greater distance— only about half the time; and for the still greater distance represented
by the length of the sciatic nerve even less time is needed (Exner).

Figure 210 shows this very well. Between the middle of the cerebral
hemisphere and the optic lobe, although the distance is short, the impulse takes
twice as long to travel as between the bulb and the lumbar enlargement. When
this time is measured in the conscious individual it is of coiir.se open to a long
series of modifying conditions, and these appear to be in part the same condi-
tions which modify the muscular endurance of the individual at different por-
tions of the day. Thus it has been determined that the speed with which
reactions can be made, as indicated by the reaction time, is subject to varia-
tions, and does not steadily decrease from the morning to the evening.

It has been the purpose of the paragraphs just preceding to indicate that
through the day it is not possible to demonstrate a steady decline of power in
the nervous system. We begin the morning, to be sure, feeling fresh, and are
fagged in the evening, but the course by which this condition has been attained
is not a simple or direct one.

D. Sleep.

Conditions Favoring Sleep. — To recover from fatigue sleep is required.
The prime condition favoring sleep is the diminution of nerve-impulses pass-
ing through the central system. This is accomplished in two ways. In the
first instance it is usual to reduce all incoming stimuli to a minimum. This is
most directly under our own control. On the other hand, the permeability of
the nervous system and the intensity with which it responds are decreased as
the result of the beginning fatigue. How these conditions are brought about
has been a matter of much speculation and some experiment.

The parts played by the sensory and that by the central cells vary some-
what at different times of life, for impulses are much less widely diffu.sed in
the early years than at maturity. Moreover, in childhood the amount of
stored material is small, large at maturity, and small again in old age, and
this holds true for all the groups of cells. Hence the cells would, by reason
of this fact, have the greatest ca])ability for work in the middle period.

740 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Between cliildliood and old a^e there i.s, huvvever, this dillerenee — tliut wliile
iu the former tlie noii-uvaihible substances in the cell are developing, not yet
having matured, those in the latter have in some way become permanently
useless. The degree to which the blood-su[)pIy can be controlled varies with
age, and the amounts of substance capable of yielding energy at various periods
of life are different ; so that, considering these factors alone, though there are
jn-obably others, it may be easily appreciated that the sleep of childhood,
maturity, and old age should be quite distinguishable.

Cause of Sleep. — It is recognized that local exercise is capable of producing
general fatigue, and the fatigued portions give rise to afferent imi)ulses which,
reaching the central system, cause some of the sensations of fatigue ; moreover,
the active tissues (nerve-cells aud muscles) yield as the result of their activity
some by-product which is carried by the blood through the central system and
becomes the chief cause of sleep. It has been shown by Mosso that if a dog
be thoroughly fatigued, giving all the signs of exhaustion, and the blood from
this dog be transfused to one that has been at rest, after the transfusion the
dog which has received the blood from the exhausted animal will exhibit
the symptoms of fatigue in full force. The inference is that from the tired
animal certain by-products have thus been transferred, and that these are
responsible for the reactions. AVe know, further, that we can distinguish in
ourselves different forms of the feeling of fatigue, and that the sensations which
follow the prolonged exercise of the muscular system differ from those follow-
ing the exercise of the higher nerve-centres.

Cessation of stimuli, decreased responsiveness of the active tissues, and a
change in the composition of the blood are the preliminaries to sleep. To
these should be added the diminiition of the blood-supply to the head.

A condition superficially resembling sleep can be induced in various ways.
Removal of all external stimuli, extreme cold, anaesthetics, hypnotic suggestion,
compression of the carotids, a blow on the head, loss of blood, all produce a
state of unconsciousness which, in so far, has a similitude with sleep. These
conditions produce this state, however, by mechanically decreasing the blood-
supply or cutting off the peripheral stimuli.

Normal sleep is tested by the fact that during its progress the changes that
occur in the central system are recuperative, whereas this feature may be more
or less absent from the states which merely resemble it.

Condition of the System during Sleep. — It apjiears that during sleep
the ca])acity of the central system to react is never lost. Were such the case
it would not be possible to awaken the sleeper. Moreover, the sleeping per-
son is far more responsive to stimuli from without than at first might be
thought. The close i*elations between dreams and external stimuli has been
recognized, and plethysmographic studies show still more clearly how the matter
stands.

It was found that when a subject fell asleep with the arm in a plethysmo-
graph various stimuli which did not waken the sleeper still served to cause a
diminution in the volume of the arm, which was certainly due to the with-

CENTRAL NERVOUS SYSTEM.

741

drawal of blood IVoin it, the blood-supply to the brain being probably at the
same time increased (see Fig. 211).

1

..il'iil,

1,1'

.III

,.|'"'"|ill|l" ''III

''''""'",l|i„(ii|i"l''i""

ii'ii'

I'l'

I"'

'"'•I, ,i,i>""'

Fig "U -ricthysinosraphif record taken from the arm of a person sleeping in the laboratory. A fall
in the curve indicates a decrease in the volume of the arm. The curve is to be read in the direction of
the arrow 1 the night watchman entering the laboratory, waking the subject, who shortly fell asleep
again- 2 the watchman spoke ; 3, watchman went out; these changes {2 and 3) occurred without awak-
ening the subject (from experiments made by Messrs. Bardeen and Nichols, Johns Hopkins Medical
School).

This oxi>erinient shows that during sleep the nervous sy.stem is capable of
reactions which are not reuierabered in any way, but which naturally form a
feature of the condition intermediate between waking and deep slumber. The
depth of sleep as determined by the strength of the stimulus necessary to elicit
an efficient response has been measured. The stimulus in these experiments
was the sound caused by the fall of a ball upon a plate, and the measure was

r

80U

-

1

/

I

yuu

/

\

600

\

500

- /

\

4U0

-

\

300

-

\

200

j

\

100

1

\

■^

' —

c na

Hours 0.5 1.0 1.5 2.0 2.5 3.0 3.b 4.U 4.i ^.u o.o txu o-a /.w /.^ /.-

Fig •'12 -Curve illustrating the strength of an auditory stimulus (a ball falling from a height) neces-
sary to waken a sleeping person. The hours marked below. The tests were made at half-hour intervals.
The curve indicates that the distance through which the ball required to be dropped increased during the
first hour, and then diminished, at first very rapidly, then slowly (Kohlschutter).

the height from which the ball must fall in order to produce a sound loud
enough to awaken a sleeping person. The results of the observations are shown
in Figure 212.

742 AN AMERICAN TEXT- HOOK OF PJIYiSIOLOGY.

It is seen fntiii this tJiat tlio jK-riod of dcop slumber is short, loss than two
hours, and is i'oliowed by a long period, that of an average night's rest, during
which a comparatively slight stimulus is sufficient to awaken. Almost the
same results have been more recently obtained by Monninghoff and Pies-
bergen.'

It is evident that the effectiveness of such a stimulus is, however, no measure
of the recupci-ative processes in the central system. Repair is by no means
accomplished during the interval of deep sleep, and experience has shown, as
in the case of persons undertaking to walk a thousand miles in one thousand
hours, that although such an arrangement left the subject with two-thirds of
the total time for rest and refreshment, yet the feat was most difficult to accom-
plish by reason of the discontinuity in the sleep. The changes leading to
recuperation needed longer periods than those permitted by the conditions of
the experiment.

Loss of Sleep. — Loss of sleep is more damaging to the organism as a
whole than is starvation. It has been found (Maniiceine) that in young dogs
which can recover from starvation extending over twenty davs, loss of sleep for
five days or more was fatal. Toward the end of such a period the body-tem-
perature may fall as much as 8° C. below the normal and the reflexes disap-
pear. The red blood-corpuscles are first diminished in number, to be finally
increased during the last two days, when the animal refuses food. The most
widespread change in the tissues is a fatty degeneration, and in the nervous
system there were found capillary hemorrhages in the cerebral hemispheres, the
spinal cord appearing abnormally dry and ancTcmie.

E. Old Age op the Central System.

Metabolism in the Nerve-cells. — Connected closely with fatigue are those
alterations both of the constituent nerve-cells and of the entire system found in
old age. The picture of the changes in the living cells is that of anabolic and
katabolic processes always going on, but varying in their absolute and relative
intensity according to several conditions. Of these conditions one of the most
important is the age of the individual. In youth and during the growing
period of life the anabolic changes appear within the daily cycle of activity and
repose to overbalance the katabolic, the total expenditure of energy increasing
toward maturity. During middle life the two processes are more nearly in
equilibrium, though the total expenditure of energy is probably greatest
then, and finally in old age the total expenditure diminishes, while at the same
time the anabolic processes become less and less competent to repair the waste.
The question why in the nervous system the energies wane with advanced age
is but the obverse of the question why they wax during the growing period.
The essential nature of these changes is in both instances equally obscure.

Decrease in Weight of Brain. — The weight of the brain in advanced
life shows that between fifty and sixty years there is a decrease in the bulk of
the encephalon in those persons belonging to the classes from which the greater
' Zeitschri/t Jur Bioloyie, 1893, Bd. xix.

CENTRAL NERVOUS SYSTEM. 743

number of the records have been obtained. So far as can be seen, there is no
marked change in the proportional development of the encephalon in old age,
save that the waste appears to be slightly greiiter in the cerebral hemispheres
than in the other portions.

Changes in Encephalon. — The thickness of the cerebral cortex diminishes
in harmony witii tlie shrinkage of the entire system. In large measure this
must depend on tiie loss of volume in the various fibre-systems, which, accord-
ing to the observations of Vulpius, show a senile decrease in the number of
fibres composing them. This decrease is more marked in the motor than in
the sensory areas. The time at which it commences cannot, however, be well
judged, owing to the small number of records after the thirty-third year.
Where records are made between this and the seventy-ninth year it appears
that there is no decided diminution until after the fiftieth year, though at the
seventy-ninth the decrease is clearly shown. Engel has shown that tiie
branches of the arbor vitae of the human cerebellum decrease in size and
number in old age.^

To the anatomy of the human nervous system in old age contributions have
been made by studies on the pathological anatomy of paralysis agitans.^

In subjects suffering from this affection the bodies of the uerve-cells are
shrunken, pigmented, and show in some cases a granular degeneration ; the
fibres in part are atrophied and degenerated ; the supporting tissues increase,
and the walls of the small blood-vessels are thickened. These changes have
been found principally in the spinal cord, being most marked in the lumbar
region. But the cords of the aged persons who do not exhibit the symptoms
of paralysis agitans show similar changes, though usually they are not so
evident, and hence the pathological anatomy of this disease resolves itself into
a somewhat premature and excessive senility of the central system.

Changes in the Cerebellum. — From the examination of the cerebral cor-
tex in the case of a man dying of old age (Hodge) no peculiarities were deter-
mined, but in the cerebellum some cells were shrunken and others (cells of
Purkinje) had completely disappeared. In the antennary ganglion of bees a
very striking difference ajDpears between those dying of old age and the adult
just emerged from its larval skin. These changes are comparable with those
described in mammals, and it further appears that in passing from the youngest
to the oldest forms cells have disappeared from the ganglia, and that in the young
form of the bee there are some twenty-nine cells present for each one found at
a later period. Shrinkage, decay, and destruction mark the progress of senes-
cence, and the nervous system as a whole becomes less vigorous in its responses,
less capable of repair or extra ^strain, and less permeable to the nervous
impulses that fall upon it ; and it thus breaks down, not into the disconnected
elements of the fetus, but into groups of elements, so that its capacities are lost
in a fragmentary and uneven way.

' Engel : Wiener medicinische Wochenschrift, 1863.

■^ Ketcber: Zeiischrift fiir Heilkunde, 1892; Eedlich : Jahrbuch j'iir Psychiatrie, 1893.

XI. THE SPECIAL SENSES.

A. Vision.

The Physiology of Vision. — Tlie eye i.s the organ by means of which
certain vibration.s of the luminiferous ether are enabled to aifect our conscious-
ness, producing the sensation which we call " light," Hence the es.-ential part
of an organ of vision is a substance or an apparatus which, on the one hand,
is of a nature to be stimulated by waves of light, and, on the other, is so con-
nected with a nerve that its activity causes nerve-impul.ses to be transmitted to
the nerve-centres. Any animal in which a portion of the ectoderm is thus
differentiated and connected may be said to possess an eye — i. e. an organ
through which the animal may consciously or unconsciously react to the exi.st-
ence of light around it.* But the human eye, as well as that of all the higher
animals, not only informs us of the existence of light, but enables us to form
correct ideas of the direction from which the light comes and of the form, color,
and distance of the luminous body. To accomplish this result the substance
sensitive to light must form a part of a complicated piece of apparatus capable
of very varied adjustments. The eye is, in other w^ords, an optical instrument,
and its description, like that of all oj)tical instruments, includes a consideration
of its mechanical adjustments and of its refracting media.

Mechanical Movements. — The first point to be observed in studying the
movements of the eye is that they are essentially those of a ball-and-.socket
joint, the globe of the eye revolving freely in the socket formed by the capsule
of Tenon through a horizontal angle of almost 88° and a vertical angle of about
80°. The centre of rotation of the eye (which is not, however, an absolutely
fixed point) does not coincide with the centre of the eyeball, but lies a little
behind it. It is rather farther forward in hypermetropic than in myopic eyes.
The movements of the eye, especially those in a horizontal direction, are sup-
plemented by the movements of the head upon the shoulders. The combined
eye and head movements are in mo.st persons sufficiently extensive to enable
the individual, without any movement of the body, to receive upon the lateral
portion of the retina the image of an object directly behind his back. The
rotation of the eye in the socket is of course easiest and most extensive when
the eyeball has an a])pr()ximately spherical shape, as in the normal or emme-
tropic eye. When the antero-posterior diameter is very much longer than those

' In certain of the lower orders of animals no local cliflTerentiations seem to have occurred,
and the whole surface of the body appears to be obscurely sen.'iitive to light. See Nagel : Der
Lichtginn augenloser Thiere, Jena, 1896.
744

THE SENSE OF VISION. 745

at riglit angles to it, as iu extroinoly inyo})ic or short-sighted eyes, the rotation
of the eyeball niav he considerably limited iu its extent. In addition to the
movements of rotation round a centre situated in the axis of vision, the eye-
ball may be uioved Ibrward and backward in the socket to the extent of about
one millimeter. This movement may be observed whenever the eyelids are
widelv opened, and is supposed to be effected by the simultaneous contraction of
both the oblique muscles. A slight lateral uiovement has also been described.
The movements of the eye will be best understood when considered as
referred to three axes at right angles to each other and passing through the
centre of rotation of the eye. The first of these axes, which may be called
the longitudinal axis, is best described as coinciding with the axis of vision
when, with head erect, we look straight forward to the distant horizon ; the
second, or transverse, axis is defined as a line passing through the centres of
rotation of the two eyes ; and the third, or vertical, axis is a vertical line nec-
essarily perpendicular to the other two and also passing through the centre of
rotation. When the axis of vision coincides with the longitudinal axis, the eye
is said to be in the primary position. When it moves from the primary posi-
tion by revolving around ehher the transverse or the vertical axis, it is said to
assume secondary positions. All other ])ositions are called tertiary positions,
and are reached from the primary position by rotation round an axis which
lies in the same plane as the vertical and horizontal axis — i. e. in the " equato-
rial plane " of the eye. AVhen the eye passes from a secondary to a tertiary
position, or from one tertiary position to another, the position assumed by the
eve is identical with that which it would have had if it had reached it from
the primary position by rotation round an axis in the equatorial plane. In
other words, every direction of the axis of vision is associated with a fixed
position of the whole eye — a condition of the greatest importance for the easy
and correct use of the eyes. A rotation of the eye round its antero-posterior
axis takes place in connection wuth certain movements, but authorities differ
■with regard to the direction and amount of this rotation.

Muscles of the Eye. — The muscles of the eye are six in number — viz :
the superior, inferior, internal and external recti, and the superior and inferior
oblique. This apparent superfluity of muscles (for four muscles would suffice
to turn the eye in any desired direction) is probably of advantage in reducing
the amount of muscular exertion required to put the eye into any given posi-
tion, and thus facilitating the recognition of slight differences of direction, for,
according to Fechner's psycho-physic law the smallest perceptible difference in
a sensation is proportionate to the total amount of the sensation. Hence if the
eye can be brought into a given position by a slight muscular effort, a change
from that position will be more easily perceived than if a powerful effort were
necessary.

Each of the eye-muscles, acting singly, tends to rotate the eye round an axis
which may be called the axis of rotation of that muscle. Now, none of the
muscles have axes of rotation lying exactly in the equator of the eye — i. e.
in a plane passing through the centre of rotation perpendicular to the axis

746 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of vision.' But all movements of the eye from the primary position take place,
as we have seen, round an axis lying in this plane. Hence all such movements
must be produced by more than one muscle, and this circumstance also is prob-
ablv of advantai^e in estimating the extent and direction of the movement. In
this connection it is interesting to note that the eye-muscles have an exception-
ally abundant nerve-supply — a fact which it is natural to associate with their
power of extremely delicate adjustment. It has been found by actual count
that in the muscles of the human eye each nerve-fibre supplies only two or three
muscle-fibres, while in the muscles of the limbs the ratio is as high as 1 to
40-125.2

Although each eye has its own supply of muscles and nerves, yet the two
eyes are not independent of each other in their movements. The nature of
their connections with the nerve-centres is such that only those movements are,
as a rule, possible in which both axes of vision remain in the same plane. This
condition being fulfilled, the eyes may be together directed to any desired point
above, below, or at either side of the observer. The axes may also be con-
verged, as is indeed necessary in looking at near objects, and to facilitate this
convergence the internal recti muscles are inserted nearer to the cornea than the
other muscles of the eye. Though in the ordinary use of the eyes there is never
anv occasion to diverge the axes of vision, yet most persons are able to effect a
divergence of about four degrees, as shown by their power to overcome the ten-
dency to double vision produced by holding a prism in front of one of the eyes.
The nervous mechanism through which this remarkable co-ordination of the
muscles of the two eyes is effected, and their motions limited to those which
are useful in binocular vision, is not completely understood, but it is supposed
to have its seat in part in the tubercula quadrigemina, in connection with the
nuclei of origin of the third, fourth, and sixth cranial nerves. Its disturbance
by disease, alcoholic intoxication, etc. causes strabismus, confusion, dizziness,
and double vision.

A nerve termination sensitive to light, and so arranged that it can be turned
in different directions, is sufficient to give information of the direction from
which the light comes, for the contraction of the various eye-muscles indicates,
through the nerves of muscular sense, the position into which the eye is nor-
mally brought in order to best receive the luminous rays, or, in other words,
the direction of the luminous body. The eye, however, informs us not only of
the direction, but of the form of the object from which the light proceeds ; and
to understand how this is effected it will be necessary to consider the refracting
media of the eye by means of which an optical image of the luminous object
is thrown upon the expanded termination of the optic nerve — viz. the retina.

Dioptric Apparatus of the Eye. — For the better comprehension of this
portion of the subject a few definitions in elementary optics may be given. A

' The axes of rotation of the internal and external recti, however, deviate but sli<,'htly from
the equatorial plane.

- P. Tergast : '" Ueber das Verhiiltniss von Nerven und Muskehi," Archie fur tuikr. Anut..
ix. 36-46.

THE SENSE OF VISION.

•-47

dioptric system in its simplest form consists of two adjacent media which have
different indices of refraction and whose surface of separation is the segment
of a sphere. A line joining the middle of the segment with the centre of the
sphere and prolonged in either direction is called the axis of the svstem. Let
the line .1 P B in Figure 213 represent in section such a spherical surface the

M'^ B

Fig. 213.— Diagram of simple optical system (after Foster).

centre of which is at iV, the rarer medium being to the left and the denser me-
dium to the right of the line. Any ray of light which, in passing from the
rarer to the denser medium, is normal to the spherical surface will be unchanged
in its direction — i. e. will undergo no refraction. Such rays are represented bv
the lines 0 F, 31 D, and 31' E. If a pencil of rays having its origin in the rarer
medium at any point in the axis falls upon the spherical surface, there will be
one ray — viz. the one. which coincides with the axis of the system, which will
pass into the second medium unchanged in its direction. This ray is called
the principal ray {OP), and its point of intersection (P) with the spherical
surface is called the principal point. The centre of the sphere (jV) through
which the principal ray necessarily passes is called the nodal jjoint. All the
other rays in the pencil are refracted toward the principal ray by an amount

F'

P'

r~~^v:

^'

p

0'

t

^^^

0

^--^^^^

A

y

^^"^^~~^~^^

Fig. 214.— Diagram to show method of finding principal foci (Neumann).

which depends, for a given radius of curvature, upon the difference in the
refractive power of the media, or, in other words, upon the retardation of light
in passing from one medium to the other. If the incident rays have their
origin at a point infinitely di.stant on the axi.s — /. e. if they are parallel to each
other — they will all be refracted to a point behind the spherical surface known

748 AN AMERICAN TEXT-BOOK OF PHYSIOLOdY.

as the principal focus, F. There is aiwther principal focu.s {F') in front of tlie
spherical surface — viz. the point from which divergin<^ incident rays will l>e
refracted into parallelism on passing the spherical surface, or, in other words,
the point at which parallel rays coining Ironi the opjxtsite direction will l)e
brought to a focus. The position of these two principal foci may be deter-
mined by the construction .shown in Figure 214. Let CA C represent a sec-
tion of a sj)hcrical refracting surface with the axis A K, the nodal point -V, and
the principal point A. The problem is to find the foci of rays parallel to the
axis. Erect perpendiculars at A and N. Set off on each perpendicular dis-
tances No, Xp, Ao', Ap' proportionate to the rapidity of light in the two media
{e. rj. 2:3). The points where the lines p'o and po' prolonged will cut the
axis are the two principal foci i^and F' — i. e. the points at which parallel rays
coming from either direction are brought to a focus after passing the .spherical
refracting surface. If the rays are not parallel, but diverging — /. e. coming
from an object at a finite distance — the point where the rays will be brought to
a focus, or, in other words, the point where the optical image of the luminou-s
object will be formed, may be determined by a construction which combines
any two of the three rays whose course is given in the manner above described.
Thus in Figure 215 let A Nhe the axis, and F and F' the principal foci of

Fig. 215.— Diagram to show method of finding conjugate foci.

the spherical refracting surface CA C, with a nodal point at y. Let B be
the origin of a pencil of rays the focus of which is to be determined. Draw
the line B C representing the course of an incident ray parallel to the axis.
This ray will necessarily be refracted through the focus F, its couree being
represented by the line C F and its prolongation. Similarly, the incident ray
passing through the focus F' and striking the spherical surface at C will, after
refraction, be parallel to the axis — i. e. it will have the direction C b. The
principal ray of the pencil will of course pass through the spherical surface and
the nodal point ^V without change of direction. These three rays will come
together at the same point 6, the position of which may be determined by con-
structing the course of any two of the three. The ])oints B and 6 are called
conjugate foci, and are related to each other in such a way that an optical image
is formed at one point of a luminous object situated at the other. When the
rays of light pass through several refracting surfaces in succession their course
may be determined by se])arate calculations for each surface, a process which
is much simplified when the surfaces are "centred" — i. e. have their centres
of curvature lying in the same axis, as is approximately the ca.se in the eye.

Refracting Media of the Eye. — Rays of light in passing through the eye
penetrate seven different media and are refracted at .seven surfaces. The media

THE SENSE OF VISION. 749

are as follows : layer of tears, cornea, aqueous humor, anterior capsule of lens,
lens, posterior capsule of lens, vitreous humor. The surfaces are those which
separate the successive media from each other and that which separates the tear
layer from the air. For purposes of practical calculation the number of sur-
faces and media may be reduced to three. In the first place, the layer of tears
which moistens the surface of the cornea has the same index of refraction as
the aqueous humor. Hence the index of refraction of the cornea may be left
out of account, since, having practically parallel surfaces and being bounded
on both sides by substances having the same index of refraction, it does not
influence the direction of rays of light passing through it. For this same
reason objects seen obliquely through a window appear in their true direction,
the refraction of the rays of light on entering the glass being equal in amount
and opposite in direction to that which occurs in leaving it. For purposes of
optical calculation we may, therefore, disregard the refraction of the cornea
(which, moreover, does not differ materially from that of the aqueous humor),
and imagine the aqueous humor extending forward to the anterior surface of
the layer of tears which bathes the corneal epithelium. Furthermore, the cap-
sule of the lens has the same index of refraction as the outer layer of the lens
itself, and for optical purposes may be regarded as replaced by it. Hence
the optical apparatus of the eye may be regarded as consisting of the fol-
lowing three refracting media: Aqueous humor, index of refraction 1.33;
lens, average index of refraction 1.45 ; vitreous humor, index of refraction
1.33. The surfaces at which refraction occurs are also three in number : An-
terior surface of cornea, radius of curvature 8 millimeters ; anterior surface
of lens, radius of curvature 10 millimeters; posterior surface of lens, radius of
curvature 6 millimeters. It will thus be seen that the anterior surface of the
lens is less and the posterior surface more convex than the cornea.

To the values of the optical constants of the eye as above given may be
added the following : Distance from the anterior surface of the cornea to the
anterior surface of the lens, 3.6 millimeters ; distance from the posterior sur-
face of the lens to the retina, 15. millimeters ; thickness of lens, 3.6 millimeters.

The methods usually employed for determining these constants are the fol-
lowing : The indices of refraction of the aqueous and vitreous humor are
determined by filling the space between a glass lens and a glass plate with the
fresh humor. The aqueous or vitreous humor thus forms a convex or concave
lens, from the form and focal distance of which the index can be calculated.
Another method consists in placing a thin layer of the medium between the
hypothenuse surfaces of two right-angled prisms and determining the angle at
which total internal reflection takes place. In the case of the crystalline lens
the index is found by determining its focal distance as for an ordinary lens,
and solving the equation which expresses the value of the index in terms of
radius of curvature and focal distance, thickness, and focal length. The
refractive index of the lens increases from the surface toward the centre, a
peculiarity which tends to correct the disturbances due to spherical aberration,
as well as to increase the refractive power of the lens as a whole.

750

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

The curvature of the retracting surfaces of the eye is determined by an
instrument known as an ophthalmometer, which measures tlie size of the
reflected image of a known object in the various curved surfaces. The
radius of curvature of the surface is determined by the following formula :
r 2Ab

B:b = A

, or r -----
2' B

in which B = the size of the object, 6 = the size of

the image, ^ = distance between the object and the reflecting surface, and
r = the radius of the reflecting surface. The distances between the various
surfaces of the eye are measured on frozen sections of the organ, or can be
determined upon the living eye by optical methods too complicated to be here
described. It should bo borne in mind that the above values of the so-called
"optical constants" of the eye are subject to considerable individual variation,
and that the statements of authors concerning them are not always consistent.
The refracting surfaces of the eye may be regarded as still further sim-
plified, and a so-called " reduced eye " constructed which is very useful for
purposes of optical calculation. This reduced eye, which for optical purposes
is the equivalent of the actual eye, is regarded as consisting of a single refract-
ing medium having an index of 1.33, a radius of curvature of 5.017 milli-
meters, its principal point 2.148 millimeters behind the anterior surface of the
cornea, and its nodal point 0.04 millimeter in front of the posterior surface
of the lens.^ The principal foci of the reduced eye are respectively 12.918
millimeters in front of and 22.231 millimeters behind the anterior surface of
the cornea. Its optical power is equal to 50.8 dioptrics.^ The position of this
imaginary refracting surface is indicated by the dotted line in figure 216. The

Fig. 216.— Diagram of the formation of a retinal image (after Foster).

nodal point, n, in this construction may be regarded as the crossing-point of all
the j)rincipal rays which enter the eye, and, as these rays are unchanged in their
direction by refraction, it is evident that the image of the point whence they
proceed will be formed at the point where they strike the retina. Hence to
determine the size and position of the retinal image of any external object —
e. q. the arrow in Figure 216 — it is only necessary to draw lines from various

1 Strictly speaking, there are in this imaginary refracting apparatus which is regarded as
equivalent to the actual eye two principal and two nodal points, each pair about 0.4 millimeter
apart. The distance is so small that the two points may, for all ordinary constructions, be
regarded as coincident.

^ The optical power of a lens is the reciprocal of its focal length. The dioptry or unit of
optical power is the power of a lens with a focal length of 1 meter.

THE SENSE OF VISION.

751

points of the object through the above-mentioned nodal point and to prolong
tiicm till they strike the retina. It is evident that the size of the retinal image
will be as nuich smaller than that of the object as the di.stau(;e of the nodal
point from the retina is smaller than its distance from the object.

According to the figures above given, the nodal point is about 7.2 milli-
meters behind the anterior surface of the cornea and about 15.0 millimeters in
front of the retina. Hence the size of the retinal image of an object of known
size and distance can be readily calculated — a problem which has frequently to be
solved in the study of physiological optics. The construction given in Figure
216 shows that from all external objects in y(?We(Z images are projected upon the
retina, and such inverted images can actually be seen under favorable condi-
tions. If, for instance, the eye of a white rabbit, which contains no choroidal
pigment, be excised and held with the cornea directed toward a window or
other source of light, an inverted image of the luminous object will be seen
through the transparent sclerotic in the same way that one sees an inverted
image of a landscape on the ground-glass plate of a photographic camera.
The question is often asked, " ^^ liy, if the images are inverted in the retina,
do we not see objects upside down ?" The only answer to such a question is
that it is precisely because images are inverted on the retina that we do not see
objects upside down, for the eye has learned through lifelong practice to asso-
ciate an impression made upon any portion of the retina with light coming
from the opposite portion of the field of vision. Thus if an image falls upon
the lower portion of the retina, our experience, gained chiefly through mus-
cular movements and tactile sensations, has taught us that this image must cor-
respond to an object in the upper portion of our field of vision. In whatever
M'ay the retina is stimulated the same eflPect is produced. If, for instance,
gentle pressure is made with the finger on the lateral portion of the eyeball
through the closed lids a circle of light known as a phosphene immediately
appears on the opposite side of the eye. Another good illustration of the
same general rule is found in the effect of throwing a shadow upon the retina
from an object as close as possible to the eye. For this purpose place a card

B

Fig. 217.— Diagram illustrating the projection of a shadow on the retina.

with a small pin-hole in it in front of a source of light, and three or four
centimeters distant from the eye. Then hold some object smaller than the
pupil — e. g. the head of a pin — as close as possible to the cornea. Under these
conditions neither the pin-hole nor the pin-head can be really seen — i. e. they

752 ^.V AMERICA X TEXT-BOOK OF PJIVSIOLOGY.

are both too near to have their image focusscd upon the retina. The pin-hole
beroraes itself a source of light, and appears as a luminous circle bounded by
the shadow thrown by the edge of the iris. Within tliis circle of light is seen
the shadow of the pin-head, but the pin-head appears inrcrted, for the obvious
reason that the eye, being accustomed to interpret all retinal impressions as
corresponding to objects in the opposite portion of the field of vision, regards
the upright shadow of the pin-head as the representation of an inverted object.
The course of the rays in this experiment is shown in Figure 217, in wiiieh
.1 B represents the card with a pin-hole in it, P the pin, and P' its upright
shadow thrown on the retina.

Accoramodation. — From what has been said ot" conjugate foci and their
relation to each other it is evident that any change in the distance of the object
from the refracting media will involve a corresponding change in the position
of the image, or, in other words, only objects at a given distance can be
focussed upon a plane which has a fixed position with regard to the refracting
surface or surfaces. Hence all optical instruments in which the principle of
conjugate foci finds its application have adjustments for distance. In the
telescope and opera-glass the adjustment is effected by changes in the distance
between the lenses, and in the photographic camera by a change in the posi-
tion of the ground-glass plate representing the focal plane. In the microscope
the adjustment is effected by changing the distance of the object to suit the
lenses, the higher powers having a shorter " working distance."

We must now consider in what way the eye adapts itself to see objects dis-
tinctly at different distances. That this power of adaptation, or "accommo-
dation," really exists we can easily convince ourselves by looking at different
objects through a network of fine wire held near the eyes. When with normal
vision the eyes are directed to the distant objects the network nearly disappears,
and if we attempt to see the network distinctly the outlines of the distant
objects become obscure. In other words, it is impossible to see both the
network and the distant objects distinctly at the same time. It is also evident
that in accommodation for distant objects the eyes are at rest, for when they
are suddenly opened after having been closed for a short time they are found
to be accommodated for distant objects, and we are conscious of a distinct
effort in directing them to any near object.*

From the optical principles above described it is clear that the accommo-
dation of the eve for near objects may be conceived of as taking place in three
different ways : 1st, By an increase of the distance between the refracting sur-
faces of the eye and the retina; 2d, By an increase of the index of refraction
of one or more of the media; 3d, By a diminution of the radius of curvature
of one or more of the surfaces. The firet of these methods was formerly sup-
posed to be the one actually in use, a lengthening of the eyeball under a pres-

' It has been shown by Beer (Archivfiir die gesammte Phymohgie, Iviii. o23) that in fishes
the eyes when at rest are accommodated for near objects, and tliat accommodation for distant
objects is effected by the contraction of a muscle for which the name " retractor lentis " is pro-
posed.

TJIK SENi^E OF VISION. 753

sure produoed by the eye-niusdes beinjj;; assumed to occur. This lengthening
would, in the ease of a normal eye accommodating itself for an object at a
distance of 15 centimeters, amount to not less than 2 millimeters — a change
which could hardly be brought about by the action of any muscles connected
with the eye. Moreover, accommodation changes can be observed upon elec-
trical stimulation of the excised eye. Its mechanism must, therefore, lie within
the eye itself. As for the second of these methods, there is no conceivable way
by which a change in the index of refraction of the media can be effected, and
we are thus forced to the conclusion that accommodation is brought about by
a change in the curvature of the refracting surfaces — i. e. by a method quite
different from auy which is employed in optical instruments of human con-
struction. Now, by measuring the curvature of the cornea of a person who
looks alternately at near and distant objects it has been shown that the cornea
undergoes no change of form in the act of accommodation. By a process of
exclusion, therefore, the lens is indicated as the essential organ in this function
of the eye, and, in fact, the complicated structure and connections of the lens
at once suggest the thought that it is in the surfaces of this portion of the eye
that the necessary changes take place. Indeed, from a teleological point of
view the lens would seem somewhat superfluous if it were not important to
have a transparent refracting body of variable form in the eye, for the amount
of refraction which takes place in the lens could be produced by a slightly
increased curvature of the cornea. Now, the changes of curvature which occur
in the surfaces of the lens when the eye is directed to distant and near objects
alternately can be actually observed and measured, with considerable accuracy.
For this purpose the changes in the form, size, and position of the images of
brilliant objects reflected in these two surfaces are studied. If a candle is held
in a dark room on a level with and about 50 centimeters away from the eye in
which the accommodation is to be studied, an observer, so placed that his own
axis of vision makes about the same angle (15°— 20°) with that of the ob-
served eye that is made by a line joining the observed eye and the candle, will
readily see a small upright image of the candle reflected in the cornea of the
observed eye. Near this and within the outline of the pupil are two other
images of the candle, which, though much less easily seen than the corneal
image, can usually be made out by a proper adjustment of the light. The
first of these is a large faint upright image reflected from the anterior surface
of the lens, and the second is a small inverted image reflected from the pos-
terior surface of the lens. It will be observed that the size of these images
varies with the radius of curvature of the three reflecting surfaces as given on
p. 749. The relative size and position of these images having been recog-
nized while the eye is at rest — i. e. is accommodated for distance — let the
person who is under observation be now requested to direct his eye to a near
object lying in the same direction. When this is done the corneal image and
that reflected from the posterior surface of the lens will remain unchanged,^

' A very slight diminution in size may sometimes be observed in the image reflected from
the posterior surface of the lens.
48

754

AN AMKincAX TEXT-JiOOK OF PHYSIOLOaY

while tliat reflected from the anterior surface of the lens will lu'conie smaller
and move toward the corneal image. This change in the size and j)osition of
the reflected image can only mean that the surface from which the reflection
takes })lace has become more convex and has moved forward. Coincident
with this change a contraction of the puj)il will be observed.

An apparatus for making observations of this sort is known as the phako-
scope of H^lmholtz (Fig. 218). The eye in which the changes due to accom-
modation are to be observed is placed at an opening
in the back of the instrument at C, and directed al-
ternately to a needle placed in the opening D and
to a distant ol)ject lying in the same direction. Two
prisms at B and B' serve to throw the light of a
candle on to the observed eye, and the eye of an
observer at A sees the three reflected images, each
as two small square spots of light. The movement
and the change of size of the image reflected from
the anterior surface of the lens can be thus much
better observed than when a candle-flame is used.
The course of the rays of light in this experi-
ment is shown diagrammatically in Figure 219.
The observed eye is directed to the point A, while
the candle and the eye of the observer are placed
symmetrically on either side. The images of the candle reflected from the various
surfaces of the eye will be seen projected on the dark background of the pupil

Fig.

^8.— Phakoscope of
Helmholtz.

Fig. 219.~Diagram explaining the change in the position of the image reflected from the anterior surface
of the crystalline lens (Williams, after Bonders).

in the directions indicated by the dotted lines ending at a, 6, and c. When the
eye is accommodated for a near object the middle one of the three images moves
nearer the corneal image — i. e. it changes in its direction from h to h' , showing
that the anterior surface of the lens has bulged forward into the position indi-

THE SENSE OF VISION. 755

catod 1)V the (lolled line. The chiinge in tlie appeariince of the images is
vepreseiiteil diaurainniat ieally in Figure 220. ( )n the left is shown the appear-
ance of the images as seen when the eye is at rest, a representing the corneal
image, b that reflected from the anterior, and c that from the posterior surface
of the lens when the observing eye and the candle are in the position repre-

FiG. 220.-Rcflcctcd images of a candle-flame as seen in the pupil of an eye at rest and accommodated

for near objects (Williams).

sented in Figure 219. The images arc represented as they appear in the dark
background of the pupil, though of course the corneal image may, in certain
positions of the light, appear outside of the pupillary region. When the eye
is accommodated for near objects the images appear as shown in the circle on
the right, the image b becoming smaller and brighter and moving toward the
corneal image, while the pupil contracts as indicated by the circle drawn round

the images.

The changes produced in the eye by an effort of accommodation are indi-
cated in Figure 221, the left-hand side of the diagram showing the condition

Fig. 221.-Showing changes in the eye produced by the act of accommodation (Helmholtz).

of the eye at rest, and the right-hand side that in extreme accommodation for
near objects.

It will be observed that the iris is pushed forward by the bulging lens and
that its free border approaches the median line. In other words, the pupil is
contracted in accommodation for near objects. The following explanation of
the mechanism by which this change in the shape of the lens is effected has
been proposed by Helmholtz, and is still generally accepted. The structure
of the lens is such that by its own elasticity it tends constantly to assume a
more convex form than the pressure of the capsule and the tension of the sus-
pensory ligaments (s, s, Fig. 221) allow. This pressure and tension are dimin-
ished when the eye is accommodated for near vision by the contraction of the
ciliary muscles (c, o. Fig. 221), most of whose fibres, having their origin at the

756

AN ANJJlilCAN TKXT-liOOK OF J'JIYSJOLOGY

point of union of the cornoa and sclerotic, extend radially outward in every
direction and are attached to the front part of the choroid. The contrac-
tion of the ciliary nuiscle, drawing;; forward the niembruue.s of the eye, will
relax the tension of the suspensory ligament and allow the lens to take
the form determined by its own elastic structure. According to another
theory of accommodation proposed by Tscherning,^ the suspensory liga-
ment is stretched and not relaxed by the contraction of the ciliary muscle.
In consequence of the pressure thus produced upon the
lens, the soft external })ortions are moulded upon the
harder nuclear portion in such a way as to give to the
anterior (and to some extent to the posterior) surface a
hyperboloid instead of a spherical form. A similar theory
has been recently brought forward by Schoeu,^ who com-
jxires the action of the ciliary muscle u|)on the lens to that
of the fingers compressing a rubber ball, as shown in Fig-
ure 222. These theories have an advantage over that
offered by Helniholtz, inasmuch as they afford an expla-
nation of the presence in the ciliary muscle of circular
fibres, which, on the theory of Helmholtz, seem to be su-
perfluous. They also make the fact of so-called " astig-
matic accommodation " comprehensible. This term is
applied to the power said to be sometimes gradually
acquired by persons with astigmatic^ eyes of correcting
this defect of vision by accommodating the eye more strongly in one meridian
than another.''

Whatever views may be entertained as to the exact mechanism by which its
change of shape is brought about, there can be no doubt that the lens is the
portion of the eye chiefly or wholly concerned in accommodation, and it is
accordingly found that the removal of the lens in the operation for cataract
destroys the power of accommodation, and the patient is compelled to use
convex lenses for distant and still stronger ones for near objects.

It is interesting to notice that the act of accommodation, though distinctly
voluntary, is performed by the agency of the unsiriped fibres of the ciliary
muscles. It is evident, therefore, that the term " involuntary " sometimes
applied to muscular fibres of this sort may be misleading. The voluntary
character of the act of accommodation is not affected by the circumstance that
the will needs, as a rule, to be assisted by visual sensations. The fact that
most persons cannot affect the necessary change in the eye unless they direct
their attention to some near or far object is only an instance of the close rela-
tion between sensory imjiressions and motor impulses, which is further exem-

FiG. 222. — To illustrate
Schoen's theory of ac-
commodation.

1 Archives de Physiologic, 1894, j). 40. ' Archiv fiir die rjesmninlc Phi/s., lix. 427.

« See p. 763.

* Recent observations by Hess {Archiv f. Ophthalmologie, xlii. 288) tend to confirm the Helm-
holtz theory by showing that the suspensory ligament is relaxed and not stretched in accommo-
dation for near objects.

THE SENSE OF VISION. 757

plified l)v siicli plK'iioiiK'iia as the paralysis of the lip of a horse caused by the
division of tlu; trifacial nerve. It is found, moreover, that by practice the
power of acconiniodating tiie eye without directino; it to near and distant
objects can be ac(juircd. The nerve-channels through which accommodation
is aftectcd arc tlic anteiior part of the imcleus of the third j)air of nerves
lying in the extn!ni(> hind j)art of the floor of the third ventricle, the most
anterior bundle of the nerve-root, the third nerve itself, the lenticular ganglion,
and the short ciliary nerves (see diagram p. 769).

The mechanism of accommodation is affected in a remarkable way by drugs,
the most important of which are atropia and physostigmin, the former para-
lyzing and the latter stimulating the ciliary muscle. As these drugs exert a
corresponding effect upon the iris, it will be convenient to discuss their action
in connection with the physiology of that organ.

The changes occurring in the eye during the act of accommodation are
indicated in the following table, which shows, both for the actual and the
reduced eye, the extent to which the refracting media change their form and
position, and the consequent changes in the position of the foci :

Accommodation for
Actual Eye. distant objects. near objects.

Radius of cornea 8 mm. 8 mm.

Radius of anterior surface of lens 10 " 6 "

Radius of posterior surface of lens 6 " 5.5 "

Distance from cornea to anterior surface of lens . . 3.6 " 3.2 "

Distance from cornea to posterior surface of lens . 7.2 " 7.2 "

Reduced Eye.

Radius of curvature 5.02 " 4.48 "

Distance from cornea to principal point 2.15 " 2.26 "

Distance from cornea to nodal point 7.16 " 6.74 "

Distance from cornea to anterior focus 12.918 " 11.241 "

Distance from cornea to posterior focus 22.231 " 20.248 "

It will be noticed that no change occurs in the curvature of the cornea, and
next to none in the posterior surface of the lens, while the anterior surface of
the lens undergoes material alterations both in its shape and position.

Associated with the accommodative movements above described, two other
changes take place in the eyes to adapt them for near vision. In the first
place, the axes of the eyes are converged upon the near object, so that the
images formed in the two eyes shall fall upon corresponding points of the
retinas, as will be more fully explained in connection with the subject of
binocular vision. In the second place, the pupil becomes contracted, thus
reducing the size of the pencil of rays that enters the eye. The importance
of this movement of the pupil will be better understood after the subject of
spherical aberration of light has been explained. These three adjustments,
focal, axial, and pupillary, are so habitually associated in looking at near objects
that the axial can only by an effort be dissociated from the other two, while
these two are quite inseparable from one another. This may be illustrated
by a simple experiment. On a sheet of paper about 40 centimeters distant

758 .l.Y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

from the eyes draw two lettere or figures precisely alike and about 3 centimeters
apart. (Two letters cut from a ncwsjjaper and fastened to the sheet will answer
the same purj)ose.) Hold a small object like the head of a pin between the
eves ami the ])apcr at the point of intersection of a line joining the right eye
and the left letter with a line joining the left eye and the right letter. If the
axes of vision are converged upon the pin-head, that object will be seen dis-
tinctlv, and beyond it will be seen indistinctly tlirce images of the letter, the
centi'al one being formed by the blending of the inner one of each pair of
images formed on the two retinas. If now the attention be directed to the
middle image, it will gradually become perfectly distinct as the eye accommo-
dates itself for that distance. We have thus an axial adjustment for a very
near object and a focal adjustment for a more distant one. If the pupil of the
individual making this observation be watched by another person, it will be
found that at the moment when the middle image of the letter becomes distinct
the pupil, which had been contracted in viewing the pin-head, suddenly dilates.
It is thus seen that when the axial and focal adjustments are dissociated from
each other the pupillary adjustment allies itself with the latter.

The opposite form of dissociation — viz. the axial adjustment for distance
and the focal adjustment for near vision — is less easy to bring about. It may
perhaps be best accomplished by holding a pair of stereoscopic pictures before
the eyes and endeavoring to direct the right eye to the right and the left eye to
the left picture — /. e. to keep the axes of vision parallel while the eyes are
accommodated for near objects. One who is successful in this species of ocular
gymnastics sees the two pictures blend into one having all the appearance of
a solid object. The power of thus studying stereoscopic pictures without a
stereoscope is often a great convenience to the possessor, but individuals differ
very much in their ability to acquire it.

Range of Accommodation. — By means of the mechanism above described
it is possible for the eye to produce a distinct image upon the retina of objects
lying at various distances from the cornea. The point farthest from the eye
at which an object can be distinctly seen is called tha far-point, and the nearest
point of distinct vision is called the near-point of the eye, and the distance
between the near-point and the far-point is called the range of distinct vision
or the range of accommodation. As the normal emmetropic eye is adapted,
when at rest, to bring parallel rays of light to a focus upon the retina, its far-
point may be regarded as at an infinite distance. Its near-point varies with age,
as will be described under Presbyopia. In early adult life it is from 10 to
13 centimeters from the eye. For every point within this range there will be
theoretically a corresponding condition of the lens adapted to bring rays pro-
ceeding from that point to a focus on the retina, but as rays reaching the eye
from a point 175 to 200 centimeters distant do not, owing to the small size of
the pupil, differ sensibly from parallel rays, there is no appreciable change in
the lens unless the object looked at lies within that distance. It is also evi-
dent that as an object approaches the eye a given change of distance will
cause a constantly increasing amount of divergence o{' the rays proceeding from

THE SENSE OF VISION.

759

it, and will therefore ucce-ssitate a constantly increasing amount of change in
the lens to enable it to focus the rays on the retina. We find, accordingly, that
all objects more than two meters distant from the eye can be seen distinctly at
the same time — /. e. without any change in the accommodative mechanism —
but for objects within that distance we are conscious of a special etfort of
accommodation which becomes more and more distinct the shorter the distance
between the eye and the object.

Myopia and Hypermetropia. — There are two conditions of the eye in
which the range of accommodation may differ from that which has just been
described as normal. These conditions, which are too frequent to be regarded
(except in extreme cases) as pathological, are generally dependent upon the
eyeball being unduly lengthened or
shortened. In Fig. 223 are shown
diagrammatically the three conditions
known as emmetropia, myopia, and
hypermetropia. In the normal or
emmetropic eye, A, parallel rays are
represented as brought to a focus on
the retina ; in the short-sighted, or
myopic, eye, B, similar rays are
focussed in front of the retina, since
the latter is abnormally distant; while
in the over-sighted, or hypermetropic,
eye, C, they are focussed behind the
retina, since it is abnormally near.

It is evident that when the eye is
at rest both the myopic and the hy-
permetropic eye will see distant ob-
jects indistinctly, but there is this
important difference : that in hyper-
metropia the difficulty can be cor-
rected by an effort of accommodation,
while in myopia this is impossible,
since there is no mechanism by M'hich
the radius of the lenticular surfaces can be increased. Hence an individual
affected with myopia is always aware of the infirmity, while a person with
hypermetropic eyes often goes through life unconscious of the defect. In this
case the accomodation is constantly called into play even for distant objects, and
if the hypermetropia is excessive, any prolonged use of the eyes is apt to be
attended by a feeling of fatigue, headache, and a train of nervous symptoms
familiar to the ophthalmic surgeon. Hence it is important to discover this defect
where it exists and to apply the appropriate remedy — viz. convex lenses placed
in front of the eyes in order to make the rays slightly convergent when they
enter the eye. Thus aided, the refractive power of the eye at rest is sufficient
to bring the rays to a focus upon the retina and thus relieve the accommoda-

FiG. 223.— Diagram showing the difference between
normal, myopic, and hypermetropic eyes.

760 AX AMERICAN TEXT- HOOK OF PlIYSIOLOaV.

tion. This action of a convex lens in hypcrmetropia is indicated by tlie dotted
lines in Fig. 222, C, and the corresponding use of a concave lens in myopia is
shown in Fi'g. 222, B.

The detection and (juantitative determination of iiypermetropia are best
made after the accommodation has been paralyzed by the use of atropia, l>y
ascertaining how strong a convex lens must be placed before the eye to pro-
duce distinct vision of distant objects.

The range of accommodation varies very much from the normal in myopic
and hypermetropic eyes. In myopia the near-point is often 5 or 6 centimeters
from the cornea, while the far-point, instead of being infinitely far off, is at a
variable but no veiy great distance from the eye. The range of accommoda-
tion is therefore very limited. In Iiypermetropia the near-point is slightly
farther than normal from the eye, and the far-point cannot be said to exist,
for the eye at rest is adapted to bring converging rays to a focus on the retina,
and such pencils of rays do not exist in nature. Mathematically, the far-point
may be said to be at more than an infinite distance from the eye. The range
of effective accommodation is therefore reduced, for a portion of the accommo-
dative power is used up in adapting the eye to receive parallel rays.

Presbyopia. — The power of accommodation diminishes with age, owing
apparently to a loss of elasticity of the lens. The change is regularly pro-
gressive, and can be detected as early as the fifteenth year, though in normal
eyes it does not usually attract attention until the individual is between forty
and forty-five years of age. At this period of life a difficulty is commonly
experienced in reading ordinary type held at a convenient distance from the
eve, and the individual becomes old-sighted or j)reshyoj)ic — a condition which
can, of course, be remedied by the use of convex glasses. Cases are occasion-
ally reported of persons recovering their power of near vision in extreme old
age and discontinuing the use of the glasses previously employed for reading.
In these cases there is apparently not a restoration of the power of accommo-
dation, but an increase in the refractive power of the lens through local changes
in its tissue. A diminution in the size of the pupil, sometimes noticed in old
age, may also contribute to the distinctness of the retinal image, as will be
described in connection with spherical aberration.

Defects of the Dioptric Apparatus. — The above-described imperfections
of the eye — viz. mvopia and hypermetrojiia — being generally (though not
invariably) due to an abnormal length of the longitudinal axis, are to be
regarded as defects of construction affecting only a comparatively small
number of eyes. There are, however, a number of imperfections of the diop-
tric apparatus, many of which affect all eyes alike. Of these imperfections
some affect the eye in common with all optical instruments, while others are
jieculiar to the eve and are not found in instruments of human construction.
The former class will be first considered.

Spherical Aberration. — It has been stated that a ]iencil of rays falling
ui)on a spherical refra»-ting surface will be refracted to a common focus.
Strictlv sjxiaking, however, the outer rays of the pencil — i. e. those which fall

THE SENSE OF VISION.

761

near the periphery <>f the refracting snrface— will be reiracted more than those
\\\\\A\ lie near the axis and will come to a focus sooner. This phenomenon,
which is called spherical aberration, is more marked with diverging tlian with
parallel rays, and tends, of course, to produce an indistinctness of the image
which wili increase with the extent of the surlace through whicli the rays
pass. The effect of a diaphragm used in many optical instruments to reduce
the amount of spherical aberration by cutting oil' the side rays is shown dia-
grammatically in Fig. 224.

Fig. 224.-Diagram showing the effect of a diaphragm in reducing the amount of spherical

aberration.

The r6le of the iris in the vision of near objects is now evident, for when
the eye is directed to a near object the spherical aberration is increased in con-
sequence of the rays becoming more divergent, but the contraction of the
pupil which accompanies accommodation tends, by cutting off the side rays, to
prevent a blurring of the image which otherwise would be produced. It must,
however, be remembered that the crystalline lens, unlike any lens of human
construction, has a greater index of refraction at the centre than at the periph-
ery. This, of course, tends to correct spherical aberration, and, in so far as it
does so, to' render the cutting off of the side rays unnecessary. Indeed, the
total amount of possible spherical aberration in the eye is so small that its
effect on vision may be regarded as insignificant in comparison with that caused
by the other optical imperfections of the eye.

Chromatic Aberration.— In the above account of the dioptric apparatus
of the eye the phenomena have been described as they would occur with mono-
chromatic light— i. e. with light having but one degree of refrangibility. But
the light of the sun is composed of an infinite number of rays of different
degrees of refrangibility. Hence when an image is formed by a simple lens
the more refrangible ravs— i. e. the violet rays of the spectrum— are brought
to a focus sooner than the less refrangible red rays. The image therefore

762 .l.V AMEIilCAX TEXT-BOOK OF Pll YSlOLOd Y.

apjx-ars bordereil by fringes of coKux'd light. This phenoiueiioii of chromatic
aberration cau be well observed by looking at objects throngh the lateral por-
tion of a simple lens, or, still better, by observing them through two simple
lenses held at a distance apart equal to the sum of their fbeal distances. The
objects will appear inverted (as through an astronomical telescope) and sur-
rounded with borders of colored light. Xow, the chromatic aberration of the
eye is so slight that it is not easily detected, and the physicists of the eighteenth
century, in their etforts to produce an achromatic lens, seem to have been
impressed by the fact that in the eye a combination of media of different
refractive powers is employed, and to have sought in this circumstance an
explanation of the supposed achromatism of the eye. AVork directed on this
line was crowned with brilliant success, for by combining two sorts of glass of
different refractive and dispersive powers it was found possible to refract a ray
of light without dispersing it into its different colored rays, and the achromatic
lens, thus constructed, became at once an essential part of every first-class opti-
cal instrument. Xow, as there is not only no evidence that the principle of
the achromatic lens is employed in the eye, but distinct evidence that the eye
is uncorrected for chromatic aberration, we have here a remarkable instance of
a misconception of a physical fact leading to an important discovery in physics.
The chromatic aberration of the eye, though so slight as not to interfere at all
with ordinary vision, can be readily shown to exist by the simple experiment
of covering up one half of the ])upil and looking at a bright source of light
e. g. a window. If the lower half of the pupil be covered, the cross-bars of

Fig. 225.— Diagram to illustrate chromatic aberration.

the window will appear bordered with a fringe of blue light on the lower and
reddish light on the upper side. The explanation usually given of the way in
which this result is produced is illustrated in Fig. 225. Owing to the chromatic
aberration of the eye all the rays emanating from an object at A are not
focussed accurately on the retina, but if the eye is accommodated for a ray of
medium refrangibility, the violet rays will be brought to a focus in front of
the retina at T^, while the red rays will be focussed behind the retina at R.
On the retina itself will be formed not an accurate optical image of the point
A, but a small circle of dispersion in which the various colored rays are mixed
together, the violet rays after crossing falling upon the same part of the retina
as the red rays before crossing. Thus by a sort of compensation, which, how-
ever, cannot be equivalent to the synthetic reproduction of white light by the
union of the spectral colors, the disturbing effect of chromatic aberration is

THE SENSE OF VISION.

763

diiiiiuished. WIrii tlu- lower half" of the pupil is eovered by the edge of a
card held in front of the cornea at I), the aberration produced in the upper
half of tlie eye is not compensated by that of the lower half. Hence the
image of a point of white light at .1 will appear as a row of spectral colors
on the retina, and all objects will appear bordered by colored fringes. Another
good illustration of the chromatic aberration of the eye is oljtained by cutting
two holes of any convenient shape in a piece of black cardboard and placing
behind one of them a piece of blue and behind the other a piece of red glass.
If the card is placed in a window some distance (10 meters) from the observer,
in such a position that the white light of the sky may be seen through the col-
ored glasses, it will be found that the outlines of the two holes will generally
be seen with unequal distinctness. To most eyes the red outline will appear
quite distinct, while the blue figure will seem much blurred. To a few indi-
viduals the blue figure appears the more distinct, and these will generally be
found to be hypermetropic.

Astigmatism. — The defect known as astigmatism is due to irregularities
of curvature of the refracting surfaces, in consequence of which all the rays
proceeding from a single point cannot be brought to a single focus on the
retina.

Astigmatism is said to be regular when one of the surfaces, generally the
cornea, is not spherical, but ellipsoidal — i. e. having meridians of maximum

Fig. 226.— Model to illustrate astigmatism.

and minimum curvature at right angles to each other, though in each meridian
the curvature is regular. When this is the case the rays proceeding from a
single luminous point are brought to a focus earliest when they lie in the
meridian in which the surface is most convex. Hence the pencil of rays will

7G4

AN AMUR/CAN TEXT- BO OK OF PHYSIOLOGY.

have two linear foci, at right augles to the nieridiaus of greatest and least
curvature separated by a space in which a section of the cone of rays will be
first elliptical, then circular, and then again elliptical. This defect exists to a
certain extent in nearly all eyes, and is, in some cases, u serious obstacle to dis-
tinct vision. The course of the rays when thus refracted is illustrated in Fig. 226,
which represents the interior of a box through which black threads are drawn
to indicate the course of the rays of light. The threads start at one end of the
box from a circle representing the cornea, and converge with different degrees
of rapidity in different meridians, so that a section of the cone of rays will be
successively an ellipse, a straight line, an ellipse, a circle, etc., as shown by the
model represented in Fig. 227. It will be noticed that this and the preced-

FiG. 227.— Model to illustrate astigmatism.

ing figure are drawn in duplicate, but that the lines are not precisely alike on
the two sides. In fact, the lines on the left represent the model as it would
be seen with the right eye, and those on the right as it would ai)pear to
the left eye, which is just the opposite from an ordinary stereoscopic slide.
The figures are drawn in this way because they are intended to j)roduce a
" pseudoscopic " effect in a way which will be explained in connection with
the subject of binocular vision. For this purpose it is only necessary to cross
the axes of vision in front of the page, as in the experiment described on page
758, for studying the relation between the focal, axial, and pupillary adju.st-
ments of the eye. As soon as the middle image becomes di.stinct it as.sumes a
stereoscopic appearance, and the correct relations between the different parts of
the model are at once obvious.

This imperfection of the eye may be detected by looking at lines such as are
shown in Figure 228, and testing each eye separately. If the straight lines

77//'; SENSE OF VISION. 765

drawn in various directions through a coninioii point cannot be seen with equal
distinctness at the same time, it is evident that the eye is better adapted to focus
rays in one meridian than in anotlier — /. c. it is astigmatic. The concentric

Fig. 228.— Lines for the detection of astigmatism.

circles are a still more delicate test. Few persons can look at this figure attentively
without noticing that the lines are not everywhere equally distinct, but that in
certain sectors the circles present a blurred appearance. Xot infrequently it
will be found that the blurred sectors do not occupy a constant position, but
oscillate rapidly from one part of the series of circles to another. This phe-
nomenon seems to be due to slight involuntary contractions of the ciliary
muscle causing changes in accommodation.

The direction of the meridians of greatest and least curvature of the cornea
of a regularly astigmatic eye, and the difference in the amount of this curvature,
can be very accurately measured by means of the ophthalmometer (see p. 750).
These points being determined, the defect of the eye can be perfectly corrected
by cylindrical glasses adapted to compensate for the excessive or deficient
refraction of the eye in certain meridians.

By another method known as " skiascopy," which consists in studying the
light reflected from the fundus of the eye when the ophthalmoscopic mirrol' is
moved in various directions, the amount and direction of the astigmatism of
the eye as a whole (and not that of the cornea alone) may be ascertained.

Astigmatism is said to be irregular when in certain meridians the curvatures
of the refracting surfaces are not arcs of circles or ellipses, or when there is a
lack of homogeneousness in the refracting media. This imperfection exists to
a greater or less extent in all eyes, and, unlike regular astigmatism, is incapable
of correction. It manifests itself by causing the outlines of all brilliant objects
to appear irregular. It is on this account that the fixed stars do not appear to
us like points of light, but as luminous bodies with irregular " star "-si i aped
outlines. The phenomenon can be conveniently studied by looking at a pin-
hole in a large black card held at a convenient distance between the eye and a
strong light. The hole will appear to have an irregular outline, and to some
eyes will appear double or treble.

Intraocular Images. — Light entering the eye makes visible, under certain
circumstances, a number of objects which lie within the eye itself. These
objects are usually opacities in the media of the eye which are ordinarily invisi-

766 ^l.Y AMERICAN TEX I- HOOK OF PHYSIOLOGY.

ble, because the retina i.s illuuiinuted bv light coiuiiij^ I'roni all parts ol" the
pupil, and witli such a broad source of light no object, unless it is a very large
one or one lying very near the back of the eye, can cast a shadow on the retina.
Such shadows can, however, be made apparent l)y allowing the media of the
eve to be traversed by parallel rays of light. This can be accomplished by
holding a small polished sphere — e.g. the steel head of a shawl-])in illuminated
bv sunlight or strong artificial light — in the anterior focus of the eye — /. e.
about 22 millimeters iu front of the cornea, or by placing a dark screen with a
pin-hole in it iu the same position between the eye and a source of uniform
diffused light, such as the sky or the porcelain shade of a student lamj). In
either case the rays of light diverging from the minute source will be refracted
into parallelism by the media of the eye, and will ])roduce the sensation of a
circle of diffused light, the size of which will depend up(jn the amount of dila-
tation of the pu])il. Within this circle of light will be seen the shadows of any
opaque substances that may be present in the media of the eye. These shadows,
being cast by parallel rays, will be of the same size as the objects themselves,
as is shown diagrammatically in Figure 229, in which .4 represents a source

Fig. 229.— Showing the method of studying intraocular images (Helmholtz).

of light at the anterior focus of the eye, and b an opacity iu the vitreous humor
casting a shadow B of the same size as itself upon the retina. It is evident that
if the source of light A is moved from side to side the various opacities will be
displaced relatively to the circle of light surrounding them by an amount de-
pending upon the distance of the opacities from the retina. A study of these
displacements will therefore afford a means of determining the position of the
opacities within the media of the eye.

Muscffi Volitantes. — Among the objects to be seen in thus examining the
eye the most conspicuous are those known as the muscce volitantes. These pre-
sent themselves in the form of beads, either singly or in groups, or of streaks,
patches, and granules. They have an almost constant floating motion, which
is increased by the movements of the eye and head. They usually avoid the
line of vision, floating away when an attempt is made to fix the sight upon
them. When the eye is directed vertically, however, they sometimes place
themselves directly in line with the object looked at. If the intraocular object
is at the .same time sufficiently near the back of the eye to ca.st a shadow which
is visible without the use of the focal illumination, some inconvenience may
thus be caused in using a vertical microscope.
• A studv of the motions of the musca: volitantes makes it evident that the

THE SENSE OF VISION. 767

phenomenon is due to small bodies floating in a liquid medium of a little
greater specific gravity than thcni.sclves. Their movements are chicifly in
planes perpendicular to the axis of vision, for when the eye is directed verti-
cally upward they move as usual through the field of vision without increasing
the distance from the retina. They are generally supposed to be the remains
of the embyronic structure of the vitreous body — i. e. portions of the cells and
fibres which have not undergone complete raucous transformation.

In addition to these floating opacities in the vitreous body various other
defects in the transparent media of the eye may be revealed by the method of
focal illumination. Among these may be mentioned spots and stripes due to
irregularities in the lens or its capsule, and radiating lines indicating the stel-
late structure of the lens.

Retinal Vessels.— Owing to the fact that the blood-vessels ramify near the
anterior surface of the retina, while those structures which are sensitive to light
constitute the posterior layer of that organ, it is evident that light entering the
eye will cast a shadow of the vessels on the light-perceiving elements of the
retina. Since, however, the diameter of the largest blood-vessels is not more
than one-sixth of the thickness of the retina, and the diameter of the pupil is
one-fourth or one-fifth of the distance from the iris to the retina, it is evident
that when the eye is directed to the sky or other broad illuminated surfaces it
is only the penumbra of the vessels that will reach the rods and cones, the umbra
terminating conically somewhere in the thickness of the retina. But if light
is allowed to enter the eye through a pin-hole in a card held a short distance
from the cornea, as in the above-described method of focal illumination, a
sharply defined shadow of the vessels will be thrown on the rods and cones.
Yet under these conditions the retinal vessels are not rendered visible unless
the perforated card is moved rapidly to and fro, so as to throw the shadow
continually on to fresh portions of the retinal surface. When this is done the
vessels appear, ramifying usually as dark lines on a lighter background, but
the dark lines are sometimes bordered by bright edges. It will be observed
that those vessels appear most distinctly the course of which is at right angles
to the direction in which the card is moved. Hence in order to see all the
vessels with equal distinctness it is best to move the card rapidly in a circle
the diameter of which should not exceed that of the pupil. In this manner
the distribution of the vessels in one's own retina may be accurately observed,
and in many cases the position of the fovea centralis may be determined by the
absence of vessels from that portion of the macula lutea.

The retinal vessels may also be made visible in several other ways — e. g.,
1. By directing the eye toward a dark background and moving a candle to and
fro in front of the eye, but below or to one side of the line of vision. 2. By
concentrating a strong light by means of a lens of short focus upon a point
of the sclerotic as distant as possible from the cornea. By either of these
methods a small image of the external source of light is formed upon the
lateral portion of the eye, and this image is the source of light which throws
shadows of the retinal vessels on to the rods and cones.

768 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Circiilation of Blood in the Retina. — W'ljen the eye is directed toward a
surface which is uniformly aud brightly illuniinated — e. g. the sky or a sheet
of white paper on which the sun is shinintr — the Held of vision is soon seen to
be filled with small brij^ht bodies moving; with considerable raj)idity in irregu-
lar turved lines, but with a certain uniformity which suggests that their
movements are confined to definite channels. They are usually better seen
Avhen one or more sheets of cobalt glass are held before the face, so tiiat the
eyes are bathed in blue light. That the phenomenon depends upon the circu-
lation of the blood globules in the retina is evident from the fact that tiie
moving bodies follow paths which correspond with the form of the retinal
capillaries as seen by the methods above described, and also from the corre-
spondence between the rate of movement of the intraocular image and the
rapidity of the capillary circulation in those organs in which it can be di-
rectly measured under the microscope. The exact way in which the moving
globules stimulate the retina so as to produce the observed phenomenon must
be regarded as an unsettled question.

We have thus seen that the eye, regarded from the optician's point of view,
has not only all the faults inherent in optical instruments generally, but many
others w'hich Avould not be tolerated in an instrument of human construction.
Yet with all its imperfections the eye is perhaps the most wonderful instance
in nature of the development of a highly specialized organ to fulfil a definite
purpose. In the accomplishment of this object the various parts of the eye
have been perfected to a degree sufficient to enable it to meet the requirements
of the nervous system with which it is connected, and no farther. In the
ordinary use of the eye we are unconscious of its various irregularities, shadows,
opacities, etc., for these imperfections are all so slight that the resulting inac-
curacy of the image does not much exceed the limit which tiie size of the
light-perceiving elements of the retina imposes upon the delicacy of our visual
perceptions, and it is only by illuminating the eye in* some unusual way that
the existence of these imperfections can be detected. In other words, the eye
is as good an optical instrument as the nervous system can appreciate and
make use of. Moreover, when we reflect upon the difficulty of the problem
which nature has solved, of constructing an optical instrument out of living
and growing animal tissue, we cannot fail to be struck by the perfection of the
dioptric apparatus of the eye as well as by its adaptation to the needs of the
organism of which it forms a part.

Iris. — The importance of the iris as an adjustable diaphragm for cutting
offside rays and thus securing good definition in near vision has been described
in connection with the act of accommodation. Its other function of protecting
the retina from an excess of light is no less important, and we must now con-
sider how this pupillary adjustment may be studied and by what mechanism
it is effected. The changes in the size of the pupil may be conveniently ob-
served in man and animals by holding a millimeter scale in front of the eye
aud noticing the variations in the diameter of the pupil. It should be borne
in mind that the iris, seen in this way, does not appear in its natural size and

THE SENSE OF VISION.

7G9

position, but soincwhnt eiilari^ctl and bulged forward by the magnifying effect
of i\w coriK'a aiul the acjueous humor. The changes in one's own pupil may
be readily observed by noticing the varying size of the circle of light thrown
upon the retina when the eye is illuniinateil by ti point of light held at the
anterior ftK-us, as in the method above described for the .study of intraocular
images.

The muscles of the iris are, except in birds, of the unstriped variety, and
are arranged concentrically around the pupil. Radiating fibres are also recog-
nized by many observers, though their existence has been called in question
by others. The circular or constricting muscles of the iris are under the con-
trol of the third pair of cranial nerves,
and are normally brought into activity
in consequence of light falling upon
the retina. Tliis is a reflex phenom-
enon, the optic nerve being the affer-
ent, and the third pair, the ciliary
ganglion, and the short ciliary nerves
the efferent, channel, as indicated in
Figure 230. This reflex is in man
and many of the higher animals bi-
lateral— i. e. light falling upon one
retina will cause a contraction of both
pupils. This may readily be observed
in one's own eye when focally illumi-
nated in the manner above described.
Opening the other eye will, under
these conditions, cause a diminution,
and closing it an increase, in the size
of the circle of light. This bilateral
character is found to be dependent
upon the nature of the decussation of
the optic nerves, for in animals in
which the crossing is complete the
reflex is confined to the illuminated
eve. The arrangement of the fibres

Course of constrictor nerve-fibres •
" dilator "

Fig. 230.— Diagrammatic representation of the
nerves governing the pupil (after Foster) : II, optic
nerve ; l. g, ciliary ganglion ; r. b, its short root from
III, motor-oculi nerve ; ^ym, its sympathetic root ; r. I,
in the optic commissure is in general its long root from F.ophthalmo-nasal branch of oph-

associated with the position of the
the head. When the

thalmic division of fifth nerve; 8. c. short ciliary
nerves ; I. c, long ciliary nerves.

eyes in the head. When the eyes
are so placed that they can both be directed to the same object, as in man
and many of the higher animals, the fibres of each optic nerve are usually
found to be distributed to bo^h optic tracts, while in animals whose eyes
are in opposite sides of the head there is complete crossing of the optic nerves.
Hence it may be said that animals having binocular vision have in general
a bilateral pupillary reflex. The rule is, however, not without exceptions,
for owls, though their visual axes are parallel, have, like other birds, a com-

49

770 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

plete crossing of the optic; uorvcs, and coiisinjueiitiy a unilateral pupillary
reflex.'

A direct as well as a reflex constri<^tion of the pupil under the influence of
light has been observed in the excised eyes of eels, frogs, and some other ani-
mals. As the phenomenon can be seen in preparations ccnisisting of the iris
alone or of the iris and cornea together, it is evident that the light exerts its
influence directlv upon the tissues of the iris and not through an intraocular
connection with the retina. The maximum effect is produced l)y the yellowish-
green portion of the spectrum.

Autatroniziuir the motor oculi nerve in its constricting influence on the
pupil is a set of nerve-fibres the function of which is to increase the size of
the pupil. Most of these fibres seem to run their course from a centre which
lies in the floor of the third ventricle not far from the origin of the third pair,
through the bulb, the cervical cord, the anterior roots of the upper dorsal
nerves, the upper thoracic ganglion, the cervical sympathetic nerve as far as
the upper cervical ganglion ; then through a branch which accompanies the
internal carotid artery, passes over the Gasserian ganglion and joins the oph-
thalmic branch of the fifth pair ; then through the nasal branch of the latter
nerve and the long ciliary nerves to the eye ^ (see diagram, p. 769). These
fibres ap})ear to be in a state of tonic activity, for section of them in any part
t)f their course (most conveniently in the cervical sympathetic) causes a con-
traction of the pupil which, on stimulation of the peripheral end of the divided
nerve, gives place to a marked dilatation. Their activity can be increased ia
various ways. Thus dilatation of the pupil may be caused by dyspnea, vio-
lent muscular efforts, etc. Stimulation of various sensory nerves may also
cause reflex dilatation of the pupil, and this phenomenon may be observed,
though greatly diminished in intensity, after extirpation of the superior cervi-
cal sympathetic ganglion. It is therefore evident that the dilator nerves of the
pupil do not have their course exclusively in the cervical sympathetic nerve.

Since the cervical sympatlietic; nerve contains vaso-constrictor fibres for the
head and neck, it has been thought that its dilating effect upon the pupil might
be explained by its power of causing changes in the amount of blood in the
vessels of the iris. There is no doubt that a condition of vascular turgescence
or depletion will tend to produce contraction or dilatation of the pupil, but it is
impossible to explain the observed phenomena in this way, since the pupillary
are more prompt than the vascular changes, and may be observed on a bloodless
eye. Moreover, the nerve-fibres producing them are said to have a somewhat
different coui*se. Another explanation of the influence of the sympathetic on
the pupil is that it acts by inhibiting the contraction of the sphincter muscles,
and that the dilatation is simply an elastic reaction. But since it is posssible to
produce local dilatation of the pupil by circumscribal stimulation at or near

' Steinach : Archir fur die (/esummte PhymAogiv, xlvii. 31i).

'^ Langley : Journal of Physiology, xiii. p. 575. For the evidence of the existence of a
" cilio-spinal " centre in the cord, see Steil and Langendorff: Archiv fiir die gesammte Phys-
iologie, Iviii. p. 155; also Scheuck : Ibid., Ixii. p. 494.

THE SENSE OF VISION. Ill

the outer border of the iris, it seems more reasonable to conclude that the
dilator nerves of the puj)il act upon radial muscular fibres in the substance of
the iris, in spite of the fact that the existence of such fibres has not been uni-
versally admitted.

Whatever view may be taken of the mechanism by which the sympathetic
nerves influence the pupil, there is no doubt that the iris is under the control
of two antagonistic sets of nerve-fibres, both of which are, under normal cir-
cumstances, in a state of tonic activity. Therefore, when the sympathetic
nerve is divided the pu])il contracts under the influence of the motor oculi, and
section of the motor oculi causes dilatation through the unopposed influence of
the sympathetic.

The movements of the iris, though performed by smooth muscles, are more
rapiil than those of smooth muscles found elsewhere— e. g. in the intestines
and the arteries. The contraction of the pupil when the retina of the oppo-
site eye is illuminated occupies about 0.3" ; the dilatation when the light is cut
off from the eye, about 3" or 4". The latter determination is, however, diffi-
cult to make with precision, since dilatation of the pupil takes place at first
rapidly and then more slowly, so that the moment when the process is at an
end is not easily determined. After remaining a considerable time in absolute
darkness the pupils become enormously dilated, as has been shown by flash-
light photographs taken under these conditions. In sleep, though the eyes are
protected from the light, the pupils are strongly contracted, but dilate on
stimulation of sensory nerves, even though the stimulation may be insufficient
to rouse the sleeper.

Many drugs when introduced into the system or applied locally to the con-
junctiva produce effects upon the pupil. Those which dilate it are known as
mydriatics, those which contract it as myotics. Of the former class the most
important is atropin, the alkaloid of the Atropa belladonna, and of the latter
physostigmin, the alkaloid of the Calabar bean. In addition to their action
upon the pupil, mydriatics paralyze the accommodation, thus focussing the eye
for distant objects, while myotics, by producing a cramp of the ciliary muscle,
adjust the eye for near vision. The effect on the accommodation usually
begins later and passes off sooner than the affection of the pupil. Atropin
seems to act by producing local paralysis of the terminations of the third pair
of cranial nerves in the sphincter iridis and the ciliary muscle. In large
doses it may also paralyze the muscle-fibres of the sphincter. With this para-
lyzing action there .appears to be combined a stimulating effect upon the dilator
muscles of the iris. The myotic action of physostigmin seems to be due to a
local stimulation of the fibres of the sphincter of the iris.

Although in going from a dark room to a lighter one the pupil at first con-
tracts, this contraction soon gives place to a dilatation, and in about three or
four minutes the pupil usually regains its former size. In a similar manner
the primary dilatation of the pupil caused by entering a dark room from a
lighter one is followed by a contraction which usually restores the pupil to its
original size within fifteen or twenty minutes. It is thus evident that the

772

AN AMERICAN TEXT-BOOK OF J'JIYSIOLOGY.

amount of light lulling u])on the retina is uot the only taet<;r in determining
the size of the pupil. In fact, if the light aets for a sufficient length of time
the pupil may have the same size under the influence of widely difl'erent
degrees of illumination.'

This so-cidled " adaptation " of the eye to various amounts of light seems
to be connected w ilh the movements of the retinal pigment-granules and with
the chemical changes of the visual purple, to be more fully described in c<jn-
nection with the physiology of the retina.

The Ophthalmoscope. — Under normal conditions the pupil of the eye
appears as a black spot in the middle of the colored iris. The cause of this
dark appearance of the pupil is to be found in the fact that a source of light
and the retina lie in the conjugate foci of the dioptric apparatus of the eye.
Hence any light entering the eye that escapes absorption by the retinal pig-
ment and is reflected from the fundus must be refracted back to the source
from which it came. The eye of an observer who looks at the pupil from
another direction will see no light coming from it, and it will therefore appear
to him black. It is therefore evident that the essential condition for perceiving
light coming from the fundus of the eye is that the line of vision of the
observing eye shall be in the line of illumination. This condition is fulfilled
by means of instruments known as ophthalmoscopes. The principles involved
in the construction of the most common form of ophthalmoscope are illustrated
diagrammatically in Figure 231.

Fig. 2.31.— Diagram to illustrate the principles of a simple ophthalmoscope (after Foster).

The rays from a source of light L, after being brought to a focus at a by
the concave perforated mirror M M, pass on and are rendered parallel by the
lens /. Then, entering the observed eye B, they are brought to a focus on the
retina at a'. Any rays which are reflected back from the part of the retina
thus illuminated will follow the course of the entering rays and be brought to
a focus at a. The eye of an observer at A, looking through the hole in the
mirror, will therefore see at a an inverted image of the retina, the observation
of which may be facilitated by a convex lens placed immediately in front of
the observer's eye.

* Schirmer : Archiv/iir Ophlhalmologie, xi. 5.

THE SENSE OF VISION.

773

The fundus of the eye thus observed presents a reddish background on
wliich the retinal vessels are distinctly visible.

Retina. — ITavin<!; considered the mechanism by which optical images of
objects at various distances from the eye are formed upon the retina, we nmst
next inquire what part of the retina is affected by the rays of light, and in
what this affection consists. To the former of these questions it will be found
possible to give a fairly satisfactory answer. Witli regard to the latter nothing
positive is known.

The structure of the retina is exceedingly complicated, but, as very little
is known of the functions of the ganglion cells and of the molecular and
nuclear layers, it will suffice for the present purpose of physiological descrip-
tion to regard the retina as consisting of fibres of the optic nerve which are
connected through various intermediate structures with the layer of rods and
cones.

A

Fig. 232

-Diagrammatic representation of the retina.

Figure 232 is intended to show, diagrammatically, the mutual relation of
these various portions of the retina in different parts of the eye, and is not
drawn to scale. It will be observed that the optic nerve 0, wdiere it enters the
eye, interrupts the continuity of the layer of rods and cones R and of the
intermediate structures /. Its fibres spread themselves out in all directions,
forming the internal layer of the retina N. The central artery of the retina
A accompanying the optic nerve ramifies in the layer of nerve-fibres and in
the immediately adjacent layers of the retina, forming a vascular layer V. In
the fovea centralis F of the macula lutea (the centre of distinct vision) the
layer of rods and cones becomes more highly developed, while the other layers
of the retina are much reduced in thickness and the blood-vessels entirely dis-
appear. This histological observation points strongly to the conclusion that
the rods and cones are the structures which are essential to vision, and that in
them are found the conditions for the conversion of the vibrations of the
luminiferous ether into a stimulus for a nerve-fibre. This view derives con-
firmation from the observations on the retinal blood-vessels, for it is found
that the distance between the vascular layer of the retina and the layer
of rods and cones determined by histological methods corresponds with that
which must exist between the vessels and the light-perceiving elements of the
retina, as calculated from the apparent displacement of the shadow caused by
given movements of the source of light used in studying intraocular images^ as

1 " Dimmer Verb. d. phys. Clubs zu Wien, 24 April, 1894," CentrcJbl. fur Physiologie, 1894, 159.

774

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

described on p. 767, Another argument in favor of this view is fcjiind in the
correspondence between the size of the smallest visible images on the retina and
the diameter of the rods and cones. A double star can be recognized as double
by the normal eye when the distance between the components corresponds to
a visual angle of 60". Two white lines on a black ground are seen to be dis-
tinct when the distance between them subtends a visual angle of 64"-73".
These angles correspond to a retinal image of 0.0044, 0.0046, and 0.0053 mil-
limeter. Now, the diameter of the cones in the macula lutea, as determined
by Kolliker, is 0.0045-0.0055 millimeter, a size which agrees well with the
hypothesis that each cone when stimulated can produce a special sensation of
light distinguishable from those caused by the stimulation of the neighboring
cones. The existence of the so-called blind spot in the retina at the point of
entrance of the optic nerve is sometimes regarded as evidence of the light-
perceiving function of the rods and cones, but as the other layers of the retina,
as well as the rods and cones, are absent at this point, and the retina here
consists solely of nerve-fibres, it is evident that the presence of the blind spot

Fig. 233.— To demonstrate the blind spot.

only proves that the optic nerve-fibres are insensible to light. Figure 233 is
intended to demonstrate this insensibility. For this purpo.se it should be held
at a distance of about 23 centimeters from the eyes [i. e. about 3.5 times the dis-
tance between the cross and the round spot). If the left eye be closed and the
right eye fixed upon the cross, the round spot will disappear from view, though
it will become visible if the eye be directed either to the right or to the left of
the cross, or if the figure be held either a greater or a less distance from the
eye. The size and shape of the blind spot may readily be determined as
follows : Fix the eye upon a definite point marked upon a sheet of white
paper. Bring the black point of a lead pencil (which, except the point, has
been painted white or covered with white paper) into the invisible portion of
the field of vision and carry it outward in any direction until it becomes vis-
ible. Mark upon the paper the point
at which it just begins to be seen, and
by repeating the process in as many
different directions as po.ssible the out-
line of the blind spot may be marked
out. Figure 234 shows the shape of
the blind spot determined by Helni-
holtz in his own right eye, a being
^*Z~~T. Z 7irTr~i , ,„ , . ,» / the i)oint of fixation of the eye, and

Fig. 234.— Form of the blind spot (Helmholtz). J _ .

the line .1 B being one-third of the
distance between the eye and the paper. The irregularities of outline, as at

TIIK SENSE OF VISION.

lib

d are cl.>e to shadows of tin- large retinal vessels. During this determination
it' is of course necessary that the head should occ-upy a fixed position with
rec^ard to the paper. This condition can be secured by holding fu.nly between
the teeth a piece of wood that is clamped in a suitable position to the edge of
the table. The diameter of the blind spot, as thus determined, has been found
to correspond to a visual angle varying from 3° 39' to 9° 47 , the average
measurement being 6° 10'. This is about the angle that is subtended by the
human face seen at a distance of two meters. Although a considerable por-
tion of the retina is thus insensible to light, we are, in the ordinary us^ of the
eyes, conscious of no corresponding blank in the field of visioiu By what
psvchieal operation we "fill up" the gap in our subjective field of vision
caused by the blind spot of the retina is a question that has been much dis-
cussed without being definitely settled. ,. r i f
The above-mentioned reasons for regarding the rods and cones as the light-
perceiving elements of the retina seem sufficiently conclusive. Whether there
is anv difference between the rods and the cones with regard to their bght-
perceivinc function is a question which may be best considered m connection
with a description of the qualitative modifications of light

The histological relation between the various layers of the retina is still
under discussion. According to recent observations of Cajal,^ the connection
between the rods and cones on the one
side and the fibres of the optic nerve
on the other is established in a man-
ner which is represented diagram-
matically in Figure 235. The pro-
longations of the bipolar cells of the
internal nuclear layer E break up into
fine fibres in the external molecular
(or plexiform) layer C. Here they are
brought into contact, though not into
anatomical continuity, with the termi-
nal fibres of the rods and cones. The
inner prolongations of the same bipolar
cells penetrate into the internal molec-
ular (or plexiform) layer F, and there
come into contact with the dendrites
coming from the layer of ganglion-cells
G. These cells are, in their turn, con-
nected by their axis-cylinder processes
Avith the fibres of the optic nerve. The

Rods.

Cones.

Fig. 235.-Diagrammatic representation of the

xvWh the fibres Ol tne OpUC neive. -lh^ structure of the retina (Cajal): A, layer of rods

AVltn tne noieb ui u ^ and cones- B external nuclearlayer; C. external

bipolar cells which serve as connective ^°^^j;^"i^; (^; plexiform) layer; e, internal un-
links between the rods and the optic J-r:ay^er;^..int.^^^^^^^^^
nerve-fibres are anatomically distin- ^^-^^^^.g^,;,.
guishable (as indicated in the diagram)

Die Retina der Wirbeltkiere, Wiesbaden, 1894.

776 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

from those wliicli perl'onn the same t'unetion lor the cones. Whatever be tlie
precise mode of connection between the rods and cones and the fibres of tlie
optic nerve, it is evident that each retinal element cannot be counectod with
the nerve-centres by a separate independent nerve-channel, since the retina
contains many millions of rods and cones, while the optic nerve has only
about 438,000 nerve-fibres,' though of course such a connection may exist in
the fovea centralis, as Cajal has shown is probably the case in reptiles and birds.
Changes Produced in the Retina by Light. — We must now inquire
what changes can be supposed to occur in the rods and cones under the influ-
ence of light by means of which they are able to transform the energy of the
ether vibrations into a stimulus for the fibres of the optic nerve. Though in
the present state of our knowledge no satisfactory answer can be given to this
question, yet certain direct effects of light upon the retina have been observed
which are doubtless associated in some way with the transformation in
question.

The retina of an eye which has been protected from light for a considerable
length of time has a purplish-red color, which upon exposure to light changes
to yellow and then fades away. This bleaching occurs also in monochromatic
light, the most powerful rays being those of the greenish-yellow portion of
the spectrum — /. e. those rays which are most completely absorbed by the pur-
plish-red coloring matter. A microscopic examination of the retina shows
that this coloring matter, which has been termed visual purple, is entirely con-
fined to the outer portion of the retinal rods and does not occur at all in the
cones. After being bleached by light it is, during life, restored through the
agency of the pigment epithelium, the cells of which, under the influence of
light, send their prolongations inward to envelop the outer limbs of the rods
and cones with pigment. If an eye, either excised or in its natural position,
is protected from light for a time, and then placed in such a position that the
image of a lamp or a window is thrown upon the retina for a time which may
vary with the amount-of light from seven seconds to ten minutes, it will be
found that the retina, if removed and examined under red light, will show the
image of the luminous object impressed ujion it by the
bleaching of the visual purple.

If the retina be treated with a 4 per cent, solution of
alum, the restoration of the visual purple will be pre-
vented, and the so-called '^ optogram" will be, as pho-
tographers say, " fixed." ^
Fig. 236.-optoKram in eye Figure 236 shows the ai)iiearance of a rabbit's retina

of rabbit (Kiihne). , • , , /> • i i i • i

on whicli the optogram oi a wnidow has been nupressed.

Although the chemical changes in the visual purple under the influence of

light seem, at first sight, to afford an cxjilanation of the transformation of the

vibrations of the luminiferous ether into a stimulation for the optic nerve, yet

the fact that vision is most distinct in the fovea centralis of the retina, which,

^ Salzer: Wiener Sitzungsberichle, 1880. Bd. Ixxxi. S. 3.

' Kiihne : Unlersuchungen a. d. phys. Inst. d. UniversUdt Heidelbeig, i. 1.

THE SENSE OF VISION. Ill

as it contains lU) rods, is destitute ol" visual purple, makes it impossible to
rejiard this colorinj>; matter as essential to vision. The most probable theory
of its tunotion is perhaps that which connects it with the adaptation of" the
eye to varying amounts of ligiit, as described on p. 772.

In addition to the above-mentioned movements of the ])igment epithelium
cells under the influence of light, certain changes in the retinal cones of frogs
and fishes have been observed.^ The change consists in a shortening and thick-
ening of the inner portion of the cones when illuminated, but the relation of
the ])henomenon to vision has not been explained.

Like most of the living tissues of the body, the retina is the seat of electri-
cal currents. In repose the fibres of the optic nerve are said to be positive in
relation to the layer of rods and cones. When light falls upon the retina this
current is at first increased and then diminished in intensity.

Sensation of Light. — Whatever view may be adopted with regard to the
mechanism by which light is enabled to become a stimulus for the optic nerve,
the fundamental fact remains that the retina (and in all probability the layer
of rods and cones in the retina) alone supplies the conditions under which this
transformation of energy is possible. But in accordance with the " law of
specific energy " a sensation of light may be produced in whatever way the
optic nerve be stimulated, for a stimulus reaching the visual centres through
the optic nerve is interpreted as a visual sensation, in the same way that
pressure on a nerve caused by the contracting cicatrix of an amputated leg
often causes a painful sensation which is referred to the lost toes to which the
nerve was formerly distributed. Thus local pressure on the eyeball by stimu-
lating the underlying retina causes luminous sensations, already described as
*' phosphenes," and electrical stimulation of the eye as a whole or of the stump
of the optic nerve after the remos'al of the eye is found to give rise to sensa-
tions of light.

Vibrations of the luminiferous ether constitute, however, the normal stim-
ulus of the retina, and we must now endeavor to analyze the sensation thus
produced. In the first place, it must be borne in mind that the so-called ether
waves differ among themselves very widely in regard to their rate of oscilla-
tion. The slowest known vibrations of the ether molecules have a frequency
of about 107,000,000,000,000 in a second, and the fastest a rate of about
40,000,000,000,000,000 in a second — a range, expressed in musical terms, of
about eight and one-half octaves. All these ether waves are capable of warm-
ing bodies upon which they strike and of breaking up certain chemical com-
binations, the slowly vibrating waves being especially adapted to produce the
former and the rapidly vibrating ones the latter effect. Certain waves of
intermediate rates of oscillation — viz. those ranging between 392,000,000,-
000,000 and 757,000,000,000,000 in a second— not only produce thermic and
chemical effects, but have the power, when they strike the retina, of causing
changes in the layer of rods and cones, which, in their turn, act as a stimulus
to the optic nerve. The ether waves which produce these various phenomena

^ Engelniann : Archivfiir die gesammte PhysMogie, xxxv. 498.

778 A^' AMERICAN TEXT-BOOK OF PHYSIOLOGY.

are often spoken of as heat rays, light rays, and actinic or chemical rays, but
it must be remembered that the same wave may produce all three classes of
phenomena, the effect dependincr upon the nature of the sub.<tance upon which
it strikes. It will be observed that the range of vibrations capable of affecting
the retina is rather less than one octave, a limitation which obviously tends to
reduce the amount of chromatic aberration.

In this connection it is interesting to notice that the highest audible note is
produced by about 40,000 sonorous impulses in a second. Between the high-
est audible note and the lowest visible color there is a gap of nearly thirty-four
octaves in which neither the vibrations of the air nor those of the luminifer-
ous ether affect our senses. Even if the slowly vibrating heat-rays which
affect our cutaneous nerves are taken into account, there still remain over
thirty-one octaves of vibrations, either of the air or of the luminiferous ether,
which may be, and very likely are, filling the universe around us without in
any way impressing themselves upon our consciousness.

Qualitative Modifications of Light. — All the ethereal vibrations which
are capable of affecting the retina are transmitted with very nearly the same
rapidity through air, but when they enter a denser medium the waves having
a rapid vibration are retarded more than those vibrating more slowly. Hence
Avhen a ray of sunlight composed of all the visible ether waves strikes upon a

plane surface of glass, the greater
1^' retardation of the waves of rapid
vibration causes them to be more
refracted than those of slower vibra-
tion, and if the glass has the form
of a prism, as shown in Figure 237,
this so-called *' dispersion " of the
rays is still further increased when
the rays leave the glass, .so that the
emerging beam, if received upon a

Fig. 237.-Diagrain iUustrating the dispersion of light ^.j^j^^ surface, instead of forming a
by a prism. ' »

spot of white light, produces a band
of color known as the solar spectrum. The colors of the spectrum, though
commonly spoken of as seven in number, really form a continuous series from
the extreme red to the extreme violet, these colors corresponding to ether vibra-
tions have rates of 392,000.000,000,000 and 757,000,000,000,000 in 1 second,
and wave lengths of 0.7G67 and 0.3970 microniilliraeters* respectively.

Colors, therefore, are sensations caused by the impact upon the retina of
certain ether waves having definite frequencies and wave-lengths, but these
are not the only peculiarities of the ether vibration which influence the retinal
sensation. The energy of the vibration, or the vis viva of the vibrating mole-
cule, determines the " intensity " of the .sensation or the brilliancy of the light.*

'One micromillimeter^ 0.001 millimeter = one ,".

^ The energy of vibration capable of producing a given subjective sensation of intensity
varies with the color of the light, as will be later explained (see p. 786).

THE SENSE OF VISION. 779

Furthermore, the sensation produced by the impact of ether waves of a definite
length will vary according as the eye is simultaneously affected by a greater or
less amount of wliite light. This modification of the sensation is termed its
degree of 'Saturation," light being said to be completely saturated when it is
" monochromatic " or produced by ether vibrations of a single wave-length.

The modifications of light which taken together determine completely the
character of the sensation are, then, three in number — viz. : 1. Color, depend-
ent upon rate of vibration or length of the other wave ; 2. Intensity, dependent
upon the energy of the vibration ; 3. Saturation, dependent upon the amount
of white light mingled with the monochromatic light. These three qualitative
modifications of light must now be considered in detail.

Color. — In our profound ignorance of the nature of the process by which,
in the rods and cones, the movements of the ether waves are converted into a
stimulus for the optic nerve-fibres, all that can be reasonably demanded of a
color theory is that it shall present a logically consistent hypothesis to account
for the sensations actually produced by the impact of ether waves of varying
rates, either singly or combined, upon different parts of the retina. Some of
the important phenomena of color sensation of which every color theory must
take account may be enumerated as follows :

1. Luminosity is more readily recognized than color. This is shown by
the fact that a colored object appears colorless when it is too feebly illuminated,
and that a spectrum produced by a very feeble light shows variations of inten-
sity with a maximum nearer than normal to the blue end, but no gradations
of color. A similar lack of color is noticed when a colored object is observed
for too short a time or when it is of insufficient size. In all these respects the
various colors present important individual differences which will be considered
later,

2. Colored objects seen with increasing intensity of illumination appear
more and more colorless, and finally present the appearance of pure white.
Yellow passes into white more readily than the other colors,

3. The power of the retina to distinguish colors diminishes from the centre
toward the periphery, the various colors, in this respect also, differing mate-
rially from each other. Sensibility to red is lost at a short distance from the
macula lutea, while the sensation of blue is lost only on the extreme lateral
portions of the retina. The relation of this phenomenon to the distribution
of the rods and cones in the retina will be considered in connection with the
perception of the intensity of light.

Color-mixture. — Since the various spectral colors are produced by the dis-
persion of the white light of the sun, it is evident that white light may be
reproduced by the reunion of the rays corresponding to the different colors, and
it is accordingly found that if the colored rays emerging from a prism, as in
Fig. 237, are reunited by suitable refracting surfaces, a spot of white light will be
produced similar to that which would have been caused by the original beam
of sunlight. But white light may be produced not only by the union of all
the spectral colors, but by the union of certain selected colors in twos, threes.

780 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

fours, etc. Any tw(3 spectral colors which by their union produce white are
said to be " complementary " colors. The relation of these pairs of comple-
mentary colors to each otlier may be best mulerstood by reference to Figure 238.

p

Fig. 238.— Color diagram.

Here the spectral colors are supposed to be disposed around a curved line,
as indicated by their initial letters, and the two ends of the curve are united
by a straight line, thus enclosing a surface having somewhat the form of a tri-
angle with a rounded apex. If the curved edge of this surface be supposed to
be loaded with weights proportionate to the luminosity of the different colors,
the centre of gravity of the surface will be near the point W. Now, if a
straight line be drawn from any point on the curved line through the point
IF and prolonged till it cuts the curve again, the colors corresponding to the
two ends of this straight line will be complementary colors. Thus in Figure
238 it will be seen that the complementary color of red is blui.sh -green, and
that of yellow lies near the indigo. It is also evident that the complementary
color of green is purple, which is not a spectral color at all, but a color
obtained by the union of violet and red. The union of a pair of colors
lying nearer together than complementary colors produces an intermediate color
mixed with an amount of white which is proportionate to the nearness of the
colors to the complementary. Thus the union of red and yellow produces
orange, but a less saturated orange than the spectral color. The union of two
colors lying farther apart than complementary colors produces a color which
borders more or less upon purple.

The mixing of colors to demonstrate the above-mentioned effects may be
accomplished in three different ways :

1. By employing two prisms to produce two independent spectra, and then
directing the colored rays which are to be united so that they will illuminate
the same white surface.

2. By looking ol)liquely through a glass plate at a colored object placed
behind it, while at the same time light from another colored object, placed in
front of the glass, is reflected into the eye of the observer, as shown in Figure
239. Here the transmitted light from the colored object A and the reflected
light from the colored object B enter the eye at C from the same direction,
and are therefore united upon the retina.

3. By rotating before the eye a disk on which the colors to be united are

THE SENSE OF VISION. 781

painted upon different sectors. Tliis is most readily accomplislied by using
a number of disks, each painted with one of the colors to be experimented
with, and each divided radially by a cut running from the centre to the circum-
ference. The disks can then l)e lapped over each other and rotated together, and
in this way two or more colors can be mixed in any desired proportions. Tiiis
method of mixing colors depends upon
the property of the retina to retain an

impression after the stimulus causing /

it has ceased to act — a phenomenon of /

\
and one which will be further discussed /

great importance in physiological optics, y \

in connection with the subject of " after- / \

images." jj/ \^

The physiological mixing of colors Fig. 239.— Diagram to illustrate color mixture by

cannot be accomplished by the mixture '^^^''^^^ ^""^ transmitted light (Heimhoitz).
of pigments or by allowing sunlight to pass successively through glasses of
different colors, for in these cases rays corresponding to certain colors are
absorbed by the medium through which the white light passes, and the phe-
nomenon is the result of a process of subtraction and not addition. Light
reaching the eye through red glass, for instance, looks red because all the rays
except the red rays are absorbed, and light coming through green glass appears
green for a similar reason. Now, when light is allowed to pass successively
through red and green glass the only rays which pass through the red glass
wall be absorbed by the green. Hence no light will pass through the combi-
nation of red and green glass, and darkness results. But when red and green
rays are mixed by any of the three methods above described the result of this
process of addition is not darkness, but a yellow color, as will be understood
by reference to the color diagram on p. 780. In the case of colored pigments
similar phenomena occur, for here too light reaches the eye after rays of cer-
tain wave-lengths have been absorbed by the medium. This subject will be
further considered in connection with color-theories.

Color-theories. — From what has been said of color-mixtures it is evident
that every color sensation may be produced by the mixture of a number of
other color sensations, and that certain color sensations — viz. the purples — can
be produced only by the mixture of other sensations, since there is no single
wave-length corresponding to them. Hence the hypothesis is a natural one
that all colors are produced by the mixture in varying proportions of a certain
number of fundamental colors, each of which depends for its production upon
the presence in the retina of a certain substance capable of being affected
(probably through some sort of a photo-chemical process) by light of a certain
definite wave-length. A hypothesis of this sort lies at the basis of both the
Young-Helmholtz and the Hering theories of color sensation.

The former theory postulates the existence in the retina of three substances
capable of being affected by red, green, and violet rays, respectively — i. e. by
the three colors lying at the three angles of the color diagram given on p. 780

782 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

— and regards all other color sensations as pro<lucetl by the simultaneous affec-
tion of two of these substances in varying proportions. Thus when a rav of
blue light fall^^ on the retina it stimulates the violet- and green-perceiving suIh
stances, and produces a sensation intermediate between the two, while simul-
taneous stimulation of the red- and green-perceiving substances produces the
sensations corresponding to yellow and orange ; and when the violet- and red-
jierceiving substances are affected at the same time, the various shades of
purple are produced. Each of these three substances is, however, supposed to
be affected to a slight extent by all the rays of the visible spectrum, a supj)o-
sition which is rendered necessary by the fact that even the pure spectral
colors do not appear to be perfectly saturated, as will be explained in connec-
tion with the subject of saturation. Furthermore, the disappearance of color
when objects are very feebly or very brightly illuminated or when they are
seen with the lateral portions of the retina (as described on p. 770) necessitates
the additional hypotheses that these three substances are all equally affected by
all kinds of rays when the light is of either very small or v^ery great intensity
or when it falls on the extreme lateral portions of the retina, and that they
manifest their specific irritability for red, green, and violet rays respectively
only in light of moderate intensity falling not too far from the fovea centralis
of the retina.

The modifications of the Young-Hemholtz theory introduced by these sub-
sidiary hypotheses greatly diminish the simplicity which was its chief claim to
acceptance when originally proposed. Moreover, there will always remain a
psychological difficulty in supposing that three sensations so different from each
other as those of red, green, and violet can by their union produce a fourth
sensation absolutely distinct from any of them — viz. white.

The fact that in the Heriug theory this difficulty is obviated has contributed
greatly to its acceptance by physiologists. In this theory the retina is supposed
to contain three substances in which chemical changes may be produced by ether
vibrations, but each of these substances is supposed to be affected in two oppo-
site ways by rays of light which correspond to complementary color sensa-
tions. Thus in one substance — viz. the white-black visual substance — kata-
bolic or destructive changes are supposed to be producetl by all the rays of the
visible spectrum, the maximum effect being caused by the yellow rays, while
anabolic or constructive changes occur when no light at all falls upon the
retina. The chemical changes of this substance correspond, therefore, to the
sensation of luminosity as distinguished from color. In a second substance red
rays are supposed to produce katabolic, and green rays anabolic changes, while
a third substance is similarly affected by yellow and blue rays. These two
substances are therefore spoken of as red-green and yellow-blue visual sub-
stances re.spectively.

It has been sometimes urged as an objection to this theory that the effect of
a stimulus is usually katabolic and not anabolic. This is true with regard to
muscular contraction, from the study of which phenomenon most of our know-
ledge of the effect of stimulation has been obtained, but it should be remem-

THE SENSE OF VISION. 783

bered tliat observations on tlie auj^intMitor and inhibitory cardiac nerves have
shown ns that norve-stimnhition may produce very contrary effects. There
seems to be, therelbro, no serious theoretieal difficulty in su|)j>osing that light
rays oi'ditrcrent wave-lengths may produce opposite metabolic effects upon the
substances in which changes are associated with visual sensations.

A more serious objection lies in the difficulty of distinguishing between the
sensation of blackness, which, on Hering's hypothesis, must correspond to active
anabolism of the white-black substance, and the sensation of darkness (such as
we experience when the eyes have been withdrawn for some time from the
influence of light), which must correspond to a condition of equilibrium of
the white-black substance in which neither anabolism nor katabolism is
occurring.

Another objection to the Hering theory is to be found in the results of
experiments in comparing grays or whites produced by mixing different colored
rays under varying intensities of light. The explanation given by Hering of
the production of white through the mixture of blue and yellow or of red and
green is that when either of these pairs of complementary colors is mixed
the anabolic and the katabolic processes balance each other, leaving the corre-
sponding visual substance in a condition of equilibrium. Hence, the white-
black substance being alone stimulated, the result will be a sensation of white
corresponding to the intensity of the katabolic process caused by the mixed
rays. Now, it is found that when blue and yellow are mixed in certain pro-
portions on a revolving disk a white can be produced which will, with a certain
intensity of illumination, be undistinguishable from a white produced by mix-
ing red and green. If, however, the intensity of the illumination is changed,
it will be found necessary to add a certain amount of white to one of the mix-
tures in order to bring them to equality. On the theory that complementary
colors produce antagonistic processes in the retina it is difficult to understand
why this should be the case.

A color theory which is in some respects more in harmony with recent
observations in the physiology of vision has been proposed by Mrs. C. L.
Franklin. In this theory it is supposed that, in its earlier periods of de-
velopment, the eye is sensitive only to luminosity and not to color — i. e. it
possesses only a white-black or (to use a single word) a ^ra2/-perceiving sub-
stance which is affected by all visible light rays, but most powerfully by those
lying near the middle of the spectrum. The sensation of gray is supposed to
be dependent upon the chemical stimulation of the optic nerve-terminations by
some product of decomposition of this substance.-

In the course of development a portion of this gray visual substance becomes
differentiated into three different substances, each of which is affected by rays
of light corresponding to one of the three fundamental colors of the spectrum
— viz. red, green, and blue. AVhen a ray of light intermediate between two
of the fundamental colors falls upon the retina, the visual substances corre-
sponding to these two colors will be affected to a degree proportionate to the
proximity of these two colors to that of the incident ray^ Since this effect is

784 AN AMERICAN TEXT- HOOK OF PHYSIOLOGY.

exactly the satnc as tlmt which is produced when the retina is acted iij)()n siinnl-
taneoiislv by light of two fundamental colors, we are incapable of distinguish-
ing in sensation between an intermediate wave-length and a mixture in proper
amounts of two fundamental wave-lengths.

When the retina is ailccted by two or more rays of such wave-lengths that
all three of the color visual substances are equally aifected, the resulting decom-
position will be the same as that produced by the stimulation of tiie gray visual
substance out of which the color visual substances were differentiated, and the
corresponding sensation will therefore be that of gray or white.

It will be noticed that the important feature of this theory is that it pro-
vides for the independent existence of the gray visual substance, while at the
same time the stimulation of this substance is made a necessary result of the
mixture of certain color sensations.

Color-blindness. — The fact that many individuals are incapable of distin-
guishing between certain colors — i. e. are more or less '* color-blind " — is one
of fundamental importance in the discussion of theories of color vision. By
far the most common kind of color-blindness is that in which certain shades
of red and green are not recognized as different colors. The advocates of the
Young-Helmholtz theory explain such cases by supposing that either the red
or the green perceiving elements of the retina are deficient, or, if present, are
irritable, not by rays of a particular wave-length, but by all the rays of the
visible spectrum. In accordance with this view these cases of color-blindness
are divided into two classes — viz. the red-blind and the green-blind — the basis
for the classification being furnished by more or less characteristic curves repre-
senting the variations in the luminosity of the visible spectrum as it appears
to the diiferent eyes. There are, however, cases which cannot easily be brought
under either of these two classes. Moreover, it has been proved in cases of
monocular color-blindness, and is admitted even by the defenders of the Helm-
holtz theory, that such persons see really only two colors — viz. blue and yellow.
To such persons the red end of the spectrum appears a dark yellow, and the
green portion of the spectrum has luminosity without color.

A better explanation of this sort of color-blindness is given in the Hering
theory by simply supposing that in such eyes the red-green visual substance is
deficient or wholly wanting, but the theory of Mrs. Franklin accounts for the
phenomena in a still more satisfactory way ; for, by supposing that the differ-
entiation of the primary gray visual substance has first led to the formation
of a blue and a yellow visual substance, and that the latter has subsequently
been differentiated into a red and a green visual substance, color-blindness is
readily explained by supposing that this second differentiation has either not
occurred at all or has taken place in an imperfect manner. It is, in other
words, an arrest of development.

Cases of absolute color-blindness are said to occasionally occur. To such
persons nature is colorless, all objects presenting simply differences of light
and shade.

In whatever way- color-blindness is to be explained, the defect is one of

THE SENSE (>!■• VISION. ''^^

considerable ,,™ctical inM.u,-.a„..o, since it .cde,. t.,„se affected by it incapable
of distinguishing tl,e .vd and (.rcen lights ordinardy nscd lor signals, bnch
; ,tl L, .ho'r„.e, unsuitable Ibr e„.,,h,y,ncnt as pilote, ra, way c„gn,c*rs

te., and it is now eusl y to test the vision of all candidates for e,„pUo^ en^

in ueh situations. It has been found that no sat.slae ory results a be
reached bv re,niring persons to nan,e colors winch are «''-;/hcnr^ ml
ehrotua.ie'sen«. is now eomuKady tested by what .s known as the Holmg.en
n> ,od," which consists in requiring the individual examu.ed to se ect from a
pi rf borstals of various eolo,-s those shades which seem to h,m to resemble
S uhrd skeins of green and pink. When e.xandned n, tins way about 4 p^
I of the n.ale a.tl one-quar.er of 1 per cent, of the female sex are found to
Te mire or less color-blind. The defect may be inherited, and the relatives
rf rilor-blind person are therefore to be tested with spcc.al care S.nee
females are less Lble to be affectcl than n.ales, it often happen that the
toghters of a color-blind person, themselves with normal v.s,on, have sons
who inherit their grandfather's infirmity.

A hough in alltheories of color vision the diiferent sensat.ons are suppose!
to depend upon changes produced by the ether vibrations of varyn,g rates
litrupon 'different subLces in the retina, yet it should be borne m mnul
It we Lve at present no proof of the existence of any sneh -bs tanees The
visual pnrple-or, to adopt Mrs. Franklin's more appropriate te.m the rod
;r™er'-was a; one tiie thought to be such a substance, but for the reasons
above o-iven cannot be regarded as essential to vision. . » • , tu„

Th^t a centre for cote vision, distinct from the visual centre exists in the
cereb a eort x is rendered probable by the occurrence of cases of hemianopsia
Trttrand also by the Experiments of Heidenhain and Cohn on the inHu-
Mice of the hypnotic trance upon color-blindness.

/lUiThe second of the above-mentioned qualitative modifications of
Ugh"s'i„te„sity, which is dependent upon the energy of v^— ^ -
molecules of the luminiferons ether. The sensation of luminosity is not, how
Tvr proportionate to the intensity of the stimulus but varies in such aw y
hit a given inc-ema.t of intensity causes a greater difference ,„ -- ""J "^^
feeble fhan with strong illuminations. This phenomenon ,s illustrated by the
Sappea le of a sh^Tlow thrown by a candle in a darkened room on a she t
oTite paper when sunlight is allowed to fall on the paper from the opposite
drectit In this ease L absolute difference in lumiuos,^- between the
iiadov^ and unshadowed portions of the paper reman^ the same, but it
teeomes imperceptible in consequence of the increased total dlinninatron.

"hough our power of distinguishing cto^.* differences in huninosi y
dimin hes as the intensitv of the illumination increases, yet with regard to

substance in connection with other substances of a hypotlietual character.

50

786

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

it must be increased by a certain constant fraction of" its total amount in order
to produce a perceptible difference in sensation. This is only a special case of
a general law of sensation known as Weber's law, which has been formulated
by Foster as follows: "The smallest change in the magnitude of a stimulus
which we can a])preciate through a change in our sensation always bears the
same proportion to the whole magnitude of the stimulus."

Luminos'dy of Different Colors. — When two sources of light having the
same color are compared, it is possible to estimate their relative luminosity
with considerable accuracy, a difference of about 1 per cent, of the total
luminosity being appreciated by the eye. W^iien the sources of light have
different colors, much less accuracy is attainable, but there is still a great differ-
ence in the intensity with which rays of light of different wave-lengths affect
the retina. We do not hesitate to say, for instance, that the maximum
intensity of the solar spectrum is found in the yellow portion, but it is import-
ant to observe that the position of this maximum varies with the illumina-
tion. In a very brilliant spectrum the maximum shifts toward the orange,
and in a feeble spectrum (such as may be obtained by narrowing the slit of
the spectroscope) it moves toward the green. The curves in Figure 240 illus-

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Fig. 240.— Diagram showing the distribution of the intensity of the spectrum as dependent upon the

degree of illumination (Konig).

trate this shifting of the maximum of luminosity of the spectrum with vary-
ing inten.sities of illumination. The ab.scissas represent wave-lengths in
millionths of a millimeter, and the ordinates the luminosity of the different
colors as expressed by the reciprocal values of the width of the slit necessary
to give to the color under observation a luminosity equal to that of an arbi-

THE SENSE OF VISION. 787

trarily chosen standard. The curves from A to H represent tlie distribution
of the intensity of light in the spectrum witli eight different grades of ilhimi-
nation. This shifting of tiie maximum of himinosity in the spectrum
explains the so-called " Purkinje's ])henoraenon " — viz. the changing rela-
tive values of colors in varying illumination. This can be best observed
at nightfall, the attention being directed to a carpet or a wall-paper
the pattern of which is made up of a number of different colors. As
the daylight fades away the red colors, which in full illumination are
the most intense, become gradually darker, and are scarcely to be distin-
guished from black at a time when the blue colors are still very readily
distinguished.

Function of Bods and Cones. — The layer of rods and cones has thus far
been spoken of as if all its elements had one and the same function. There
is, however, some reason to suppose that the rods and cones have different
functions. That color sensation and accuracy of definition are most perfect
in the central portion of the retina is shown by the fact that when we desire
to obtain the best possible idea of the form and color of an object we direct
our eyes in such a way that the image falls upon the fovea centralis of the
retina. The luminosity of a faint object, however, seems greatest when we
look not directly at it, but a little to one side of it. This can be readily
observed when we look at a group of stars, as, for example, the Pleiades.
When the eyes are accurately directed to the stars so as to enable us to count
them, the total luminosity of the constellation appears much less than when
the eyes are directed to a point a few degrees to one side of the object. Now,
an examination of the retina shows only cones in the fovea centralis. In the
immediately adjacent parts a small number of rods are found mingled with
the cones. In the lateral portions of the retina the rods are relatively more
numerous than the cones, and in the extreme peripheral portions the rods alone
exist. Hence this phenomenon is readily explained on the supposition that
the rods are a comparatively rudimentary form of visual apparatus taking
cognizance of the existence of light with special reference to its varying
intensity, and that the cones are organs specially modified for the localization
of stimuli and for the perception of differences of wave-lengths. The view
that the rods are specially adapted for the perception of luminosity and the
cones for that of color derives support from the fact that in the retina of cer-
tain nocturnal animals — e. g. bats and owls — rods alone are present. This
theory has been further developed by Von Kries,^ who in a recent article
describes the rods as differing from the cones in the following respects : (1)
They are color-blind — i. e. they produce a sensation of simple luminosity
whatever be the wave-length of the light-ray falling on them ; (2) they are
more easily stimulated than the cones, and are particularly responsive to light-
waves of short wave-lengths ; (3) they have the power of adapting themselves
to light of varying intensity.

On this theory it is evident that we must get the sensation of white or
' Zeitschrifi fur Psychologie und Physiologie der Sinnesorgane, ix. 81.

788 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

colorless light in two different ways : (1) In consequence of the stimulation
of the rods by any sort of light-rays, and (2) in consequence of the stimula-
tion of the cones by certain combinations of light-rays — i. e. complementary
colors. In this double mode of white perception lies perhaps the explanation
of the effect of varying intensity of illumination upon the residts of color-
mixtures which has been above alluded to (see p. 783) as an objection to the
Hering theory. The so-called " Purkinje's phenomenon," described on p. 787,
is readily explained in accordance with this theory, for, owing to the greater
irritability of the rods, the importance of these organs, as compared with the
cones, in the production of the total visual sensation is greater with feeble
than with strong illumination of the field of vision. At the same time, the
power of the rods to respond particularly to light-rays of short wave-length
will cause a greater apparent intensity of the colors at the blue than at the red
end of the spectrum. In this connection it is interesting to note that the phe-
nomenon is said not to occur wlien the observation is limited to the fovea
centralis, where cones alone are found.^

Saturation. — The degree of saturation of light of a given color depends, as
above stated, upon the amount of white light mixed with it. The quality of
light thus designated is best studied and appreciated by means of experiments
with rotating disks. If, for instance, a disk consisting of a large white and a
small red sector be rapidly rotated, the effect produced is that of a pale pink
color. By gradually increasing the relative size of the red sector the pink
color becomes more and more saturated, and finally when the white sector is
reduced to zero the maximum of saturation is produced. It must be borne
in mind, however, that no pigments represent completely saturated colors.
Even the colors of the spectrum do not produce a sensation of absolute
saturation, for, whatever theory of color vision be adopted, it is evident that
all the color-perceiving elements of the retina are affected more or less by all
the rays of light. Thus when rays of red light fall upon the retina they will
stimulate not only the red-perceiving elements, but to a slight extent also (to
use the language of the Helmholtz theory) the green- and violet-perceiving
elements of the retina. The effect of this will be that of mixing a small
amount of white with a large amount of red light — /. e. it will produce the
sensation of incompletely saturated red light. This dilution of the sensation
can be avoided only by previously exhausting the blue- and green-perceiving
elements of the retina in a manner which will be explained in connection with
the phenomena of after-images.

Retinal Stimulation. — Whenever by a stimulus applied to an irritable
substance the potential energy there stored up is liberated the following phe-
nomena may be observed : 1. A so-called latent period of variable duration
during which no effects of stimulation are manifest ; 2. A very brief period
during which the effect of the stimulation reaches a maximum ; 3. A period
of continued stimulation during which the effect diminishes in consequence of
the using up of the substance containing the potential energy — i. e. a period
' Von Kries : Centralblalt Jiir Physiologic, 1896, i.

THE SENSE OF VISION. 789

of fatigue ; 4. A j)criod after tlie stimulation has ceased in which the effect
slowly passes away.

Fig. 241.— Diagram showing the effect of stimulation of an irritable substance.

The curve drawn by a muscle iu tetanic contraction, as shown in Figure

241, illustrates this phenomenon. Thus, MAD represents the duration of the
stimulation, A B indicates the latent period, B C the period of contraction,
C 1) the period of fatigue under stimulation, and D E the after-effect of
stinndation showing itself as a slow relaxation. When light falls upon the
retina corresponding phenomena are to be observed.

Latent Period. — That there is a period of latent sensation in the retina
{i. e. an interval between the falling of light on the retina and the beginning
of the sensation) is, judging from the analogy of other parts of the nervous
system, quite probable, though its existence has not been demonstrated.

Rise to Maximum of Sensation. — The rapidity with which the sensation of
light reaches its maximum increases with the intensity of the light and varies
with its color, red light producing its maximum sensation sooner than green
and blue. Consequently, when the image of a white object is moved across
the retina it will appear bordered by colored fringes, since the various con-
stituents of white light do not produce their maximum effects at the same
time. This phenomena can be readily observed when a disk on which a
black and a white spiral band alternate with each other (as shown in Figure

242, A) is rotated before the eyes. The white band as its image moves out-

A B

Fig. 242.— Disks to illustrate the varying rate at which colors rise to their maximum of sensation.

ward or inward over the retinal surface appears bordered with colors which
vary with the rate of rotation of the disk and with the amount of exhaustion
of the retina. Chromatic effects due to a similar cause are also to be seen
when a disk, such as is shown in Figure 242, B (known as Benham's spectrum

790 AX AMEIUCAX TEXT-BOOK 01 J'JI YSJOLOG Y.

top), is rotated with moderate rapidity. The eoncentric bands of color appear
in reverse order Aviien the direction of rotation is reversetl. The ap])arent
movement of colored figures on a background of a different color when the
eve moves rapidly over the object or the object is moved rapidly bef<jre the
eve seems to depend upon this same retinal peculiarity. The phenomenon
mav be best observed when small pieces of bright-red paper are fastened u|X)n
a bright-blue sheet and the sheet gently shaken i>efore the eyes. The red
figures will appear to move upon the blue background. The effect may be
best observed in a dimly-lighted room.

In this connection should be mentioned the phenomenon of " recurrent
images" or " oscillatory activity of the retina." ^ This may be best observed
when a black disk containing a white sector is rotated at a rate of about one
revolution in two seconds. If the disk is brightly illuminated, as by sunlight,

and the eye fixed steadily upon the axis of rota-
tion, the moving white sec-tor seems to have a
shadow upon it a short distance behind its ad-
vancing border, and this shadow may be fijllowed
by a second fainter, and even by a third still
fainter shadow, as shown in Figure 243. The
distance of the shadows from each other and
from the edge of the sector increases with the rate
of rotation of the disk and corresponds to a time
Fig. 243.-TO illustrate the oscniatorj- interval of about 0.015". It thus appears that

activity of the retina (Charpentier). ,. , . ii i i

when light is suddenly thrown upon the retina
the sensation does not at once rise to its maximum, but reaches this point by
a sort of vibratory movement. The apparent duplication of a single very
brief retinal stimulation, as that caused by a flash of lightning, may perhaps
be a phenomenon of the same sort.

Fatigue of Hetina. — When the eye rests steadily upon a uniformly illu-
minated white surface (e.g. a sheet of white paper), we are usually unconscious
of any diminution in the intensity of the sensation, but it can be shown that
the longer we look at the paper the less brilliant it appears, or, in other words,
that the retina really becomes fatigued. To do this it is only necessary to place
a disk of black paper on the white surface and to keep the eyes steadily fixed
for about half a minute upon the centre of the disk. Upon removing the disk
without changing the direction of the eyes a round spot will be seen on the
white paper in the place previously occupied by the disk. On this spot the
whiteness of the paper will appear much more intense than on the neighboring
portion of the sheet, because we are able in this experiment to bring into direct
contrast the sensations produced by a given amount of light upon a fresh and
a fatigued portion of the retina.^

* Charpentier: Archives de Physiologie, 1892, pp. .541, 629; and 1896, p. 677.

^ Although the retina is here spoken of as the pf)rtion of tlie visual apparatus subject to
fatigue, it should Ije borne in mind that we cannot, in the present state of our knowledge, dis-
criminate between retinal fatigue and exhaustion of the visual nerve-centres.

THE SENSK OF VISION. 791

The rapidity with which the retina becomes fatiirued varies witli the color
of the liglit. Hence when intense white light falls upon the retina, as when
we look at the setting sun, its disk seems to undergo changes of color as one
or another of the constituents of its light becomes, through fatigue, less and
less conspicuous in the combination of rays whi(-h produces the sensation of
white.

Tlie After-effect of Stimulalion. — The persistence of the sensation after the
stimulus has ceased causes very brief illuminations (e. g. by an electric spark) to
produce distinct effects. On this phenomenon depends also the above-described
method of mixing colors on a revolving disk, since a second color is thrown
upon the retina before the impression produced by the first color has had time
enough to become sensibly diminished. The interval at which successive stim-
ulations must follow each other in order to pro-
duce a uniform sensation (a process analogous
to the tetanic stimulation of a muscle) may be
determined by rotating a disk, such as repre-
sented in Figure 244, and ascertaining at what
speed the various rings produce a uniform sen-
sation of gray. The interval varies with the
intensity of the illumination from 0.1" to
0.033". The duration of the after-effect de-
pends also upon the length of the stimulation
and upon the color of the light prodqcing it,
the most persistent effect being prodnced by the ''-^-fi^J^rS'CmSr"
red rays. In this connection it is interesting to

note that while with the rapidly vibrating blue rays a less intense illumination
suffices to stimulate the eye, the slowly vibrating red rays produce the more
permanent impression.

After-images. — When the object looked at is very brightly illuminated the
impression upon the retina may be so persistent that the form and color of the
object are distinctly visible for a considerable time after the stimulus has ceased
to act. This appearance is known as a " positive after-image," and can be best
observed when we close the eyes after looking at the sun or other bright source
of light. Under these circumstances we perceive a brilliant spot of light which,
owing to the above-mentioned difference in the persistence of the impressions
produced by the various colored rays, rapidly changes its color, passing gen-
erally through bluish green, blue, violet, purple, and red, and then disappear-
ing. This phenomenon is apt to be associated with or followed by another
effect known as a " negative after-image." This form of after-image is much
more readily observed than the ])ositive variety, and seems to depend upon the
fatigue of the retina. It is distinguished from the positive after-image by the
fact that its color is always complementary to that of the object causing it. In
the experiment to demonstrate the fatigue of the retina, described on p. 790,
the white spot which appears after the black disk is withdrawn is the " nega-
tive after-image" of the disk, white being complementary to black. If a

792 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

colored disk be placed upon a sheet of white paper, hioketl at attentively for a
few seconds, and then withdrawn, the eye will perceive in its place a spot of
light of a color complementary to that of the disk. If, for example, the disk
be vellow, the vellow-perceiving elements of the retina become fatigued in
looking at it. Therefore when the mixed rays constituting white light are
thrown upon the portion of the retina which is thus fatigued, those rays which
produce the sensation of yellow will produce less effect than the other rays for
which the eye has not been fatigued. Hence white light to an eye fatigued for
yellow will appear blue.

If the experiment be made with a yellow disk resting on a sheet of blue
paper, the negative after-image will be a spot on which the blue color will
appear (1) more intense than on the neighboring portions of the sheet, owing
to the blue-perceiving elements of that portion of the retina not being fatigued ;
(2) more saturated, owing to the yellow-perceiving elements being so far
exhausted that they no longer respond to the slight stimulation which is pro-
duced when light of a complementary color is thrown upon them, as has been
explained in connection with the subject of saturation.

Contrast. — As the eye wanders from one part of the field of vision to
another it is evident that the sensation produced by a given portion of the
field will be modified by the amount of fatigue produced by that portion on
which the eye has last rested, or, other w'ords, the sensation will be the result

Fig. 245.— To illustrate the phenomenon of contrast.

of the stimulation by the object looked at combined with the negative after-
image of the object previously observed. The effect of this combination is to
produce the phenomenon of successive contrast, the ])rinciple of which may be
thus stated : Every part of the field of vision appears lighter near a darker

THE SENSE OF VISION. 793

part and darker near a lighter part, and its color seen near another color
approaches the complementary color of the latter. A contrast phenomenon
similar in its effects to that above described may be produced under conditions
in which negative after-images can play no part. This kind of contrast is
known as simnltaneous contrast, and may perhaps be explained on the theory
that a stimulation of a given portion of the retina produces in the neighboring
portions an effect to some extent antagonistic to that caused by direct stimulation.
A good illustration of the phenomenon of contrast is given in Figure 245,
in which black squares are separated by white bands which at their points of
intersection appear darker than where they are bordered on either side by the
black squares.

A black disk on a yellow background seen through white tissue-paper
appears blue, since the white paper makes the black disk look gray and the
yellow background pale yellow. The gray disk in contrast to the pale yellow
around it appears blue.

The phenomenon of colored shadows also illustrates the principle of con-
trast. These may be observed whenever an object of suitable size and shape
is placed upon a sheet of white paper and illuminated from one direction by
daylight and from another by gaslight. Two shadows will be produced, one
of which will appear yellow, since it is illuminated only by the yellowish gas-
light, while the other, though illuminated by the white light of day, will
appear blue in contrast to the yellowish light around it.

Space-perception. — Rays of light proceeding from every point in the
field of vision are refracted to and stimulate a definite point on the sur-
face of the retina, thus furnishing us with a local sign by which we can
recognize the position of the point from which the light proceeds.
Hence the size and shape of an optical image upon the retina enable us to
judge of the size of the corresponding object in the same way that the cutane-
ous terminations of the nerves of touch enable us to judge of the size and
shape of an object brought in contact with the skin. This spatial perception
is materially aided by the muscular sense of the muscles moving the eyeball,
for we can obtain a much more accurate idea of the size of an object if
we let the eye rest in succession upon its different parts than if we gaze fixedly
at a given point upon its surface. The conscious effort associated with a given
amount of muscular motion gives, in the case of the eye, a measure of distance
similar to that secured by the hand when we move the fingers over the surface
of an object to obtain an idea of its size and shape.

The perception of space by the retina is limited to space in two dimensions
— i. e. in a plane perpendicular to the axis of vision. Of the third dimension
in space — i. e. of distance from the eye — the retinal image gives us no know-
ledge, as may be proved by the study of after-images. If an after-image of
any bright object — e. g. a window — be produced upon the retina in the man-
ner above described and the eye be then directed to a sheet of paper held in
the hand, the object will appear outlined in miniature upon the surface of the
paper. If, however, the eye be directed to the ceiling of the room, the object

794 AX AMERICAN IKXT-BOOK OF PHYSIOLOGY.

will appear enlarged and at a distance corresponding to that of the surface
looked at. Hence one and the same retinal image may, under tlitferent cir-
cumstances, o-ive rise to the impression of objects at different distances. We
must therefore regard the jierception of distance not as a direct datum of vision,
but, as will be later explained, a matter of visual judgment.

When objects are of such a shape that their images may be thrown suc-
cessively upon the same part of the retina, it is possible to judge of their rela-
tive size with considerable accuracy, the retinal surface serving as a scale to
which the images are successively applied. When this is not the case, the
error of judgment is much greater. We can compare, for instance, the relative
length of two vertical or of two horizontal lines with a good deal of precision,
but in comparing a vertical with a horizontal line we are liable to make a con-
siderable error. Thus it is difficult to realize that the vertical and the hori-
zontal lines in Figure 246 are of the same length. The error consists in an

over-estimation of the length of the vertical
lines relatively to horizontal ones, and appears to
depend, in part at any rate, upon the small size
of the superior rectus muscle relatively to the
other muscles of the eye. The difference amounts
to 30-45 per cent, in weight and 40-53 per cent,
in area of cross section. It is evident, therefore,
that a given motion of the eye in the upward
direction will require a more powerful contraction
of the weaker muscle concerned in the movement

Fig. 246.— To illustrate the over-esti- than will be demanded of the stronger muscles

mation of vertical lines. . , i ^ ii . i a

moving the eye laterally to an equal amount.
Hence we judge the upward motion of the eye to be greater because to accom-
plish it we make a greater effort than is required
for a horizontal movement of equal extent.

The position of the vertical line bisecting the
horizontal one (in Fig. 246) aids the illusion, as
may be seen by turning the page through 90°, so
as to bring the bisected line into a vertical posi-
tion, or by looking at the lines in Figure 247, in
which the illusion is much less marked than in
Figure 246.

The tendency to over-estimate the length of

vertical lines is also illustrated by the error

commonly made in supposing the height of the

crown of an ordinarv silk hat to be greater ~ ~"

" Fi<i. '247.— To illustrate the over-estima-

than its breadth. tion of vertical lines.

Irradiation. — Many other circumstances
affect the accuracy of the spatial perception of the retina. One of the most
important of these is the intensity of the illumination. All brilliantly illumi-
nated objects appear larger than feebly illuminated ones of the same size, as is

THE SENSE OF VISION. 795

well shown by the ordinary incandescent electric lamp, the delicate filament of
which is scarcely visible when cold, but when intensely heated by the electric
current glows as a broad band of light. The phenomenon is known as " irra-
diation," and seems to depend chiefly upon the above-described imperfections
in the dioptric apparatus of the eye, in consequence of which points of light
produce small circles of dispersion on the retina and bright objects produce

Fig. 248.— To illustrate the phenomenon of irradiation.

images with imperfectly defined outlines. The white square surrounded by
black and the black square surrounded by white (Figure 248), being of the
same size, would in an ideally perfect eye produce images of the same size on
the retina, but owing to the imperfections of the eye the images are not sharply

Fig. 249.— To illustrate the phenomenon of irradiation.

defined, and the white surfaces consequently appear to encroach upon the darker
portions of the field of vision. Hence the white square looks larger than the
black one, the difference in the apparent size depending upon the intensity of
the illumination and upon the accuracy with which the eye can be accommo-

796

A^' AMERICAN TEXT-BOOK OF PHYSIOLOGY .

dated for tlio distance at which tlie ubjects are viewed. The ellect of irradi-
ation is most manifest when the dark portion of the field of vision over which
the irradiation takes phice lias a considerable breadth. Thus the circidar white
spots in Figure 249, when viewed from a distance of three or four meters,
appear hexagonal, since the irradiation is most marked into the triangular dark
space between three adjacent circles. A familiar example of the effect of irra-
diation is afforded by the a])poarance of the new moon, whose sun-illuminated
crescent seems to be part of a much larger circle than the remainder of tiie
disk, which shines only by the light reflected upon it from the surface of the
earth.

Subdivided Space. — A space subdivided into smaller portions by inter-
mediate objects seems more extensive than a space of the same size not so sub-
divided. Thus the distance from Aio B (Fig. 250) seems longer than that from

D E

Fig. 250.— To illustrate the illusion of subdivided space.

B to C, though both are of the same length, and for the same reason the square
D seems higher than it is broad, and the .square E broader than it is high, the
illusion being more marked in the case of D than in the case of E, because, as
above explained, vertical distances are, as a rule, over-estimated.

The explanation of this illasion .seems to be that the eye in passing over a
subdivided line or area recognizes the number and size of the subdivision.s,
and thus gets an impression of greater total size than when no subdivisions
are present.

A good example of this phenomenon is afforded by the apparently increased
extent of a meadow when the grass growing on it is cut and arranged in hay-
cocks.^

The relations of lines to each other gives rise to numerous illusions of
spatial perception, among the mo.st striking of which are those afforded by the
so-called " Zollner's lines," an example of which is given in Figure 251. Here

^ It is interesting to note tliat a similar illusion has been observed when an interval of time
subdivided by audible signals is compared with an equal interval not so subdivided (Hall and
Jastrow : Mind, xi. 62).

THE SENSE OF VISION. 797

the horizontal lines, though strictly parallel to each other, seem to diverge and
converge alternately, their apparent direction being changed toward greater per-

///////

///////////

Fig. 251.— ZoUner's lines.

pendicularity to the short oblique lines crossing them. This illusion is to be ex-
plained in part by the tendency of the eye to over-estimate the size of acute and to
under-estimate that of obtuse angles — a tendency which
also affords a partial explanation of the illusion in
Figure 252, where the line d is the real and the line/
the apparent continuation of the line a. The illusion
in Zollner's figures is more marked when the figure is
so held that the long parallel lines make an angle of
about 45° with the horizon, since in this position the
eye appreciates their real position less accurately than
when they are vertical or horizontal. It is dimin-
ished, but does not disappear, when the eye, instead
of being allowed to wander over the figure, is fixed

upon any one point of the field of vision. Hence the ^^^ ^^^ _^^ _^^^^^^^^^ .^^^^.^^
motions of the eye must be regarded as a factor in, but of space-perception.

not the sole cause of, the illusion.

Our estimate of the size of given lines, angles, and areas is influenced by
neighboring lines, angles, and areas with which they are compared. This
influence is sometimes exerted in accordance with the principle of contrast,
and tends to make a given extension appear larger in presence of a smaller.

Fig. 253.— To illustrate contrast in space-perception (Miiller-Lyer).

and smaller in presence of a larger extension. This effect is illustrated in
Figure 253, in which the middle portion of the shorter line appears larger
than the corresponding portion of the longer line, in Figure 254, in which a
similar effect is observed in the case of angles, and in Figure 255, in which

798 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the space between the two squares seems smaller than that between the two
oblong figures.

In some case, however, an influence of the opposite sort' seems to be

Fig. 254.— To illustrate contrast in space-perception (Miiller-Lyer).

exerted, as is shown in Figure 256, in which the middle one of three parallel
lines seems longer when the outside lines are longer, and shorter when they
are shorter than it is itself, and in Figure 257, where a circle appears larger

Fig. 255.— To illustrate contrast in space-perception (Miiller-Lyer).

if surrounded by a circle larger than itself, and smaller if a smaller circle is
shown concentrically within it.

Lines meeting at an angle appear longer when the included angle is large

Fig. 256.— To illustrate so-called " confluxion " in space-perception (Miiller-Lyer).

than when it is small, as is shown in Figure 258. This influence of the
included angle aflx)rds a partial explanation of the illusion shown in Figure
259, where the horizontal line at B seems longer than at A ; but the distance

^ For this influence the name "confluxion" has been proposed by Miiller-Lyer, from whose
article in the Archivfiir Phyaiologie, 1889, Sup. Bd., the above examples are taken.

THE SENSE OF VISION.

799

between the extremities of the oblique lines seems also to aifect our estimate
of the horizontal line in the same way as the outside lines in Figure 256
influence our judiruKMit of the length of the line between them.

Perception of Distance. — The retinal image gives us, as we have seen,
no direct infornintion as to the distance of the object from the eye. This

Fig. 257.— To illustrate so-called " confluxion " in space-perception (Muller-Lyer).

knowledge is, however, quite as important as that of position in a plane per-
pendicular to the line of vision, and we must now consider in what way it is
obtained. The first fact to be noted is that there is a close connection between
the judgments of distance and of actual size. A retinal image of a given
size may be produced by a small object near the eye or by a large one at a

Fig. 258.— To illustrate the influence of angles upon the apparent length of lines (Muller-Lyer).

distance from it. Hence when we know the actual size of any object (as, for
example, a human figure) we judge of its distance by the size of its image on
the retina. Conversely, our estimate of the actual size of an object will
depend upon our judgment of its distance. The fact that children constantly
misjudge both the size and distance of objects shows that the knowledge of

Fig. 259.— Illusion of space-perception.

US

this relation is acquired only by experience. If circumstances mislead
with regard to the distance of an object, we necessarily make a corresponding
error with regard to its size. Thus, objects seen indistinctly, as through a fog,
are judged to be larger, because we suppose them to be farther off, than they
really are. The familiar fact that the moon seems to be larger when near the
horizon than when near the zenith is also an illustration of this form of illu-

800 ^^V AMERICAN TEXT-BOOK OF PHY'SIOLOGY.

sion. When the moon is higli above our heads we have no means of esti-
mating its distance from us, since there are no intervening objects with which
we can compare it. Hence we judge it to be nearer than when, seen on the
horizon, it is obviously farther oif than all terrestrial objects. Since the size
of the retinal image of the moon is the same in the two cases, we reconcile
the sensation with its appaient greater distance when seen on the horizon by
attributing to the moon in this position a greater actual size.

If the retinal image have the form of a familiar object of regular siiape —
e. r/. a house or a table — we interpret its outlines in the light of experience
and distinguish without difficulty between the nearer and more remote parts of
the object. Even the projection of the outlines of such an object on to a plane
surface (/. e. a perspective drawing) suggests the real relations of the different
parts of the picture so strongly that we recognize at once the relative distances
of the various portions of the object represented. How powerfully a familiar
outline can susrirest the form and relief usuallv associated with it is well illus-
trated by the experiment of looking into a mask painted on its interior to
resemble a human face. In this case the familiar outlines of a human face
are brought into unfamiliar association with a receding instead of a projecting
form, but the ordinary association of these outlines is strong enough to force
the eye to see the hollow mask as a projecting face.* The fact that the pro-
jecting portions of an object are usually more brightly illuminated than the
receding or depressed portions is of great assistance in determining their rela-
tive distance. This use of shadows as an aid to the perception of relief pre-
supposes a knowledge of the direction from which the light falls on an object,
and if we are deceived on the latter we draw erroneous conclusions with
regard to the former point. Thus, if we look at an embossed letter or figure
through a lens which makes it appear inverted the accompanying reversal of
the shadows will cause the letter to appear depressed. The influence of
shadows on our judgment of relief is, however, not so strong as that of the
outline of a iamiliar object. In a case of conflicting testimony the latter
usually prevails, as, for example, in the above-mentioned experiment with the
mask.

Aided by these peculiarities of the retinal picture, the mind interprets it as
corresponding in its different parts to points at different distances from the eye,
and it is interesting to notice that painters, whose work, being on a plane sur-
face, is necessarily in all its parts at the same distance from the eye, use similar
devices in order to give depth to their pictures. Distant hills are painted with
indistinct outlines to secure what is called " aerial perspective." Figures of
men and animals are introduced in appropriate dimensions to suggest the dis-
tance between the foreground and the background of the picture. Landscapes
are painted preferably by morning and evening light, since at these liours the
marked shadows aid materially in the suggestion of distance.

^ In the experiment the mask should be placed at a distance of about two meters and one
eye closed. Even with both eyes open the illusion often persists if the distance is increased to
five or six meters.

THE SENSE OE VISION. 801

The eve, however, can aid itself in the perception of depth in ways which
the painter has not at his disposal. By the sense of effort associated with the
act of accommodation we are able to estimate roughly the relative distance of
objects before us. This aid to our judg!;ment can, of course, be employed only
in the case of objects comparatively near the eye. Its effectiveness is greater
for objects not far from the near-point of vision, and diminishes rapidly as the
distance is increased, and disappears for distances more than two or three meters
from the eye.

When the head is moved from side to side an apparent change in the rela-
tive position of objects at different distances is produced, and, as the extent of
this change is inversely proportional to the distance of the objects, it serv^es as
a measure of distance. This method of obtaining the "parallax" of objects
by a motion of the head is often noticeable in persons whose vision in one
eye is absent or defective.

Binocular Vision. — The same result which is secured by the comparison
of retinal images seen successively from slightly different points of view is
obtained by the comparison of the images formed simultaneously by any object
in the two eyes. In binocular vision we obtain a much more accurate idea of
the shape and distance of objects around us than is possible with monocular
vision, as may be proved by trying to touch objects in our neighborhood with
a crooked stick, first with both eyes open and then with one eye shut. When-
ever we look at a near solid object with two eyes, the right eye sees farther
round the object on the right side and the left eye farther round on the left.
The mental comparison of these two slightly different images produces the
perception of solidity or depth, since experience has taught us that those objects
only which have depth or solidity can affect the eyes in this way. Conversely,
if two drawings or photographs differing from each other in the same way that
the two retinal images of a solid object differ from each other are presented,
one to the right and the other to the left eye, the two images will become
blended in the mind and the perception of solidity will result. Upon this fact
depends the effect of the instrument known as the stereoscope, the slides of
which are generally pairs of photographs of natural objects taken simultaneous-

FiG. 260.— To illustrate stereoscopic vision.

ly with a double camera, of which the lenses are at a distance from each other
equal to or slightly exceeding that between the two axes of vision. The prin-
ciple of the stereoscope can be illustrated in a very .simple manner by drawing
circles such as are represented in Figure 260 on thin paper, and fastening each

51

802

^iV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

pair across the end of a piece of brass tube about one inch or more in diameter
and ten inches long. Let the tubes be held one in front of each eye with the
distant ends nearly in contact with each other, as shown in Figure 261. If
the tubes are in such a position that the small circles are brought as near to
each other as possible, as shown in Figure 260, the retinal images will blend,

the smaller circle will seem to be much
nearer than the larger one, and the eyes will
appear to be looking down upon a truncated
cone, such as is shown in Figure 262, since
a solid body of this form is the only one

Fig. 261. — To illustrate stereoscopic vision.

Fig. 262.— To illustrate stereoscopic vision.

bounded by circles related to each other as those shown in this experiment.

Stereoscopic slides often serve well to illustrate the superiority of binocular
over monocular vision. If the slide represents an irregular mass of rocks or
ice, it is often very difficult by looking at either of the pictures by it.self to
detei-mine the relative distance of the various objects represented, but if the
slide is placed in the stereoscope the true relation of the different parts of the
picture becomes at once apparent.

Since the comparison of two slightly dissimilar images received on the two
retinas is the essential condition of stereoscopic vision, it is evident that if the
two pictures are identical no sensation of relief can be produced. Thus, when
two pages printed from the same type or two engravings printed from the same
plate are united in a stereoscope, the combined picture appears as flat as either
of its components. If, however, one of the pictures is copied from the other,
even if the copy be carefully executed, there will be slight differences in the
distances between the lines or in the spacing of the letters which will cause
apparent irregularities of level in the different portions of the combined pic-
ture. Thus, a suspected banknote may be proved to be a counterfeit if, when
placed in a stereoscope by the side of a genuine note, the resulting combined
picture shows certain letters lying apparently on different planes from the rest.

Pseudoscopic Vision. — If the pictures of an ordinary stereoscopic slide be
reversed, so that tiie picture belonging in front of the right eye is presented to
the left eye, and ince versd, the stereoscopic gives place to what is called a pseudo-
scopic effect — i. e. we perceive not a solid but a hollow body. The effect is best

THE SENSE OF VISION. 803

obtained with the outlines of geometrical solids, photographs of coins or medals
or of objects which may readily exist in an inverted form. Where the photo-
graphs represent objects which cannot be thus inverted, such as buildings and
landscapes, the pseudoscopic effect is not readily produced — another example
of the power (see p. 800) of the outline of a familiar object to outweigh other
sorts of testimony.

A pseudoscopic effect may be readily obtained without the use of a stereo-
scope by simply converging the visual axes so that the right eye looks at the
left and the left eye at the right picture of a stereoscopic slide. The eyes mav
be aided in assuming the right degree of convergence by looking at a small
object like the head of a pin held between the eyes and the slide in the manner
described on p. 758. Figure 260, viewed in this way, will present the appear-
ance of a hollow truncated cone with the base turned toward the observer. A
stereoscopic slide with its pictures reversed will, of course, when viewed in this
way, present not a pseudoscopic, but a true stereoscopic, appearance, as shown
by Figures 226 and 227.

Binocular Combination of Colors. — The effect of binocnlarly combin-
ing two different colors varies Avith the difference in wave-length of the colors.
Colors lying near each other in the spectrum will generally blend together
and produce the sensation of a mixed color, such as would result from the
union of colors by means of the revolving disk or by the method of reflected
and transmitted light, as above described. Thus a red and a yellow disk
placed in a stereoscope may be generally combined to produce the sensation
of orange. If, however, the colors are complementary to each other, as blue
and yellow, no such mixing occurs, but the field of vision seems to be occupied
alternately by a blue and by a yellow color. This so-called " rivalry of the
fields of vision " seems to depend, to a certain extent, upon the fact that in
order to see the different colors with equal distinctness the eyes must be dif-
ferently accommodated, for it is found that if the colors are placed at different
distances from the eyes (the colors with the less refrangible rays being at the
greater distance), the rivalry tends to disappear and the mixed color is more
easily produced.

An interesting effect of the stereoscopic combination of a black and a
white object is the production of the appearance of a metallic lustre or polish.
If, for instance, the two pictures of a stereoscopic slide represent the slightly
different outlines of a geometrical solid, one in black upon white ground and
the other in white upon black ground, their combination in the stereoscope
will produce the effect of a solid body having a smooth lustrous surface.
The explanation of this effect is to be found in the fact that a polished surface
reflects the light differently to the two eyes, a given point appearing bril-
liantly illuminated to one eye and dark to the other. Hence the stereoscopic
combination of black and white is interpreted as indicating a polished surface,
since it is by means of a polished surface that this effect is usually produced.

Corresponding- Points. — When the visual axes of both eyes are directed
to the same object two distinct images of that object are formed upon widely

804 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

separated parts of the nervous system. Yet but a sinfjle object is perceived.
The phencnnenon is the same as that which occurs when a grain of sand is
held between the thuiiil) and finger. In both cases we have learned (chiefly
through the agency of muscular movements and the nerves of muscular sense)
to interpret the double sensation as produced by a single object.

Any two points, lying one in each retina, the stimulation of which by rays
of light gives rise to the sensation of light proceeding from a single object are
said to be " corresponding points." Now, it is evident that ih^fovece centrnleft
of the two eyes must be corresponding points, for an object always appears
single when both eyes are fixed upon it. That double vision results when the
images are formed on points which are not corresponding may be best illus-
trate<:l by looking at three pins stuck in a straight rod at distances of 35, 45,
and 55 centimeters from the end. If the end of the rod is held against the
nose and the eyes directed to each of the three pins in succession, it will be
found that, while the pin looked at appears single, each of the others appears
double, and that the three pins therefore look like five.

The two fovece centrales are not, of course, the only corresponding points.
In fact, it may be said that the two retinas correspond to each other, point for
point, almost as if they were superposed one upon the other with the foveae
together. The exact position of the points in space which are projected on to
corresponding points of the two retinas varies with the position of the eyes.
The line or surface in which such points lie is known as the " horopter." A
full discussion of the horopter would be out of place in this connection, but
one interesting result of its study may be pointed out — viz. the demonstration
that when, standing upright, we direct our eyes to the horizon the horopter is
approximately a plane coinciding with the ground on which we stand. It is
of course important for security in walking that all objects on the ground
should appear single, and, as they are known by experience to be single, the
eye has apparently learned to see them so.

Since the vertical meridians of the two eyes represent approximately rows
of corresponding points, it is evident that when two lines are so situated that
their images are formed each upon a vertical meridian of one of the eyes, the
impression of a single vertical line will be produced, for such a line seen bin-
ocularly is the most frequent cause of this sort of retinal stimulation. This
is the explanation commonly given of the singular optical illusion which is
produced when lines drawn as in Figure 263 are looked at with both eyes fixed
upon the })oint of intersection of the lines and with the plane in which the
visual axes lie forming an angle of about 20° with that of the paper, the dis-
tance of the lines from the eyes being such that each line will lie approximately
in the same vertical plane with one of the visual axes. Under these circum-
stances each line will form its image on a vertical meridian of one of the eyes,
and the combination of these images results in the perception of a third line,
not lying in the plane of the paper, but apparently passing through it more or
less vertically, and swinging round its middle point with every movement of
the head or the paper. In this experiment it will be found that the illusion

THE SENSE OF VISION.

805

of a lino placed vertically to the plane of the paper does not entirely dis-
appear when one eye is closed. Hence it is evident that there is, as Mrs,

Fig. 264.— Monocular illusion of vertical lines.

C. L. Franklin has pointed out,^ a strong tendency to regard
lines which form their images approximately on the vertical
meridian of the eye as themselves vertical. This tendency
is well shown when a number of short lines converging
toward a point outside of the paper on which they are
drawn, as in Figure 264, are looked at with one eye held
a short distance above the point of convergence. Even
when the lines are not convergent, but parallel, so that their
images cannot fall upon the vertical meridian of the eye, the
illusion is not entirely lost. It will be found, for instance,
that when the Zollner lines, as given in Figure 251, are
looked at obliquely with one eye from one corner of the
figure, the short lines which lie nearly in a plane with the
visual axis appear to stand vertically to the plane of the
paper.
In this connection it may be well to allude to the optical illusion in conse-
quence of which certain portraits seem to follow the beholder with the eyes.
This depends upon the fact that the face is painted looking straight out from
the canvas —i. e. with the pupil in the middle of the eye. The painting being
upon a flat surface, it is evident that, from whatever direction the picture is
viewed, the pupil will always seem to be in the middle of the eye, and the
eye will consequently appear to be directed upon the observer. The phenom-
enon is still more striking in the case of pictures of which the one repre-
sented in Figure 265 may be taken as an example. Here the soldier's rifle

' Am. Journal of Psychology, vol. i. p. 99.

Fig. 263,— Binocu
Jar illusion of a ver
tical line.

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AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 265.— Illusion of lines always pointing
toward observer.

is dnnvn as it appears to an eye looking straight down tlie barrel, ami, as this
foreshortening is the same in all positions of the observer, it is evident that

when such a picture is hung upon tlie wall
of a room tlie .'^oldier will appear to be
aiming directly at tlie head of every person
present.

In concluding this brief survey of some
of the most important subjects connected
with the physiology of vision it is well to
utter a word of caution with regard to a
danger connected with the study of the sub-
ject. This danger arises in part from the
fact that in the scientific study of vision it
is often necessary to use the eyes in a way
quite different from that in which they are
habitually employed, and more likely, there-
fore, to cause nervous and muscular fatigue.
We have seen that in any given position of
the eye distinct definition is limited to an
area which bears a very small proportion to
the whole field of vision. Hence in order to obtain an accurate idea of the
appearance of any large object our eyes must wander rapidly over its whole
surface, and we use our eyes so instinctively and unconsciously in this way
that, unless our attention is specially directed to the subject, we find it diffi-
cult to believe that the power of distinct vision is limited to such a small
portion of the retina. In most of the experiments in physiological optics,
however, this rapid change of direction of the axis of vision must be carefully
avoided, and the eye-muscles held immovable in tonic contraction.

Our eyes, moreover, like most of our organs, serve us best when we do not
pay too much attention to the mechanism by which their results are brought
about. In the ordinary use of the eyes we are accustomed to neglect after-
images, intraocular images, and all the other imperfections of our visual appa-
ratus, and the usefulness of our eyes depends very much upon our ability thus
to neglect their defects. Now, the habit of observing and examining these
defects that is involved in the scientific study of the eye is found to interfere
with our ability to disregard them. A student of the physiology of vision
who devotes too much attention to the study of after-images, for instance, may
render his eyes so sensitive to these phenomena that they become a decided
obstacle to ordinary vision.

THE SENSE OF HEARING.

807

B. The Ear and Hearing.
Anatomy and Histology of the Ear.— The organ of hearing may con-
veuiently be divided into three parts : (1) The external ear, including the
pinna or auride and the external auditory meatus; (2) the middle ear, called
the " tympanic cavity " or ti/mpamim ; and (3) the internal ear, or labyrinth.
The labyrinth is situated in the dense petrous bone, and it contains a mem-
branous sac of complex form which receives the peripheral terminations of the
auditory nerve. This sac, therefore, is to the ear what the retina is to the eye ;
as the lens, cornea, etc. of the eye are simply physical media for the production
of sharp images on the retina, so all parts of the organ of hearing are devoted
solely to the accurate transmission of the energy of air-waves to the internal

ear.

The External Ear. — The pinna or auride, commonly known simply as
the " ear " (Fig. 2(36), is a peculiarly wrinkled sheet of tissue, consisting es.sen-

FiG. 266.-Diagram of organ of hearing of left side (Quain, after Arnold) : 1, the pinna; 2, bottom of
concha ; 2-2'. meatus externus ; 3, tympanum ; above 3, the chain of ossicles ; 3', opening into the mastoid
cells- 4, Eustachian tube; 5, meatus internus, containing the facial (uppermost) and auditory nerves;
6 placed on the vestibule of the labyrinth above the fenestra ovalis ; a, apex of the petrous bone ; 6,
internal carotid artery; c, styloid process; d, facial nerve, issuing from the stylo-mastoid foramen; e,
mastoid process ; /, squamous part of the bone.

tially of yellow elastic cartilage covered with skin, and forming at the entrance
of the auditory meatus a cup-shaped depression called the " concha."

17? e concha, and to some extent the whole auricle, serves a useful purpose
in collecting, like the mouth of a speaking-trumpet, the waves of sound falling
upon it ; but in many of the lower animals the concha is relatively larger than
in man, and, their ears being freely movable, the auricle becomes of greater
physiological importance.

External Auditory Meatus.— In man the external auditory meatus or audi-
tory canal is about one and a quarter inches in length, and it extends from

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AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the bottom and anterior edge of the concha to tlie membrana tympani, or

tympanic membrane. Starting
from the bottom of the conclia,
the general direction of the audi-
tory canal is first obliquely up-
ward and backward for about
half an inch, and then inward
and forward. Therefore, to look
into the ear or to introduce the
aural speculum the canal must be
straightened by pulling the pinna
upward and backward. The
canal-wall is cartilaginous and
movable for about half an inch
from the exterior, but is osseous
for the rest of its extent ; it is
lined by a reflexion of thin skin,
on whose surface, in the cartilag-
inous part of the canal, open the
ducts of numerous sebaceous and
ceruminous glands.

Tympanum. — The middle ear,
or tympanum (Figs. 2G6, 267), is
shut oif from the auditory canal
by the tympanic membrane. It

is an air-holding cavity of irregular shape in the petrous bone, and it is broader

behind and above than it is below and

in front. Posteriorly it is in open com-
munication with the comj)lcx system of"

air-cavities in the mastoid bone known

as the mastoid antrum and the mastoid

cells. Anteriorly it is continuous with the

pharynx through the Eustachian tube.

The inner wall slants somewhat outward

from top to bottom, and it is formed

chiefly by part of the bony envelope of

the internal ear. The surface of this wall

is pierced by two apertures, the fenestra

ovalis, or oval window, and the fenestra

rotunda, or round window, leading into

the cavity of the bony labyrinth ; in life

each fenestra is covered by a thin sheet

of membrane, and the foot of the stapes

h fastened by a ligamentous fringe in the

oval window. The outer wall of the middle ear is made up of the tymj>anic

Fig. 267.— Tympanum of left ear, with ossicles m situ
(after Morris) : 1, suspensory ligament of malleus ; 2, head
of malleus ; 3, epitympanic region; 4, external ligament
of malleus ; 5, processus longus of incus ; 6, base of stapes ;
7, processus brevis of malleus; 8, head of stapes; 9, o>!
orbicnlare; 10, manubrium ; 11, Eustachian tube ; 12, exter-
nal auditory meatus: 13, membrana tympani; 14, lower
part of tympanum.

Fig. 268.— ()tosco|iic view of left membrana
tympani (Morris): 1, viembrana flaccida ; 2,2',
folds bounding the former ; 3, reflection from
processus brevis of malleus ; 4, processus lon-
gus of incus (occasionally seen) : .'>, mem-
brana tympani ; 6, umbo and end of manu-
brium ; 7, pyramid of light.

THE SENSE OF HEARING.

809

membrane and tlie ring of bone into which tliis membrane is inserted.
The roof is formed by a thin plate of bone, the tegrnen, which separates it
from the cranial cavity, and the narrow floor, concave upward, is just above
the jugular fossa. The cavity is lined by mucous membrane continuous with
that of the Eustachian tube and the pharynx, and the membrane, like that
of the Eustachian tube, is ciliated except over the surfaces of the ossicles ahd
the tympanic membrane. Suppurative inflammation of the middle ear may
not only involve the mastoid cells, but may also cause absorption of the tiiin
plate of bone forming the roof of the tympanic cavity and the mastoid
antrum. In this and in other ways inflammation may extend from the tym-
panic to the cranial cavity, making otitk media, or inflammation of the middle
ear, the commonest source of pyogenic atfections of the brain.*

Tympanic Membrane, or Drum-skin. — The membrana tympani (Figs, 268,
269) is a somewhat oval disk whose longer axis is directed from behind and above

downward and forward, and
whose length is about nine
millimeters. The membrane
is inserted obliquely to the
axis of the . auditory canal,
so that the floor of the canal
is longer than its roof. The
membrana tympani, though
so thin as to be semi-trans-
parent, is composed of three
layers of tissue. Externally
it is covered by a thin plate
of skin ; internally, by mu-
cous membrane; and between
these lies the proper sub-

FiG. 2692— Tympanum of right side with ossicles in place, viewed
from within (after Morris) : 1, body of incus ; 2, suspensory ligament
of malleus ; 3, ligament of incus ; 4, head of malleus ; 5, epityra-
panic cavity ; 6, chorda tijmpani nerve ; 7, tendon of tensor tympani
muscle; 8, foot-piece of stirrup; 9, of orbiculare ; 10, manubrium:
11, tensor tympani muscle; 12, membrana tympani; 13, Eustachian
tube.

Fig. 270.— The chain of auditory
ossicles, anterior view (after Tes-
tut) : 1, head of malleus; 2, long
process of incus ; 3, stapes.

Stance (membrana propria) of the membrane, made up chiefly of fibrous tissue.
The greater number of the fibres of the membrana propria radiate from near
the centre to the periphery of the membrane ; but there are also circular filjres
of elastic tissue which are most numerous in a ring near the attached margin
of the membrane. The surface of the tympanic membrane is' not flat, but is
funnel-shaped, with the apex of the funnel pointing inward. Moreover, lines

^ Macewen : Pyogenic Diseases of the Brain and Spinal Cord, 1893.

' Figs. 267, 268, and 269 are taken by permission from Morris's Text-Book of Anatomy, Phila., 1893.

810

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

drawn from the centre to the margin of the membrane would not be straight,
but would be curved slightly, with the convexity outward, this shape being
due to the tension of the clastic circular fibres of the meml)rane. The mem-
brane, throughout the greater part of its circumlerence, is inserted in a groove
in a bony ring set in the wall of the auditory canal, but a small arc at its
superior portion is attached directly to the wall of the canal. The segment of
membrane corresponding to this arc, known as the membrnna Jlaccida, lacks
the tenseness of the rest of the drum-skin.

Viewed through the aural speculum, the normal tympanic membrane has
a pearly lustre (Fig. 268). The handle of the malleus, or manubrium, inserted
within its fibrous layer, can be seen as an opaque ridge running from near the
upper anterior margin downward and backward and ending in the umbo, or
central depression, where the membrane is drawn considerably inward by the
tip of the manubrium. It is from this point that the radial fibres of the mem-
brana prop-ia diverge.

At the top of the manubrium is a shining spot which is the reflection
from the short process of the malleus where it presses against the membrane.
From this point two delicate folds of the membrane run to the periphery —
one forward and the other backward. They form the lower border of the
membrana jlaccida, or ShrapneU's membrane, in which there is less fibrous tissue
than in the remaining part of the membrane, and the cutaneous and mucous
layers are also less tense than elsewhere. A bright reflection of triangular
shape, known as the " pyramid of light," is seen in the lower quadrant of tiie

tympanic membrane. The apex of this
bright triangle is at the tip of the manu-
brium, and its base is on or near the
peripheiy of the membrane.

Auditory Ossicles. — The tympanic
membrane is put into relation with the
internal ear by a chain of bone, the
auditory ossicles, known as the malleus,
the incus, and the stapes, so called from
their fancied resemblance to a hammer, an
anvil, and a stirrup (Figs. 267, 269, 270).
The malleus (Fig. 271) is 18 to 19 milli-
meters long ; it presents a rounded head,
grooved on one side for articulation with
the incus, a short neck, and a long handle
or manubrium, which is inserted in the
tissue of the tympanic membrane from
a point on its upper periphery to a little below its centre. The processus
bi-evis of the malleus is a low conical projection which springs from the top
of the manubrium and presses directly against that segment of the tympanic
membrane known as the membrana Jlaccida, through which it can be seen
shining on inspection with the ear-speculum. The processus gracilis, or pj-o-

FiG. 271.— Malleus of the right side : a, anterior
face; b, internal face (after Testut): 1, capitu-
lum or head of malleus ; 2, cervix or neck ; 3,
processus brevis ; 4, processus gracilis ; 5, manu-
brium ; 6, grooved articular surface for incus ;
7, tendon of m. tensor tympani.

THE SENSE OF HEARING.

811

cessus Folianus, long and slender, arises from an eminence just below the
neck of the malleus, and, passing forward and outward, is inserted in the
Glaserian fissure in the wall of the tympanum. The malleus is held in posi-
tion ])artly by ligaments; the suspensory or superior ligament passes downward
and outward from the roof of the tympanum to be inserted into the head of
the malleus. The main portion of the anterior ligament is attached to the
neck of the malleus just above the processus gracilis ; it embraces the latter,
and, passing forward, finds its origin
in the anterior wall of the tympanum
attd in the Glaserian fissure. Another
division of this ligament, the external
ligament, arises and is attached more
externally than that just described.
The lig-aments of the malleus serve to
keep its head in position. The exter-
nal ligament, being attached above the
axis of rotation of the hammer, pre-
vents the head of this bone from
moving too far inward, and the manu-
brium from being pushed too far outward. The superior ligament, owing to
its oblique course, restrains the head of the hammer from moving too far
outward.

The incus, umbos, or anvil-bone (Fig. 273) is shaped somewhat like a bicus-
pid tooth. Its thicker portion is hollowed on the surface and is covered with

cartilage for articulation with the
^ ^ head of the malleus. It has two

processes, a long and a short,
which project at right angles to

Fig. 272.— Ligaments of the ossicles and their axis
of rotation (from Foster, after Hensen). The figure
represents a nearly horizontal section of the tym-
panum, carried through the heads of the malleus
and incus : M, malleus ; 1, incus ; t, articular tooth
of incus ; Ig.a and Ig.e, external ligament of mal-
leus ; Ig.inc, ligament of the incus ; the line a-x rep-
resents the axis of rotation of the two ossicles.

Fig. 273.— The incus of the right side : a, anterior face; B,
internal face (after Testut) : 1, body of incus ; 2, processus
brevis ; 3, processus longus ; 4, articular surface for the mal-
leus ; 5, a convex tubercle, processus lenticularis, for articu-
lation with stapes ; 6, rough surface for attachment of the
ligament of the incus.

Fig. 274.— The stapes (after Testut) : 1,
base ; 2, anterior crus ; 3, posterior eras ;
4, articulating surface of head of the
bone ; 5, cervix or neck.

each other ; the former has a length of 4^ millimeters, and the latter a length
of 3 to ^ millimeters. When in position the long process descends nearly
parallel with the manubrium, but it has less than three-fourths the length of
the latter. The free end of the long process is turned sharply inward at right
angles, and terminates in a round projection, the os orbiculare, which is provided
with cartilage for articulation with the head of the stapes. The short process is

812 .i;V' AMERICAN TEXT-BOOK OF PHYSIOLOGY.

coniciil ill -sliape and is thicker thau the long process. It lias a horizontal ])()si-
tion, and is attached by a thick ligament to the posterior wall of the tympanum.

The stapes (Fig. 274) articulates with the end of the long process of the
incus ; its plane is horizontal and about at right angles to that process. It
measures 3 to 4 millimeters in length and about 2J millimeters in breadth.
The base of the stapes is somewhat oval in shape, the superior margin being
convex and the inferior being slightly concave. It is set in the fenestra ovalis,
an aperture measuring about 3 millimeters by 1^ millimeters, and is held in
place by a narrow membrane made up of radial fibres of connective tissue.
When in position, the inner face of the base of the stirrup is covered with
lymphatic endothelium and is washed by the perilymph of the internal ear;
the outer face, like the other tympanic bones and the wall of the cavity, is
covered by thin mucous membrane.

Movement of the Ossicles. — The malleus-incus articulation is so arranged
that with outward movements of the manubrium the head of the malleus
glides freely in the joint; but the lower margins of the articulating surfaces
project in such a way that the prominences lock together when the manubrium
moves inward. Thus, in inward movements of the tympanic membrane and
its attached manubrium, the malleus and the incus move together like one
rigid piece of bone, the motions of the manubrium and the long process of the
incus being parallel. Of the malleus-incus articulation Helmholtz' says:
" In its action it may be cora])ared with the joints of the well-known Breguet
watch-keys, which have rows of interlocking teeth, oifering scarcely any resist-
ance to revolution in one direction, but allowing no revolution whatever in the
other." In the outward movements the locking teeth or projections are prob-
ably still kej)t in apposition, under ordinary circumstances, through the elastic
reaction of the ligament and the stapedial attachment of the incus. Should,
however, the tympanic membrane be forced unduly outward, as by increase of
pressure within the tympanum or by rarefaction of air in the auditory meatus,
the incus only follows the malleus for a certain distance, the latter completing
its motion by gliding in the joint. Tiiere is thus no danger of the stapes being
torn out of the oval window. The hammer and the anvil, suspended by their
ligaments, move freely about an axis one end of which is found at the origin of
the anterior part of the anterior ligament of the malleus, and the other end in
the origin of the ligament which is continuous with the short process of the incus
(Fig. 272). In inward motions of the tympanic meml)rane the ossicles move like
a single bone around the axis of suspension ; and as the distance measured from
the axis of rotation to the tip of the manubrium, where the power is applied, is
about one and one-half times the distance to the end of the long process of tlie
incus, where the effect is produced, the motions transmitted to the stapes can have
but two-thirds the am])litude of the movements of the tip of the manubrium, but
have one and one-half times their force. It will be noticed that a large ])ro-
portion of the mass of both anvil and hammer is found above their axis of rota-
tion ; this upper portion acts as a counterjwise to the parts below which are directly
' Sensations of Tone, trans, by Ellis, 1885, p. 133.

THE SENSE OF HEARING. 813

concerned in the lever action. The bony lever being thus balanced, it is less
diHicult to understand its known sensitiveness to impulses that are inconceivably
weak. The tense tympanic membrane, by reason of its funnel shape, resists
strong inward compression ; hence the stapes is prevented from being pressed
too far inward. The maximum amplitude of motion of the stapes in the
fenestra is very small, being only about -jlg- millimeter to -^ millimeter, while
that of the centre of the tympanic membrane is about -^ millimeter to ^
millimeter.

The functional movements of the auditory ossicles are not molecular but
are molar vibrations, the chain of bones moving in a body. The sole purpose
of this apparatus of the middle ear is to transmit exactly the variations of
pressure in the air of the external auditory meatus to the perilymph which
bathes the foot of the stapes — in other words, to convert air- waves into a
similar series of water-waves. In the words of Helmholtz,^ " The mechanical
problem which the apparatus within the drum of the ear had to solve was to
transform a motion of great amplitude and little force, such as impinges on
tiie drum-skin, into a motion of small amplitude and great force, such as had
to be communicated to the fluid in the labyrinth."

The adaptation of the apparatus of the middle ear to this end is worthy
of careful consideration. In the first place, it will be noticed that the area
of the fenestra ovalis which receives the impulses of the stapes is but a small
fraction of the surface of the tympanic membrane on which the air-waves
impinge, the latter area being some fifteen to twenty times greater than the
former, so that the energy of air-motion is, in a fashion, concentrated. In the
second place, as previously observed, the lever mechanism of the auditory
ossicles is such that the movements of the end of the long process of the incus
have two-thirds the amplitude of those of the tip of the manubrium, but
about one and one-half times their force. It should also be noticed that the
membrane fastening the foot of the stapes in the fenestra is somewhat less
tense on the upper side, so that the top of the oval foot-piece has a freer
motion than the bottom, and the head of the stirrup rises slightly with inward
motions. In the third place, it has been demonstrated by Helmholtz^ that the
shape of the tympanic membrane peculiarly adapts it for transforming weak
movements of wide amplitude into strong ones of small compass. For this
membrane is not a simple funnel depressed inwardly, but the radii are slightly
curved with the convexity outward, a shape chiefly due to the tension of the
elastic circular fibres of the membrane on its inner face, these being most
numerous toward the circumference. Air-waves beating upon this convexity
flatten the curve somewhat, and their whole energy must be concentrated, witli
increased intensity but loss of motion, at the central point of the membrane.
This effect may be illustrated by holding a slightly-curved brass wire, several
inches in length, with its plane perpendicular to the surface of a table and
supported on its ends. When one end of the wire is held immovable, up-and-
down motions of the arch are transferred to the free end with diminished
' Op. cit., p. 134. ^ Op. cit.

814 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

amplitude. The wire represents a single radial fibre of the tympanic mem-
brane, and the tunnel shape of this membrane is adapted to concentrating this
motion of the radial fibres upon the manubrium. The same effect is illus-
trated by the fact that when a string or a rope is stretched between two })oints,
no matter how tightly, it always sags at its middle ; the weight of the cord,
however slight, is sufficient to give it a curved course, and produces a corre-
sponding traction on the points of support.

Eustachian Tube. — That the tympanic membrane may maintain its
freedom of motion, it is obviously necessary that the averacje atmospheric
pressure on each side of it should remain the same. This equalitv of pressure
is maintained through the medium of the Eustachian tube, a somewhat trumpet-
shaped canal which, beginning in the lower anterior walls of the tympanum,
runs downward, forward, and inward, and terminates in a slit in the side of
the upper i)art of the pharynx. The Eustachian tube is lined, like the walls
of the tympanum, with ciliated epithelium, the cilia working in such a way
as to carry into the pharynx such secretions as may arise from the mucous
membrane of the middle ear. The pharyngeal opening of the Eustachian tube
is probably normally closed, but it may easily be made to open by increase or
decrease of air-pressure within the pharynx, as may be produced by closing
the nose and mouth and either forcing air into the pharynx by strong expiration
or rarefying it by suction. In the former case the air-pressure within the
tympanum is increased, and in the latter it is diminished. When air is thus
made to enter or to leave the tympanum, a sensation of a sudden snap and
a dull crackling noise in the ear is experienced. The lower end of the tube
is normally opened during the act of swallowing, and it is at this moment that
the intra- and extra-tympanic air-pressures are equalized.

Muscles of the Middle Ear. — Two muscles are devoted to adjusting the
tension of the auditory mechanism of the middle ear. The tensor tympani is
lodged within a groove which is just above and about parallel with the Eusta-
chian tube. It terminates externally in a long tendon which bends nearly at
right angles round the outer edge of the groove and is inserted into the
handle of the malleus near the neck. Contraction of the tensor tympani thus
results in pulling the tympanic membrane inward and rendering it more tense
(PI. 2, Fig. 1). This increase of tension of the membrane seems to adapt it
better to the more rapid vibrations of high musical notes, but allows less ready
response to lower notes. It is said that the tensor tympani comes normally
into action at the beginning of a sound, thus tuning the membrane for the
note that is to follow, and then relaxes. One of its effects is probably to bring
closely together the toothed processes of malleus and incus at the beginning
of a sound, so that there shall be no loss of motion during the vibrations
of the membrane. The stapedius is a small muscle imbedded in the inner
wall of the tympanum near the fenestra ovalis. Its tendon, ])assing forward,
is inserted into the neck of the stapes. Contraction of the muscle would cause
a slight rotation of the stapes round a vertical axis, so that the hinder part
of the foot of the ossicle would be pressed more deeply into the fenestra, while

THE SENSE OF HEARING. 815

the retnainiug portion would be drawn out of it. Its action probably reduces
tiie pressure in the cavity of the perilymph, and thus is antagonistic to that
of the tensor tynipani (PI. 2, Fig. 2, a, b).

Vibrations of the Tympanic Membrane. — It is a general physical law
that every elastic body can be made to vibrate more easily at one definite rate
than at any other. The musical tone represented by this rate of vibration is
known as the prime or fundamental tone of the body. Membranes have funda-
mental tones (see p. 827), whose pitch is determined by their area, thickness,
and tension, but they differ from rods and strings in being less strictly confined
to a single fundamental tone in their vibration. The tympanic membrane is
quite peculiar in that it can hardly be said to have a definite fundamental tone.
It would obviously be a great imperfection in an organ of hearing were cer-
tain sounds intensified by it out of proportion to others, as would be the case
if the tvmpanic membrane had a marked fundamental tone of its own. This
is prevented in the case of the membrana tympani probably both by reason of
the peculiar form of its surface and its structure, and also because its oscilla-
tions are damped by the pressure of the malleus held in position by tlie other
mechanisms of the tympanum. When the tympanic membrane is perforated
or is wholly removed, without destructive inflammatory changes in the middle
ear, sounds are still heard, though usually with diminished loudness. A
musician who had suffered this accident was no longer able to play his violin,
probably because sounds of different pitch ceased to be perceived in their true
relations of loudness. We may thus conclude that the function of the tym-
panic membrane is not only to guard against injury to the delicate mem-
branes of the fenestrse and the internal ear, but also to transmit to the ossicles
sonorous vibrations with their true proportion of intensity. The membranes
covering the round and oval windows of the internal ear have no means of
damping sympathetic vibrations (see p. 829), and, should complex air-waves
strike directly upon them, they would, probably, by sympathetic resonance,
respond more powerfully to tones of certain pitch than to any others.

The sensation of sound may be excited by conduction through the bones
of the skull as well as in the ordinary way. Thus, a tuning-fork set vibrating
and held between the teeth or on the forehead is heard perfectly, and more
loudly when the ears are closed than when open. The vibrations thus con-
ducted probably partly affect the internal ear directly, and partly indirectly by
setting in oscillation the tympanic membrane. When a sounding tuning-fork
is held between the teeth until the sound dies away, it may still be heard if
held in front of the ear, though the contrary statement is frequently erroneously
made. When the sound of the fork held between the teeth has failed, it may
again be heard by stopping the ears.

The Internal Ear, or Labyrinth. — The internal ear is the site of the true
organ of hearing. The membranous labyrinth (PI. 2, Fig. 4 ; Fig. 278) is a com-
plicated system of membranous tubes and sacs, in which terminate at particular
points the filaments of the auditoiy nerve ; it is contained within a chamber,
the bony labyrinth, hollowed out in the petrous bone. The cavity of the bony

81(5

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

lal)yrintli(Fig.s. 275, 270) consists of a median part, the vestibule, which is pro-
lougt'd posteriorly in the system of semicircular canals and anteriorly in the
cochlea. The vestibule is a space which measures about one-fifth of an inch
in diameter, and it is perforated in its outer wall by an oval opening known
as the Jenesira ovalis. The semicircular canals are three tubes of ciroular

Fig. 275.— Right bony labyrinth, viewed from
outer side : the figure represents the appearance
produced by removing the petrous bone down to
tlie denser layer immediately surrounding the
labyrinth (from Quain, after Sommering): 1, 2,3,
the superior, posterior, and horizontal semicir-
cular canals; 4, 5, 6, the ampullae of the same;
7, the vestibule ; 8, the fenestra ovalis ; 9, fenestra
rotunda ; 10, first turn of the cochlea ; 11, second
turn ; 12, apex.

Fig. 276.— Interior view of left bony labyrinth after
removal of the superior and external walls (from
Quain, after Sommering) : 1, 2, 3, the superior, pos-
terior, and horizontal semicircular canals ; 4, fovea
hemi-elliptica; o, fovea hemisphcrica; 6, common
opening of the superior and jioRterior semicircular
canals ; 7, opening of the aqueduct of the vestibule ;
8, opening of the aqueduct of tlie cochlea; 9, the
scala vestibuli ; 10, scala tympani ; the lamina spiralis
separating 9 and 10.

section, known respectively as the anterior or superior, the posterior, and the
external or horizontal semicircular canal. Their planes are at right angles to
one another, so that they occupy the three possible dimensions of space. The
external canal lies in a nearly horizontal plane, while the other two approach
the vertical. Each canal is dilated at one extremity into a globular cavity

which is more than twice the diameter of the
canal itself, and which is known as the am-
pulla. The anterior and posterior canals
unite near the ends not provided with am-
pull?e, and they enter the vestibule as a com-
mon tube. Anteriorly the cavity of the
vestibule is continued as a tube of complex
internal structure which is coiled upon itself
two and one-half times, and which, from its
resemblance to the shell of a snail, is known
as the cochlea (PI. 2, Fig. 3). The osseous
cochlea may be conceived as formed by a bony tube turned about a bony central
pillar, the modiolus, which diminishes in diameter from the base to the apex
of the cochlea. From the modiolus a bony shelf stretches into the cavity of
the tube, incompletely dividing it into two tubular chambers, winding round
the modiolus like a circular staircase, the upper of which chambers we shall

Fig. 277.— Diagram of the osseous cochlea
laid open (after Quain) : 1, scala vestibuli ;
2. lamina spiralis ; 3, scala tympani ; l, cen-
tral pillar or modiolus.

Explanation of Plate 2.

Fig. 1. — Schematic representation of displacement of the auditor)' ossicles due to contraction of the
tensor tympani muscle (.Testut) : ((.external auditory meatus; ti, tympanic cavity; c, vestibule of the
bony labyrinth ; d, fenestra ovalis ; 1, membrana tympani ; 2, handle of malleus ; 3, head of malleus ; 4,
insertion of tendon of tensor tympani ; 5, long or vertical process of incus ; 6, head of incus; 7, stapes.
(The arrow indicates the direction of traction of the tensor tympani muscle ; and the lines in red indi-
cate the change in the position of the parts produced by it.)

Fig. 2.— Schematic representation of the displacement of the stapes due to contraction of the stape-
dius muscle (Testut) : A, the stapes in repose; B, stapes^ during contraction of stapedius muscle; 1, base
of stapes; 2, anterior border of fenestra ovalis ; 3, the pyramid ; 4, tendon of stapedius muscle ; a, anterior
portion of annular ligament of stapes, longer than b, posterior portion of same ligament ; x, x, antero-
posterior diameter of fenestra ovalis, passing through the base of the resting stapes; y, point of passage
of the vertical line which represents the axis of rotation of the stapes.

Fig. 3.— The three parts making up the bony cochlea (schematic, from Ttstut) : A. the columella; B,
spiral tube containing the scalae ; C, lamina spiralis ; J>. the three parts in their normal relations.

Fig. 4.— Schematic representation of the perilymphatic and endolymphatic sfiaces. The former
apfjear in black, and the latter are colored blue (Testut i : 1, utricle ; 2, saccule ; 3, semicircular canal ; 4,
caualis cochlearis ; 5, ductus endolymphaticus with its two branches of origin ; 6, saccus endolymph-
aticus ; 7, canalis reuniens, or canal of Ilensen ; 8, scala tympani ; 9, scala vestibuli ; 10, their communi-
cation at the helieotrema ; 11, aqua-ductus vestibuli ; 12, aqua^ductus cochlearis : 13, periosteum ; 14, dura
mater; 15, stapes in the fenestra ovalis ; 16, fenestra rotunda with its membrane.

77//; s/:.\s/': or u earing.

I'LATK ±

Fif!. 1.

Fig. 2.

THE SENSE OF HEARING.

817

soon learn to know as the .sm/a vesfibull, and the lower chamber as the scala
tympani (Fig. 277 ; PI. 2, Fig. 3). The bony shelf mentioned above as partly
bisecting the cochlear tube has, of course, like the latter, a spiral course, and is
known as the lamina spiralis; its importance as a supporter of the auditory-
nerve filaments will soon be seen.

Contained within the cavity of the bony labyrinth, and parallel with its walls,
is the manhranom labijrinth, in which are found the essential structures of the
organ of hearing (PI. 2, Fig. 4 ; Fig. 278). The membranous labyrinth is filled
with a somewhat watery, mucin-holding fluid, the endolymph, while a similar
fluid, the perilymph, is found outside it and within the osseous labyrinth. The
perilymph space, which is lined by lymphafic epithelium, is in communication,
along the sheath of the auditory nerve, with the subdural and subarachnoid
lymph-areas of the brain. Numerous sheets and bars of connective tissue cross
from the wall of the bony to that of the membranous labyrinth and help support
the latter. That part of the membranous labyrinth lying within the vestibule
is composed of two separate sacs — a larger posterior, known as the utricle or
utrimlus, and a smaller, more anterior, known as the saccule or sacculus. The
plane of division between the two sacs ends opposite the fenestra ovalis (PI. 2,
Fig. 4). Though the sacs are quite separate, their cavities are indirectly continu-

— 9

Fig '>78 -Diagram of right membranous labyrinth seen from the external side (after Testut) : 1, utri-
cle -23 4 superior, posterior, and horizontal semicircular canals ; 5, saccule ; 6, ductus endolymphat-
Icus.withV, 7', its twigs of origin ; 8, saccus endolymphaticus ; 9, caualis cochlearis, with 9', its vestibular
cul-de-sac, and 9", its blind extremity ; 10, canalis reuniens.

ous, through the union of two small tubes arising from either sac, which tubes
unite to form the ductus endolijmphaficus, a tube running inward through a
canal in the petrosal bone and ending blindly in a dilated flattened extremity,
the saccus endolymphaticus, this being supported between the layers of the
dura mater within the cavity of the skull (PI. 2, Fig. 4). Bundles of audi-
tory-nerve fibres penetrate the wall of each sac. The utricle gives rise to the
membranous semicircular canals, which communicate with it at five points,
it being remembered that the anterior and posterior canals fuse into a single
tube at* the ends not piwided with ampulla, and that they have a common
entrance into the utricle. The saccule is continuous by a narrow tube, the
canalis rmniens, with that division of the membranous labyrinth contained

52

818

^l.Y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

withiu tlie cochlea and known as the cdnalia cochlearis. The auditory nerve
really consists of two distinct divisions having separate origins and different
distributions. One of these branches passes finally to the cochlea, and the
other to the vestibule and the semicircular canals. The nerve approaches the
labyrinth by way of a canal known as the meatus andUorius interntts, and
on reaching the angle i)etween the vestibule and the base of the cochlea the
cochlear division pa.sses to the cochlea. The remainder of the nerve consists
of two divisions, the supericn- of which is distributed to the utricle and to the
ampullas of the anterior and horizontal semicircular canals; the inferior branch
supplies the saccule and the posterior semicircular canal. The inner wall of
both utricle and saccule is developed at a particular spot into a low mound,
the macula acustica, made up of an accumulation of the connective-tissue ele-
ments of the membranous wall and covered by a peculiarly modified epithe-
lium, the auditory epithelium (Fig. 279). All the auditory-nerve filaments that
enter the saccule and utricle respectively pass to these mounds and there enter
into relation with the auditory epithelium.

As the auditory-nerve endings are confined to a particular ai-ea in the
utricle and the saccule, so the nerve-fibres supplying the semicircular canals

are limited to a certain part of the
ampulla of each canal. The tissue of
the wall of the ampulla is developed
into a ridge projecting into, the cavity
in a direction across its long axis.
This ridge, present in each ampulla, is
called the crista acustica ; it is capped
by a thick layer of columnar epithelial
cells, the auditory epithelium, which
thins away at the border of the crista
into the sheet of flattened cells by
which the rest of the ampulla is lined.
The auditory cells(Fig. 279) are said to
be of two kinds — t)ne, cylindrical in
shape and reaching only part way to
the basement membrane, the hair-cells;
the other, narrow and elongated, the
supporting or sustentacular cells. The former are peculiar in the fact that
from their free ends there project long, stiff, hair-like processes. The fila-
ments of the ampullary-nerve branches pass through the cristas and encircle
the bodies of the hair-cells. The cells covering the maculee acusticce have
essentially the same structure as those just described, though in the maculae
the auditory hairs are shorter than in the cristie. Seated on the free surface
of the macular epithelium is a fibrous mass which is said to be a normal
structure, and not, like a somewhat similar mass found covering the crista^ in
post-mortem sections, a coagulum due to the method of preparation. Im-
bedded in the membrane over the maculae of both saccule aud utricle are

Fig. 279.— Diagram showing the epithelial cells of
a macula or a crista (after Foster) : 1, cylinder or
hair-cell ; 2, the same, enveloped in a nest of nerve-
fibrils ; 3, 4, 5, forms of rod- or spindle-cells.

THE SENSE OF HEARING.

819

small crvstals, oioJUhs or ofocouia, composed chiefly of carlx>nate of lime. Oto-
conia are also found less constantly in the ampullai and even in the peri-
lymph space of the cochlea. In fishes there are large masses of calcareous
matter, otoliths, attached to the wall (»f the auditory sac.

General Anatomy of the Cochlea. — ]5y far the most complex structure of
the ear is found in the cochlea (PI. 2, Figs. 1, 3, 4 ; Figs. 275-278). The bony
cochlea continues from the anterior wall of the vestibule, and in the upright posi-
tion of the head the axis of the modiolus is nearly horizontal, pointing, from base

Fig. 280.-Diagram of a transverse section of a whorl of the cochlea (after Foster) : Sc.V, scala vestib-
uli- Sc.T, scala tympani; C.Chl, canalis cochlearis; Lam.sp, lamina spiralis; Gg.sp, ganglion spirale ;
n.aud, auditory nerve; m.R, membrane of Reissner; Str.v, Stria vascularis; Lg.sp, ligamentum spirale;
tl Ivmphatic epithelioid lining of basilar membrane on the tympanic side; m.b, basilar membrane;
Org.'c, organ of Corti ; L.t, labium tympanicum; lb, limbus ; L.v, labium vestibulare; m.t, tectorial
membrane.

to apex, outward and slightly down and forward, the base of the cochlea being
formed by the inner surface of the petrous bone. The membranous cochlea,
canalis or ductus cochlear^, is a tube of nearly triangular cross-section which
winds round the modiolus from base to apex (Fig. 280). The base or outer side

820 AN AMERICAN TEXT- BOOK OE PHYSIOLOGY.

of this triangle is attached closely to tlie bony wall of the cochlea; the upper
bide, supposing the modiolus to be vertical with its apex above, is made of a tliin
sheet of cells known us the membrane of lieissner ; the lower side is made up
partly of the bony margin of the lamina spiralis and partly of a membrane,
radially striated, .•stretched across from the edge of the spiral lamina to the side
wall of the cochlea; this is called the basilar membrane, mcmbruna basilaris.
The coiled tube forming the bony cochlea is thus divided by the lamina spiralis
and the camdia cocldcaris into three tubes which wind sj)irally and parallel
round the modiolus. The canalis cochlearis contains endolymph, and its cav-
ity ends blindly above and below, but is continuous by way of the narrow
canalis reuniens with that of the saccule. The tubes above and below the
canalis cochlearis are perilymph-spaces ; it will be noticed that there is no
such space on the outer side of the membranous cochlea.

The upper tube, when followed down to the base of the cochlea, is found
to open freely into the vestibule of the labyrinth ; it is therefore known
as the sca/a vestibidi. The hjwer tube ends blindly at the base of the
cochlea, but, where this part bulges into the tympanum as the *' promontory "
of its inner wall, it is perforated by, the aperture known as the fenestra
rotunda, whose ])roper mend)rane alone prevents the i)erilymph from escaping
into the middle ear. This tube is therefore known as the scala tymponi.
From its central position the membranous cochlear canal is frequently known
as the scala media. The scala vestibuli and the scala tympani both decrease in
size as they wind from the base to the apex or cupola of the cochlea ; the
membranous cochlear canal, on the contrary, increases in section from base to
apex until near the top; hence the width of the basilar membrane and the
length of its radial fibres increase from below upward. The scala vestibuli
and the scala tympani have no communication except through a small ai)erture
under the cupola of tiie cochlea, known as the helirotrema ; this is bounded
by the hook-like termination, the hamnlns, of the bony lamina spiralis, which
forms the greater part of a ring completed by the jiointed blind extremity of
the eanalis cochlearis fastened above it to the cupola.

The Transmission of Vibrations through the Labjrrinth. — Vibrations
of the tvmpanic membrane are transmitted as pulses of very small amplitude to
the membrane covering the fenestra ovalis. The relatively considerable body of
perilymph bathing the inner face of this membrane must be thus set in motion,
and there starts a fluid-wave which is free to make its way throughout the
perilvmph-spaces of the vestibule and the semicircular canals. It may pass
from the vestibule along the scala vestibuli to its top, through the helicotrema,
and back by way of the scala tympani, at whose bottom it finally surges
against the membrane covering the fenestra rotunda; or the wave may be
transmitted directly across the membranous cochlea. The fluids of the laby-
rinth being ])hysically incompressible, the function of the fenestra rotunda as
a sort of safety-valve seems evident. Politzer inserted a glass tube in the
round window, and found that fluid in the tube rose when strong air-i)ressure
was brought to bear on the outer side of the tympanic membrane. The cavity

THE SENSE OF HEARING. 821

of the membranous labyrinth (PI. 2, Fig. 4) is nowliere in communication with
the perilymph-space al)out it, and we must therefore assume that the irritation
of the auditory cells seated in its wall must depend on vibrations transmitted
from the perilymph directly through tlie membranous sacs and tubes.

Like the perilymph-space, the cavity of the membranous labyrinth is in
communication throughout, though in certain situations the connection of
adjacent parts is very indirect. Thus, though the semi(;ircular canals open
freely at both ends into the utricle, the utricle and saccule are only brought
into union by the two narrow tubes that unite to form the ductus endolym-
phaticus. It will be noted that by means of this duct the membranous laby-
rinth is really continued into the cranial cavity. The saccule in turn is
continuous with the scala media of the cochlea by way of the canalis reuniens.

The Membranous Cochlea and the Organ of Corti (Figs. 280-282).—
The cochlear division of the auditory nerve, together with the nutrient blood-
vessels, penetrates the modiolus at its base and runs up th'rough the spongy
interior of the bony pillar. As the nerve ascends through the modiolus its
fibres are gradually all diverted to run in a radial direction between the bony
plates of the lamina spiralis, to terminate in the organ of Corti of the canalis
cochlearis. A collection of nerve-cells is interposed in the course of the audi-
tory fibres at the base of the lamina spiralis.

A complete view of the nerves of the cochlea would show a central pillar
of nerve-fibres diminishing in thickness from below upward, and winding
round this pillar a spiral sheet of radially-disposed nerve-fibres containing,
near their point of departure from the central pillar, a spiral line of ganglion-
cells; this collection of cells is therefore known as the ganglion spirale. The
thin, free edge of the bony lamina spiralis is, in the recent state, thickened by
a development of connective tissue forming a promontory known as the limbus.
Tlie free edge of the limbxis is in turn shaped in such a way as to make a short,
sharp projection in the plane of the upper surface of the lamina and a longer
projection in the plane of its lower surface, leaving the free margin between
them hollowed out. The upper projection, which is known as the vestibular
lip, labium vestibulare, serves for the attachment of the tectorial membrane,
membrana tecforia, presently to be described. The lower projection is called
the tympanic lip {labium tympanicum) ; to it is attached the inner margin of
the basilar membrane, on whose inner half is seated the very complex struct-
ure known as the organ of Corti.

The basilar membrane is a thin sheet of fibrillated connective tissue stretched
tightly between the tympanic lip of the limbus on the inside and the spiral
ligament (see p. 824) on the outside. The more median part of the membrane,
which supports the organ of Corti, is thin and rigid and is fibrillated in a
radial direction. The outer part, which is first thicker and then thinner again
near its point of attachment, is distinctly composed of radial fibres cemented
together; the isolated fibres are characterized by being stiff and brittle.

The organ of Corti (Figs. 280, 281) has as its supporting basis a series of
peculiarly modified epithelial cells, known as the rods of Coiii (Fig. 282, b, b'),

822

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

which are disposed iiloug the edge of the spiral lamina iu two rows, an inner
and an outer. The inner rods have their feet on the basilar membrane near its
median attachment; thoy lean outward and upward, and at their uj)pcr extrem-
ity join or articulate with the heads of the outer rods, whose feet are fastened to
the basilar membrane more exteraally. The two rows of rods are thus joined
together like the rafters of a house, and enclose beneath them a canal known
as the tunnel of the organ of Corti. The inner rods arc more numerous than
the outer, so that the latter are fastened rather between than to the ends of the
former. Leaning against the inner or median side of the inner row of rods
is a single row of hair-cells (Fig. 281), much like those described as seated on
the maculae and cristas of the labyrinth, to which hair-cells filaments of the

m.t

ig.sj)

Fig. 281.— Diagram of the organ of Corti (from Foster, after Retzius) : i.r, inner rod of Corti ; o.r, outer
rod of Corti; i.hc, inner hair-cell ; n.c, the group of nuclei beneath it; o.hc, outer hair-cells, or cells of
Corti ; CD, the twin cells of Deiters (four rows) ; n.aud, the auditory nerve perforating the tympanic lip,
U, and lost to view among the nuclei beneath the inner hair-cells ; i.spn, the inner spiral strand of nerve-
fibrils ; t.»pn, the spiral strand of the tunnel ; o.spn, the outer spiral strand belonging to the first row of
outer hair-cells ; the three succeeding spiral strands belonging to the three other rows are also shown ;
nerve-fibrils arc shown stretching radially across the tunnel"; H.c, Hensen's cells ; Cl.c, Claudius' cells ;
t.l, lymphatic epithelioid lining on the side toward the seala tympani ; l(/.sp, ligamentum spirale ; c, cells
lining the spiral groove, overhung by the vestibular lip, /.r; m.t, tectorial membrane; a fragment, torn
from it, remains attached to the organ of Corti just outside the outermost row of hair-cells.

auditory nerve are distributed. Closely applied to the single row of hair-
cells, on the inner side, are several rows of columnar cells gradually decreas-
ing in size toward the median line, and beneath the whole is a group of nuclei.
External to the outer row of rods, and separated from it by a space, are four
parallel rows of hair-cells known as the cells of Corti ; their bodies do not
reach downward as far as the basilar membrane, and just below each row is a
bundle of nerve-fibres which have traversed the tunnel of Corti and then have
changed their direction from a radial to a longitudinal or spiral one. These
fibres, and others having a more direct course, one by one end in clusters
encircling the individual hair-cells.

Four rows of peculiarly-modified columnar cells, the ceUs of Deiters, are
inserted closely between the cells of Corti, the outermost row being external
to the fourth row of Corti. These cells rest below on the basilar membrane.
Still external to these groups of cells is a series of rows of tall columnar cells
of simple character supported upon the basilar membrane, and rapidly decreas-
ing in height externally into a layer of cubt)idal epithelium covering the outer
part of the basilar membrane. The rods of Corti are peculiarly shaped at the

THE SENSE OF HEARING.

823

top, the upper extremity of each being bent at an angle so as to project exter-
nally and parallel with the basilar membrane ; these projections are the pha-
lanyar processes of the rods, the phalanges of the inner row overlapping those
of the outer row. These phalangar processes of the rods form the points of
attachment — in fact, the beginning — of the reticulate membrane (viembrana
reticulata), a peculiar cuticular, network-like structure formed of rings and
cross-bars, having the appearance of certain vegetable tissues seen under the
microscope. The reticulate membrane stretches across the outer rows of hair-

^o.r.h

m.b

Fig. 282.-Diagram of the constituents of the organ of Corti (from Foster, after Retzius) : a, inner hair-
cell; A', the head, seen from above; b, inner, b', outer, rod of Corti; ph, in each, is the phalangar pro-
cess ; c, the twin outer hair-cell ; C.c, the cell of Corti ; h, its auditory hairs ; n, its nucleus ; x, Hensen's
body ; D.c, cell of Deiters ; n', its nucleus ; ph.p, its phalangar process ; fil, the cuticular filament ; m.b,
basilar membrane; m.r, reticulate membrane; c', the head of a cell of Corti, seen from above; d, the
organ of Corti, seen from above ; i.hc, the heads of the inner hair-cells ; i.r.h, the head and phalangar'pro-
cess of the inner rod ; o.r.k, the head of the outer rod, with ph.p, its phalangar process, covered to the left
hand by the inner rods, but uncovered to the right; o.h.c, the heads of the cells of Corti, supported bj
the rings of the reticulate membrane ; ph, one of the phalangae of the reticulate membrane.

cells, the body of each of which is enclosed and is held at its top within a ring
of the network (Fig. 282, d).

Each of the cells of Deiters, described above, is continued upward in a
process which is attached to a cross-bar or a ring of the reticulate membrane
next outside its companion-cell of Corti. The inner or median line of the
Deiters cell is also modified into a cuticular thread fused below to the basilar
membrane and above to a ring of the reticulate membrane. Thus the audi-
tory hair-cells of Corti may be regarded as suspended from the reticulate mem-
brane, which in tarn is supported by the cuticular processes of the cells of
Deiters, which rest upon the basilar membrane, and by the phalangar pro-

824 AN AMERICAN TEXT-BOOK OF PHYSIOLOaV.

cesses of the nxls of Corti. The pliysical contact of the cells of Corti with
those of Deitei-s is so intimate — if, indeed, their substance is not continuous —
that impulses generated in the one can probably easily be communicated to
the other.

The upper wall of the canalis cochlearis is made of a sheet of homogenous,
fibrillated connective tissue covered with flat cells, and stretches from the
lirnbus of the spiral lamina outward and upward to the side wall of the
cochlea. It is known as the membrane of Re'iHsner. The periosteal con-
nective tissue of the bony wall of the cochlea is generall}'' well developed
within the area enclosed between the membrane of Reissner and the membrana
basilaris; it is particularly thick at the line of division between the scala media
and the seala tympani, where it forms a projecting ridge at the outer attach-
ment of the basilar membrane. This ridge is the spiral ligament ; an exten-
sion from it, gradually decreasing in thickness, reaches into both the vestibular
and the tympanic scala.

A thick layer of both columnar and cuboidal epithelium lines the con-
nective tissue forming the outer wall of the canalis cochlearis. This epithe-
lium is peculiar in that the blood-vessels of the underlying connective tissue
penetrate between the epithelial cells themselves. The tectorial membrane
{membrana tectoria) is a sheet of radially-fibrillated tissue, thin at its point of
attachment to the vestibular lip of the lirnbus, and becoming thicker and then
thinner again as it stretches out over the organ of Corti, reaching as far as the
most external row of hair-cells. It is said to lie in actual contact with the
rods of Corti and the free ends of the hair-cells, and it has been presumed to
serve as a damper for the vibrations imparted to the organ of Corti.

Theory of Auditory Sensation. — It may now be mentioned that the
generally-accepted theory of auditory sensation, as concerned with irn])ulses
generated in the cochlea, supposes that the vibrations of the perilym})h, the
endolymph, or of both are imparted to the basilar membrane. This membrane,
from its fibrillated structure, may perhaps rightly be regarded as a sheet of
parallel w^ires like those of a- piano-board. As the wires of a piano have dif-
ferent rates of vibration according to their length, and respond .'sympathetically
to correspondingly different notes sounded in their neighborhood, so it has been
supposed that different radial fibres of the basilar membrane are set into sym-
pathetic vibration by different rates of vibration in the fluids bathing them.
These vibrations must be imparted to the structures in the organ of Corti, and
the irritation of the nerves connected with the cells of Corti is a natural
sequel. It may be repeated that, though the canal of the bony cochlea as a
whole diminishes in diameter from base to cupola, the canal of the mem-
branous cochlea, the .scala media with its hnver wall or basilar membrane,
increases in diameter. Thus the radial fibres of the basilar membrane are
longest near the apex of the cochlea. The radial width of the basilar mem-
brane, measured near the bottom, middle, and top, rcsjiectivcly, is given as
.21 millimeters, .34 millimeters, and .30 millimeters. The number of fibres
of the basilar membrane is said to be 24,000; the number of inner hair-

THE SENSE OF HEARING. 825

i^ells, 3500, and of outer hair-cells in four rows, 12,000; outer rods of Corti,
3850 ; and inner rods of Corti, 5600.

C. The Relation between Physical and Physiological Sound.

Production of Sound-"waves. — Sound, in its physiological meaning, is a
sensation which is the conscious appreciation of internal clianges occurring in
certain cells of the cerebral cortex. Fibres of the auditory nerve come into
close relation with those cells, and in whatever way those fibres are excited
the result is one and the same, a sensation of sound.

The elaborate apparatus of the middle and internal ear is so constructed
that the energy of mechanical oscillations in the external air is transmitted to
the terminations of the auditory nerves in a manner to excite them.

Sound, in a physical sense, consists in waves of alternate condensation and
rarefaction travelling in the air from the point of origin of the sound, much as
waves radiate over the surface of water from the point where a stone is dropped.
Any sudden impulse, such as a ])uff of air, or the vibration of a solid body,
as a stretched string or a tuning-fork, pushes the adjacent molecules of air
against those further removed, and this impulse produces an area, or aerial
shell, of increased density or condensation. The air being perfectly elastic,
the molecules, relieved from pressure, spring back even beyond the position
of equilibrium, and leave an area of decreased density or rarefaction. Thus
a wave, consisting of a shell of condensation succeeded by a shell of corre-
sponding rarefaction, moves through the air. This single air-wave is the
simplest element of physical sound. When a number, no matter how great,
of sound-waves simultaneously excite the same particle of air, the resultant
motion of that particle is the algebraic sum of all the motions imparted to it
by the single sound-waves considered separately. As any elastic body, when
set vibrating, continues its oscillations for a time, so is it probable that strictly
isolated air- waves do not occur. Any elastic body, such as a stretched string,
or a tuning-fork, when set in vibration, sends out from itself a series of air-
Avaves which succeed one another at a rate identical with the rate of vibration
of the elastic body. Such a regular succession of air-waves striking upon the
tympanic membrane sets the latter into correspondingly regular oscillations
and produces in the auditory apparatus the sensation of musical tone.

Loudness and Musical Pitch. — The more vigorous the vibrations of the
oscillating body, the more forcibly are the air-molecules which are struck by it
driven forward ; and thfe greater their excursion or amplitude of movement,
the greater is the force with which the tympanic membrane is driven inward
when the moving air-wave strikes it. The loudness of the tone manifestly
depends upon the extent of motion of the tympanic membrane, as does this on
the amplitude of air-motion. Diiferent elastic bodies have different natural
rates of oscillation. The more rapid the rate, the more frequent is the succes-
sion of air-waves that strike upon the ear. Musical pitch is determined by
the number of air-waves which pass a given point in a unit of time, or, in
other words, by the rate of vibration of the sound-producing body. When

826 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

the vibration-rate increases the pitch is elevated, and vice versd. If some l)ody
capable of producing .sound should have its rate of vibration changed grad-
ually from 5 or 10 vibrations per second to 50,000 per second, no sensation
of sound would be aroused until the vibrations reached the rate of about from
16 to 24 per second. The droning note of the 16-foot organ-pipe and the
lowest bass of the piano represent a vibration-rate of 33 per second. In
most persons sounds cease to be audible when the air- waves have a fre-
quency of 16,000 per second, though to some the note produced by 40,000
vibrations is perceptible. It seems clear that some animals hear tones whose
pitch is so elevated as to make them inaudible to human ears. When a mov-
ing bell or whistle, as of a locomotive, rapidly approaches, its pitch seems to
rise, and then to fall as it recedes. The reason for this variation is that the
motion of the locomotive adds to or subtracts from the number of sound-
waves reaching the ear in a given time. In musical execution and in the
ordinary uses of life the limits in the pitch of sounds are much narrower.
Thus, as just stated, the lowest bass of the piano (Ci) represents a vibration-
rate of 33 in a second, while the highest treble [c'"") has that of 4224. As
to the absolute number of vibrations necessary to produce the sensation of
sound, it has been found that 2 or 3 vibrations excite the sensation of a mere
stroke ; 4 or 5 vibrations are necessary to give a tone ; and some 20 or 40 are
required to develop the full musical qualities of a tone.' That is to say, when
a musical tone falls upon the ear its characteristics cannot be appreciated until
20 to 40 vibrations have been completed.

Thus, from a physical scale representing aerial vibrations of indefinitely
various rapidity the mind selects and appreciates as sound a very small
fraction.

Tympanic Membrane as an Organ of Pressure- sense. — There is good
reason to suj)pose that variations in air-pressure succeeding one another too
slowly or too irregularly to produce sound-sen.sation are still of great import-
ance in the extensive realm of sensations which but obscurely excite our con-
sciousness. Slow inward movements of the tympanic membrane may still
give rise to a perception of external changes. Thus, a blind man has been
able to say correctly that he has passed by a fence, and whether it be of solid
board or of open picket. If any one with clo-sed eyes holds a book at half-arm's
length in front of the ear, a different sensation will be experienced according
as the book is turned flat or edgewise to the face ; the feeling is one of " shut-
in-ne&s" or " open-ne.ss," respectively. The air is in cea.seless agitation, and
its waves, striking against various objects, must be reflected to the ear with an
intensity dependent on the position and the physical character of the reflecting
media. AVe may assert that the tympanic membrane is the peripheral organ
of a 2iressiire-seyise by which we become more or less accurately aware of the
nature and position of surrounding objects, irrespective of the .sensations of
sight and hearing. Whether that group of sensations depends on the excite-

^ Mach : Physikallschen Notizen Lotos, Aug., 1873; V. Kries unci Auerbach : Du Bois-Rey-
mond's Archiv filr Physiologic, 1877, p. 297 ; Helmlioltz : Sensations of Tone, translated by Ellis.

THE SENSE OF HEARING. 827

ment of tactile nerves iu the tympanic membrane or of" tlie auditory filaments
in the internal ear is yet uncertain.' Such sensations probably form an import-
ant quota of that complex system of sensations which do not obtrude themselves
on consciousness, but which, nevertheless, bring information from the outer
world, and have an intimate association with the more or less reflex move-
ments that preserve the equilibrium of the body.

Over-tones and Quality of Sound. — We have thus far considered only
simple tones produced by simple vibrations of elastic bodies. Thus, a stretched
string plucked at its middle vibrates throughout its whole length, the greatest
amplitude of movement being at the middle point, which moves to and fro
like a pendulum. It is very rare that a body set vibrating confines itself to
a single pendular movement. Thus, a stretched string when struck not only
moves as a single cord, but the string may break up, as it were, into two halves,
each vibrating independently, but with twice the rate of movement of the
whole length of string. Not only is this the case, but the string in its vibra-
tion also breaks up into chords of one-third, one-fourth, one-fifth, etc. of its
original length, giving rise to vibrations three, four, and five times as rapid as
those produced by the whole string. In musical phrase, the middle c of the
piano, when this key is struck, gives not only a note c representing 132 vibra-
tions, but also its octave c' of 264 vibrations, the fifth above this of 396
vibrations, the second octave, 528, the third above this, 660, and so on. The
vibration of a string, then, sends to the ear a complex series of tones each of
■which represents a simple pendular motion of the air. The lowest tone, that
produced by the slowest rate of vibration of the string as a whole, is known
as the fundamental tone.

The pitch of the fundamental tone determines our estimate of the pitch
of the whole complex note. The other tones produced by segmental vibration
of the string are known as partial tones, upper partials, or overtones. The
fundamental tone is usually stronger than its accompanying overtones, the
successively higher upper partials diminishing rapidly in intensity. Some
musical instruments produce notes with a longer series of overtones than do
others ; the human voice is particularly rich in overtones. Instruments differ
also in the greater or lesser strength and in the relative prominence of the
individual overtones accompanymg the fundamental. It is the number and the
relative prominence of the overtones in a musical note that determine its quality.
Thus, a violin, a cornet, and a piano, though sounding a note of the same
pitch, would never be mistaken the one for the other ; our discrimination of
their notes depends simply upon the difference in the relative strength and the
number of their overtones, the fundamental tone being the same throughout.
The brilliancy and richness of musical notes is dependent on their w^ealth of
upper partials. It is believed that a sound-producing body, like a stretched
string, does not send to the ear a separate set of waves representing each of its
segmental vibrations, but that all the waves aroused by it fuse together into
a single series of waves of peculiar form. Such a composite wave may be
^ W. James : Psychology, 1890, vol ii. p. 140.

828

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

represented graj)liic'ally by depicting under one another a series of waves having
two, three, four, etc. times the rate of succession of the curve indicating the
fundamental tone. If a vertical line be drawn across the series representing
the vibration-rates of the various tones, and an algebraic addition be made of
the distance of each point of intersection above or below the line of rest, the
result will determine the position of the composite curve on the same vertical
(Fig. 283). It is evident that the form of the composite wave must change
with every change in the number and relative prominence of musical overtones,
and the movement imparted by it to the tympanic membrane and the wave

B e

Fig. 283.— The curve b represents twice the vibration-rate of a. When the two curves are combined
by the algebraic addition of their ordinates, the result is the periodic curve c (solid line), having a dif-
ferent form ; the dotted line of c is a reproduction of a. If b is displaced to the right until e falls under
d in A (change of phase), the combination of a and b will give the curve d, the dotted line in d repre-
senting A as before.

generated in the perilymph must have corresponding differences. Notes of
different quality are produced by composite air-waves of different forms. But
waves differing in form may still produce notes of the same quality ; for if,
in the graphical figure, one or more of the curves representing simple tones
be slid to the right or the left, the form of the composite wave will thereby be
changed, but not the quality of the sound jiroduced by it. In other words,
change of phase of the partial tones does not alter the quality of the note.'
The quality of any complex note may be reproduced by sounding together
a series of tuning-forks which have, respectively, the vibration-rate of the
fundamental tone and that of one of the overtones of the complex note.

Analysis of Composite Tones by the Ear. — According to the theory
outlined on page 824, the composite wave, beating against the sensitive organ
of the cochlea, is again analyzed into the elements composing it, one j)art of
the basilar membrane vibrating synij)athetically with one partial tone, another
with another. The isolated irritation of each nerve-element arouses in the
mind the idea of a tone of a certain pitch and loudness; but when a number

' Ilelmholtz, op. cit., pp. ."0-34.

THE SENSE OF HEARING. 829

of sucli elements are simultaneously stimulated, the mind takes note, not of thft
individual sensations thereby aroused, but of a resultant sensation formed by
the fusion of these.

That apparently simple tones are actually made up of a ninnber of partials,
having rates of vibration which form simple multiples of the fundamental
tone, may easily be demonstrated at the open piano. If any note, as c in the
bass clef, be struck -while the key of its octave c is depressed, and then the
struck string be damped, it will be found that the octave c rings out with its
proper note. So in turn the g above that, the second octave and the e above
that, may be made to sound when the lower c is struck, because each of these
strings is so tuned that its fundamental note has the same vibration-rate as
one of the overtones of the lower c. A note sung near the piano may in
the same way be analyzed more or less completely into its component tones.
The organ of hearing certainly has some such power of musical analysis, for
some cultivated ears can not only follow any special instrument in a play-
ing orchestra, but can even distinguish the overtones in a single musical
note.

The ear has little or no power of distinguishing difference of pitch in tones
of less than 40 or more than 4000 vibrations per second ; but in the upper
median parts of the musical scale the sensitiveness to change of pitch is very
acute. Thus, according to Preyer,^ in the double-accented octave a difference
of pitch of one-half vibration in a second can be detected ; that is, in the
octave included between 500 and 1000 vibrations per second, 1000 degrees of
pitch can be perceived.

Every elastic body is capable of sympathetic vibration; that is, air- waves
beating upon it at its own natural rate of vibration set it into corresponding
motion. In the same manner a heavy pendulum may be forced into violent,
movement by exceedingly light taps with the finger, the only necessary condi-
tion being that the impulses imparted by the finger be exactly timed to the
periodic motion of the pendulum or to some multiple of it. A body cai)able
of sympathetic vibration with some particular tone is set into vibration by that
tone, and reinforces or magnifies it, whether the tone exists alone or as the
fundamental of a complex note, or is contained in the latter simply as an
upper partial.

The analysis of musical sounds is usually carried out by the use of resona-
tors, which are hollow cylinders or spheres of glass or of metal, rather widely
open at one pole, and narrow-pointed at the opposite end for insertion into
the ear. The mass of enclosed air vibrates, according to its size and shape,
at some particular rate, and it is very readily set into sympathetic vibration
whenever its fundamental tone is contained in any sound reaching it. By this
means it is possible strongly to magnify, and thus select, the individual over-
tones contained in a note. The vowel sounds of human speech owe their
difference of quality to the adjustment in size and shape of the resonant air-
chambers above the vocal cords.

' Veber die Grenzen der Tonwahrnehmuny, June, 1876.

8.30 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Inharmonic Overtones. — It will be remembered that all the overtones eon-
tainecl in a miisii-al note are produced by vibrations which are simple multiples
of the rate of the fundiimental tone. These overtones are properly called
harmonic upper partials ; they are, according to Helmholtz, particularly charac-
teristic of stretched strings and narrow organ-pipes. But most clastic bodies
have proper tones which are not exact multiples of the fundamental, and
which may be termed inharmonic upper partials. The high-pitched jingle
heard when a tuning-fork is first struck represents the inharmonic upper par-
tials of the fork. Stretched membranes have a great number of such inhar-
monic overtones. Inharmonic upper partials, as might be expected, rapidly
die out in a note of which they form a part. It is evident that inharmonic
proper tones, when nearly of the same pitch, must interfere with one another
and repress the development of a well-marked fundamental tone.

Production of Beats. — When two tones of slightly different pitch are
sounded together, the more rapid vibrations overtake the slower, so that at
certain periods the crests, or phases of condensation, of two waves fall together,
and the result is a phase of increased condensation and louder sound. The
waves immediately cease to correspond, and diverge more and more until the'
crest of one falls upon the trough of another, the result being silence, or at
least great diminution in the intensity of the sound. Such alternate augmenta-
tion and diminution of the waves give rise to pulses in the sound, known
technically as beats. This is one of the most familiar and important phenom-
ena of musical art. If two tuning-forks on resonance-boxes vibrate in unison,
a piece of wax stuck to the prong of one fork will lower its tone and give rise
to beats. The undulating sound caused by striking a bell or the rim of a thin
glass tumbler is due to beats. When two notes not included in a perfect chord
are sounded on the piano, beats are heard not only from the interference of the
fundamental tones, but of the upper partials as well. It is the absence of beats
in notes which should be in harmony, as those of the major chord, that deter-
mines the instrument to be in tune. When two tones produce beats, the
number of beats in a given time is equal to the diiference between the number
of vibrations involved in the two tones in the same time. For example, a tone
produced by 256 vibrations in a second sounded with one of 228 vibrations
would give 28 beats in a second. It is evident that the frequency of beats
may be increased either by increasing the interval between the tones or by
striking tones of the same interval in a higher part of the scale. Beats which are
not too frequent — from four to six in a second — have important musical value,
but when they number thirty or forty in a second they become exceedingly dis-
agreeable, irritating the ear in a manner analogous to the etlcct of a flickering
light on the eye. When sufficiently near together the beats no longer produce
an intermittent sensation. The number of beats in a second required to result
in this fusion increases as we ascend the musical scale, varying from 16 beats
at c of 64 vibrations per second to 1 36 beats at c'" of 1024 vil)rations.' The
reason for this variation lies in the progressive shortening of the waves as the

» Mayer: Sound, 1891.

THE SENSE OF HEARING. 831

sound becomes higher in pitch ; for it is obvions that as we ascend the scale,
and the waves of sound become progressively shorter, spaces would be left
between the individual waves unless their number w^ei'e jH'oportionately
increased.

Harmony and Discord. — Tones are concordant, or harmonize, when they
produce no beats on being sounded together ; thoy are di.HCOi-dant wlien beats
are produced, and the painful sense of dissonance increases in intensity up to
about 33 beats per second. Perfect concord is obtained by blending notes
whose vibrations are to each other as small whole numbers.

Thus, in tiie major cord c E G c

the vibration-numbers are 132 165 198 264

their ratios are 4 5 6 8

If notes the ratios of whose vibration-rates can be represented only by large
w'hole numbers are combined, a discord is formed, for the reason that their
upper partials interfere with one another and cause beats ; there is no especial
virtue in the small integer.^

Thus, in the discord c D E

the vibration-numbers are 132 148.5 165

which are not reducible to small whole numbers.^

Combinational Tones. — When two tones are sounded together, there is
produced a new, usually weaker, tone, whose vibration-number is the numerical
difference between the vibration-rates of the original tones. It is therefore
known as a differential tone. Such tones may arise from upper partials as well
as from the fundamentals; they do not appear to be formed, as might be sup-
posed, by the fusion of beats. Other "combinational" tones of more intricate
relations, as well as beats, arise from the interaction of vibrations when many
different notes, as those of an orchestra, are sounded together. To calculate
the physical result of the combination of these impulses, which it is the duty
of the tympanic membrane to transmit, is a problem of exceeding complexity.

ReswiiL — To sum up the subject, musical sounds are distinguished in sen-
sation by the three factors, loudness, pitch, and quality, sometimes called color
or timbre. These sensations depend in turn on definite physical characters of
air-waves : their amplitude, or the extent of motion of the air-molecules ; their
frequency, or rate of succession of the waves; their form, which is deter-
mined by the pitch and relative predominance of the upper partials combined
with the fundamental tone.

Fatigue. — That the ear is subject to fatigue toward a note that has been
sounded is easily demonstrated in the following way : Strike a single note of,
say, a major chord on the piano, and immediately afterward sound the full
chord; the quality of the latter will be altered from its normal character,
owing to the lessened prominence of the note which had been struck.* We
may therefore not improperly speak of a successive contrast in auditory sensa-

*Tyndall: Sound. * Waller: Human Physiology, 1891.

* Foster : Text-book of Physiology, 5th ed., 1891.

832 ^.V AMERICAN TEXT- BOOK OF PHYSIOLOGY.

tions, analogous to visual successive contrast, by which our perception of every
sound is colored by the sounds which have preceded it.

Imperfections of the Ear. — Notwithstanding the mechanical provisions
for making the external and middle ear a j)erfect transmitting apj)aratus^
sound-perception is more or less modified by the action of the mechanism
under certain conditions. Thus, Helmholtz believed that various combina-
tional tones owe their origin chiefly to a perio<lic clicking in the joint between
the malleus and incus bones. The resonance of the ear is a familiar fact,
and througli it high-pitched tones between e"" and g"" are reinforced and
heard with undue loudness. Certain hissing sounds, the chirp of a cricket or
the note of a locust, thus gain their intensity. This resonance probably is a
feature of the external auditory meatus, since it is at once destroyed by apply-
ing a small resonator to the ear (Helmholtz).

Perception of Time Intervals. — The ear is eminently the sense apparatus
for determining small intervals of time. Flashes of light succeeding each
other at the rate of twenty-four in a second are fused in a continuous luminous
impression by the eye, but by the ear at least one hundred and thirty-two audi-
tory impulses as beats may be heard separately in a second. The |X)wer which
the ear possesses of resolving complex air-waves into the host of pendular
vibrations which may enter into their formation finds no analogy in the eye
(Helmholtz).

Musical Tones and Noises. — The important feature of the physical
processes which give rise to musical tones is their penodicifi/. Every musical
tone is produced by a regular succession of alternate rarefactions and condensa-
tions in the air. The remaining class of sounds, known as noises, differs from
musical sounds in the respect that such sounds are j)roduced by an irregular
succession of air-waves — one in which tlie interval between phases of conden-
sation and rarefaction does not remain constant as in a musical note. Noises
are for the most part made up of short musical notes so associated as not to
" harmonize " with one another. As expressed by Helmholtz, the sensation
of a musical tone is due to a rapid periodic motion of a sonorous body ; the
sensation of a noise, to non-periodic motions.

Functions of Different Parts of the Ear. — Concerning the functions of
the different parts of the internal ear in their relation to sound-perception, it
is generally believed, as previously stated, that the basilar membrane of the
cochlea, with the nervous elements seated on it, is the organ concerned in the
reception and transmission of musical sounds. There are a sufficient number
of fibres in the basilar membrane to allow several to vibrate with every
audible tone.

It cannot, however, too strongly be impressed that no theory of physiolog-
ical action should be accepted definitively without rigid experimental proof, and
such evidence concerning the definite functions of the cochlea is almost wholly
wantinor. The sensorv hair-cells on the maculfe of the saccule and the utricle
have been thought to have the duty of vibrating in response to any agitation
imparted to the perilymph, without regard to its periodic character ; they

THE SENSE OF HEARING.

833

might thus be termed sense organs for the perception of noises. Evidence
will be adduced later (p. 848) lor the belief that they are peripheral organs
for the preservation of static equilibrium.

The hair-cells on the cristae of the ampullse of the semicircular canals seem
to have a special function in giving rise to sensations caused by changing the
position of the head ; they thus are organs concerned with the preservation of
the equilibrium of the body.

Judgment of Direction and Distance. — The distance and direction from
which sounds come to the ear are not perceived directly, but our estimate of
them is a judgment based on the loudness and quality of the sound sensation,
combined with a power of reasoning from past experience. Thus, in seeking to
discover the direction whence a sound comes, it is usual for an observer to turn

Fig. 284.— End-bulbs from human conjunctiva (from Quain, after Lo'fagworth) : A, ramification of nerve-
fibres in the mucous membrane, and their termination in end-bulbs, as seen with a lens; b, end-bulb,
highly magnified ; a, nucleated capsule ; b, core, the outlines of its component cells not seen ; c, entering
nerve-fibre branching, its two divisions to end in the bulb at d.

the head to the position in which the sound is heard loudest, and thus to form
an opinion a.s to the direction whence it comes. Errors of judgment as to the
direction are frequent, owing to the sound reflected from some object appearing
louder than that coming in a direct line from its source. It is said that when
there is total deafness in. one ear every sound seems to have its origin on the
side of the healthy ear. The quality as well as the loudness of a sound varies
according to the distance of its source. Thus, the lower tones die away earliest
as a sound recedes, bringing the overtones into undue prominence. The art of
the ventriloqui.st consists largely in altering the quality of the sounds he pro-
duces to imitate the quality they would naturally have if arising under the
conditions which he would lead his hearers to i)elieve to be their origin. A
comparatively feeble sound near at hand may have the same quality as a loud

53

834

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

one lieard at a distance; thas, a frog croaking in an adjoining room was once
niistaiceu by the writer lor a large dog barking outside the building,

D. Cutaneous and Muscular Sensations.

General Importance of the Cutaneous and Muscular Sensations. —
Cutaneous sensations arc aroused by the operation of some form of energy on
the skin, and they include the sensations of touch, of temperature, and of pain.
By vimcular sensatio)i is meant the appreciation which we have of the intensity
and direction of muscular etibrt. Closely allied to this sensation is a yeneral
■sensibility through which we gain a c

knowledge of the relative position
of the parts of our bodies, irrespec-
tive of movements. The direction,
size, distance, and surface features
of external objects are usually made
known to us through the sense of

4.. ^C9t

Fig. 28.'). — Tactile corpuscle
within a papilla of the skin of
the hand (from Quain, after Ran-
vier) : n, n, two nerve-fibres pass-
ing to the corpuscle : a, a, ter-
minal varicose ramifications of
the axis-cylinder within the cor-
puscle.

Fig. 286.— other tactile corpuscles (from Quain ; a, b, after Meckel ;
c, after Fischer) : a, longit\idinal section showinjc the interior trav-
ersed by connective-tissue septa derived from the capsule ; the nerve-
fibres are cut across, b, transverse section at the point of entrance
of a nerve-fibre, showing the axis-cylinder branching; other fibres
cut obliquely, c: 1, entering nerve-fibre, medullated ; 2, 2, the same
cut variously within the corpuscle; 3,3, clear spaces around the
fibres ; 4, 4, nuclei of the transverse and spirally-disposed cells of the
corpuscle.

sight or of hearing. Yet these fundamental facts regarding the things
about us do not become a part of knowledge through direct visual and audi-
tory perception. Such knowledge is ba.sed on complex judgments concern-
ing the meaning of auditory and visual phenomena according as they have, in
past experience, been interpreted by tactile and mu.scular perceptions. That is,
when reduced to its simplest terms, our most practical and important knowledge
of the world is the outgrowth of tactile and mu.scular perceptions ; by and
with them all other sense-perceptions of objects have been corrected and com-
pared. Thus, so simple a feat as the estimate of the size of a distant object is

CUTANEOUS AND MUSCULAR SENSATIONS.

835

the result of a complex juilj^ment bii-sed on tactile aud muscular experience.
Through tlie sense of sight we perceive the ratio of the visual angle subtended
by the object to that of the whole tield of vision; but as objects of different
size may fill the siuue visual angle when at difierent distances from the eye,
our estimate of their size depends upon the distance at which we suppose
them to be situated. The distinctness of the surface features of the body
af!brd the mind an important clue, since experience shows that details of
surface in a body become more obscure as we recede from that body. But
more important data C(Micerning distance come from the sense of muscular
innervation, or feeling of the intensity of nniscular contraction, by which we
estimate the degree of convergence of the optic
axes when the object is focussed, and still more by
the jierception of the amount of muscular effort
necessary to sweep the optic axes over the ground
surface intervening between the observer and the
object. When objects approach the near-point of
vision the sense of innervation of the pupillary
muscles affords important evidence of their distance.

That fundamental etlucation concerning the outer
world which engages the earliest years of every child
consists in accunmlating aud systematizing with
other sense-perceptions tactile and muscular im-
]>ressions of objects. A sensation is no sooner felt
than some muscular movement involving a definite
muscular feeling is made by which the character of
the sensation is changed and experimentally tested
under different conditions. The physiological pro-
cess involved in building up sense-knowledge, there-
fore, embraces in alternation sensation excited by
external objects, motion accompanied by muscular
sensation, and change in the original sensation. In
other words, the motor and sensory impulses form a
sort of balance, and both are necessary.

Ending- of Sensory Nerve-fibres in the Skin. —
The afferent nerves supplied to the skin have several
modes of termination. In the commonest form the
plexus of medullated nerve-fibres found in the dermis
close under the epidermis gives off twigs which, losing the medullary sheath,
pierce the epidermis and here form a network among the cells of the Mal-
pighian layer, the single fibres ending freely in this position (Fig. 294). Other
sensory nerves do not penetrate the epidermis, but end in various peculiar
terminal organs in the dermis or in the subcutaneous tissue underneath. These
terminal organs are known respectively as end-bulbs, touch-corpuscks, and
Pacinian bodies (Figs. 284-287). Each organ consists of a more or less conical
bodv in which a nerve-fibre terminates. The end-bulbs are found only on the

Fig. iST.-Magnified view of a
Pacinian body from the cat's
mesentery (from Quain, after
Ranvier): n, stalk with ner\'e-
fibre enclosed in sheath of Henle,
passing to the corpuscle; u', its
continuation through the coil, tn,
as a j«ile fibre ; a, termination of
the nerve in the distal end of the
core (the terminations are not
always arborescent^ ; rf, lines
separating the tunics of the cor-
puscles; /, channel through the
tunics, traversed by the nerve-
fibre ; c, external tunics of the
corpuscle.

83(3 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Senilis of tlie conjunotiva and the lips, and in modified form on the sensitive
surfaees of the genital organs (Fig. 284). The toach-corpi(sc/e.s, though appar-
ently absent from the greater part of the body, occur in great nmnbers in the
sUin of the palmar surface of the hand and that of the fingers, especially at
their tips; at the edge of the eyelids and the lii)s; on the soles of the feet
and the toes ; and on the surface of the genital organs. The touch-corpuscle
often occupies a papilla of the dermis directly under the epidermis (Fig. 285).
The Pacinian bodie.s, which are oval corpuscles, larger than the foregoing,
and easily visible to the unaided eye, are found not in the skin proper, but
in the subcutaneous connective tissue beneath it. They are found in abundance
beneath the skin of the })alm of the hand and the sole of the foot; they are
also numerous along the nerves of the joints, and even among the sympathetic
nerves supplying the abdominal organs (Fig. 287). Sensory nerves also end
in tendons as somewhat arborescent exi)ausions of axis-cylinder matter known
as the organs of GoUji, and in muscles near their tendinous attachments.

1. Sense of Touch. — The Relations between Sensation and Stimulus. —
Many so-called " tactile sensations," such as wetness, hardness, roughness, etc.,
are not simple sensations at all, but are complex judgments built up out of the
association of certain tactile, temperature, and nmscular sensations, and con-
veying to us a knowledge of the surface, substance, and form of bodies.

AVhen analyzed, the sense of touch is nothing more than a sense o^ pressure
applied to the skin. To test the pressure sensihiliiy of the skin the object
whose weight is to be estimated must not be lifted in the ordinary way, for
that would bring into j)lay the muscular sensations. If the skin of the hand
is to be tested, the hand must be placed upon some firm support, such as a
table, and the weights be laid upon the skin. The smallest perceptible weight
that can thus be felt varies with the situation to which it is api)lied. Thus,
the greatest sensitiveness to pressure is found on the forehead, the temples,
the back of the hand, and the forearm, where a weight of .002 gram (^
grain) can be perceived. The Aveight nuist be increased to .005 to .015 gram
to be felt by the fingers, and to 1.0 gram when laid on the finger-nail.^

The power of discriminating differences of pressure applied to the skin is
tested by finding the smallest increase that must be added to a weight in order
that it may be perceived as being heavier. This increment is not, as might
be supposed, the same for weights of different value, but it bears a distinct
proportion to them. Thus, a weight of 11 grains may just be perceptibly
heavier than one of 10 grains; but if we start with a weight of 100 grains,
a sinirle iri'ain added to it will arouse no difference of sensation, an increment
of 10 grains being necessary in order that one weight may a])j)car heavier
than the other. This fact is the basis for Weber's law of the relation between
stimulus and sensation; this law may be formulated as follows: T7ie amount
of stimulus necessary to provoke a perceptible increase of sensation always bears
the .same ratio to the amount of stimulus already applied. This law is found
to be only approximately correct, especially when very small and very large
' Aubert and Kammler: MoleKchotCs Untersnehungen, 1859, vol. v. p. 145.

TIIH SKXSK OF rilESSURE. 837

weights lire compaml. I'Vcliiicr attempted to express more exiidly the ivlation
between the intensity of stinuilns and sensation in liis " psyelio-physical law,"
tlnis: The Intemity of Komdion varle.s with the hf/arithm of the dimiilns. In
other words, the sensation increases in arithmetieal progression, while the
stimulns increases in geometrical jirogression. With moderate weights a
difference of ])ressnrc is perceptible when the ratio of increase is smaller tiian
when either very small or very large weights are nsed ; that is, sensitiveness
to jn-essnre-change is keenest under moderate stimulation.

It is said that the forehead, the lips, and the temples appreciate an increase
of -jJ^^ to ^V of t^'C weight estimated, while the skin of 'the head, the fingers,
and the fijrearm requires an increase of ^\ to j\ for its perception. In this
as in other kinds of sensation it is the difference, or variation of intensity, of
the sensation of which the mind takes particular cognizance. One touch-
sensation is more acutely perceived when contrasted with another than wlien
felt alone. Weber ^ found the discrimination of pressure-differences to be
finer when two weights were laid in rapid succession on the same skin-area
than when the weights were applied either sinniltaneously or successively to
different parts. If a finger be dipped in a cup of mercury or of water having
the same temi)erature as the skin, the pressure will be marked only at the
margin between the air and the fluid, and if the finger be moved up and
down it will seem as if a ring were being slid back and forth njwn it. Tiie
fingers are particularly sensitive to intermittent variations of pressure— a
factlity the use of wliich is manifest when the function of these parts is
considered.

Two weights, in being tested, should press upon equal areas of skin ; accord-
incr to Weber,^ if two equal weights have different superficial expanse, that
which touches the larger skin-surface, and thereby excites the greater number
of touch-nerves, will appear to be the heavier. This result, however, cannot
always, nor indeed usually, be verified. The simultaneous excitement of other
sensations may modify that of pressure ; thus, when two coins of equal weight,
but one warm and the other cold, are laid upon the hand or the forehead, the
cold one appears to be much the heavier.

There is a sensation of after-pressure depending for its strength on the
amount of the weight and the length of time this weight has been applied.
In fact, this after-sensation may produce a striking effect on consciousness,
a familiar example of which is the persistence of the sense of pressure of
the hat-band after the head-covering is removed. Even light weights leave
an after-sensation, and, in order to be perceived as separate, must be applied at
intervals of not less than -j|^ to g|o of a second. It is said that when the
finger is applied to the rim of a rotating wheel provided with blunt teeth, the
sep'arate teeth are no longer felt, and the margin seems smooth, when the con-
tacts succeed each other at the rate of 500 to 600 in a second.' Vibrations of

1 "Tastsinn nnd Gemeinsefiihl," Wagner's Handnwierbuch der Pkysiolngie, 1846.
'Quoted in Hermann's Handbuch der Physiologie, Bd. iii. 2, S. 336.
=* Landois and Stirling: Human Physiology, 1886.

838 ^l.y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a string cease to be api)reciate(l by the finger when tliey have a rate of" between
1500 and 1600 per second.

Tlie Localization of Touch-sensation. — When a touch-sensation is felt, the
mind inevitably refers the irritation to some particular part of the surface
of the body, and the sensation seems to be localized in this area. On the
accurate localization of tactile sensations depends not only the safety of the
individual, but also the performance of the ordinary acts of life.

We may suppose that to each area of peripheral distribution of tactile
nerve-fibres in the skin there corresponds an area of tactile nerve-cells in the
brain. It can hardly be doubted that the nerve-cells are divided into physio-
logical groups characterized l)y inherent and inborn quality-ditierences in the
sensations aroused by their respective excitements. The reference of the sen-
sations aroused by the excitement of definite nerve-cells to definite parts of the
periphery is a power acquired through the physiological experiences of the
earliest months of life. Through the sense of sight the seat of irritation is
recognized, and through muscular sensation its relation to surrounding parts
is experimentally explored, so that cunmlative harmonious experiences of tactile,
visual, and muscular sensations finally bring into correspondence the various
areas with definite varieties of touch-sensation, or, to use an expression of
Lotze's/ every area of the skin acquires a " local sign " by which it is dis-
tinguished in consciousness.

This power of localization differs widely for different parts of the skin.
The fineness of the localizing sense for any skin-area is easily estimated by
determining how far apart the tips of a pair of compasses, applied to the skin,
must be separated in order to be felt as two. For this experiment the compass-
points must be smooth, and they should not be applied heavily. The general
result of such an inquiry is that the compass-points may be nearer together,
and still be distinguished as two, in proportion as the surfaces to which they
are applied have greater mobility. Since it is just such parts of the body as
the tips of the tongue and the fingers that are chiefly used in determining the
position of ol)jects, the advantage of such an arrangement is obvious. The
skin can thus be marked out in area.s (tactile areas)^ within each of which the
compass-points are felt as a single object, but if they are separated so as to fall
beyond the borders of these areas, they are at once perceived to be two.

The following figures" represent the distances at which the compass-points
can just be distinguished as double when applied to various parts of the body :

Tip of tongue 1-1 mni.

Palm of last phalanx of finger 22"

Palm of second phalanx of finger , . . . . 4.4 "

Tip of nose <'-6 "

Back of second phalanx of finger H.l "

Back of liand 29.8 "

Forearm -^9.6

Sternum 44

Back 66 "

' Kunke. in Hermann's Ifandbuch der Physiologie, Bd. iii. 2, S. 404.

2 Foster's Physiology, 5th ed., 1891.

THE SENSE OF PRESSURE.

839

It will be observed that accuracy of localization and sensitiveness to pre»5ure
find their most perfect manifestations in widely separate regions of the skin.

Tactile areas are found to have a general oval form with the long axis
parallel with the long axis of the member investigated. If the compass-points,
separated, say, half an inch apart, be pa.«^sed over the skin of the palm from
the middle of the hand to the finger-tips, the sensation will be that ot a single
line gradually separating into two diverging lines. The result, of course,
depends on the compass-points passing successively through areas of finer
localization. If an area be marked out on. a part of the skin where localiza-
tion is poor, within which area two points simultaneously applied appear to be
one; a single point moved within it is still perceived to change its place, and
two points successively applied may be perceived to occupy different positions
The mental fusion or separation of the two compass-points cannot depend
altogether on their being placed over the terminal twigs of the same or of two
adjoining nerve-fibres, for, were this the case, the points could be discriminated
when separated by a verv small distance across the line drawn between the
endinos of adjoining nerve-fibres, while on either side the points would have
to be much more widely separated in the area of distribution of a single filjre.
The important factor in the mental separation of two stimulated points is, that
between such points there shall be found a certain number of sensory elements
which are unstimulated.^ Practice in such experiments greatly increases the
power to localize impressions. This improvement is evidently due not to
the establishment of new nerves, but to a more perfect discrimination of sen-
sations in the nerve-centres. When, by practice, the localizing power of
the skin of a finder of one hand has been increased, it is found that the
same improvement has been acquired by the corresponding, but untrained,
fino-er of the other hand ; in other words, the localizing power is central,

not peripheral.

Presmre-points.— It has been found that if a light object, such as a lead-
pencil, be allowed to rest by a narrow extremity successively on different parts
of the skin, its weight will appear very different according to the part which
is touched. If the spots on which the weight appears greatest be marked with
ink, they will be found to have a constant position, and the skin may therefore
be mapped out in areas of pi-essure-points, which are believed to indicate the
place of ending of pressure-nerve filaments.

The Importance of the End-organ.— The sense of touch or pressure is a
special sense; that is, any irritation conveyed to the nerve-centres in which
the nerves of pressure terminate gives rise to a feeling of touch, just as dis-
turbance in the visual or the auditorv centre is recognized in consciousness as
a sensation of sight or of sound. The complex anatomical structures known as
sense-organs may be considered as instruments each of which is differentiated
in a manner to make it particularly irritable toward some special form of
energy. Thus, the retina is most sensitive to the luminiferous ether; the organ
of Corti, to waves of endolymph, etc. To this differentiation of structure the

1 Weber: "Tastsinn und Gemeingefuhl," Wagne/s Handworterbuch der Physiologic, 1846.

840 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

sensitiveness of the body to the forces of nature is chicHy due. 'J'lic j)erij)lieral
ending of the pressure nerve, whether a naked axis-cylinder or a touch-corpus-
cle, is no doubt niodificd to be particidarly irritable toward that form of energy
manifested in the molecular vibration of the tissue solids, brought about by
contact with foreign objects. . Hairs, j)articularly those in certain localities of
some animals, as the whiskers of the cat, appear to have the function of trans-
mitting mechanical vibrations to the nerve-endings in greater intensity than
could be accomplished through the skin alone.

No true sense of touch is aroused by direct irritation of a nerve-trunk or
exposed tissue, and touch-sensations do not arise from iri'itation of the internal
surfaces of the body. A fluid of the temperature of the body gives, when
swallowed, no sensation in the stomach ; wlien cooler or warmer than the
body, there is a sensation due, probaljly, to a transmission of temperature
chanyce to the skin of the abdomen.

Touch Illusions. — Certain peculiar errors in judgment may arise when
tactile sensations are associated in a manner unusual in experience. Thus, in
an experiment said to have b^en devised by Aristotle, if the forefinger and
the middle finger be crossed, a marble rolled between their tips will appear to
be two marbles; if the crossed finger-ends be applied to the tip of the nose,
there seems to be two noses. The illusion is due to the fact that under
ordinary circumstances simultaneous tactile sensations from the radial side of
the forefinger and the ulnar side of the middle finger are always caused by
two different objects. It is a not uncommon surgical o})eration to replace a
loss of skin on the nose by cutting a flap in the skin of tiie forehead, without
injury to the nerves, and sliding the flap round ujjon the nose. Touching
the piece of transplanted skin gives the patient the sensation of being touched,
not upon the nose, but upon the forehead ; after a time, however, a new fund
of experience is accumulated, and the sensation of contact with the transplanted
flap is rightly referred to the nose. Persons who have suffered amputation of
a lower limb often complain of cramps and other sensations in the lost toes.
The illusion no doubt comes from irritation, in the nerve-stump, of fibres
which previously bore irritations from the toes.

2. Temperature Sense. — The skin is also an organ for the detection of
changes of temperature in the outer world. Such temj)erature difllerenccs ]>rob-
ably make themselves manifest by raising or lowering the temperature of the
skin itself, and thus in someway irritating the terminal parts of certain sensory
nerves, the tonperature nerves. The sensitiveneas of the skin to temj)erature
variations is not the same in all parts; thus, it is more acute in the skin of the
face than in that of the hand ; in the legs and the trunk the sensibility is least.
We refer temperature sensations, somewhat like those of touch, to the peri|)hcry
of the body, and localize them on the surface. The skin over various parts
of the body may have different temperatures without exciting corresponding
local differences of sensation. Thus, the forehead and the hand usually seem
to be of the same temperature, but if the palm be laid upon the teniples,
there is commonly felt a decided sensation of temperature change in one or

THE SENSE OF TEMPERATURE.

841

both surfaces. As iu other sensations, fatigue and contrast play an ini}K)rtant
j)art in the sense perceptions of temperature, and stimuli of rapidly-changing
intensity provoke the strongest sensations; thus, when two fingers are both
dipped into hot or cold water, the Huid seems hotter orcolder to that finger
which is alternately raised and lowered.

In changing to a place of different temperature the skin for a time seems
warmer or cooler, but soon the temperature sensation declines, and on return-
ing to the original temperature the reverse feeling of cold or of warmth is
experienced. For every part of the skin, then, there is a degree of tempera-
ture, elevation above or depression below which arouses respectively the
feeling of warmth or of cold, and the temperature of the skin determining
the pliysiological null-point may vary within wide limits.

The smallest differences of temperature that can be perceived fall, for most
parts of the skin, within 1° C. The skin of the temples gives perception of
differences of 0.4°-0.3° C. The surface of the arm discriminates 0.2° ; the
hollow of the hand, 0.5°-0.4° ; the middle of the back, 1.2°.^

The size of the sensory surface affected modifies the intensity of temperature
sensation : if the Avhole of one hand and a single finger of the other hand be
dipped into warm or cold water, the temperature will seem higher or lower to
the member having the greatest surface immersed.

Cold and Warm Points. — The skin is not uniformly sensitive to tem-
perature changes, but its appreciation of them seems to be limited to certain
points distributed more or less thickly over the
surface. These spots appear to be the places of
termination of the temperature nerves in the epi-
dermis (Fig. 288). There is little doubt that there
are two distinct varieties of temperature nerves,
one of which appreciates elevation of temperature,
or heat, and the other diminution of temperature,
or cold. Thus, if a blunt-pointed metal rod be
warmed and be touched in succession to various
parts of the skin, at certain spots it will be felt as
very warm, while at others it will not seem warm
at all. If, on the contrary, the rod be cooled, a
series of cold points may in the same way be made
out. The point of an ordinary lead-pencil may
be used with some success to pick out the cold
spots. The " cold points " are more numerous
than the " hot," and those of each variety are
more or less distinctly grouped round centres, as
would be expected from the manner of nerve-distribution, though the groups
overlap to some extent (Fig. 288). Certain substances appear to act, prob-
ably by chemical means, as specific excitants of the two sets of nerves.
Thus, menthol applied to the skin gives a sensation of cold, while an atmo-
' Nothnagel: Deutsche. Archiv/iir fcUnische Medicin, 1866, ii. S. 284.

Fii;. -JSN— Cutaneous "cold" spots
(vertical shading) and "hot" spots
(horizontal shading), anterior sur-
face of the thigh (from Waller, after
Goldseheider).

842 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

spliere of carbon dioxide surrouiidiug uii area of skin gives a sensation of
Avarnitli.'

The specific difference of the two sets of temperature nerves is indicated by
the fact that when a warm and a cold body held close together are simulta-
neously brought near the sUiii, the sensation is either one of both warmth and
cold, or now one and now the other sensation predominates.^ Any stimulation,
whether mechanical or electrical, applied to the sensitive points thus far de-
scribed in the skin, for the appreciation of either pressui'e, heat, or cold, pro-
vokes, when effective, only the proper sensation of that point ; any irritation
of a cold, hot, or pressure point gives rise, respectively, to the sensation of
cold, heat, or pressure alone.

As in other organs of special sense, the peripheral terminations of the
temperature nerves seem modified to be especially irritable toward their appro-
priate form of physical stimulus. Cold or heat directly applied to the nerve-
trunk excites no temperature sensation. Thus, if the elbow be dipped into a
freezing mixture, as the lowered temperature penetrates to the ulnar nerve the
sensation will be one, not of cold, but of dull pain, and it will be referred to
the hand and the fingers. The internal nuicous surfaces of the body, from
the oesophagus to the rectum, inclusive, have no power of discriminating
temperature sensations ; a clyster of water cooled to from 7° to 16° C, if not
held too long, is only perceived as cold when the water escapes through the
skin of the anus.

Tiie doctrine of specific nerve energy, enunciated by E. H. AVeber, was
intended to convey the idea elaborated above, that each nerve of special sense,
however irritated, gives rise to its own peculiar quality of sensation. But it
seems clear that the existence and quality of the sensation are, respectively,
properties of the activity, not of the nerve-fibre, but of the peripheral end-
organ and the nerve-centres.

3. Common Sensation and Pain. — '^Fhe sensations thus far considered
have been called special sensaiion.s, because each affects the consciousness in
quite a different way, and any irritation which excites the sense apparatus
provokes a sensation of definite quality and measurable intensity.

Pain is a sensation which, according to common but erroneous belief, is the
result of sufficiently intensifying any of the simple sensations.

Pains have received various names to distinguish their quality, according to
the mode in which experience shows they may have been produced, as cutting,
tearing, burning, grinding, etc. One peculiar mark that distinguishes painful
sensations is the lack of complete localization. While lesser pains are referred
with fair exactness to different parts of the body, and even to those internal
parts devoid of tactile sensibility, greater pains radiate and seem diffused over
neighboring parts. Pain also differs from special sensation in the long latent

' Goldscheider : Da Bois-Reymon(V s Archiv fiir Phydoloyie, 1886, 1887 ; Blix : Zeilfchrlfl fiir
Biologic, 1884; Donaldson : Mind, vol. 39, 1885.

* Czermak: Silzungsberichte d. Wiener Akad., 1855, p. 500; Klug: Arb. d. physiol. Anstall zu
Leipzig, 1876, p. 168.

THE SENSE OF PAIN. 843

period preceding its development. The evidence of physiological experiment
is against the belief that any irritation of the nerves of so-called "special
senses" can j)rodiU'e j)ains, bnt it teaches that this sensation is the resnlt of the
excessive or unnatnral stimulation of a group of nerves whose function is to
give rise to what is indefinitely called " common sensation." By this term is
designated that consciousness which we more or less definitely have, at any
moment, of the condition and position of tiie various parts of our bodies.
When tactile, temperature, and visual sensations are eliminated, we are still
able to designate with considerable accuracy the position of our limbs, and we
become aware with extraordinary exactness of any change in that position,
indicating the possession of a podure sense. The nerves of common sensation
must, then, be continuously active in carrying to the sensorium im])ulses
which, though they do not excite distinct consciousness, probably are of the
utmost importance in keeping the nerve-centres informed of the relative posi-
tions and physiological condition of the various parts of the organism, and it
is not improbable that they are the afferent channels for many reflex acts
which tend to preserve the equilibrium of the body. The sudden failure of
these sensations in a part of the body would probably be felt as acutely as the
silence which succeeds a loud noise to which the ear has become accustomed.
Pain is thought to be the result of excessive stimulation of the nerves of com-
mon sensation, though it must be admitted that we know next to nothing
of the anatomical and physiological conditions on which this sensation is
dependent. It is said not only that most internal organs possess no def-
inite tactile or thermal sensibility, but that, when normal, such irritation as
is caused by cutting, burning, and pinching seems to cause no pain ; ^
let them, however, become inflamed, and their sensitiveness to pain is suf-
ficiently acute. The facts of labor-pains, of colic, and other visceral dis-
turbances which are attended by no inflammatory condition show, however,
that the factors on which the existence of pain depends are not as yet fully
understood.

The physiological facts on which is based the belief in " common sensa-
tion " are indisputable, but the evidence for a special nervous apparatus for
such sensibility is based rather on exclusion of known nerve-organs than on
positive demonstration. In the category of common sensations have been
included also such feelings as " tickling," shivering, hunger, thirst, and sexual
sensations. The feeling of fatigue which follows either muscular or mental
exertion may be })laced in the same group.

A general feature of common sensations is their subjective character; they
are not definitely localized within the body, nor are they projected external to
it, as in the case of the " special senses."

Between the common sensation and its existing cause there is no measurable

proportion, as is found, for instance, in the study of the pressure sense. It

may be stated that pressure and temperature sensations were within a recent

period grouped among common sensations, and future investigations may pos-

» Foster's Physiology, 1891, p. 1420.

844 .l.V AMERICAN TEXT-HOOK OF I'JI YsrOLOGY.

sihlv limit eacli of tlie looliii<j;8 now cla-SisCtl together as "coininoii sensations"
to definite anatomical structures,

AVlien the punctiform distribution of various sensations iu the skin is inves-
tisjated, some points are found in which no other sensation than tiiat of jiain
can be excited, and it has been thought that such spots mark the jjlace of
ending of nerves of common sensibility.

Transferred or " Sympathetic" Pains; Allochiria. — It has long been a
matter of clinical observation that disease seated in certain internal organs is
often accompanied by superficial pain and tenderness in widely removed parts
of the body; for example, a decayed tooth frequently causes intense pain in
the ear; disease of heart or of aorta may cause pain l)etween the shouKlers,
etc. The subject lias received most accurate investigation from Head,^ who
has shown that there is an intimate nervous connection between tiie internal
organs and definite areas of the skin, manifested by pain and tenderness
appearing in sharply-localized regions on the surface when definite organs
become disordered. He has also demonstrated that disorders of the thoracic
and abdominal viscera not only ]m)duce pain and tenderness on the surface of
the bodv, l)ut also cause pain and tenderness over certain areas of the scalp.
Head is inclined to explain the topographical association of skiu-tenderness
with visceral disorders by the assumption that the nerve-supplies of the parts
so related find their origin within the same segment of the spinal cord. The
sensorv result of visceral irritation may be summarized in the following way :
" When a painful stimulus is applied to a part of low sensibility iu dose cen-
tral connection with a part of much greater sensibility, the pain produced is
felt in the part of higher sensibility rather than in the part of lower sensibility
to which the stimulus was actually applied."

That this transferred localization may characterize other sensations than
those of pain has been definitely observed by Obersteiner," who found that in
patients suffering from certain central nervous lesions tactile irritation of a cer-
tain point on the skin was referred by them to some other part of the body,
usually the corresponding point on the other side. He designated this trans-
ference of sensation by the term al/ocJilria, meaning a confusion of sides.

4. Muscular Sensation. — Closely allied to common sensation, if not a
part of it, is muscular sr)isation. If two weights are to be compared, we
naturally do not lay them on the skin to determine their pressure-difference,
but we lift and weigh them in the hands, and experience shows that a nuich
more accurate estimate may thus be made.

We undoubtedly have a keen perception of the tension of a muscle, and
therefore of the amount of resistance against which it is contracting. This per-
ception mav be the outcome of a direct consciousness of the amount of motor
energy sent out from the motor cells, or it may be due to the inflow of sensorv
impulses which show the tension to which the muscles have been subjected.
The latter view has more to be said in its fixvor. The sensory nerves involved
in this process are probably distributed rather to the tendons in which the mus-
1 Brain, 1893-94. ' Ibid., 1881.

MUSCULAR .SEiXSATION. «4:)

cles terminate than to the muscular suhstance itself. There is reason to believe
that the joints are partieularly rich in sueh a nerve-supply. Golgi ^ has de-
scribed two distinct modes of nerve-ending in tendon and at the line of divis-
ion between muscle and tendon ; and Sherrington - has shown terminal sensory
fibres to be enclosed in peculiar isolated groups of muscle-fibres, the " muscle
spindles," found at the origin of tendons. According to the latter author,
from one-third to one-half of all the spinal-nerve fibres found in muscle are
sensory in function.

Wiien we consider that it is through muscular sensation that we derive our
most accurate conceptions of the form, weight, and position of objects, and through
which we explore our own body-surface and distinguish its areas of localization ;
that this is the fundamental sense by which the sensations arising in most
other organs are tested and verified ; and that it is from the sense of muscular
movement that we can form ideas of time and space, — it may well be regarded
as the mother of all sense-perceptions. Normal muscles, even when function-
ally inactive, are still in a state of tonic contraction ; it is not improbable that
this tone is a reflex action whose sensory element is formed by the impulses
travelling along nerves of muscular sensation. Such impulses are probai)ly
indispensable to the ])reservation of the equilibrium of the body.

The clinical study of disease in the central nervous system affords strong
evidence of the functional independence of the sense organs involved in the
appreciation of touch, heat, cold, and pain. In certain diseases of the spinal
cord, areas of skin may be mapped out in which sensations of pressure are
lost, but those of temperature remain, and vice versd. In other diseases the
patient can appreciate warmth applied to the skin, but not cold.

The sensations of cold and pressure seem to be usually lost or retained
together, while those of warmth and pain have a similar connection. It is a
peculiar fact that sometimes in the early stages of ether and chloroform narco-
sis the sense of touch remains while that of pain is abolished. Funke* refers
to two cases in which, while the tactile sense was preserved, muscular sensation
was lost, and an object could be held in the grasp only while the eyes were
turned upon it.

Hunger and Thirst. — Hunger and thirst are peculiar sensations which
depend partly on local and partly on general causes. Diminution in the bulk
of water and of circulating aliment in the body no doubt causes excitement
of sensory nerves on which depend the feelings of thirst and hunger, but in
ordinary life these feelings are dependent on the physical condition of certain
mucous surfaces. Any circumstance which causes drying of the lining mem-
brane of the mouth provokes thirst, and some condition of the empty stomach
arouses hunger. Thirst may be assuaged by introducing water directly into
the stomach through a gastric fistula, though to eifect the purpose a larger
quantity must be employed in this way than by the mouth. Hunger in a

* Hofmann und Schtvalbe's Jahresbericht, Abth. I. Bd. vii. S. 93.

* Journal of Physiology, vol. xvii. p. 211.

3 " Der Tastsinn," Hermann's Handbuch der Physioloffie, Bd. iii. S. 2.

846 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

somewhat similar manner may be appeased by rectal alimentation. It seems
probable, however, that these sensations as usually felt are the result of a
sort of habit, depending on the ])hysiological condition of the secreting and
absorbing mechanisms of the alimentary canal.

Clinical observation has shown that "bulimia," or voracious appetite, is
frequently a result of disease in certain parts of the central nervous system.
We are therefore justified in speaking of a " hunger-centre." '

E. The Equilibrium of the Body; the Function of the
Semicircular Canals.

The term equilibrium, as a})plied to the condition of the body, whether at
rest or in motion, indicates a state in which all the skeletal muscles are under
control of nerve-centres, so that they combine, when required, to resist the
effect of gravitv or to execute some co-ordinated motion. The preservation
of equilibrium is manifestly of fundamental importance in animal life, and we
find, accordingly, several mechanisms sharing in this function. That the motor
co-ordinating centres may act projierly, they nuist receive sensory imjires-
sions conveving information of the relative position of the body at any given
moment. The sum-total of these sensations may be characterized as the sense
of equilibrium, and it is probably not going too for to assume that every known
sensation contributes to this fund of information. Thus, in ordinary life the
position of objects is commonly determined by the sense of sight : when one
tries to walk while looking through a prism, objects are not properly localized
bv vision, and improper co-ordination results. The contact of the soles of the
feet with the ground, and that of the surface of the body with various objects,
are common sources of information as to our relation ^vitIl the environment.
Standing upright, and still more when in motion, the muscular sense is active
in appreciating the tension, active or passive, of the muscles. In the erect
position, with eyes closed, a writing point attached to the head will show that
the bod V sways in a peculiar manner indicating successive contraction of differ-
ent groups of muscles; and a person with failure of muscular and tactile sen-
sibility, as in locomotor ataxy, cannot stand with eyes closed, and his move-
ments, even when sight is employed, are exaggerated and unnatural. Attention
has previously been called to the fact that air- waves, irrespective of those
producing sound-sensations, exert an influence upon the tympanic membrane
by which we are capable of appreciating the presence and, to some extent, the
phvsical character of objects. Whether this sensation involves the nerves of
touch, those of common sensibility, or those distributed to the internal ear, is
uncertain.

In the absence of any of these sensations the loss may be made up by more
perfect development of others. Ordinarily, the sensory information from all
these sources, when compared in consciousness, harmonizes and gives rise to
a concrete idea of position. Frequently, however, one of the sources of sense-
impression suddenly fails us or its testimony conflicts with that of other sense
' Ewald : Diseases of the Stomach, p. 397.

THE SENSE OF EQUILIBRIUM. 847

organs ; the result is disturbance of equilibrium. A very common outcome
of this conflict of sensations is dizziness or nausea. The distress arising from
wearing ill-fitting glasses and the sensations experienced when one looks down
from a high eminence are examples in point. Internal disorders exciting nerves
of common sensation have the same effect, though the relation borne by visceral
sensations to equilibrium is very ill known. A false idea of position of the
body, a sense of falling in one direction or another, may lead to sudden effort
of recovery by which the person is precipitated to the o})})osite side. Thus,
when looking at rapidly-moving water erroneous ideas of equilibrium are
gained through the visual sense, and there is a strong tendency for the body
to precipitate itself in one direction or another. When, in going up a stair-
case, one miscalculates the number of steps, a peculiar sensation of want of
equilibrium is aroused through the muscular sense. It is clear, then, that
the sense of equilibrium is served by various sense organs, and a comj)lete
discussion of this function would entail a consideration of the whole field of
nerve-muscle physiology. There is, however, good reason for believing that
there is a special sense organ for determining the position and direction of
movement of the head and, by inference, of the whole body. The terminal
organ of this sense apparatus of equilibrium is found in the system of semi-
circular canals of the internal ear.

Ex})eriments on the lower animals, chiefly performed on birds, show a con-
stant motor disturbance to follow division of any or all of the semicircular
canals. These disturbances are of two kinds. When the animal is at rest it
does not stand in a natural fashion, but sprawls in a more or less exaggerated
degree. It holds its head in an unnatural position, as with the vertex touch-
ing the back, or with the beak turned down toward the legs or bent over to
one side. Immediately after the operation, and whenever it is disturbed, the
animal goes through peculiar forced movements, together with rolling or
twitching of the eyes, of various kinds and degrees of violence, depending on
the position and number of canals severed. The disturbance varies from
simple unsteadiness in gait, with swaying motions of the head, to complete
lack of co-ordination and a violence of movement almost comparable to that
of a chicken whose head has been cut off. Essentially the same results have
been determined to follow injury of the semicircular canals of widely different
groups of animals.

These results have been explained by the assumption that the hair-cells on
the cristw acustlca^ of the ampullae of the semicircular canals are irritated by
increase or decrease of pressure of the endolymph upon them, and thus give
rise to sensory impressions from which ideas of change of position are derived.
Section of the canal, by draining off the endolymph, would cause abnormal
pressure-irritation. The anatomical relations of the semicircular canals afford
an obvious basis for this view, for the canals of each ear are almost exactly at
right angles to one another, occupying the three planes of space ; considering
the two ears, the horizontal canals are nearly in the same plane, and the ante-
rior vertical canal of one side is nearly parallel with the posterior vertical canal

848 A.X AMERICAN TEXT-BOOK OF PHYSIOLOGY.

of the other side. Any possible movement of the head would thus pioduce
an increase of eudolymph-pressure upon the hair-cells in one ampulla and a
decrease of pressure in the ampulla of the parallel ciuial, and every change of
position would be accompanied by the irritation of definite ampulhc with defi-
nite degrees of excitement (Fig. 289). Experiments on man allbrd considerable
, support to this theory of the function of the

I semicircular canals. A person with eyes closed

and with muscular and tactile sensations elimi-
nated, supported on a table which can be rotated
in all directions, can determine with consider-
able accuracy not only thai; he is moved, but
I in what direction and, to some extent, through

' how great an angle. Further, mIicm brought

Fig. 289. —Diagrammatic horizontal ° . „ .

section through the head to iihistrate to rcst after a scries of rotations the person
the planes occupied hy the semicircu- ^^^1^^. observation feels a scusatiou of motion

lar canals (after Waller): s, superior

canal ; p, posterior canal ; H, horizontal in the Opposite direction. Eacll of thcSC re-
sults should be expected to follow were the
theory in question correct. The observations of James have shown that
with deaf mutes in whom the internal' ear was at fault rapid rotation in
an ordinary "swing" failed to produce the dizziness which is the common
effect in ordinary individuals. On the other hand, diseases which may be sup-
posed to alter the intra-labyrinthine pressure are characterized by the symp-
toms of vertigo and inco-ordination of movement. The presumable effect of
cutting the semicircular canals is that the escape of endolymph changes the
pressure upon the sensory hair-cells and gives the animal the sensation of
falling in one direction or another, so that he is impelled to make compensa-
tory QX Jorocd movements to counteract this imaginary change of position. In
birds and in fishes, whose life is passed more or less exclusively in a medium
in which tactile and muscular sen.satiou can contribute little to the sense of
equilibrium, the semicircular canals are especially well developed.^ In fishes,
though section of the canals themselves produces no disturbance, division of
the nerves supplying the ampulla? usually gives rise to marked forced move-
ments, as shown in somersaults, spiral swimming, etc. when set free in the
water. When, however the nerves are cut with great care, with sharp scis-
sors, .so as to avoid traction on or crushing of the nerves, such forced move-
ments do not follow. The movements in this case, then, as in that of the
pigeon, are the outcome of direct irritation of the equilibrium mechanism,
and, according to our present conception of the function of the .'semicircular
canals in its relation to equilibrium, we must regard it as a terminal organ
which is exceedingly .sensitive to such mechanical irritations as may arise from
variations of eudolymph-pressure upon the anipullary hair-cells, but which
may be destroyed without causing inco-ordination of movement, and which
may therefore more or less com})letely be substituted in function by other
sense organs.

' Sewall : Journal of Physiology, 1884, iv. p. 339.

THE SENSE OF SMELL.

849

According to Lee' aiul others, the equilibriurii of rest and motion, or static
and dynamic equilibrium, depends upon the irritation of dit!erent nerve-ter-
minals. The manner of action of the latter has been considered. As to the
nervous mechanism on which datic equilibrium depends, Lee is of the opinion
that the knowledge of the position of the head while at rest comes from the rela-
tion of the otoliths in the vestibular sacs to the nerve-endings on the viuculce
acusticce. These otoliths form considerable masses in the ears of fishes, and the
intensity and direction of their pressure upon hair-cells must vary with the
spatial relations of the head, and thus be comparable, in the sense of i)Osi-
tiou which they Srouse, to the tactile sensations derived from the soles of
the feet in man.

F. Smell.

The complex paired cavity of the nose is divisible into a lower respiratory
and an upper olfactory tract, the mucous membrane over each of which is
distinctive. The covering of the respiratory tract is known as the Sckneider-
ian or pituitary membrane; its surface is overlaid with cylindrical ciliated
epithelium, the ciliary current of which is directed posteriorly toward the
pharynx.

The Schneiderian membrane lines the lower two-thirds of the septum, the
middle and inferior turbinated bodies, and the bony sinuses which communi-
cate with the nasal chamber. The mem-
brane upon the turbinated bodies and
the lower part of the septum is composed
largely of erectile tissue.

The function of the respiratory tract
is threefold : it restrains the passage
of solid particles into the lungs ; it
warms the air inspired to approximately

Fig. 290.— Section of olfactory mucous mem-
brane (after V. Brunn) : the olfactory cells are in
•black.

Fig. 291.-06118 of the olfactory region (after V.
Brunn) : a, olfactory cells ; 6, epithelial cells : n,
central process prolonged as an olfactory nerve-
fibril : I, nucleus ; c, knob-like clear termination
of peripheral process ; h, bunch of olfactory hairs.

the temperature of the body ; and it gives up moisture sufficient nearly to
saturate the air.

^ Journal of Physiology, xv. p. 311 ; xtii. p. 192.

54

850

^l.V AMElUi'Ay TEXT-BOOK OF PllYSlOLOOY

The oliiK'tory inueous nu'inbninc, wliioli alone is the peripheral or^aii for
smell, is sealed in the iip})er part of" the na.sal ehainber, away ironi the line
of the direct eurrent of inspired air. The membrane is thick and is covered
by an epithelium composed ol' two kinds of cells, columnar and rod cells.
The latter are the true olfadovy ct//*- (Figs. 290, 2U1), with which the fibres
of the olfactory nerve are known to be connected. These olfactory cells, in
fact, are comparable to nerve-cells in that the fibres connected with them, the
fibres composing the olfactory nerve, are direct outgrowths from the cells
(Fig. 292), essentially similar in every way to the uerve-fibre processes s])ringing
from nerve-cells in the nerve-centres. In this respect the olfactory cells differ
from the sensory cells in other organs of special sense. The membrane

Fig. 292.— Diagram of the connections of cells and fibres in the olfactory hnlh (Schafer. in Quain'e Anat-
omy): oy.c, cells of the olfactory mucous membrane: o[f.n, deepest layer of the bulb, comi>osed of the
olfactory nerve-tlbres which are prolonged from the olfactory cells: <?/, olfactory elomeruli, containing
arborization of the olfactory nerve-fibres and of the dendrons of the mitral cells: vi.c, mitral cells;
a, tliin axis-cylinder process passing toward the nerve-fibre layer, n.tr, of the bulb tfi become continuoiis
with fibres of the olfactory tract : these axis-cylinder processes are seen to give off collaterals, some of
which pass again into the deeper layers of the bulb; «', a nerve-fibre from the olfactory tract ramifying
in the gray matter of the bulb.

aj^pears to be not ciliated except near its juncture with the Schneiderian
membrane, where the columnar cells acquire cilia and gradually pass over
into the cells covering the respiratory tract. Substances exciting the sense
of smell exi.'it as gases or in a fine state of division in the air inspired.
They reach the olfactory mucous membrane by diffusion, assisted by the
modified inspiratory movements of "sniffing" and "smelling," and are
most acutely jierceived when the air containing them is warmed to the
body-temperature. The amount of odoriferous matter that may thus be
recognized is extraordinarily small ; thus, it is said that in one liter of air
the odor of 0.000,005 gram of musk and of 0.000,000,005 gram of oil of
jiepperraint can be perceived.* The odoriferous particles probably excite the
J Passy : Compte»-rendus de la Sociite de Biologic, 1892, p. 84.

Till-: si'Lxsi-: or taste. 851

sense of stndl l»y coiniii*"; into contact witli the olfactory cjtitlioliiirn after solu-
tion iti the layer of moisture covering it. This epitlicliuin is easily thrown
out of function, as the common loss of smell when there is a "cold in the
head " testifies. Wiien the nostiil is filled with water in which an odorous
substance is dissolved, no sensation of smell is excited, but it is said that if
normal salt-solution, whicli injures tlie living tissues less tlian water, be used
as the solvent, the odor can still be perceived. In many lower animals the
sense of smell has an acuteness and an importance in their economy unknown
in the human race. It is probable that not only do different races have their
distinctive odors, but that each individual exhales an odor ]>eculiar to himself,
distinguishable by the olfactory organs of certain animals. The classification
of odors is not very definite, and the relation of odors to one anotiier in the
way of contrast and harmony is ill understood. No limited number of pri-
mary sensations, as in vision, have been discovered out of which otiier sen-
sations can be composed. Certain sensations, as those due to the inhalation
of ammonia and other irritant gases, are thought to be due to excitement of
tile nasal filaments of the fifth nerve, and not of the olfactory.

Subjective sensations of smell are sometimes experienced, the result of some
irritation arising in the olfactory apparatus itself.

Finally, in man sensations of smell have their most important uses in con-
nection with taste; many so-called "tastes" owe their character wholly or
partly to the unconscious excitement of the sense of smell.

G. Taste.

The peripheral surfaces concerned in taste include, in variable degree, the
upper surface and sides of the tongue and the anterior surfaces of the soft
palate and of the anterior pillars of the fauces. Other parts of the buccal
and pharyngeal cavities are, in most persons, devoid of taste.'

The chief peripheral sensor\^ organs of taste are groups of modified epi-
thelial cells, known as tdste-hiuh (Fig. 293), seated in certain papillae of the
tasting surfaces. According to some authors, only parts provided with taste-
buds can give taste-sensations.^

The structure of taste-buds is most easily studied in the papilla foliata of
the rabbit, a patch of fine, parallel wrinkles found on each side of the
back part of the tongue of the animal. The taste-bud is a somewhat globular
body seated in the folds of mucous membrane between tlie furrows of the
pa])illa. It is made up of a sheath of flattened, fusiform cells enclosing a
number of rod-like cells each of which terminates in a hair-like process. These
cells surround a central pore which opens into a furrow of the papilla.
The hair-bearing cells recall the appearance of the olfactory rod-cells, and
are probably the true sensory cells of taste, since between them terminate the
filaments of the gustatory nerve. In the human tongue taste-buds are con-

' V. Vihtscligaii : " Geruchsinn," Henminn's Handhuch der Physiologie, iii. 2, 1880.
'Camerer: Zeitschrift filr Biologie, 1870, vi. S. 440; Wilczynsky : Hofnann und Schwalbe's
Jahresbericht der Physiol., 1875.

852

.l.V AMElilCAX TEXT-BOOK OF PHYSIOLOGY.

v^i 7/1 ft>-> >,sj^ '^^&

fined to the fuiifrifonn papilljo, scon often as red dots scattered over the upper
surface; to the circunivalhite papilhe, the pores of the buds opening into the
groove around the papilhi ; and to an area just in front of the anterior pillar
of the fauces, which somewhat resembles the papilla foliata of the rabbit.

The sensory nerves distributed to the tongue include filaments from the
glosso-pharyngeal, the lingual branch of the fifth, and the chorda tympani.
The relation of these nerves to the sense of taste has been the occasion of
much dispute. The weight of evidence probably favors the belief that the
glosso-pharyngeal is the nerve of taste for the ])osterior third of the tongue,
while the lingual and, to some extent, the chorda carry taste-impressions from
the anterior two-thirds. Clinical cases have been cited to show that all the
gustatory fibres arise from the brain as part of the glosso-pharyngeal nerve,
whatever may be their subsequent course to the tongue. On the contrary,

other cases have shown a marked loss
of taste-sensation following upon lesions
of the fifth nerve at or near its origin
from the brain, while still others indi-
cate that some of the taste-fibres may
arise in the seventh nerve. The point
is of practical importance in diagnosis,
in the interpretation of loss of taste
over any given part of the tongue, but
the contradiction in the clinical cases
reported has led to the general belief
that the origin and course of the gusta-
tory fibres are subject to considerable
individual variations.

Our taste-percei)tions are ordinarily
much modified by simultaneous olfac-
tory sensations, as may easily be dem-
onstrated by the difficulty experienced
in distinguishing by taste an apple, an
onion, and a potato, when the nostrils are closed. Sight has also an import-
ant influence, at least in quickening the expectancy for individual flavors.
Every smoker knows the blunting of his perception for burning tobacco
while in the dark ; various dishes having distinctive flavors are said to lose
much of their gustatory characteristics when the eyes are bandaged.

The intensity of gustatory sensation increases with the area to which the
tasted substance is applied. The movements of mastication are peculiarly
adapted to bring out the full taste value of substances taken into the mouth,
and the act of swallowing, by which the morsel is rubbed between the tongue
and the palate, has been proved to develop tastes not appreciable by simple
contact with the sensory surface. A considerable area in the mid-dorsum of
the tongue is said to be devoid of all taste-sensibility.'

■ Shore: Journal of Physiology, 1892, vol. xiii. p. 191.

mM

--;i//i?

%%ii!v':ihl-3A.:iiVri^

Fig. 293.— Section through one of the taste-buds
of the papilla foliata of the rabbit (from Quain,
after Kanvier), highly magnificrl : p, gustatory
pore; », gustatory cell; r, sustentacular cell; m,
leucocyte containing granules ; e, superficial epi-
thelial cells ; H, nerve-fibres.

THE SENSE OF TASTE.

85;i

The sensitiveuess of taste-sensation is greatest when the exciting substance
is at the temperature of the body. Weber ^ found tliat when the tongue was
dipped during one-half to one minute in water either at the freezing tempera-
ture or warmed to 50° C, the sweet taste of sugar could no longer be appre-
ciated by it. It is probable that sapid substances reach the sensory endings
of the nerves of taste only after being dissolved in the natural fluids of the
mouth, and any artificial drying of the buccal surfaces or alteration of their
secretion must affect taste-perceptions.

The excitement of the taste-nerves appears to depend not so much on the
absolute amount of the substance to be detected as on the concentration of the

A udiiory.

Gustatory.

Tactile.

'^ y

Fig. 294.— Diagram showing the mode of termination of sensory nerve-fibres in the auditory, gustatory,
and tactile structures of vertebrata (from Quain, after Retzius). Each sense organ may be considered as
essentially constructed of a nerve-cell with two processes, one finding its way centrally to cluster round
other nerve-cells or their processes, and the other to terminate in the periphery. Ir>the organ of smell
the peripheral process is very short and is directly irritated by foreign particles, the original nerve-cell
being represented by the olfactory cell (Fig. 291). In the organs of touch the nerve-cell is found in the
ganglion of the posterior spinal nerve-root; the peripheral process is very long and is acted fm indirectly
through the modified epithelium round which it clusters. The same may be said of the other sense
organs. See Quain's Anatomy, 10th ed., vol. iii. pt. 3, p. 1.52.

solution containing it. Thus, when 1 part of common salt to 213 of water
was tasted by Valentin/ 11 cubic centimeters of the fluid was suflicieut to give
a saltish taste ; when diluted so that the ratio of salt to water was 1 to 426,
12 cubic centimeters taken in the mouth scarcely gave the salt taste. Snl]>hate
of quinine dissolved in the proportion 1 to 33,000 gave a decided bitter taste,
but a solution 1 to 1,000,000 was with difficulty perceived as bitter.

It has generally been conceded that all gustatory sensations may be built
up out of four primary taste-sensations — namely, bitter, sweet, sour, and salt.
Some authors even limit the list to tastes of bitter and sweet (V. Vintschgau).

' Archwfiir Anatomie und Physiologic, 1847, S. 342. * Lehrhuch der Phyaiologie, 1848.

854 ^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

There is strnncr reason to believe that corresponding to tlie tour prirnarv taste-
sensations there are separate centres and nerve-fibres, each of which, when
excited, gives rise only to its appropriate taste-sensation. Substances which
arouse the sense of taste are not appret.'iated in uniform degree over the surface
of the tongue. Thus, to V. Vintschgau, at the tip of the tongue acids were
perceived acutely, sweets somewhat less plainly, and bitter substances hardly
at all. It is generally admitted that sweet and sour tastes are recognized
chiefly at the front, and bitter, together with alkaline tastes, by the posterior
part of the tongue. Strong evidence in favor of the specific difference between
various taste-nerves is found in the fact that the same substance may excite a
different gustatory sensation according as it is aj)plied to the front or the back
of the tongue. Thus, it has been demonstrated that a certain compound of
saccharin (para-brom-benzoic sulphimide) appears to most persons to be sweet
when ajiplied to the tip of the tongue, but bitter in the region of the circum-
vallate papilhe.'

OehrwalP has examined the different fungiform papillae scattered over the
tongue with reference to their sensitiveness to taste-stimuli. One hundred and
twenty-five separate papillae were tested with succinic acid, quinine, and sugar.
Twenty-seven of the papillae gave no response at all, indicating that they were
devoid of taste-fibres. Of the remaining ninety-eight, twelve reacted to suc-
cinic acid alone, three to sugar alone, while none were found which were acted
upon by quinine alone. The fact that some papillae responded with only one
form of taste-sensation is again evidence in favor of the view that there are
separate nerve-fibres and endings for each fundamental sensation ; but the
figures given in the experiments show that the majority of the papillae are
provided with more than one variety of taste-fibre.

An extract of the leaves of a tropical plant, Gi/mnema silvestre, when
applied to the tongue, renders it incapable of distinguishing the taste of sweet
and bitter substances ; it probably paralyzes the nerves of sweet and bitter
sensations. AVhen a solution of cocaine in sufficient strength is painted on
the tongue, the various sensations from this member are said to be abolished
in the following order: (1) General feeling and pain; (2) bitter taste; (3)
sweet taste; (4) salt taste; (5) acid taste; (6) tactile perception (Shore).

That there are laws of contrast in taste-sensation has long been empirically
known. Thus, the taste of cheese enhances the flavor of wine, but sweets
impair it (Joh. Muller). It is unfortunate, from a hygienic standpoint at
least, that in this most important department of the physiology of sensation
investigations are almost wholly wanting.

Certain tastes may disguise others without physically neutralizing them;
when, for example, sugar is mixed with vinegar, the overcoming of the acid
taste is probably effected in the central nerve-organ.^

1 Howell and Kastle : Studies from the Biological Laboratory of Johns Hopkins University.
1887, iv. 13.

* SkandinavLsches Archivfur Physiologic, 1890, vol. ii. p. 1.

* Br'ucke : Vorlesungen iiber Physiologic, 1876.

XII. PHYSIOLOGY OF SPECIAL MUSCULAR
MECHANISMS.

A. The Action of Locomotor Mechanisms.
The Articulations. — The form, posture, and movements of vertebrates
are largely determined by the structure of the skeleton and the method of
union of the bones of which it is composed. There are two hundred bones in
the human skeleton, and they are so connected together as to be immovable,
or to allow of many varieties and degrees of motion. There are four prin-
cipal methods of articulation :

1. Union by Bony Substance (Sutures). — This form of union occurs
between the bones of the skull. These bones, which at birth are independent
structures connected by fibrous tissue, gradually grow together and make
a continuous whole, only a more or less distinct seam remaining as witness
of the original condition.

2. Union by Pibro-Cartilages (Symphyses). — The bodies of the verte-
brse and the pelvic bones are closely bound together by disks of fibro-cartilage.
This material, which is very strong, but yielding and elastic, permits of a
slight amount of movement when the force applied is considerable, and restores
the bones to their original position on the removal of the force. The inter-
vertebral disks act, moreover, as elastic cushions or buffers to deaden the
eflfect of sudden jars.

3. Union of Fibrous Bands (Syndesmoses). — Some of the bones, as of
the carpus and tarsus, are connected by interos.seous ligaments which, at the
same time that they bind the bones together, admit of a certain amount of
play, the extent of the movement varying with the character of the surfaces
and the length of the ligaments.

4. Union by Joints. — The adjacent surfaces of most of the bones are so
formed as to permit of close contact and freedom of movement in special
directions. Tiie parts of the bones entering into the joint are clothed with
very smooth cartilage, and the joint-surfaces are lubricated by synovial fluid,
a viscid liquid secreted by a delicate membrane which lines the fibrous capsule
by which the joint is sun-ounded. The joint-capsule is firmly attached to the
bones at the margin of the articular cartilages, and, at the same time that it
completely surrounds and isolates the joint-cavity, helps to bind the bones
together. The bones are further united by strong ligaments, in some cases
within and in other cases Avithout the capsule. These ligaments are so placed
that they are relaxed in certain positions of the joints and tightened in others ;

855

856 ^iV AMERICAN TEXT- BOOK OF PHYSIOLOGY.

they guitle and limit tho niovenient.s of the joiuts. Tlie joint-surfaces always
toucli, although in souie joiuts the parts in contact change with the position
of the joint. If coutiuuous contact of the joint-surfaces is to be maintained
and free movement is to take place in special dii-ections, it is evident that the
opposing surfaces must not only be so constructed that they shall fit each
other with great accuracy, but also have forms especially adapted to the move-
ments peculiar to each of the joints.

The different joints exhibit a great variety of movements and inav be clas-
sified as follows: gliding joints, hinge joiuts, condyloid joints, saddle joints,
ball-and-socket joints, pivot joints. For a description of the structure and
the peculiarities of these joints the student is referred to works on anatomy.'
The contact of the surfaces of the joint is secured in part by the fibrous capsule,
in part by the joint ligaments, and in part by the tension of the muscles. The
elastic muscles are attached under slight tension, and, moreover, during wak-
ing hours are kept slightly contracted by tonus impulses of reflex origin.
Another less evident but no less important condition is the atmospheric pres-
sure. The capsule fits the joint closely and all the space within not occupied
by the bones is filled by cartilages, fibrous bauds, fatty tissues and synovial
fluid. The joint is air-tight, and, as was first demonstrated by the Weber
brothers, the atmospheric pressure keeps all parts in close apposition. This
force is sufficiently great in the case of the hip-joint to support the whole
weight of the leg even after all the surrounding soft parts have been cut
through. The proof that the air-pressure gives this support is found in the
fact that the head of the femur maintains its place in the acetabulum after
all the soft parts which surround the joint have been divided, but falls out
of its socket if a hole be bored in the acetabulum and air be permitted to
enter the cavity of the joint. Though the air-pressure keeps the boues in
constant contact it offers no resistance to the movements peculiar to the joints.

The movements of the bones is effected chiefly by muscular contractions,
but the direction and extent of the movements is for the most part determined
by the form of the joint-surfaces and the limitations to movement which result
from the method of attachment of the ligaments. In the case ot^ sliding joints,
in which the articular surfaces are nearly flat, a sliding movement may occur in
various directions, but the extent of the movement is slight, being limited by the
capsule and the ligaments. Hinge joints have but a single axis of rotation,
because the convex and somewhat cylindrical surface of one bone fits quite
closely the concave surface of the other, and because of tense lateral ligaments
which permit of movements only in a single plane. The joint between the
humerus and the ulnar at the elbow is an example. The knee-joint^ is a less
simple form of hinge joint. The presence of the semilunar cartilages and

* Qitain's Anatomy, vol. ii. pt. 1.

' W. Braunne and Fischer have studied with mathematical accuracy the construction and
movements of many of the joints of the human body. Their articles are published in the
Ahhandl ungen der math.-phys. Classe der konigl. Sikhsischer GeaelUchaft der Wissenschaflen, Bd.
xvii., and others.

THE ACTION OF LOCOMOTOR MECHANISMS. 857

the shape of the joiut-surluces euu.se flexion to be produced by the conibiued
action of sliding, rolling, and rotation movements. In complete extension
the lateral ligaments and the posterior and anterior crucial ligaments are
put on the stretch, and there is a locking of the joint, no rotation being
possible; in complete flexion, on the other hand, the posterior crucial
ligament is tight, but the others are sufficiently loose to allow of a consider-
able amount of pronation and supination. In the mddk-joint there is a
double axis of rotation — <\ fj. the articulation of the trapezius with the first
metacarpal bone permits of rotation about an axis extending from before back-
ward, and another, at nearly right angles to this, extending from side to side.

The ball-and-socket joint, of which the shoulder- and hip-joints are exam-
ples, permits of the greatest variety of movements, any diameter of the head
of the bone serving as an axis of rotation.

Method, of Action of Muscles upon the Bones. — The bones can be
looked upon as levers actuated by the forces which are applied at the points
of attachment of the muscles. All three forms of levers are represented in
the body; indeed, they may be illustrated in the same joint, as the elbow.

An example of a lever of the first class, in which the fulcrum is between
the power and the resistance, is to be found in the extension of the forearm in
such an act as driving a nail : the inertia of the hammer, hand, and forearm
offers the resistance, the triceps muscle acting upon the olecranon gives the
power, and the trochlea, upon which the rotation occurs, is the fulcrum. The
l)alancing of the head upon the atlas is another example: the front part of the
head and face is the resistance, the occipito-atlantoid joint the fulcrum, and
the muscles of the neck the power.

In the case of a lever of the second order, the resistance is between the ful-
crum and the power ; for example, when the weight of the body is being
raised from the floor by the hands : the fulcrum is where the hand rests on the
floor, the weight is applied at the elbow-joint, and the power is the pull of the
triceps on the olecranon. The raising of the body on the toes is another ex-
ample : the fulcrum is at the place where the toes are in contact with the
floor, the resistance is the weight of the body transmitted through the tibia to
the astragalus, and the power is applied at the point of attachment of the
tendo Achillis to the os calcis.

The raising of a weight in the hand by flexion of the forearm through
contraction of the biceps gives an example of a lever of the third order, in
which the power is applied between the fulcrum and the weight. This form
of lever, because of the great length of the resistance arm, as compared with
the power arm, is favorable to extensive and rapid movements, and is the
most usual form of lever in the body.

The power is applied to best advantage when it is exerted at right angles
to the direction of a lever, as in the case of the muscles of mastication and of
the calf of the leg. If the traction be exerted obliquely, the effect is the less
the more acute the angle between the tendon of the muscle and the bone ; for
example, when the arm is extended the flexor muscles work to great disad-

858 .l.V AMERICAX TEXT-HOOK OF J'll YSKjLOUY.

vantage, lor a large part ot" the force i.s expended in pulling the ulnar and
radius against the liunierus, antl is lost for movement, but as the elbow is
flexed the force is directed more and more nearly at right angles to the bones
of the forearm, and there is a gain in leverage, which is of course again
decreased as flexion is completed. This gain in leverage which accompanies
the shortening of the muscles is the more important, since the power of the
muscle is greatest when the muscle has its normal length, and continually
lessens as the muscle shortens in contraction. There are a number of special
arrangements which help to increase the leverage of the muscles by lessening
the obliquity of attachment — viz. the enlarged heads of the bones, and in some
cases special processes projecting from the bones, the introduction of sesamoid
bones into the tendons, and the presence of pulley-like mechanisms.

The contraction of a muscle causes the points to which it is attached to
approach one another, and the direction of the movement is often determined
by the direction in which the force of the contracting muscle is applied to the
bones. In the case of certain joints, however, the form of the joint-surfaces
and the method of attachment of the ligaments limits the direction of move-
ment to special lines; and when this is not the case the movement is usually
the resultant of the action of many muscles rather than the effect of the con-
traction of any one muscle. This question has been made the subject of
careful study by Fiek.^

In the case of many muscles, both of the bones to which they are attached
are movable, and the result of contraction depends largely on which of the
extremities of the muscles becomes fixed by the contraction of other muscles.
Though most muscles have direct influence over only one joint, there are certain
muscles which include two joints between their points of attachment, and pro-
duce correspondingly complex effects. The accurate adjustment and smooth
graduation of most co-ordinated muscular movements is due to the fact that not
only the muscles directly engaged in the act, but the antagonists of these mus-
cles take part in the movement. It would appear from the observations of
certain writers^ that antagonistic muscles may be not only excited to contrac-
tion, but inhibited to relaxation, and that the tension of the muscles is thereby
accurately adjusted to the requirements of the movement to be performed.
The importance of the elastic tension and reflex tonic contractions of muscles
to ensure quick action, to protect from sudden strains, and to restore the parts
to the normal position of rest has been referred to elsewhere.

The shape of the muscle has an important relation to the work which it
has to perform. A muscle consists of a vast number of fibres, each of which
can be regarded as a chain of contractile mechanisms. The longer the fibre,
the greater the number of these mechanisms in series and the greater the total
shortening effected by their combined action ; consequently, a muscle with
long fibres, such as the sartorius, is adapted to the production of extensive
movements. In order that a muscle shall be capable of making powerful

' JJermamx! » Ilandbuch der Physiologie, 1871, Bd. i. pt. 2. p. 241.
^ Sherrington: Proceedings of the Royal Society, Feb., 1893, vol. liii.

THE ACTION OF LOCOMOTOR MECHANISMS. 859

movements it is iiooessarv that inaiiy lil)n>s shall be placed side by side, as in
the case of the gluteus: " Many liaiids, li-;lit work."

Standing. — In spite of the ease with which tin; many joints of the body
move, the erei't position is maintained with comparatively little muscular
exertion. It is an act of balancing in which the centre of gravity of the
body is kej)t directly over the base of support. In the natural erect position
of the body the centre of gravity of the head is slightly in front of the oc-
cipito-atlantoid articulation, so that there is a tendency for the head to rock
forward, as is seen from the nodding of the head of one falling asleep. The
centre of gravity of the head and trunk together is such that the line of
gravity falls slightly behind a line drawn between the centres of the hip-
joints, which would incline the body to fall backward. The line of gravity
of the head, trunk, and thighs falls slightly behind the axis of the knee-
joints, and the line of gravity of the whole body slightly in front of a line
connecting the two ankle-joints, so that the weight of the body would tend to
flex the knee- and ankle-joints.

We cannot here consider in detail the mechanical conditions which limit
the movements possible to the diflfereut joints in the erect position of the body.
Although these conditions help to support the body in the upright position,
they are not alone sufficient to the maintenance of this posture, as is shown by
the fact that the cadaver cannot be balanced upon its feet. That standing
requires the action of the muscles is further proved by the fatigue which is
experienced when one is forced to stand for a considerable time. The body
may be supported in the standing position in various attitudes. Thus, the
soldier standing at "attention" places the heels together, turns the toes out,
makes the legs straight and parallel, so as to extend the knees to their utmost,
tilts back the pelvis, straightens the spine, and looks directly forward. In
this position many of the muscles are relieved from action, for the complete
extension of the knee, by bringing the line of gravity slightly in front of the
axis of rotation and tending to produce further extension, puts the ligaments
on the stretch and so locks the joint. Similarly, in the case of the hip-joint
the tilting backward of the pelvis causes the line of gravity to fall slightly
behind the joint and puts the strong ilio-femoral ligament on the stretch. The
ankle-joint cannot be locked, and the tendency of the body to fall forward is
resisted by the strong nuiscles of the calf of the leg. The erect position of
the spine and the balancing of the head have likewise to be maintained by
the action of muscles. Although this position gives great stability, it cannot
be long maintained with comfort. It is less fatiguing to allow the joints to
be a little more flexed, and to keep the balance by the action of the muscles,
the position being frequently changed so as to bring fresh muscles into action.
Perhaps the most restful standing position is found in letting the weight of
the body be supported on one leg, the pelvis being tilted so as to bring the
weight of the body over the femur, and the other being used as a prop to pre-
serve the balance. Absolute stability in standing is impossible for any length
of time ; the body is continually swaying, and a pencil resting on a writing

8(50 AN AMERICAN TKXT-HOOK OF PHYSIOLOGY.

surface })l:K'eil upon the head is I'ouml to write a very eouiplieuted euive.
There is a normal sway for every individual, and this may become markedly
exaggerated under pathological conditions. The maintenance of equilibrium
requires that afferent impulses shall continually pass to the co-ordinating cen-
tres which control the muscles involved in this act, and if any of these normal
impulses fail the sway of the body is increased ; for example, it is more diffi-
cult to stand steadily when the eyes are closed than when they are open ; the
absence of tiie normal sensory impulses from the skin of the feet, the muscles,
joints, etc., also makes standing more difficult and tends to increase the sway.
The effect of the normal sway of the body is to shift the pressure and strain
from point to point and to relieve the different muscles from continuous action.

Locomotion.' — The movements of animals were first studied by careful
observation, accompanied by more or less accurate direct measurements, and
by these simple methods the Weber brothers ^ arrived at quite accurate con-
clusions as to the nature of the processes, walking, running, jumping, etc.
These results were greatly extended by Marey,^ who employed elaborate
recording methods, and exact pictures of all stages of these processes were
later obtained through the remarkable revelations of instantaneous photog-
raphy.^

Walking. — During the act of walking, at the same time that the body is
j)ropelled forward it is continually supported by the feet, one or the other of
which is always touching the ground. Preparatory to beginning the move-
ment the weight of the body is thrown upon one leg, while the other leg is
placed somewhat behind it, the knee and ankle being slightly flexed. At the
start the body is given a slight forward inclination, then the back leg is ex-
tended and impels the body forward. As the centre of gravity progresses so
as to be no longer over the supporting leg, it would fall were it not that the
back leg is at the same instant swung forward to sustain it. As the body
moves forward and its weight is received by the leg which has just been
advanced, the leg which has been its support is freed from the weight
and becomes inclined behind it. This leg and foot are next extended, the
body thereby receiving another forward impulse, and then the hip-, knee-,
and ankle-joints flexing slightly, the leg swings forward past the supporting
leg and again becomes the support of the body. The forward movement of
the body is due in part to a slight inclination which tends to cause it to fall
forward, and in part to a push given it by each leg in turn as it leaves the
ground.

Tiie amount of work performed by the legs in ordinary walking is com-
l)arutively slight, since the swing of the leg is, like that of a pendulum, largely

^ Beannis: Physiologic humaine, 1888, vol. ii. p. 2G9, gives many references to the litera-
ture of this subject.

* W. and E. Weber: Mechnnih der menschlichen Geheiverkzeufje, 1836.
' La Melhode graphique, 1885.

* Marey : Melhode graphique {supplement), 1885 ; Muybridge : The Horse in Motion, as Shown
by Instantaneous Photography, 1882.

VOICE AND SPEECH. 861

a passive act. Speed in walking is attained by inclining the body somewhat
more and by flexing the legs somewhat more, so that the hind limb in extend-
ing can pnsii the body forward with greater force. Tlu; more rapid move-
ment of the body is also accompanied by a more rapid forward swing of the
leg, the muscles aiding the force of gravity. The transfer of the weight of
the body from one leg to the other causes it to oscillate slightly from side to
side, and the falling motion, interrupted by the support olfered by the receiving
limbs, causes a slight up-and-down movement. These oscillations are, how-
ever, very slight ; the tendency for the centre of gravity to move from side to
side as the legs alternately {nish the body forward is in part balanced by the
swino- of the opposite arm ; and the vertical oscillation is largely obviated,
because the supporting leg is extending — i. e. lengthening— as the body moves
forward, and so sustains the jwlvis until its weight is taken by the other leg.

In running the body is inclined more than in walking, and the legs are
more flexed in order that the extension movement of the back leg, which
drives the body forward, may be more effective. In running the body is pro-
pelled by a series of spring-like movements and there are times when both
feet are oiF the ground, the back leg leaving the ground before the other
touches it. The increase in speed is due in part to the greater forward incli-
nation of the body, but more especially to the vigorous action of the muscles.

B. Voice and Speech.
1. Structure of the Larynx.

Voice-production. — The human voice is produced by vibration of the
true vocal cords, normally brought about by an expiratory blast of air passing
between them while they are approximated and held in a state of tension by
muscular action. Mere vibration of the cords could produce but a feeble
sound ; the voice owes its intensity both to the energy of the expiratory blast
(Helmholtz) ^ and to the reinforcement of the vibrations by the resonating
cavities above and below the cords.

A true conception of the action of the larynx can only be gained by a pre-
liminary study of the organ in situ, in its relations with the trachea, pharynx,
tongue, extrinsic muscles, and hyoidean apparatus. Removed froin its con-
nections, the larynx, in vertical transverse section, is seen to be shaped some-
what like an hour-glass, the true vocal cords forming the line of constriction
half way between the top of the epiglottis and the lower border of the cri-
coid cartilage (Fig. 295). In median vertical section the axis of the larynx
above the vocal cords extends decidedly backward, and below the cords the
axis is nearly perpendicular to the plane in which they lie. The epiglottis is an
ovoid lamella of elastic cartilage, shaped like a shoe-horn, that leans backward
over the laryngeal orifice so that the observer nuist look down obliquely in
order to*inspect the cavity of the laiynx (Fig. 299). The mucous membrane
is thickened into a slight prominence, known as the " cushion," at the base of
^ Quoted by Griitzner: Hernumn's Handb. der Phyxiohicjlr, Bd. 11, Th. 2, S. 14, 1879.

862

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

\ -10

the oj)ii>;lottis. The e|)igh)tti.s, \\\\\v\\ is extremely movable in a median ])lane,
may be tilted backward so as to close completely the entrance into tlie hirynx.

Functions of the Epiglottis. — One
fnnetion of tlie e])iglottis seems obviously
to serve as a cover lor the superior entrance
of the larynx, over which it is said to shut
in the act of swallowing. But it is found
tiiat deglutition occurs in a normal manner
when the epiglottis is wanting or is too small
to cover the aperture, the sphincter nniscles
surrounding the latter being cajiable of pro-
tecting the larynx against the entrance of
foreign substances. It is held by some
that the epiglottis has an important influ-
ence in modifying the voice according as it
more or less completely covers the exit to
the column of vibrating air. It is also held
that the epiglottis acts as a sort of sounding-
board, taking up and i-einforcing the vibra-
tions of the air-column impinging against it.'
Sweeping dowuAvard and backward from

Fig. 295.— Vertical transverse section of each edge of the epiglottis is a sheet of
the larvnx (after Testut): 1, posterior face of i ,i • ; .,• rij

epiglottis, Ivith 1', its cushion; 2, aryteuo- MUCOUS membrane, the ary-cpighftw fold,
epiglottic fold; 3, ventricular band, or false which forms the lateral rim of the Superior

vocal cord ; 4, true vocal cord ; 5, central c .\ ^ j i • i i •

fossaofMerkei; 6, ventricle of larynx, with aperture of the larvnx and Avhich ends lU,
6', its ascending pouch; 7, anterior portion ^^^^ covers posteriori V, the arytenoid carti-

of cricoid ; 8, section of cricoid ; 9, thyroid, mi i ^ • ±\

cut surface; 10, thyrohyoid membrane; 11, lagcs. The rouuded prominence on the pos-
thyrohyoid muscle; 12, aryteno-epigiottic terior corncr of this fold is made bv the car-

muscle; 13, thyro-arytenoid muscle, with ^ _ "

13', its inner division, contained in the vocal tilage of Santorini, and a second, less marked,
r«ti^r;:o4',^l%TX;"Mir.S»': ^welUng external toit,l,ytl,e ,a,iila,,e.f

Wrisherg (Fig. 302). Looking down into
the larynx, it is seen that its lateral walls approach each other by the develop-
ment on each side of a permanent ridge of mucous membrane, known as the
ventricular hand or fahe vocnl cord (Fig. 295).

Ventricular Bands and Ventricles of Morg-agni. — The ventricular hands
or false vocal cords arise from the thyroid cartilage near the median line, a
short distance above the origin of the true cords. They are inserted into the
arytenoid cartilages somewhat below the apices of the latter. Their free bor-
der is more or less ligamentous in structure. They are brought into contact
by the sphincter muscles of the larynx, and thus protect the glottis. It has
even been stated that, in paralysis of the true cords, they may be set in vibra-
tion and be the seat of voice-formation. So-called " oedema of tlie glottis " is
chiefly due to accumulation of fluid in the wide lymph-spaces found in the
false cords.

' Mills: Journ. of Physiology, 1883, vol. iv. p. 135.

VOICE AND SPEECH. 863

The ventricular bduds are luirallcl with and just above tlic true vocal cords,
from which thov arc separated by a narrow slit. They do not, however, reach
so near the middle line as the true cords, winch can be seen between and below
the bands. The ventricular bands project more or less into the cavity of the
larynx like overhanging lips, so that each band forms the inner wall of a
space closed by the true vocal cords below, and communicating with the cavity
of the larynx through the narrow slit above mentioned. The spaces thus
bounded internally by the false cords are known as

Tlie Ventndes of Morgagni (Fig. 295). — No complete explanation has been
offered as to the purposes served by the ventricles of Morgagni and the false
vocal cords. Numerous mucous and serous glands seated in the ventricular
bands pour their secretions into the ventricles, whence the fluid may be trans-
mitted bv the overhanging lips of the ventricular bands to the true vocal
cords; hence, an important function of the former structure, probably, is to
supply to the vocal cords the moisture necessary to their normal action. The
secretion contained within the ventricle is protected by the ventricular band
from the desiccating influence of the passing air-currents. The existence of
the ventricular spaces also permits free upward vibration of the true cords.
The ventricles of Morgagni in some of the lower animals, as the higher apes,
communicate with extensive cavities which serve an obvious purpose as reso-
nating chambers for the voice, and perhaps the preservation of this function in
the ventricles themselves is still of importance in the human being. It is not
improbable that the ventricular bands find their most important function as
sphincters of the larynx, the superior opening of which may be firmly occluded
by their approximation. The well-known fact that during strong muscular
effort the breath is held from escaping is, according to Brunton and Cash,'
due to the meeting of the false cords in the middle line. The overhanging
shape of the cords allows them to be readily separated by an inspiratory blast,
but causes them to be more firmly approximated by an expiratory effort. This
mechanism recalls the mode of action of the semilunar valves of the heart.

The true vocal cords arise from the angle formed by the sides of the thyroid
cartilage where they meet in front, a little below its middle point, and, passing
backward, are inserted into the vocal i)rocesses of the arytenoid cartilages.
The aperture between the vocal cords and between the vocal processes of the
arytenoids is known as the glottis or rima glottidis (Figs. 301, 302). Since, as
will be seen later, the vocal cords may be brought together while the vocal pro-
cesses of the arytenoids are widely separated at their bases, the space between
the cords themselves is sometimes called the rima vocalis and that between the
vocal processes the rima respiratoria.

In the adult male the vocal cords measure about 15 millimeters in length
and the vocal processes measure 8 millimeters in addition. In the female the
cords are from 10 to 11 millimeters in length. The free edges of the cord are
thin and straight and are directed upward ; their median surfaces are flattened.
Each cord is composed of a dense bundle of fibres of yellow elastic tissue,

* Brunton and Cash : Journ. Anat. and Phys., 1883, vol. xvii.

864

AX AMERICAN TEXT- BO OK OF PHYSIOLOdV

which fibres, tliough having a general h)ngitutlinal course, are interwoven, and
send off shoots hiterally into the subjacent tissue. The compact ligament,
known commonly as the " vocal cord," forms only the free edge of a reflexion
from the side wall of the larynx. Tiiis reflexion is wedge-shaped in a vertical,
transverse section and contains much elastic tissue and the internal and part
of the external thyro-arytenoid muscle (Fig. 295). This whole structure

properly forms the vocal cord, and by
contraction of its contained muscle its
thickness and vibrating qualities may
be greatly modi tied.

Like the trachea, tiie larynx, with the
exception of the vocal cords, is lined

Fig. 296.— Cartilages of the larynx, separated
(Stoerk) : 1, epiglottis ; 2, petiolus ; 3, median
notch of thyroid ; 4, superior cornu of thyroid ;
5, attachment of stylo-pharyngeus muscle ; 6,
origin of thyro-epiglottic ligament : 7, origin of
the thyro-arytenoid muscle ; 8, origin of true
vocal cord : 9, inferior cornu of thyroid ; 10, car-
tilage of Wrisberg ; 11, cartilage of Santorini ; 12,
12', arytenoid cartilages, showing attachments of
the transverse arytenoid muscle ; 13, 13', pro-
cessus muscularis, showing attachments of the
posterior and lateral crico-arytenoid muscles;
14, base of the arytenoid cartilage ; 15, vocal pro-
cesses of the arytenoids ; 16, articular surface for
the base of the arytenoid cartilage ; 17, po.sterior
view of cricoid cartilage, with outline of attach-
ment of the posterior crico-arytenoid muscle;
18, articular surface for inferior cornu of thyroid
cartilage.

Fig. 297.— Cartilages and ligaments of the
larynx, posterior view (after Stoerk) : 1, epiglot-
tis : 2. cushion of the epiglottis : 3. cartilage of
Wrisberg ; 4, ary-epiglottic ligament : r>, ^, mucous
membrane ; 6, cartilage of Santorini : 7, arytenoid
cartilage: 9, its processus muscularis; 10, crico-
arytenoid ligament: 11. cricoid cartilage; 12, in-
ferior cornu of thyroid cartilage: 13, posterior
superior cerato-cricoid ligament; 13'. posterior
inferior cerato-cricoid ligament ; 14, cartilages
of the trachea: Ui, membranous jiortion of
trachea.

by columnar, ciliated epithelium, the direction of whose movement is upward
toward the pharynx. The vocal cords are covered by thin, flat, stratified epi-
thelium. The inner surface of the epiglottis, the walls of the ventricles, and
the ventricular bands contain ranch adenoid tissue, the spaces of which are apt
to become distended with fluid, giving ri,<e to a'dema of tho.se parts. The
whole mucous membrane of the larynx, except over the vocal cords, is richly
supplied with glands both mucous and .serous in character.

VOICE AND SPEECH. 865

Cartilages of the Larynx. — The niechanisin of the larynx is supported
by a skeleton composed of several pieces of cartilage. The lowermost of these
cartilages is the cricoid cartilage, so called from its resemblance to a signet ring
(Fig. 296). The cricoid cartilage is situated above the topmost ring of the
trachea to which it is attached by a membrane. The vertical measurement of
the cricoid cartilage is about one inch on its posterior, and one-quarter inch on
its anterior surface. Superior to, and partly overlapping the cricoid, is the
thyroid cartilage, which forms an incomplete ring, being deficient postei'iorly
(Fig. 296). The free corners of the thyroid behind are prolonged upward or
downward into projections known as the cornaa. The upper pair are attached
to the extremities of the greater cornua of the hyoid bone, while by the inner
surface of the ends of the lower cornua the thyroid is articulated with the
cricoid cartilage and rotates upon it around an axis drawn through the points
of articulation. The lower anterior border of the thyroid cartilage is evenly
concave, but its upj)er border has a deep narrow notch in the middle line.
The upper half of the thyroid in front projects sharply forward in an elevation
known as Adam's apple (pomum Adami), which is much more marked in adult
males than in females. The elliptical space between the cricoid and thyroid
cartilages in front is covered by a membrane. Adam's apple, the anterior part
of the cricoid ring, and the space between the two, can easily be felt in the liv-
ingsubject ; they rise perceptibly toward the head with each swallowing movement.

The arytenoid cartilages are two in number and are similar in shape (Figs.
296, 297). Each cartilage, which has somewhat the form of a triangular
pyramid, is seated on, and articulates with, the highest point on the posterior
part of the cricoid cartilage some distance from the middle line. Of the free
faces of the pyramid, one looks backward, one toward the middle line, and the
third outward and forward. Each face is more or less concave. The apex of
each arytenoid cartilage is capped by a small body called the cartilage of 8an-
torini or, from its bent shape, corniculum laryngis (Figs. 296, 297). Outside
and in front of the latter is the minute cuneiform cartilage or cartilage of
Wrisberg, enclosed in the ary-epiglottic fold. The lateral posterior corner of
the arytenoid cartilage forms a blunt projection which serves for the attach-
ment of muscles, the processus muscidaris. The anterior, lower, and median
part of each cartilage is of especial interest, since it serves for the posterior
attachment of the vocal cord ; it is known as the processus vocalis.

The thyroid and cricoid cartilages and the body of the arytenoids are of
hyaline cartilage, and tend to become ossified in middle life. The other carti-
lages and the vocal processes of the arytenoids are composed of the elastic
variety.

The Muscles of the Larynx may be divided into two classes — the extrinsic
and the intrinsic ; the former find their origin outside the larynx, and the latter
both arise and are inserted within it.

Extrinsic Muscles. — To this group belong the sterno-hyoi.d, the sterno-thy-
roid, and the omo-hyoid muscles, which depress the larynx or hyoid bone ; the
thyro-hyoid muscle, which depresses the hyoid bone or elevates the thyroid

866

AiY AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cartilage. To the elevators of the laryux belong the (jenio-hyoid , the mylo-
hyoid, the digastric, the stylo-hyoid, and the hyo-ylossiis. The muscles of the
palate and the constrictore of the pharynx enter into coordinated action with the
above. When food is passing through the pharyx in the act of swallowing,
the hyoid bone is drawn upward and forward, raising the larynx with it ; the
tongue is thrown backward so that the epiglottis covers the entrance into the
larynx, and the constrictoi-s of the larynx contract, completely closing the
entrance into that organ.

The intrinsic muscles of the larynx are the crico-thyroids, the lateral crico-
arytenoids, the posterior crico-arytenoids, the arytenoid, the aryteno-epiglot-
tideans, and the thyro-arytenoids ; all being in pairs except the arytenoid,
which crosses the middle line. The crico-thyroid muscle arises from the front
and side of the cricoid cartilage and, passing upward and backward, is inserted
into the lower edge of the thyroid cartilage (Fig. 298). The action of the crico-
thyroid muscle is to diminish the distance between the thyroid and cricoid car-
tilages in front, either by depressing the front of the thyroid or by elevating
that of the cricoid cartilage, or both. In the first case the distance between
the anterior attachment of the vocal cords and the vocal processes of the

arytenoid cartilages is increased by movement of
the thyroid, and in the second case the same effect
is produced by backward rotation of the edge of
the cricoid upon which the arytenoid cartilages are
seated (Fig. 297). The muscle, therefore, is a
tensor of the vocal cords. It is, probably, the
mechanism we ordinarily use in raising the pitch
of the voice when the vocal machinery has been
"set" by the other muscles (see below). If the
fingers be placed on the cricoid ring and on the
pomum Adami while the ascending scale is sung
in the middle chest register, both descent of the
front of the thyroid and ascent of the cricoid can
be made out. The kdercd crico-arytenoid muscle
arises from the upper, lateral border of the cricoid
cartilage, and passes upward and backward to be
inserted into the outer edge of the arytenoid car-
tilage, on and in front of the lateral prominence
(Fig. 299). Its main action is to wheel the
vocal process of the arytenoid toward the middle
line and thus approximate the vocal cords. The j^osterior crico-arytenoid is a
large muscle, which rises from the median posterior surface of the cricoid car-
tilage and passes upward and outward to be inserted into the outer surface of the
ar}i;enoid cartilage, behind and above the insertion of the lateral crico-arytenoid
(Fig. 300). Its action is to turn the vocal processes outward and thus abduct the
vocal cords. The posterior crico-arytenoid occupies an important position in the
group of respiratory muscles ; during vigorous inspiration it is brought into action

Fig. 298.— Lateral view of the
cartilages of larynx with the crico-
thyroid muscle {Qiiain'i' Anatomy,
after Willis): 1, crico-thyroid mus-
cle : 2, crico-thyroid membrane ; 3,
cricoid cartilage ; 4, thyroid carti-
lage ; 5, upper rings of the trachea.

VOICE AND SPEECH.

867

and widens the glottis. Paralysis of tliis muscle is a most serious condition, since
it is followed by ai)})roximation of, and inability to separate, the vocal cords.
The arytenoid, or trmisva'se or posterior arytenoid muscle, the single unpaired

Fig. 300.— Larynx with its muscles, posterior
view (Stoerli) : 1, epiglottis ; 2, cushion ; 3, ary-
epiglottic ligament ; 4, cartilage of Wrisberg ;
5, cartilage of Santorini ; G, oblique arytenoid
muscles; 7, transverse arytenoid muscle; 8,
posterior crieo-arytenoid muscle ; 9, inferior
cornu of thyroid cartilage; 10, cricoid car-
tilage ; 11, posterior inferior cerato-cricoid lig-
ament; 12, cartilaginous portion; 13, mem-
branous portion of trachea.

Fig. 299.— Larynx and its lateral muscles after
removal of the left plate of the thyroid cartilage
(Stoerk) : 1, thyroid cartilage ; 2, thyro-cpiglottic mus-
cle ; 3, cartilage of Wrisberg ; 4, ary-epiglottic mus-
cle; 5, cartilage of Santorini; 6, oblique arytenoid
muscles ; 7, thyro-arytenoid muscle ; 8, transverse
arytenoid muscle ; 9, processus muscularis of aryte-
noid cartilage ; 10, lateral crico-arytenoid muscle; 11,
posterior crico-arytenoid muscle ; 12, crico-thyroid
membrane ; 13, cricoid cartilage ; 14, attachment of
crico-thyroid muscle; 15, articular surface for the
inferior cornu of the thyroid cartilage; 16, crico-
tracheal ligament; 17, cartilages of trachea; 18,
membranous part of trachea.

muscle of the larynx, is a considerable baud pa.ssing across the middle line from
the posterior surface of one arytenoid cartilage to that of the other (Fig. 300).
Its action is to draw the arytenoid cartilages together in the middle line and
approximate the vocal processes; its action is essential in closing the glottis. In
the resting larynx the arytenoid cartilages are kept apart by the elastic tension
of the parts. The aryteno-epiglottidean, sometimes called the oblique arytenoid,
muscles consist of two bundles of fibres seated upon the surface of the arytenoid
muscle (Fig. 300). Each muscle arises from the outer posterior angle of the
arytenoid cartilage, and, passing upward and inward, crosses in the middle line
partly to be inserted into the outer and upper part of the opposite cartilage,
partly to penetrate the ary-epiglottic fold as far as the epiglottis, and the
remainder to join some fibres of the thyro-arytenoid muscle. The action of
the aryteno-epiglottidean muscles is to close the glottis. The thyro-arytenoid
is a muscle of complex mechanism, usually described as formed of two parts,
an external and an internal. The external thyro-arytenoid arises from the lower

sns

,LV AMKlilCAy TEXT- HOOK OF PHYSIOLOGY.

}>:irt (it' tilt' uiiu'le of the tliyroid carlllajre; its fibres jniss, for the most part,
baekwanl and soinewliat u])\vanl and outward to be inserted into the outer
edge of the arytenoid cartilage and its lateral processus miisculcn-ls (Figs. 295,
301). Some of its bundles of fibres, however, have different directions, and
a portion of them pai>s upward into the ventricular bauds. The internal thyro-
(iri/tenoid, wedge-shaped in trausverse section, lies between the muscular divis-
ion just described and the vocal ligament, by which its thin median edge is
covered. The internal thyro-arytenoid arises from the anterior angle of the
thvroid cartilage and is inserted into the processus vocal is and the outer face of
the arytenoid cartilage. Certain fibre-bundles of this, as of the external
division of the muscle, pass in various directions, some of them being inserted
into the free border of the vocal cord. The action of the muscle is, on the
whole, to draw the arytenoids forward and thus relax the vocal cords; but, by
its contraction, the cords may also be approximated and their thickness, and
probably their elasticity, extensively modified.

Specific Actions of the Laryngeal Muscles. — To sum uj) the various
effects of the muscular action on the larynx : A sjiliincfer action of the laiyux
is brought about by the combined contraction of all the muscles with the
exception of the crico-thyroids and the posterior crico-arytenoids ; the rocal

cords are adducted and the glottis nar-
ronrd by the trausvei*se and oblique ary-
tenoids, the external thyrt)-arytenoids,
.^m.thi/.ar.i. mjj ^\'^^, lateral crico-arytenoids ; the
.m.ihy.ar.e. vocal cords are abducted and the glottis
.Xm.thy.ar. n-idcned chiefly or wholly by the poste-
rior crico-arytenoids ; the vocal cords
arc made toise by contraction of the
crico-thyroids; the vocal cords arc slack-
ened by the combined action of the
sphincter group and especially by the
external thyro-arytenoids.

It will easily be seen that in the
larynx, as in the skeleton at large, the
efficiency of any single nmscle involves
the action of accessory uniscles; thus,
contraction of the crico-thyroid could
have little effect in tightening the vocal
cords were not the arytent)id cartilages
fixed by contraction of the posterior crico-arytenoid and arytenoid Jiniscles.
Nerve-supply of the Larynx. — The larynx receives its nerve-sui>])ly from
the superior and the inferior or recurrent laryngeal nerves. The extremely
scnisitive surface of the mucous membrane of the organ above the vocal cords
is supplied by sensory filaments of the superior laryngeal nerve. The superior
laryngeal also supplies motor fibres to the crico-thyroid muscle, whose action
as a tightener of the vocal cords is peculiar. All the other muscles of the

Fig. 301.— Diagram to illustrate the thyro-aryte-
noid muscles; the figure represents a transverse
section of the larynx through the bases of the
arytenoid cartilages (redrawn from Foster) : Ary,
arytenoid cartilage: p.m, processus nuiscularis;
p.v, processus vocalis : TTi, thyroid cartilage; c.i;,
vocal cords ; (E is placed in the cesophagus ;
m.thy.ar.i, internal thyro-arytenoid muscle;
vi.tky.ar.e, external thyro-arytenoid muscle;
m.thy.ar.ep, part of the thyro-ary-epiglottic mus-
cle, cut more or less transversely ; m.ar.t, trans-
verse arvtenoid muscle.

VOICE AND SPEECH.

869

larynx receive tlioir motor impulsos iVoiii the inferior larvnt^otil nerve. Much
of the nervous mechanism of the larynx is still in dispute.

Laryngoscopic Appearance of the Larynx. — Much may be learned hy
inspection of the larvnx dnrinji; life hy means <tf tli<' larynj^oscopic mirror. It
is not difficult for an observer to examine his own larynx by placing himself
before a second mirror in which may be seen the image reflected from the
laryngoscope. To inspect the larynx the tongue must be held well out so
as to pull forward the epiglottis, then the structures below appear in the
laryngoscopic mirror in reversed position. Beneath the middle of the e])iglottis
the cushion may be seen as a slight swelling, and continuing downward aud
backward from the edges of the cartilage, may be seen the ary-epiglottic folds,
each marked at its extremity by two rounded nodules, the cartilages of AVris-
bergand Santorini (Fig. 302). In quiet breathing the glottis is nearly stationary
and opened to the extent of from 3 to 5 millimeters. The vocal cords bounding
it look white and glistening in contrast with the red color of the general mucous
membrane. The cartilages of Santorini are several millimeters apart, and a
sheet of mucous membrane reaches from one to the other. The ventricular

Fig. 302.— The larj-ugoscopic image in easy breathing (Stoerk): 1, base of the tongue; 2, median
glosso-epiglotticligament; 3, vallecula; 4, lateral glosso-epiglottic ligament; 5, epiglottis; 6, cushion of
epiglottis ; 7, cornu major of hyoid bone ; 8, ventricular band, or false vocal cord ; 9, true vocal cord ;
opening of the ventricle of Morgagni seen between 8 and 9: 10, folds of mucous membrane; 11, sinus
pyriformis; 12, cartilage of Wrisberg; 13, aryteno-epiglottic fold; 14, rima glottidis; 15, arytenoid carti-
lage ; 16, cartilage of Santorini ; 17, posterior wall of pharynx.

bands are seen as red shelves reaching to the outer margin of the shining
cords and separated from the latter by a dark line which is the entrance into
the ventricles of Morgagni.

When a deep inspiration is taken the glottis is widely opened, even to the
extent of half an inch ; an angle is formed between the vocal process of the
arytenoid and the vocal cord, the space between the cartilages of Santorini is
widened, and the rings of the trachea, and even its bifurcation may be seen
below. With the succeeding expiration the glottis again becomes narrow.
When the voice is sounded the picture at once changes. The space between
the cartilages of Santorini is obliterated, the vocal processes aud cords ar^

870 AN AMERTCAN TEXT-BOOK OF PHYSIOLOGY.

brouj^C^it togetlier, aiul the ^vllole rim of the glottis or the vocal cords alone,
according to the pitch of the note, may be seen to vibrate.

2. The Voice.

The vocal machinery consists of — (1) the motive jiower or breath ; (2)
the larvnx, which forms the tone; (3) the chest, the pharynx, the mouth, and
the nose, which color the tone; and (4) the organs of articulation.^

The production of voice is nndoubtedly accomplished by the vibration of
the vocal cords which have previously been approximated in the middle line
and made tense through action of the nerve-muscular ai)paratus already de-
scribed. A blast of air from below pressing against the cords so adjusted,
causes them to separate and fall into vibration. We have to distinguish in
voice the three features of loudness, jyitch, and quality.

The loudness of the tone depends on two factors: (1) the strength of the
tone-producing blast as determining not only the amplitude of vibration of
the vocal cords, but also the energy with which the air is expelled; (2)
the resonance of the two chambers between which the vocal cords are sus-
pended, the chest below and the cavities of the head above, whose walls and
contained air, by their sympathetic vibration, powerfully reinforce the oscilla-
tions imparted to them.

The pitch of the voice is determined by the thickness, tension, and length
of the vocal cords, conditions which regulate the pitch of the note obtained
from anv vibrating string. The thickness and the elastic quality of the cords
are probably largely under the control of the thyro-aryteuoid muscle. The
principal tensor of the cords is the crico-thyroid muscle. Other muscles, as
described above, may so fix the arytenoid cartilages that their vocal processes
may be prevented from taking part in the vibration of the cords throughout
the whole and also, possibly, throughout part only of their length. This
dampening of the vocal processes of the arytenoids may be accomplished either
by pressure applied to them throughout their M'hole length, in which case the
posterior part of the glottis is closed, or they may be pressed together at the
tips alone, leaving the respiratory glottis open as a triangular aperture.

Quality. — Variation in the quality of the voice depends on the fact that
vibrations of the vocal cords are composite in character, giving rise to notes
made up of a fundamental tone combined with upper partial tones (see p. 827).
Bv reason of the varied adjustments that may be imparted to it, the larynx is
capable of producing many more qualities of tone than is any artificial instru-
ment.^ Change in the size and shape of the resonance-chamber above and
below the vocal cords produces a corresponding change in their fundamental
notes and, therefore, in the partial tones of the voice which they reinforce by
sympathetic vibration (see p. 829). According to Helmholtz,^ the difference
in quality between the various vowel sounds of the human voice depends on

' C. H. Davis: The Voice, 1879.

» Helmholtz: Sensations of Tone, trans, by Ellis, 1885, p. 98.

» Op. ciL, p. 104.

VOICE AND SPEECH. 871

the number and relative promiiienee of the various overtones determined by-
altering the shape and size of the na.sal and buccal resonance-chambers.

By a simple experiment the production of voice by the vocal cords can
easily be illustrated. Take a glass tube, about \ inch in diameter and of con-
venient length, and press one end firmly against the palmar surfaces of the
proximal phalanges of two fingers at their line of division when they are
brought together. By blowiug smartly into the other end of the tube, a
musical note will be produced by the vibration of the folds of the skin be-
tween which the air is forced. By relaxing the pressure with which the
fingers are held together, the length of the vibrating segment of skin is in-
creased and its tension diminished; its note is accordingly lowered. The
reverse conditions are produced when the fingers are held together tightly and
the tube applied firmly ; the pitch of the note is then raised. In these ways
the pitch of the note may be varied through two octaves, which is the range
of a good singing voice. Various upper partials of the note so produced may
be made prominent by sympathetic resonance, if the vibrating air-stream is
sent across the opening of a wide-mouthed bottle, of about a pint capacity.
The air within the bottle is thrown into sympathetic vibration when its funda-
mental tone is contained in the note emitted through the fingers ; when the
volume of the air is diminished by slowly pouring water into the bottle, the
fundamental tone of the resonator is changed, and it responds to one after
another of the partials contained in the musical note.

The marvellous adjustment of muscular action by which, at will, notes
mav be struck of definite pitch and quality, is evidence of an elaborate
nervous machinery for the larynx, not only on the efferent side but, possibly
through a muscular sense, on the afferent side as well. The various phe-
nomena of aphasia, and the anatomical importance of the cerebral areas
devoted to the elaboration of speech, point in the same direction. The
relations between the centres for speech and hearing are most intimate. The
ear plays a constant part, as a critical medium, in the tuition of the vocal
organs in either speech or song. So-called "dumbness" is the result, usually,
not of defects in the vocal organs, but of lack of hearing and, hence, of
inability to control by the ear the pitch or quality of the vocal notes.

The voice and the larynx of the child fall naturally in a group with those
of the female as contrasted with the adult male. At the age of puberty a
boy's larynx becomes congested and undergoes rapid development. The voice
changes rapidly from the juvenile to the adult quality. During this change,
the voice frequently "breaks" or rapidly returns from the newly-acquired
chest register to the head or falsetto notes of childhood (see p. 873). In boys
who are castrated a good while before the age of puberty is reached, the larynx
does not undergo its characteristic development, and the voice remains of a
peculiar quality, much valued in some countries in the rendition of vocal
music. The practice of castration for aesthetic purposes has, accordingly, in
certain districts, long been in vogue. In the female the changes in the larynx
and in the voice at puberty are much less marked than in the male.

872 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Arrangements for Changing the Pitch of the Voice. — As has i'niquently
been mentioned, the voeal eords are stretehed, and tlie piteh of their note is
elevated, by contraction of the crieo-thyroid muscle. But the change that is
thus produced in the tension of the vocal cords is by no means capable of
accounting for the full range of pitch which i'alls within the com})ass of the
voice. AVhcn the arytenoid and the crico-arytenoid muscles sufficiently con-
tract, the vocal ])rocesses are brought tightly together and their vibration is
prevented. Voice-production must then be limited tc» the vocal cords them-
selves, and the stretching action of the crico-thyroids may begin anew and
reach its maximum with the glottis so set that only its ligamentous borders can
vibrate. It can also be seen that the vocal cords themselves may be shortened
functionally, or even be broken uj) into segmeuts, or the main body of the cord
be changed in thickness, by contraction of the complex thyro-arytenoid muscles;
each such condition would be accompanied by a change in the rate of vibra-
tion. We are j)robably justified in assuming that, when the musical scale is
sung, the lowest notes are produced by vibration of the glottic borders through-
out their full length, and the elevation of pitch is affected by the gradually-
increased tension of the vocal ligaments through the action of the crico-thyroid
muscle. This contraction having leached its maximum, the muscle probably
relaxes, only to contract again after the vibrating segments of the glottis are
shortened by a partial or complete clamping together of the vocal processes
in the manner described above. There are thus two or three, or more,
adjustments which may be imjiarted to the vibrating mechanism of the lar-
ynx, each of which is distinguished by giving rise to a note of different
pitch that may further be altered by action of the crico-thyroid muscle.
It might be anticipated that the voice whose pitch was gradually ele-
vated in the manner described would suffer some alteration in quality
at those points in the scale where there is a change in the set of the lar-
vnx producing a shortening of the vibrating segment. Such, indeed, is

the fact.

Registers.— Ijong before the invention of the laryngoscope, and before any-
thing definite was known of the method of voice-production, it was recognized
that in ascending the musical scale there occur certain breaks, as it were, where
the voice changes in quality as well as in piteh. It is an object in musical
education to render these breaks as little prominent as possible. The kinds of
voice included between these breaks were distinguished as the vocal "registers."
There is no general agreement among musicians as to how many registers are
compassed by the voice, and the nomenclatures used to distinguish them differ
in the most confusing fashion. According to some authors, the range of the
voice is included within two registers only; more commonly three distinct
registers are described, to which, in certain cases, a fourth is said to be prob-
ably added. The most common designation of the lowest register is the " chest
voice," though it has also l)een called " thick " ^ as distinguished from the
" thin " register ; another term applied to it is the " long-reed " register as con-
> Browne and Behnke: Voice, Song, and Speech, 1890, p. 135.

VOICE AND SPEECH.

873

trasted with the " sliort-ret'd " register.' Tlie middle register of all voices is
by some authors (Garcia,^ Mme» Seiler') denominated the "falsetto," while
other writers use this t(!rni to distinguish certiiin higher notes of the male
voice of a peculiar quality not in ordinary use. The third and highest series
of vocal sounds is usually known as the " head " register.

The lowest or chest register is that used in ordinary life. It is so called
from the strong vibrations of the chest-wall which may be felt while the voice
is sounded. In passing to the higher register the chest vibration is found to
diminish and that of the head bones to increase; in the one case the cavity of
the head acts strongly as a resonance chamber, and in the other that of the
thorax. According to Madame Seiler, in the lowest register both the vocal
ligaments and the vocal processes of the arytenoids vibrate. In the middle
register the vocal processes are clamped together and the vibrati(ni of the liga-
ments seems confined chiefly to their sharp edges; while in the highest register
the ligaments themselves appear to be damped throughout the greater part of
their length, the vibrations being confined to the edges of an oval slit at their
ABC

Fig. 303.— The voicing (female) larynx (after Browne and Behnke). A, Small or highest register. B,
Upper thin or middle register. C, Lower thin or middle register: T,T, tongue; F,F, false vocal cords;
S,S, cartilages of Santoriui; I^', W, cartilages of Wrisberg; V, V, vocal cords.

anterior ends (Fig. 303). Within any definite register the quality of individual
voices is determined by the size and elasticity of the parts of the larynx, and
probably also by peculiarities of the resonating chambers ; voices are accord-
ingly classified as base, tenor, alto, and soprano.

A Whistling Register. — A friend and former pupil of the author's has the remark-
able power of emitting from the larynx notes which are indistinguishable in quality from
an ordinary whistle. He writes, "The whistle cannot be made to 'slide ' into vocal tones
of any sort, nor can any other tones be produced simultaneously with it. Its range is
about one and a half octaves, or half an octave less than my singing voice.

"The lips have nothing to do with the sound except as their position changes the reso-
nance-quality of the tone by ' reinforcement ' or otherwise, for I can whistle almost as read-
ily with the teeth closed and the lips wide parted as with the jaws and lijis firmly closed as
in the ordinary position. Any other movement of the air-column destroys the sound at
once." Some years ago the author made a laryngoscopic examination of this larynx while
it was in the act of whistling. No notes were written at the time, but the picture remem-
bered is that of vocal cords closely approximated, except for an oval slit between their
anterior and middle portions, as in singing head tones, the cords vibrating chiefly along
their free edges.

Speech. — Language consists, in general, of a combination of short musical

sounds, vowels or sonants, which are produced purely by vibration of the vocal

' Mackenzie : Hygiene of the VocmI Orgmifi, 1891, p. 55.

^ Garcia: Lond., Edin., and Dub. Mag., vol. x. 1855, p. 218. (Quoted by Seiler.)

■* Seiler : op. cit.

874 JliV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

cords, together with superadded noises or modes of obstruction, consonants,
produced by action of the mouth-parts. The vowel sounds usually carry the
accent of syllables, and the consonants, for the most part, are sounded only
with, or represent peculiar modes of obstructing the former. No classification
of vocal signs can be made in which exceptions do not form important addenda
to general rules.

Articulation is the motlifieation of sound in speech, usually effected by action
of the lips, the tongue, the palate, or the jaws, and the place of articulation
depends, in any definite case, on the mode in which a sound is formed. Its use
as an expression of thought is the chief physiological distinction between man
and the lower animals. Distinctness of articulation, so essential to clearness
of language, not to mention its aesthetic value, depends on the accuracy of the
muscular adjustments used in forming sounds, especially consonantal sounds.

The speaking is distinguished from the singing voice partly by the fact that
most sounds in the first case are articulate or formed in the mouth, while in
the latter their quality is only there modified. In singing the tone is sustained
at the same pitch for a considerable interval, while in speaking the voice is con-
tinually sliding up and down on the vowel sounds. In speaking the conso-
nantal noises and obstructions are more prominent because of their more abrupt
formation.'- ^

Voicel sounds owe their origin to vibration of the vocal cords, and their
quality to the selective resonance of the cavities above the cords. In sounding
the series of vowels, a, e, i, o, u (pronounced ah, a, e, o, oo), it is found that the

Fig. 304.— Section of the parts concerned in phonation, and the changes in their relations in sound-
ing the vowels A(<^),I («), U (") (after Landois and Stirling) : T, tongue ; p, soft palate ; e, epiglottis ; g, glot-
tis ; h, hyoid bone ; 1, thyroid ; 2, 3, cricoid ; 4, arytenoid cartilage.

form and size of the mouth-cavity, the position of the tongue, the position of
the soft palate separating or allowing communication between the nasal and
pharyngeal cavities, undergo a progressive change (Fig. 304). Helmholtz has
shown that the vowel sounds owe their differences of quality to the varied
resonance of the mouth-cavity, dependent on its shape, through which now one,
now another, of the overtones in the note produced by vibration of the vocal
cords is reinforced.^ This result is dependent on the fact that when the mouth
is set in position for the formation of the various vowel sounds the pitch of its

* Browne and Behnke : op. cit., p. 28.

* Monroe: Manual of Physical and Vocal Training, 1869, p. 51.
' Helmholtz: he. cit.

VOICE AND SPEECH. 875

fundamental note, or the rate of vibration to which it sympathetically responds,
varies accordingly.' That the resonance of the mouth cavity changes with
its shape is ilkistratcd in the various pitch of the notes produced by flipping
the edge of an incisor touth, the cheek, or Adam's apple with the finger-nail,
while the mouth assumes the positions for production of the different vowels.
Vowels whose normal pitch is low, as o, u, cannot be sounded easily in the
higher part of the musical scale ; conversely, high-pitched vowels, as e in fed,
lose their character in the lower part of the scale. Language is, therefore,
much less distinct in song than in speech.^^

Since the mouth cavity is set to a definite pitch for each vowel sound, it
follows that when the same vowel is voiced in different parts of the musical
scale, those tones which are strengthened by resonance remain the same, imt
their distance from the fundamental will be different. That is, the resonated
partial depends not only on its relation to the fundamental, but also on its
vibration nite.^ This feature of vocal resonance distinguishes the human
larvnx from most musical instruments. That the ground is not covered by
these facts was shown by Auerbach,* who demonstrated that the strength of
upper partials in vowel sounds depends also on the strength of their production
by the vocal cords and, therefore, upon their relation to the fundamental tone.
That is to say, the quality of a vowel is dependent not only on the absolute
vibration numbers of its upper partials, according to which they are or are not
reinforced by the position of the mouth, but also on the relative position of these
upper partials as compared with the fundamental tone.

The peculiar esthetic value of the human voice is dependent on the fact
that, on account of its varied powers of adjustment, the larynx is capable of pro-
ducing manv more kinds of tone-qua]ity than any artificial instrument. Helm-
holtz^ found no less than sixteen overtones to accompany the fundamental.

The posture of the mouth-parts differs markedly when set for the various
principal vowel sounds ; but as we know that each vowel sound has several
modifications or gradations so that a tone may pass by an easy glide from one
to another, so the form of the mouth passes by insensible steps from one vowel
position to another. It will be seen later that several articulate sounds play
the part now of vowels, now of consonants, according to their position in the
syllable or mode of formation. There has also been shown reason for believ-
ing that the form of the chest cavity and the tension of its walls are factors in
determining the pitch of its fundamental tone ; so that through the varied
sympathetic resonance of the thorax the reinforcement of laryngeal tones may
here be altered somewhat, as in the mouth itself.®- ^

Whispering is a mode of speech in which noise largely replaces peudular
musical vibrations. The glottis remains more or less widely open and the
vocal cords are not tense ; the vibrations are produced both in the larynx and
in the buccal-pharyngeal chambers. Vowel sounds may be produced in whis-

1 Helmholtz : op. cit., p. 108. ' Op. cit., p. 114. => Op. cU., p. 118.

* Quoted by Griitzner: op cit, p. 179. * Op. cit, p. 103. * Op. cU., p. 93.

♦ Sewall and Pollard : Journal of Physiology, vol. xi., 1890, p. 159.

876 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

pering as well as in true voice because, from the multitude of irregular vibra-
tions, those waves are reinforced which make up the vowel sounds determined
bv the set of the mouth. Gentle whispering requires much less effort than does
speaking, and inspiratory whispering is less easily distinguished from expiratory
than is the strained voice of ins])iration from the natural sound of expiration.
Consonants, as already indicated, may sometimes play the part of vowels, but
})ure consonants do not appear in syllables except in combinations with vowels,
which combinations always carry the syllable accent.

Consonants. — The distinction between consonants and vowels lies in the
fact that the tones of the latter are produced by vibration of the vocal cords,
the parts above which act only as resonance-boxes and modify the sound, and
never offer marked obstruction to the exit of air ; whereas in the formation of
consonants there is some adjustment in the mouth-passage either in the nature
of a local narrowing, by which a peculiar noise is added to the vocal sound, or
in the nature of a sudden closing or opening of the air-channel by which a
characteristic noise is likewise added to the vocal sound. In other words, the
parts above the larynx mahc the sounds of consonants but only modify those
of vowels.' No sharp line of separation can be drawn between vowels and
consonants, since certain characters, according to their associations, now fall
into one, now into another class. In the classification of consonantal sounds
much confusion exists, dependent chiefly on the fact that several letter charac-
ters change their modes of formation and expression with their place in the
svllable. The same facts, also, are expressed by different authors l>y different
nomenclatures, and soiuids occur in one language that are not found in another.
Adopting the general classification of Griitzner,^ we may divide consonants
into the following three groups:

1. Semi-vowels or Uquids,\\\\\c\\ can be used either as vowels or consonants;
this group includes the sounds m, n, ng, I, and r. In expressing the function
of a consonant, the letter is not to be sounded as if it stood alone, but its cha-
racter given as actually expressed in a syllable; thus the sound of p is not pee,
but is the abbreviated labial expression, as in jjaeZ; or piece when all the letters
are eliminated after tiie first. Of the liquids the n, m, and ng (sometimes
called "resonants") have the nature of vowels when final (as in him, hen,
being), and are then produced by vibration of the vocal cords, the lij)s having
previously been closed for the m, and the tongue applied to the roof of the
mouth to cut off the exit of air for n and iig ; the expelled air escapes alto-
gether through the nose, which acts as a resonance-chamber. Used as conso-
nants, as in make and no, m and n are seen to have the characters of the second
group, — Explosives. L is pronounced somewhat like n, but air is allowed to
escape through the mouth on each side of the tongue ; it may be produced
either Avith voice or without voice (in whispers). It may have vowel charac-
ters as in play. R is characterized as a inbrative and may have several seats
of articulation, as by the thrill of the tip of the tongue against the hard
palate, or that of tiie hind part of the tongue against the soft palate, or even
' Grutzner: op. cit., p. 196. ^ Op. cit., p. 197.

VOICE AND SPEECH.

^11

by the coarse vibnitiou of the vocal cords tlieniselves. In the first two cases
it may be sounded either with or without voice. Its vowel nature is shown in
such words as pray.

2. Explosives, wliich are produced either when an obstruction is suddenly
offered to or removed from tlie exit of air from the mouth ; at the same time
a characteristic noise is produced. They may be subdivided according to the
place of articulation into labuds (p, v) ; Unguo-pcdutals (f, d) ; gutturals (k, (j).
The similarity in the method of formation of j) and 6, t and c?, k and (j, is
striking. They are frequently characterized as being formed idtii or u-Hhout
voice; that is, 6, d, and g require voice for their distinct recognition, and when
whispered they are easily mistaken i'or p, t, I:, which latter do not require voice
(vibration of the voeal cords) for their recognition. A consonant, then, is said
to be formed icith voice when it can be rendered distinctly only by an accom-
panying vibration of the vocal cords, without voice when articulated clearly
without laryngeal aid. The former are sometimes called sonants, the latter
surds. This classification only approximates the truth, for the suddenness and
energy with which the obstruction to the breath is removed determines our
recognition of the consonant irrespective of voice.^

Table of Consonantal Elements!^

Oral.

Place of Articulation.

Lips

Lips and teeth

Tongue and teeth . . .
Tongue and hard palate

(forward)

Tongue and hard palate

(back)

Tongue, hard palate, and

soft palate

Tongue and soft palate .
Various places

Momentarj'.

Continuous.

Surds I Sonants Surds ' Sonants

(without voice), (with voice), (without voice), (with voice).

Nasal.
Continuous.

Sonants
(with voice).

t
ch

f
th(in)

s

sh

th(y)
z, r
zh, r

V, 1

3. Friction sounds or frictionals, often called asjnrates, are all noises pro-
duced by the expired blast pa.ssing through a constriction in its passage, at
which point a vibration is set up. No obstruction being offered to the sound,
they are known as continuous as di.stinguished from the momentari/ sounds of
group 2. They may be divided into labio-dental frictionals, f (v^^'ithont voice) ;
V, w (with voice) ; the Ungual frictionals s, th (as in them); sh, ch soft (with-
out voice) ; z, j (with voice). The sound of h may be regarded as due to the
viljration of the separated vocal cords. It is peculiar, however, in appearing
to be formed in any part of the vocal chamber ; when it is formed the mouth
parts take on no peculiar position, but assume that of the vowel following the
h, as hark, hear, etc.

' Grtitzner, op. cit., pp. 211, 213.

' Webster s International Dictionary. 1891, p. Ixvi.

XIII. REPRODUCTION.

The principles and problems of Physiology that have been already pre-
sented in this voluino, compri.sing nutrition and the functions of the mu.scular
and tiie nervous sy.stems, have reference to the individual man or woman.
Through the normal activity of those functions and tlieir appropriate co-
ordination the individual lives his daily life or performs his daily tasks as an
indo}iendent organism. But man is something more than an independent
orgaiiism ; he is an integral part of a race, and as such he has the instincts of
racial continuance. The continuance of the race is assured only by the pro-
duction of new individuals, and the strength of the human reproductive
instinct is indicated in some measure by the large proportion of energy that is
expended by woman in the bearing of children and by both sexes in the nur-
ture and education of the young. The function of reproduction is not limited
to the daily life and well-being of independent organisms. It has a deeper
significance than that. Its essence lies in the fact that it has reference to the
species or race. Many of its problems are, therefore, broad ones ; they in-
clude not only the immediate details of individual reproduction, but larger
ones relative to the nature and significance of reproduction and of sex, and to
heredity. In the following discussion some of these broader aj)plications of
the facts presented will be indicated.

A. Reproduction in General.

In all forms of organic reproduction the essential act is the separation from
the body of an individual, called the parent, of a portion of its own material
living substance, which under suitable conditions is able to grow into an inde-
pendent adult organism.

Among living beings two methods of reproduction are recognized, the
asexual and the sexual methods. Both are widespread among animals and
plants, but the asexual method is the more primitive of the two and is rela-
tivelv more frequent in low organisms. The sexual method, the only one
present in the production of new individuals among the higher animals, has
evidently been acquired gradually, and has probably been developed from the
asexual method.

Asexual Reproduction. — Asexual reproduction, or agamogcnesis, is the
chief method of reproduction among unicellular plants and animals, and
throughout the plants and in the lower multicellular animals it is important.
Among various species it takes various forms, known as fission or division,
gemmation or budding, endogenous cell-formation or spore-formation or multi-

878

REPRODUCTION. 879

pie fission ; but all the varieties are luodiHcations of the simplest form, fission
or division. In fission, found only in unicellular orjj^anisms and typified in
Amoeba, the protoplasm of the single cell, together with the nucleus, becomes
divided into two approximately equal portions which separate from one
another. In the process no material is lost, and two independent nucleated
organisms result, each approximately half the size' of the original. The
parent has become bodily transformed into the two offspring, which have only
to increase in size by the usual processes of assimilation in order themselves
to become parents. In higher organisms, even where sexual processes alone
prevail in the production of new individuals, the asexual method has per-
sisted in the multiplication of the individual cells that constitute the body;
embryonic growth is an asexual reproductive process, a continued fission, dif-
fering from the amreboid type in the facts that the resulting cells do not sepa-
rate from one another to form independent organisms, but remain closely
associated, undergo morphological differentiation and physiological specializa-
tion, and together constitute the individual. Likewise in the adult the pro-
duction of blood-corpuscles and of epidermis, the regrowth of lost tissues, and
the healing of wounds are examples of asexual cell-reproduction. From the
standpoint of multicellular growth Spencer and Haeckel have happily termed
the process of asexual reproduction in unicellular organisms " discontinuous
growth."

Sexual Reproduction. — Sexual reproduction, or gamogenesis, occurs in
unicellular organisms, where it is known as conjugation, and is the prevailing
form of reproduction in most of the multicellular forms. In most of the
invertebrate and vertebrate animals it is the sole form of reproduction of
individuals. In its simple form' of conjugation, typified in the minute monad,
Heteromita, it consists of a complete fusion of the bodies of two similar indi-
viduals, protoplasm and nuclei, followed by a division of the mass into
numerous spore-like particles, each of which grows into an adult Heteromita.
In the higher infusorian, Paramoecium, the fusion of the two similar individ-
uals is a partial and temporary one, during which a partial exchange of
nuclear material takes place ; this is followed by separation, after which each
individual proceeds to live its ordinary life and occasionally to multiply by
simple fission.

In the highly specialized sexual reproduction of higher animals, including
man, the individuals of the species are of two kinds or sexes, the male and
the female, with profound morphological and physiological differences, between
them ; in each the protoplasm of the body consists of two kinds of cells, somatic
cells and germ-cells, the former subserving the nutritive, muscular, and nervous
functions of daily life, the latter subserving reproduction. The germ-cells of
the male, called spermatozoa, are relatively small and active, those of the
female, called ova, are relatively large and passive ; the reproductive process
consists of a fusion of a male and a female germ-cell, the essential part being
a fusion of their nuclei ; and this is followed by continued asexual cell-division
and growth into a new individual. Among both plants and animals it is not

880 AN AMERICAN TEXT-BOOK OF PIIYSIOLOOY.

difficult to find a series of forms showing pro<;ressively greater and greater
deviations from the typical asexual toward the typical sexual method of
reproduction, and the existence of such a series is indicative of the derivation
of tiie latter from tlie former tvjie.

Origin of Sex, and Theory of Reproduction. — It is obvious that the
production of new individuals is necessary to tiie continued existence of any
species. It w^ould be interesting to know the origin and significance of the two
existing methods of reproduction. Apropos of the asexual })rocess, Leuckart,.
and especially Herbert Spencer, have pointed out that during the growth of
a cell the mass increases as the cube, but the surface oidy as the square, of
the diameter — i. e. the quantity of protoplasm increases much more rapidly
than the absorptive surface. It follows from this tliat during the growth of a
unicellular organism a size will ultimately be reached beyond which the cell
will not be able to absorb sufficient food for the maintenance of the proto-
plasm. In order that growth may continue beyond this point, a division of
the cell, which ensures a relative increase of surface over mass, is absolutely
necessary. Fission is, therefore, a necessary corollary of growth, and, although
we are ignorant of the details of its mechanism, it is conceivable that the method
of asexual reproduction arose through causes connected with growth.

The explanation of sexual reproduction is much more difficult, for here, in
addition to the budding off of the germ-cells from the parental bodies, which
has probably the same fundamental cause as fission in unicellular forms, we
must account for the differentiation into sexes, the existence of special sexual
cells, and the fusion of the male and the female germinal substance ; in short,
we must account for the conception of sexuality itself and all that it implies.

Regarding the origin of sexuality itself, as fo the question whether sexuality
is an original and fundamental attribute of protoplasm or has been acquired,
we may say at once that at present we know really nothing. Yet, whatever
view is held as to the origin of sexuality, it seems entirely probable that the
method of reproduction known as sexual is a derivative of the method known
as asexual — the latter is primitive, the former has arisen from it. From the
wide distribution and prominence of the former among vital phenomena we
must believe, with biologists generally, that sexual differentiation and sexual
processes have arisen from natural causes, and for the reason that sexual repro-
duction is of advantage to living beings and to species. In what way it is of
advantage, however, is disputed. Three views, all of which have evidence in
their favor and which are not mutually exclusive, are at present engaging the
attention of scientific men. The first to be mentioned is the theory advocated
by Hen.sen, Edouard van Beneden, and Butschli, according to whom the fusion
of the cells in sexual reproduction exists for the purpose of rejuvenating the
living substance. The power possessed by cells of dividing asexually is
limited; in time the protoplasm grows old and degenerates; its vital powers are
weakened, and without help the extinction of the race must follow. But the
mingling of another strain with such senescent protoplasm gives it renewed
youth and vigor, restores the power of fission, and grants a new lease of life to

REPROD UCTION. 881

the species. From his observations upon the Infusoria, Maupas' has brought
forward valuable evidence which has been quoted in favor of this view. Sty-
loni/rhid norniallv })ro(hK'es by fission 130 to 180 (generations or individuals,
Onijcluxlroiaus 140 to 230, and Leacophrys patuta 300 to 450, after which con-
jugation is necessary to continued division. If conjugation be prevented, the
individuals become small, their ]>liysiological ])owers become weakened, their
nuclei atrophy, and the chromatin disappears; all of which changes are evidence
of the oncoming of senile degeneration, and this ultimately results in death.
Analogous to this is doubtless the fact, pointed out by Hertwig,^ that in sexual
animals an unfertilized ovum within the oviduct soon becomes over-mature
and enfeebled, and subsequent fertilization, even though possible, is abnormal.
Even if the idea of " rejuvenescence" be regarded as fanciful and as a com-
parison rather than an explanation, it seems to be a principle of nature that
occasional fusion of one line of descent with another is necessary to continued
reproduction and continued life.

A second theory, defended by Hatschek and Hertwig, argues that sexual
reproduction prevents variation, and thus preserves the uniformity of the race.
The mingling of two different individuals possessing different qualities must
give rise to an individual intermediate between the parents, but differing from
them. Such differences between parents and offspring are numerous, but in a
single generation are minute, and they are easily obliterated by a subsequent
union, which latter in turn gives rise to other minute differences. Hence sexual
reproduction, although constantly producing variations, as constantly eradicates
them, and, by striving always toward the mean between two extremes, tends
toward homogeneity of the species. The essential truth of such a view seems
obvious.

A third theory, advocated by Weismann and Brooks, is quite the 0})posite
of the last, and maintains that the meaning of sexual reproduction lies in the
production of variations. " The process furnishes an inexhaustible supply of
fresh combinations of individual variations." These minute variations, seized
upon by natural selection, are augmented and made serviceable, and a variety,
better able to cope with the conditions of existence, results. The transformation,
not the homogeneity, of the species is thereby assured. The two latter views are
not necessarily mutually exclusive. Both claim that fertilization brings into
evidence variations. It is quite conceivable that subsequent fertilizations may
obliterate some and augment others, the result of union being the algebraic sum
of the characteristics contributed by the two sexes.

Primary and Secondary Characters. — In the human species, as in all
the higher sexual animals, the characters of sex, anatomical, physiological, and
psychological, are divisible into two classes, called primary and secondary.
Primary sexual characters are those that pertain to the sexual organs them-
selves and to their functions. They are naturally the most pronounced of all

^ E. Maupas : Archives de Zoologie experimentale ei generate, 2e serie, vii., 1889.
* O. und R. Hertwig : Experimentelle Studien am thierischen Ei vor, wdhrend und nach der
Befruohtung, i., 1890.
56

882 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

sexual attributes. Secondary sexual characters comprise those attributes that
are not directly connected with the sexual organs, but that, nevertheless, con-
stitute marked differences between the sexes ; such are the greater size and
strength of man's body as compared with woman's, the superior grace and
delicacy of woman's movements, the deeper, rougher voice of man, and the
higher, softer voice of woman. In reality, all secondary sexual characters are
accessorv to the primary ones, and the greater portion of the present article
will be devoted to a discussion of the latter. The primary seximl characters
of the male centre in the production of spermatozoa and the process of impreg-
nation, those of the female in the production of ova and the care of the devel-
oping embryo.

Sexual Organs. — Sexual organs are classified into essential and accessory
organs. The essential organs are the two testes of the male and the two
ovaries of the female. The accessory organs of the male comprise the vasa
deferentia, the seminal vesicles, the urethra, the penis, the prostate gland, Com-
peres glands, and the scrotum and its attached parts. The accessory organs of
the female comprise the oviducts or Fallopian tubes, the iderus, the vagina, the
various external parts included in the imlva, and the mammary glands. During
the greater part of life the sexual organs perform but a portion of their duties ;
only at intervals, and in some individuals never, do they complete the cycle
of their functions by engaging in the reproductive process itself. In the fol-
lowing account we shall discuss first the habitual physiology of the organs of
the male and of the female, and later their special activities in the repro-
ductive process.

B, The Male Reproductive Organs.

The male reproductive organs, already mentioned, have as their specific
functions the production of the essential male germ-cells, the spermatozoa, the
production of a fluid medium in which the spermatozoa can live and imdergo
transportation, the temporary storing of this seminal fluid, and its ultimate
transference to the outside world or to the reproductive passages of the female.

The Spermatozoon. — Spermatozoa were first discovered by Hamm, a
student at Leyden, in 1677. Hamm's teacher, Leeuwenhoek, first studied
them carefully. They were long believed to be parasites, even until near the
middle of the present century, when their origin and fertilizing function were
established. Spermatozoa are cells modified for locomotion and entrance into
the ovum. Human spermatozoa are slender, delicate cells, averaging 0.055
millimeter (^i^ of an inch) in thickness, and consisting of a head, a middle-
piece, and a tail (Fig. 305). The head (A) is flattened, egg-shaped, with a thin
anterior edge and often slightly depressed sides. It terminates anteriorly in a
slender projecting and sharply pointed thread or spear. Its chief component
appears to be chromatic substance, and it is to be regarded probably as a
nucleus covered by an excessively thin layer of cytoplasm, von Bardeleben '

^ K. V. Bardeleben: Verhandlungen der Anatomischen Gesellschaft ; Anatomischer Anzeiger,
vii., 1892.

REPRODUCTION. 883

claims the number of chromosomes in the chromatic substance after matura-
tion to be eight.

The middle-piece (m) is a short, cytoplasmic rod, probably containing a cen-
trosome. The tail {() is a delicate filiform, apparently cytoplasmic structure,
and analogous to a single cilium of a ciliated cell. The tail is tipped by an
excessively fine, short filament, the end-piece (e). The most
abundant of the solid chemical constituents of the spermato-
zoon is nuclein, probably in the form of nucleic acid, which
is found in the head. Other constituents are proteids, prota-
mine, lecitiiin, cholesterin, and fat.

The structure and power of movement of the spermatozoon
plainly show it to be adapted to activity. It is not burdened
by the presence of food-substance within its protoplasm. It
is the active element in fertilization ; it seeks the ovum, and
it is modified from the form of the typical cell for the special
purpose of fertilization. The nucleus is the fertilizing agent-
The head is plainly fitted for facilitating entrance into the
ovum. The tail is a locomotor organ capable of spontaneous
movements, and, after expulsion of the semen, it propels the
cell, head forward, through the fluid in ^vhich it lies. The
movement is a complex one, and is effected by the lashing
of the tail from side to side, accompanied by a rotary move-
ment about the longitudinal axis. The rate of movement has fig. sos.-Human
been variouslv estimated at from 1.2 to 3.6 millimeters in the spermatozoa (after

' . Retzius) : A, sperm-

minute. loward heat, cold, and chemical agents spermatozoa atozoon seen e?; /ace,-
behave like ciliated cells. "'. ^''^'^'- ™; °^^'^'^^^-

piece ; t, tail ; e, end-

Ripe spermatozoa appear to be capable of living for months piece: b, c, seen
within the male genital passages, where they are probably ^''*^°^ ^^^ s^^®-
quiescent. Outside of the body they have been kept alive and in motion for
forty-eight hours. It is not certain how long they may remain alive within
the genital passages of the human female. They have been found in the os
uteri and capable of movement more than eight days after their discharge. It
seems not improbable that within the female organs their environment is favor-
able to a somewhat prolonged existence. In this connection it is of interest to
know that spermatozoa capable of fertilizing have been known to live within
the receptaculum seminis of a queen bee for three years.

Spermatozoa are produced in large numbers. Upon the basis of observa-
tions in several individuals, Lode ^ computes the average production per week
as 226,257,000, and in the period of thirty years from twenty-five to fifty-five
years of age the total production as 339,385,500,000. This excessive produc-
tion is an adaptation by nature that serves as a compensation for the small
size of the cells and the small chance of every cell finding an ovum. With-
out large numbers fertilization would not be ensured and the continuance of
the species would be endangered.

•A. Lode : Ffluger^s Archivf'dr die c/esammte Physiologie, 1., 1891.

884 AN AMERICAN TEXT-BOOK OF PIIYSIOLOO Y.

Maturation of the Spermatozoon. — Considerable thcijretieal interest
attaches to tlie question as to tiie real niorphologieal value of tiie spermatozoon.
It is undoubtedly a cell, and has arisen by division from one of the testicular
cells, called the primary spermatocyte or sometimes the mother-cell of the
spermatozoon. But is it the morphological equivalent of one of the mother-
cells? In most animals, and probably also in man, each primary spermatocyte
gives rise to four spermatids, which grow directly into four spermatozoa. The
process of derivation of the spermatozoa may be called, by analogy with the
process in the ripening of the ovum, maturation. The details and essence of
the process have been much discussed. Van Beneden foun<l in an interesting
worm, AHi'drxH, that the number of chromosomes in the nucleus of a single
spermatozoon is only half that in the original testicular cell ; that is, the pro-
cess of maturation of the spermatozoon consists in a reduction of the chromo-
somes by one half. This discovery has since been extended to many otiicr
forms, including mammals and man,' and it has been shown further that the
mature spermatozoon contains only one-half the number of chromosomes cha-
racteristic of the tissue-cells of the species in question. In the light of the
subsequent process of fertilization these facts are interesting. Hertwig and
Weismann, who reo;ard the chromatic substance of the nucleus as the bearer
of the hereditary qualities, interpret this halving of the chromatin as a pro-
vision for the reduction of the hereditary mass, which later will be restored to
its full amount by unifju with the egg. As we shall see, the maturation of
the ovum follows a somewhat similar course, and, since the process has been
more fully studied there, we shall reserve further discussion until that subject
is reached (p. 889).

Semen. — Semen consists of spermatozoa, together with fluid and dissolved
solids, coming partly from the testes themselves, but chiefly secreted by the
accessory sexual glands — namely, the glands within the va.srt deferoitia, the
seminal vesicles, the prostate gland, and Cowper's glands. It is a whitish,
viscid, alkaline fluid, with a slight characteristic odor. The amount passed out
at any one time has been estimated at between 0.5 and 6 cubic centimeters- Its
chemical composition has not been examined exhaustively. Besides water, it
contains approximately 18 per cent, of solid substances, which comprise nuclein,
protamine, })roteids, xanthin, lecithin, eholesterin, and other extractives, iiit, and
sodium and potassium chlorides, sulphates, and phosphates. Under proper treat-
ment colorless crystals, called Charcot's crystals, may be obtained from semen.
They appear to be a phosphate of a nitrogenous base, which has been called ftpenn-
ine. Interest in the semen centres in its histological rather than its chemical
features. The fluid portion serves as a vehicle for the transportation of and pos-
sibly also for the nutrition of the ripe spermatozoa. Colorless j)articles, called
seminal granules, exist in semen. They are possibly parts of nuclei of disin-
tegrated cells. Comparatively little is known of the composition or the specific
function of the individual secretions contributed by the various organs. The
disintegration of the nutritive cells of the testis probably furnishes some of the

* V. Bardeleben : loc cit.

lirj'iionrcTiox.

885

nutritive substance of the fluid. I'rostatic secu-etion is viscid and opalescent, and
contains 1.") jut cent, of solids, comprising niaitdy |)rotcids and sails. It con-
tributes the substance of Charcot's crystals to tiic scnicn, and their partial decom-
position is said to be responsible for the characteristic odor of the seminal fluid.
The secretion from the seminal vesicles is fairly abundant, is albuminous, and
in some animals at least seems to contain fl])rino<>:en. This enables the fluid to
clot after its reception in the female passages, and thus to i)revent loss of sper-
matozoa. Cowper's glands secrete a mucous fluid. By careful experiments
upon white rats Steinach ' has shown that removal of the seminal vesicles and
the prostate gland, while not diminishing the sexual passion and the ability to
j)erform the sexual act, including the actual discharge of spermatozoa, j)revents
entirely the fertilization of the ova; removal of the seminal vesicles alone
markedly weakens the fertilizing power
of the semen. The secretions of these
accessory glands are essential to the mo-
bility of the spermatozoa, and they may
have other important functions.

The Testis.— The testes (Fig. 306, t)
are compound tubular glands with a
unique structure. Formed early in em-
bryonic life as solid structures, with the
seminiferous tubules {ts) represented by
solid cords of cells, they remain in the
embryonic condition until the time of
puberty. Some of the cells, the mother-
ed Is of the spermatozoa, then begin
actively to divide, and the result of di-
vision with differentiation is the mature
spermatozoa. These latter accumulate
at the centre of the tubules, the walls
being formed largely of the dividing
cells or immature spermatozoa. Other
cells do not produce spermatozoa, but
seem to disintegrate and give rise to the
nutritive fluid and nuclear particles that
are found mixed with the sperm-cells.
From the time of puberty on, usually
throusrhout life, this cellular activitv

proceeds, the rate and regularity proba- entia ; e, canal of the epididymis ; v.a, vas aberrans ;

,, . J, -ii ^ T • 1* 1 1 v.d, v.d, vas deferens ; v.s, seminal vesicle ; d.e, ejac-

blyvaryinggreatlyWlthindlVldualsand ulatoryduct; pr, prostate gland; 6, urinary blad-

depending largely on the frequency of «^er ; C.g, Cowper's gland ; u, urethra; pn, penis.

discharge of the semen. Spermatozoa

may be wanting in old men, but they have been found in individuals at
eighty or ninety years of age. The spermatozoa accumulate within the seminal
' K. Steinach : PflUrjer's ArchivfOr die gesammte Fhysiologie, Ivi., 1894.

t

Fig. 306.— Diagram of the male reproductive
organs: t, testis; t.s, seminiferous tubules; t.r,
tubuli recti ; r.v, rete vasculosum ; v.e, vasa eflTer-

886 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tubules, and by the constant formation of others behind them are gradually
pushed outward along the ducts.

The Duds of the Testis. — The ducts of the testis (Fig. 306) comj>rise a
succession of tubes of different morphological and physiological values.
They are approximately twenty-five feet in length, and are named, in
order, tubuli recti, rete vascidosum, vasa effercntia, canal of the epididymis,
vas deferens, and ejacidatory duct. The tubuli recti (t.r) and rete vasculosum
(r.v), being mere channels for the passage of spermatozoa, present no special
physiological features. The vasa efferentia {v.e) and the canal of the epididymis
{c) contain smooth muscular tissue in their walls, and, moreover, are lined
by ciliated epithelium, the cilia causing a movement outward ; both of
these features doubtless aid in the outward passage of the spermatozoa.
The excretory duct of the testis, or vas deferens (v.d), wath its offshoot, the
seminal vesicle, is more important physiologically. It is nearly two feet in
length, with a diameter throughout the greater part of its course of one-tenth
of an inch. Near its termination, however, it is larger and sacculated, and
resembles the seminal vesicle ; it is known here as the ampulla of Henle. Its
epithelium is not ciliated, but its walls contain a very thick, plain muscular
layer consisting of outer longitudinal and inner circular fibres. In the walls
of the ampulla of Henle exist small tubular glands. The vas deferens is an
important storehouse for the spermatozoa. The glands near its termination
supply a part of the fluid of the semen. The muscles in its walls, by contract-
ing, aid in the seminal discharges. The seminal vesicle (v.s) is a branched diver-
ticulum from the vas deferens. In structure it is not radically unlike the
ampulla of Henle, its walls containing muscular layers and glands. Its chief,
if not its only, function is to contribute fluid to the semen. Of all the organs,
the seminal vesicles contribute probably the greatest share of fluid. Micro-
scopic examination does not confirm the old belief that the vesicles are store-
houses for semen, and this idea is now largely laid aside. The ejacidatory
duct (d.e) on each side is a short, thin-walled muscular tube, passing partly
through the substance of the prostate gland and serving to convey the semen
to the urethra.

The Urethra. — The urethra (Fig. 306, w), the common excretory duct
for the urine and the semen, is commonly described as consisting of three parts,
named, respectively, the prostatic, the membranous, and the spongy portions.
The first is characterized by the presence of the prostate gland, the second by
the absence of special features, and the third by the presence of Cowper's glands
and the penis. Throughout its length the wall of the urethra contains plain
muscular tissue arranged longitudinally within and circularly without ; and,
except at the external opening, the small racemose mucous [/lands of LUtrL
Its wall is hence contractile and its lumen is kept moist. Beyond these its
special physiological features are given it by the organs above mentioned.

The Prostate Gland. — The prostate gland (Fig. 306, pr) is a compound
tubular gland whose alveoli are mingled with a large quantity of plain mus-
cular tissue. It completely surrounds the urethra at the base of the bladder,

REPRODUCTION. 887

and opens into it b}' numerous small ducts situated about the openings of the
vasa deferentia. Its function is to contribute prostatic fluid to the semen. The
composition of this fluid has been already mentioned (p. 885) ; its specific use
is not known.

Cowper's Glands. — Chwper's glands (Fig. 306, C.g), two in number, are
tubulo-raccmose glands, the ducts of which open into the spongy portion of
the urethra by two orifices situated some two inches below the openings of the
vasa deferentia. Their viscid secretion is thought to be one of the components
of the seminal fluid, but its specific function is unknown. It has been sug-
gested that Cowper's fluid cleanses the urethra of urine and of semen, instead
of contributing actually to the seminal fluid.

The Penis. — The penis (Fig. 306, pii) has as its constant function merely
the conveying of the urine to the outside world, and for this purpose it has no
special features beyond those belonging to the urethra, which rinis throughout
its whole length. Specifically, however, it is the intromittent organ, and
serves to convey the semen into the genital passages of the female. This
function is based upon its power of erection, and this power is dependent
upon the presence of the erectile tissue which constitutes the bulk of the
organ. The erectile tissue is arranged in the form of three long cylindrical
masses imperfectly separated from, but parallel to, one another and extending
lengthwise. Of these, the two corpora cavernosa lie at the sides, and meet each
other in the middle line along the upper side of the penis ; the corpus spongi-
osum lies in the middle line below, and is pierced throughout its length by the
urethra. At its proximal end each corpus is enlarged into a bulbous part,
and is covered by a layer of muscular fibres constituting a distinct muscle — the
bulbs of the corpora cavernosa by the ischio-cavernosi {erectores penis), that of
the corpus spongiosum (called bulbus urethra;) by the bulbo-cavernosus {accel-
erator urince). At its distal end each corpus cavernosum terminates bluntly,
while the corpus spongiosum projects farther and enlarges to form the extrem-
ity of the organ, the glans penis. Each corpus is spongy in consistence, being
formed of a trabecular framework of white and elastic connective tissue and
plain muscular fibres, with cavernous venous spaces, and is covered by a tough
fibrous tunic. When the spaces are distended with blood the whole organ
becomes hard, rigid, and erect in position. The mechanism of erection will
be studied more in detail later (p. 901). The penis, especially toward its ter-
mination, is beset with end-bulbs. Pacinian bodies, and other nerve-termina-
tions, that make it particularly sensitive to external stimulation.

C The Female Reproductive Organs.

The female reproductive organs, already mentioned, have as their specific
functions the production of the essential female germ-cells, the ova, their trans-
ference to the uterus, and, if unfertilized, to the outside world ; if fertilized,
the protection and nutrition of the developing embryo, its ultimate transfer-
ence to the outside world, and the nutrition of the child during early in-
fancy.

888

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 307.— Human ovum (modified from Na-
Kel): n, nucleus (germinal vesicle) containing
the amceboid nucleolus (germinal spot); d, deu-
toplasniie zone; p, protoplasmic zone; z, zona
radiata ; «, perivitelline space.

The Ovum. — The ljunmn ovum wjls discovered in 1827 by Von JJaer, and
it was he who first conipletely traced tlie connection between ova in the gene-
rative passages and ova in the Graafian
. " ^~^^ follicles of the ovary. The conception

of ova as the essential female element
had, however, long been held, and Har-
vey's dictum of the seventeenth century,
that everything living is derived from
an egg {omne vivum ex ovo), is well
known. The human ovum, as it comes
from the ovary, is a spherical, proto-
plasmic cell (Fig. 307), averaging with
the zona radiata, approximately 0.2 milli-
meter (y^ inch) in diameter. As in
other cells, the cell-body may be distin-
guished fron\ the nucleus, the proto-
plasm of the former being called cyto-
plasni. In its finer structure the cyto-
plasm consists of an excessively delicate
network of protoplasmic substance. As in other mammalian eggs, it proba-
bly contains, adjoining the nucleus, a minute, specially differentiated portion,
consisting of a single or double centrosome surrounded by an attraction sphere
(Fig. 308, A). For some distance inward from the border the cytoplasm is
pure and transparent, and this portion is oflen called the protoplasmic zone
(Fig. 307, ])). Throughout the centre of the cell, however, it is obscured by
the presence of an abundance of yolk-substance, or deutoplasm, from which
the corresponding part of the ovum is sometimes called the deutoplasmic
zone (d). Deutoplasm is non-living substance ; it consists of granules of
yolk imbedded in the meshes of the cytoplasmic network, and, like its ana-
logue, the yolk of the hen's egg, it serves as food for the future cells of the
embryo.

A comparison of the respective amounts of food in the human and the
fowl's egg, with the manner of embryonic development, is suggestive. The
chick develops outside the body of the hen, and, therefore, requires a large
supply of nutriment, which it finds in the yolk and the white of the eg^. The
child develops within the mother's body and receives its nourishment from the
maternal blood; hence the supply of food within the egg is only enough to
ensure the beginning of growth, special blood-vessels being formed to facilitate
its continuance.

The miclcuK ()i), commonly called by its early name, the gcrmincd i^caicle, is
spherical, and usually occupies a slightly eccentric position. Its protoplasm
consists of a network composed of two kinds of material : the more delicate,
slightly staining threads are the achromatic substance, the coarser, deeply
staining portion, the chromatic substance or chromatin. The former is con-
tinuous with, and probably of exactly the same nature as, the cytoplasm.

REPRODUCTION. 889

The diroinatiii is peculiar to tlic iiiieleiis, and at certain stages in the nuclear
history is resolved into distinct grannies or filaments, the chromosomes (Fig.
308, A), the nun\l)er of which in the human ovum is iniknown. There
is much reason for believing that the chromatin is the hearer of whatever is
inherited from the mother. The nucleus is limited by a nuclear membrane,
and contains a strongly marked nucleolus, which has likewise retained its
original name of germinal spot. Tiiere is probably no j)roj)er cell-wall, or
vitelline membrane, such as is said to exist in many mammalian and other eggs.
The ovum is, liowever, surrounded by a thick, tough, transparent membrane of
ovarian origin, about 0.02 millimeter {^i^-j^ inch) in thickness, and called the
zona radiata or zona pcUucida (Fig. 307, z). It is pierced by a multitude of fine
lines radiating from the surface of the zona to the ovum ; these are thought
to represent pores, to contain fine protoplasmic processes of the surrounding
ovarian cells, and thus to serve as channels for the passage of nutriment to
the egg. Between the zona radiata and the ovum a narrow space, the peri-
vitelline space (s), exists. Attached to the outside of the zo7ia radiata are
usually patches of cells derived from the discus prolige^'us of the Graafian fol-
licle of the ovary, which may form a complete covering and constitute the corona
radiata. They disappear soon after the egg is discharged from the ovary.

Regarding the chemistry of the mammalian ovum little is known definitely,
and of the human ovum nothing whatever except by inference from the eggs
of lower animals. The protoplasmic basis undoubtedly resembles other undif-
ferentiated protoplasm in its general composition, with an abundance of proteid
among its solid constituents. Deutoplasm is a rich mixture of food-substance
in concentrated form, and contains among its solids probably vitellin, nuclein,
albumin, lecithin, fats, carbohydrates, and inorganic salts.

The form and the structure of the egg suggest the part that it plays in
reproduction. It is not locomotor; in fertilization it is the passive element;
it remains in its place and is sought by the spermatozoon. Its nucleus is the
equivalent of that of the spermatozoon. Its form renders easy the entrance of
the male element. Its bulk consists largely of food in a very concentrated
form, and, as development proceeds, it supplies this food to the growing cells.

In lower forms of animal life, where eggs are fertilized outside the body
of the parent in the water into which they are set free, they are usually pro-
duced in enormous numbers. Some fail of fertilization, while others are
destroyed by enemies, and the large number is a compensatory adaptation by
nature for their poor chance of survival. In mammals and man, however,
ova have a much better opportunity of being fertilized and of developing into
adults, and their number is correspondingly reduced. Their relative fewness,
as compared with the spermatozoa, is in harmony with their larger size and
the fact that, wdiile awaiting fertilization, they are carefully protected within
the body of the mother.

Maturation of the Ovum. — Attention has been called to the maturation
of the spermatozoon. The ovum undergoes an analogous process of ripening,
which has been studied very carefully, and from its theoretical interest has

890

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Fig. 308.— Stages in the matviration of the ovum ; diagraminatic (mainly from Wilson) : A, the orig-
inal ovarian ovum ; n, its nucleus, containing four chromosomes ; c, its double centrosome, surrounded
by the attraction sphere; in 6 much of the chromatin has begun to degenerate; the rest has become
arranged into two quadruple groups of chromosomes, or tetrads; the formation of the spindle and the
asters has begun; in Cthe first polar amphiaster, bearing the chromosomes, is completed ; in D the am-
phiaster has become rotated and has travelled toward the surface of the ovum ; g. v, the degenerated
remains of the nucleus; in E the division of the tetrads into double groups of chromosomes, or dyads,
has begun, and the first polar body, p. 6', is indicated ; in Fthe first polar body, containing two dyads, has
been extruded ; the formation of the second polar amphiaster has begun ; in G the first polar body is pre-
paring to divide ; the second polar amphiaster is fully formed ; in // the division of the dyads into single
chromosomes in both the first polar body and the egg has begun, and the second polar body, p. b^. is in-
dicated ; in / the formation of the polar bodies is completed ; 9 , the egg-nucleus, containing two small
chromosomes, one-half the original number. In fertilization the spermatozoon will bring in two addi<
tional chromosomes, thus restoring the total number of four.

REPRODUCTION. 891

given rise to a large amount of discussion. Maturation occurs approximately
as the ovum is leaving the ovary, the exact time-relations being not yet deter-
mined. It consists of a karyokinetic division of the nucleus, essentially like
karyokinesis (mitosis) in ordinary cell-division, and an expulsion of one por-
tion from the cell. This occurs twice in succession. The cast-off bits of pro-
toplasm are known as -polar bodies. The details of the process of maturation
are as follows (Fig. 308) : The nucleus of the original ovarian ovum contains
the same number of chromosomes as the ordinary tissue-cells (A). At the begin-
ning of maturation much of the chromatic substance begins to degenerate, and
later it disappears wholly (B, C, D). The remainder is rearranged into groups
of chromosomes, usually four in each group, which is called a "quadruple-
group " or " tetrad " {B). The number of tetrads is always one-half the num-
ber of original chromosomes, while the total number of chromosomes in the
nucleus at this stage is double the original number. The nucleus moves from
its position in the interior of the egg toward the surface, and the nuclear mem-
brane begins to disappear. At the same time the two minute cytoplasmic
structures, the centrosomes, which lie close beside the nucleus, separate and
take up positions at a considerable distance apart from each other, in some
cases even upon opposite sides of the nucleus. The substance lying between
them — either the cytoplasmic network or the achromatic substance of the
nucleus — loses its reticular appearance, becomes filamentous, and arranges itself
in the form of a spindle with the threads extending from pole to pole (C, D).
The groups of chromosomes become attached to the spindle threads midway
between the poles. At each pole lies a centrosome, and about it the cytoplasm
becomes arranged in the form of a star, the aster. The spindle with the two
asters is known as the polar amphiaster, and the complicated structure seems
to be formed, as in ordinary cell-division, for the sole purpose of dividing
the nucleus into two portions. This is now performed (E) ; each quadruple-
group of chromosomes splits into two, and these, known as " double-groups,"
or " dyads," are drawn apart from each other and toward the spindle poles,
probably by contraction of the fibres of the spindle. The nucleus is thus di-
vided into halves. While the division has been proceeding, the spindle has
wandered halfway outside the egg, and, when it is completed, one of the result-
ing nuclear halves, comprising one-half of the full number of dyads, together
with the centrosome and the aster, finds itself entirely extruded from the egg
and lying within the perivitelline space. It is known as the first polar body
{F,p. b^). The diminished nucleus within the ovum proceeds at once to under-
go a second karyokinetio division similar to the first (G, H, I) ; each of the
remaining dyads divides into two single chromosomes, which are pulled apart
from each other ; and a second polar body (p. b^), containing one-half the
number of single chromosomes characteristic of the tissue-cells, is extruded.
Apparently the two polar bodies are of no further use. In many animals the
first divides into two, but sooner or later both degenerate and disappear. The
remnant of the nucleus left within the egg, much reduced in size, wanders
back to the interior. Its chromosomes, reduced to one-half the number

892 AN AMERICAN TEXT-BOOK OF PIIYSIOLOd Y.

helonging to the ovarian ovum, are resolved again into seatterecl clironiatio
.substance. Jt develops a membrane and becomes again a resting nucleus. It
is known henceforth as the egg-nucleus, or female pronucleus, and it awaits the
coming of the male. Its centrosome gradually degenerates and disa})pears.

Thus the curious process of maturation of the ovum is different in detail
from that of maturation of the S])ermatozoon. In the latter the primary
spermatocyte divides into four functional spermatozoa; in the former the pri-
mary ovocyte divides into two functionless polar bodies (or, by subdivision of
the first, three, which have been called abortive eggs) and one functional ovum.
It is entirely probable, however, that the essence of the process is exactly the
same in the two cases, and lies in the reduction of the chromatic substance of
the nucleus. Van Beneden found in Ascaris that in the maturation of the
ovum, as in that of the spermatozoon already referred to, the number of chro-
mosomes is halved and that the number in the two germ-cells is the same.
This has since been proved abundantly in other forms, as well as the further
associated fact that the mature germ-cells contain each one-half the number
of chromosomes that are characteristic of the somatic cells ; it is wholly })rob-
able that these facts are universal in sexual reproduction. Each mature germ-
cell, therefore, while in reality a cell, is, when compared with the somatic cells,
incomplete. The subsequent union of the two in fertilization restores the
chromosomes to their normal inimber. Inasmuch as the chromatin is probably
the all-important constituent of the germ-cells, the bearer of the paternal and
the maternal inherited characteristics, the phenomena of maturation are of
great interest. Most biologists follow Hertwig and Weismann in regarding
maturation as an adaptation for the ]>revention of the constant increase in
quantity of the hereditary substance that would otherwise take place with
every union of ovum and spermatozoon. Without a reducing process the
quantitv of chromatin in cells would become in a very few generations incon-
veniently great. Maturation is a j)reparation of each germ-cell for union with
its mate.

The Ovary ; Ovulation. — The ovaries (Fig. 309, o) are often spoken of as
glands, but they are not glands according to the ordinary histological and
physiological use of the term. They are solid organs with a structm-e peculiar
to themselves, and their function is the production of ova. Their stroma con-
sists of fine connective tissue with numerous connective-tissue cells. The ova
are developed in the interior within cavities called, from their discoverer,
Graafian follicks{G.f), from primitive ova that are modified cells of the germinal
epithelium of the embryo. It has been calculated that the two human ovaries
at the age of eighteen years contain an average of 72,000 primitive ova, but
that not more than four hundred of these arrive at maturity. Each Graafian
fi)llicle is lined by an ei)ithelial layer several cells thick, the membrava
granulosa, and is filled with clear viscid fluid, the liquor follmiU, which con-
tains albuminoid matter. Imbedded in the epithelium upon one side is
usually a single ovum, completely surrounded by the cells and forming a
prominent hillock which projects well into the cavity of the follicle. The

BEPROD UCTION.

893

epitlu'Iiuni iiuinodiatcly surroimdintr the ovum is the discus prol'icjerus. Within
the discus the ovum grows and becomes surrounded by tl»e zona pellucida. In
the process of growth the (Jraafian loUide approaches the surface of the ovary,

Fig. 309.— Diagram of the female reproductive organs (modified from Henle and Symington) : o, ovary ;
O.f, Graafian follicle containing an ovum ; c.l, corpus luteum ; p, parovarium ; /, fimbriated end of F. t,
Fallopian tube ; u, body, and c, cervix of uterus ; o e, os uteri externum ; vg, vagina ; h, hymen ; u, open-
ing of urethra ; v, vulval cleft ; n, labia minora, or nymphiE ; l.m, labia majora.

and finally comes to form a minute rounded vesicular projection covered only
by the ovarian epithelium. When fully ready for discharge, the wall of the
follicle becomes ruptured, probably by the increasing pressure of the contained
liquid, and the ovum with its zona pellucida and a portion or all of the discus
proUyerus, now called the corona radiata, is cast out upon the surface of the
ovary to be taken up by the Fallopian tube. The empty follicle undergoes
changes and becomes the corpus luteum (cl). Usually the corpus luteum de-
generates within a few days and ultimately disappears. If, however, pregnancy
follows ovulation, it grows very large, perhaps because of the congested state
of the reproductive organs, and remains for months before the retrograde
metamorphosis sets in. Not all Graafian follicles reach maturity and burst,
for many, after developing to a considerable size, undergo degenerative
changes, characterized by liquefaction and disappearance of their contents.

The discharge of the ovum is known technicallv as ovulation. In most
animals ovulation is a periodic phenomenon accompanying certain seasons, and
is marked by general sexual activity. In woman and many domesticated ani-
mals the relation to the seasons no longer exists, but too little is known of the
causes and time-relations of the phenomenon and its general bearings upon
other physiological processes, notably upon menstruation in woman. A lar;;e

894 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

but not wholly decisive literature upon the subject in the human being has
been written. It is a common belief", originating in the seventeenth century,
that ovulation in woman is a periodic phenomenon occurring regularly every
month and contemporaneous with the occurrence of the menstrual flow, and
numerous post-mortem observations of the presence in the ovary of freshly-
discharged Graafian follicles at the menstrual ])eriod afford evidence of the
frequent coincidence of the two phenomena. But ovulation at the time of
menstruation, though probably usual, is not exclusive of ovulation at other
times, for intermenstrual observations of fresh ovarian sears are not rare, and
prove without doubt that discharge of an ovum may occur at any time between
two successive periods (see under Menstruation, p. 895). Graafian follicles
develop even during infancy ; most of them, and perha])s all, retrograde with-
out discharging their ova, but the occasional instances of pregnancy at the ages
of seven, eight, or nine, prove that ovulation may occur during childhood.
Ovulation usually begins at puberty, its commencement thus coinciding with that
of menstruation, and continues until the climacteric. After the climacteric it
may occur in exceptional cases, although here, as before puberty, retrogressive
degeneration of the Graafian follicles is the rule. It is commonly believed that
ovulation is at a standstill during both pregnancy and lactation. The un-
doubted possibility of a pregnancy originating during lactation would, how-
ever, seem to prove the possibility of ovulation during the latter period. It is
not decided whether removal of the uterus does away wholly with ovulation.

The Fallopian Tube. — Each of the Fallopian tubes (Fig. 309, F. t), or
oviducts, opens into the peritoneal cavity about one inch from the correspond-
ing ovary. Around the opening is an expanded fringe of irregular processes,
ihejimhrice (/), one of which is attached to the ovary. The length of the tube is
between three and four inches, and the opening into the uterus is extremely
small. The chief structures in the walls of the oviducts that are of physio-
logical interest are the double layer of plain muscle, an outer longitudinal
and an inner circular coat, longitudinal fibres from which pass also into the
fimbriae ; and the cilia with which the tube is lined throughout, and which are
present also upon the inner side of the fimbriae. The direction of the ciliary
movement is from the ovary toward the uterus. The primary function of the
Fallopian tubes is to convey ova from the ovary to the uterus ; they also con-
vey spermatozoa in the reverse direction ; and within them the union of ovum
and spermatozoon usually takes place.

The mechanism of the receipt of the ovum by the tube is not fully under-
stood. After ovulation the ovum is slightly adherent to the surface of the
ovary by the agency of the viscid liquor folliculi. It is possible, but it has
not been proved, that in the human being, as has been seen in some animals,
the expanded, fimbriated end of the Fallopian tube clasps the ovary when
the egg is discharged. The passage of the ovum into the tube is probably
brought about by the cilia lining the fimbriae. Once within the tube, the
ciliarv action, assisted perhaps by contraction of the muscular fibres in the
walls, carries the ovum slowly along toward and finally into the uterus. In

REPRODUCTION. 895

some luaiuraals the passage occupies three to five clays; tlie time in woman is
not known.

The Uterus. — The uterus (Fig. 309, w), or womb, receives tlie ovum from
the Fallopian tube and passes it on, if unimpregnated, to the vagina ; on the
other hand, it receives from the vagina spermatozoa and transmits them to the
Fallopian tubes ; it is the seat of the function of menstruation ; when impreg-
nation has taken place, it retains and nourishes the growing embryo, and ulti-
mately expels the child from the body. Its structure accords with these func-
tions. Its thick walls consist largely of plain muscular tissue arranged
roughly in the form of three indistinctly marked layers. Of these, the exter-
nal and the middle coats are thin ; the fibres of the former are arranged in
general longitudinally, those of the latter more circularly and obliquely.
The third, most internal layer, which is regarded by some as a greatly hyper-
trophied muscularis mucosae, forms the greater part of the uterine wall. Its
fibres are arranged chiefly circularly ; toward the upper part they become trans-
verse to the Fallopian tubes, and at the cervix longitudinal fibres lie within
the circular ones. The individuality of the muscular layers and uniformity
in the course of the fibres is largely interfered with by the numerous blood-
vessels of the uterine walls. The uterus is lined by an epithelium composed
of columnar ciliated cells, except in the lower half of the cervix, where a stratified
non-ciliated epithelium exists. The direction of the ciliary movement in woman
is not definitely known ; in other mammals the cilia appear to sweep toward the
OS uteri. The mucous membrane is thick, and contains very numerous branch-
ing tubular glands that are lined by ciliated epithelium and have a tortu-
ous course, terminating in the edge of the muscular layer. They secrete a
viscid mucous fluid. Between the glands are branched connective-tissue
cells that are not unlike the connective-tissue cells of embryonic structures,
and wandering cells. Lymph-spaces and blood-capillaries exist. The
development of the tissue goes on slowly up to the time of puberty, and,
as we shall see, after puberty the mucous membrane is subject to constant
change.

Menstruation. — Except during pregnancy the most striking activities of
the uterus are associated with that peculiar female function which, from its
monthly periodicity, is called menstruation. The most obvious external fact
of this phenomenon is the discharge every month of a bloody, mucous fluid
through the vagina ; the most obvious internal facts are the bleeding and the
degeneration and disappearance of a portion of the mucous membrane of the
body of the uterus. This curious process, though having analogies in lower
animals, occurs most markedly in the human female, and from before the time
of Aristotle to the present, among both primitive and civilized races, its signifi-
cance has been the cause of much speculation. The detailed phenomena of
menstruation are not as well known as they should be. Experimentation is
practically out of the question, and the opportunities of careful post-mortem
study of normal healthy uteri at different stages are rare. The main facts are
as follows :

896 .l.V AMKRlCAy TEXT-BOOK OF PHYSIOLOGY.

Some (lays hefoi-i' tlio flow occurs the raucous membrane of the body of the
uterus begins to tliicken, partly by an active growth of its connective tissue
elements and partly by an excessive filling of its capillaries and veins with
blood. The cause of this swelling is not known. It continues until the
membrane has doubled or trebled in thickness, and, according to some authori-
ties, the uterine cavity becomes a mere slit between the walls. Then occurs an
infiltration of blood-corpuscles and plasma, probably largely by diapedesis,
although possibly assisted by rupture, through the walls of the swollen capil-
laries into the connective-tissue spaces beneath the epithelial lining of the
uterine wall. The epithelium is thus pressed up from beneath, and begins
rapidlv to undergo disintegration (perhaps fatty degeneration) and to disa])pear.
The immediate cause of the degeneration is not definitely known. The con-
nective-tissue elements and the upper portion of the glands are involved in
the degenerative change. The capillaries, thus laid bare, burst, and the dark
blood oozes forth and, mixed with disintegrated remains of the uterine tissues,
with the mucous secretion of the uterus and the vagina, and with the escaped
Ivniph, passes away, drop by drop, from the body. There is great difference of
opinion as to the extent of the destruction of uterine tissue. On the one extreme
side are those who claim that the loss of tissue is normally wholly trivial and
secondary, the hypersemia and the bloody glandular discharge being the
important events. Other authorities, equally extreme, have observed a disap-
pearance of the whole mucous membrane except the deepest layers containing
the bases of the glands ; this is probably pathological. From all the evidence an
opinion intermediate between these two views seems most reasonable — namely,
that usually and physiologically only the superficial portion of the mucous
membrane disintegrates. Differences in the amount undoubtedly occur.
Occasionally it happens that the membrane^ instead of disintegrating, comes
away in pieces of considerable size. The term decidua memtrualis is ai)plied
to the lost coat. The flow continues upon an average four days or more.
From observations upon 2080 American women Emmet ' finals the average
duration of the flow at puberty to be 4.82 days, the average in later life 4.66
days. The amount of blood discharged can be determined only with great diflR-
culty. It probably varies greatly, but is commonly estimated at from 100
to 200 cubic centimeters (4-5 ounces). The blood is slimy, with abundant
mucus ; usually it does not coagulate. Epithelium cells, red corpuscles, leuco-
cytes, and detritus from the disintegrated tissues, occur in it, and it has a cha-
racteristic odor. As the flow ceases, a new growth, of connective-tissue cells,
capillaries, glands, and from the glands superficial epithelium, begins, and the
raucous membrane is restoretl to its original amount. Whether a resting period
fijllows before the succeeding tumefaction occurs, is not definitely known, but
it seems probable. The durations of the various steps in the uterine changes
are not well known, and probably vary in individual cases. Minot^ suggests
the following approximate times :

' T. A. Emmet: The Principkn and Practice of Oyncecology, 2d ed., 1880.
*C. S. Minot: Human Embryology, 1892.

REPB OD UCTION. 897

Tumefaction of the mucosa, with accompanying structural changes 5 days.

Menstruation proper .... 4

Restoralion of the resting mucosa ... 7

Resting period 12

Total 28 days.

The menstrual ehanges in tlie uterus are accompanied by characteristic
phenomena in other parts of tlie body. The FaUopian tubes are congested,
and, according to some authorities, their mucous membrane degenerates and
bleeds like that of the uterus. The ovaries are likewise congested. As has
been stated, it is commonly believed, but not definitely proved, that ovulation
accompanies each period. Frequent accompaniments are turgescence of the
breasts, swelling of the thyroid and the parotid glands and the tonsils, con-
gestion of the skin, dull complexion, tendency toward the development of pig-
ment, and dark rings about the eyes. The skin and the breath may have a
characteristic odor. In singers the voice is often impaired, which is one
instance of a general nervous and muscular enervation. Mental depre.>?sion
often exists. In most cases sexual instincts do not appear to be heightened.
Pain is a frequent accompaniment, and nervous and congestive pathological
phenomena may, at times, become very pronounced. Recent work has shown
that the various phenomena accompanying menstruation are evidences of a
profound physiological change, with a monthly periodicity, that the female
human organism undergoes, and of which the uterine changes are only a part.
Thus, during the intermenstrual period there is a gradual increase of nervous,
tension and general mobility, of vascular tension manifested by turgescence of
the blood-vessels, a gradual increase of nutritive activity manifested by
increased production and excretion of urea and increased temperature, and
a gradual increase of the heart's action in strength and rate,^ These various
activities of the organism usually attain a maximum a few days before the
menstrual flow begins and then undergo a rapid fall, which reaches a minimum
toward the close of the flow ; a second lesser maximum may occur a few days
after the flow ceases. All organic activities that have been carefully investi-
gated show evidences of such a monthly rhythm. It is not known that the
male pos.sesses such a period.

The first menstruation is usually regarded as the index of the oncoming of
puberty or sexual matiu'ity, and in temperate climates occurs usually at the age
of fourteen to seventeen. Its onset is earlier in warm than in cold climates, in
city than in country girls, and varies in time with food, growth, and environ-
ment. Exceptionally menstruation may begin in infancy or later than puberty,
and it has even been known to be wholly wanting in otherwise normal women.
Normally, it ceases during pregnancy, and probably usually during lactation,
although there are frequent exceptions to the latter rule. Complete removal
of the ovaries appears to put an entire end to menstruation. Its final cessation,

^ Cf. Mary Putnam .Jacobi : " The Question of Rest for Women during Menstruation,"
B&ylston Prize Essay, 1876 ; C. Reinl : Sammlung kliuische Vorlrdge, 2^o. 243, 1884 ; O. Ott :
Nouvdles archives d'obstetrique et de gynecologie, v., 1890.
67

898 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

-which is a gnuliial process extending over several months, usually marks the
climacteric (menopause) or end of the sexual life, and occurs usually at the
aije of fortv-four to foi'ty-scvcn. Excei)tionally the flow may cease early in
life or extend to extreme old age.

Comparative Physiology of Ilenstruation. — The comparative physiology of
menstrnation, although it has been studied only incompletely in a few domesti-
cated animals and some monkeys,^ sheds some valuable light upon the phe-
nomenon in woman. In animals lower than man, in a wild state, the desire
and power of reproduction are usually limited to seasonal periods. At such
times conception is possible, and probably usually takes place. Snch periods
are known as "rut," "heat," and "oestrus." During the rest of the year
sexual activities arc in abeyance. Domestication, with its artificial condi-
tions of regular food-supply, warmth, and care, has increased productiveness
(Darwin) and rendered the reproductive periods more frequent. If imj)regna-
tion be prevented, as is often the case in domesticated animals, the periods of
"heat" appear with great frequency and regularity (monkey, mare, buffalo,
zebra, hippopotamus, four weeks ; cow, three weeks ; sow, fifteen to eighteen
days ; sheep, two weeks ; bitch, nine to ten days.) They are characterized by
general nervous excitement, desire and power of conception, congestion and
swelling of the external genital organs, and a uterine discharge. The latter is
scanty, mucous, and bloody, the amount of blood increasing in ascending the
evolntionary scale. The histological processes occurring in the uterns have
been studied carefully by Retterer in the dog and by Heape in the monkey.
In the latter the processes seem to be nearly identical with those of man. In
the dog, growth and congestion of the mucosa occur, and are followed by rup-
tnre of the capillaries, extravasation of blood, and degeneration of the tissues,
but it is doubtful whether the epithelium is actually shed. It is generally
believed that " heat " in the lower mammals is accompanied by ovulation. It
is not necessarily so in monkeys. The phenomena of " heat " are thus closely
similar to those of human menstruation, the similarity being most marked in
the monkeys. In addition to these more hidden phenomena there is present
sexual desire, which in the human female is largely absent at such periods.

Theory of Menstruation. — The significance of menstruation is in great dis-
pute. All modern theories agree in regarding it as associated in some way
with the function of childbearing. The flow was early believed to be a means
employed by the body to get rid of a plethora of nutriment. This was fol-
lowed by the well-known hypothesis, put forward especially by Pfliiger (18G5),
and even now widely accepted. According to this hypothesis,^ the menstrual
bleeding and the uterine denudation occur for the purpose of providing a fresh
uterine surface to which the egg, if impregnated, can readily attach itself, just
as in o-rafting, the gardener provides a wounded surface upon which the young

^ Of. A. Wiltshire: Brilii^h Medical Journal, March, 18S3; E. Rettercr : Comptes rendm des
seances et memoires dc la Societe de biologie, 1892; W. Heape : Philosophical Transactions of the
Eoyal Society (B). vol. 185, pt. i., 1894.

^ E. F. W. Pfliiger : Untersuchungen axis dem physiologischen Laboratorium zu Bonn, 1865.

REPR OD UCTION. 899

scion is set, or, in miiting two menibrane-coveral tissues, the surgeon first wounds
or freshens their surfaces. The mechanism of this uterine process is as fol-
lows : The constant growth of tiie ovarian cells and the consequent swelling of
the ovary subject the ovarian nerve-fibres, and through them the spinal cord,
to a constant slight stimulation. Through the summation of the stimuli within
the cord a reflex dilatation of the vessels in the genital organs is produced.
The excessive blood-supply leads in turn to the tumefaction of the uterus, and
frequently to the ripening of a Graafian follicle. The bleeding follows, and
at the same time or slightly later the rupture of the follicle occurs, provided
the latter be sufficiently advanced in growth. The menstrual flow and ovulation
are, therefore, two phenomena conditioned usually by the same cause, namely,
the menstrual congestion, yet either may occur without the other. Pfluger's
hypothesis accounts clearly for the absence of menstruation after removal of
the ovaries. Numerous other theories have been proposed, no one of which
can be said to be widely and generally accepted. The present tendency in
belief is as follows : Ovulation and menstruation are in great part independent
phenomena ; they may or they may not coexist • the uterine growth is a prep-
aration for the future embryo ; the tissue of the decidua mmstrualis is the fore-
runner of the decidua graviditatis (p. 909) ; if an ovum, whenever it is discharged,
be fertilized, it attaches itself to the thickened uterine wall, the tissues become
the decidua graviditatis, pregnancy follows, and the decidua is not discharged
until the time of parturition ; if, however, fertilization does not take place,
there is no attachment, the tissues degenerate and become the decidua men-
strualis, and the flow occurs. The suggestion of Jacobi ^ is not an extreme
one : " The menstrual crisis is the physiological homologue of parturition."
Its monthly periodicity is not explained. Regarding its mechanism the above
hypothesis of Pfliiger, although not yet proven experimentally, seems not
unreasonable.

The mysterv of menstruation largely ceases when we recognize what is un-
doubtedly a fact, that the phenomenon is a highly developed inheritance from
our mammalian ancestors, and that, although in the human race under the
influence of civilization and social life it has largely lost its technical sexual
significance, it is, nevertheless, primarily a reproductive phenomenon derived
directly from the lower females. Nature has endowed the latter, in a manner
yet unknown, with reproductive periods that are pronounced in the wild state
and are coincident with certain of the seasons. A primitive seasonal period
may perhaps still be shown in woman by the greater proportion of births that
take place during the winter months than at other times of the year : this sig-
nifies greater sexual activity during the months of spring, as is the case in
most animals.^

* Mary Putnam Jacobi : American Jotimal of Obstetrics, xviii., 1885.

'^ " The largest number [of human births] almost always falls in the month of February,

.... corresponding to conceptions in May and .June Observations tend to show the largest

number of conceptions in Sweden falling in June ; in Holland and France, in May-June ; in
. Spain, Austria, and Italy, in May ; in Greece, in April. That is, the farther south the earlier
the spring and the earlier the conceptions."— Mayo-Smith : Statistics and Sociology, 1895.

900 ^^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Domestication has, however, interfered with the original plan of nature.
It has rendered the lower forms more prolific and has made more frequent
their reproductive periods. Civilization has done exactly the same for woman.
It has rendered her more prolific and has made more frequent her reproduc-
tive periods. It is wholly probable that the menstrual periods of woman are
the homologues of the frequent reproductive periods of the lower forms. It
has been seen that the latter are characterized by the same kind of phenomena
that exist in the former ; the characteristic human menstrual phenomena are
least developed in the lower mammals, much more so in the monkey, and are
most pronounced in the human female. For what purpose this evolution of
function has taken place we do not know. Below the human species concep-
tion is confined to these times of " heat ; " in woman it is possible at other
than her menstrual periods. In this respect woman is more highly endowed
than her mammalian ancestors.

The Vagina. — The vagina (Fig. 309, vg) is the broad passage from the
uterus to the external organs. Its walls consist of smooth muscle fibres,
arranged both circularly and longitudinally. It is lined by stratified scaly
epithelium and is surrounded by erectile tissue. Its walls contain few glands.
Its specific functions are connected solely with the reproductive process ; in
copulation it receives the penis and the semen. Its cavity is the pathway out-
ward for the products of menstruation and, in parturition, for the child.

The Vulva and its Parts. — The vulva (Fig. 309) comprises the genital
organs that are visible externally — viz. the moy\s Veneris, the labia majora (l.m),
the labia minora or nymphce (71), the clitoris, w'hicli is the diminutive homologue
of the penis of the male, and the hymen (/*), or perforated curtain that guards the
entrance to the vagina and is usually ruptured at the time of the first coition.
The vulva receives the openings of the vagina, the urethra (m), and the ducts of
Bartholini's glands. Its parts are capable of turgidity through its rich vas-
cular supply, and perform minor ill-defined, adaptive, and stimulating func-
tions in copulation. Their surface is covered by mucous membrane which is
moistened and lubricated by a secretion from numerous mucous follicles, seba-
ceous glands, and the glands of Bartholini. Tiie latter are comparable to
Cowper's glands of the male and secrete a viscid fluid.

The Mammary Glands. — The mammary glands, being active only during
the period of lactation, may best be studied in connection with that function
(see p. 201).

Internal Secretion. — A priori, the reproductive organs can scarcely be
regarded as organs that are quiescent during the greater part of life and pas-
sively await the reproductive act. The view that they are more than this is
sn})ported by some, although slight, experimental evidence. Notwithstanding
the fact that removal of the testis or the ovary in adult life is often unaccom-
panied by great somatic changes, the profound effects of early castration upon
development, in both the male and female, show that upon the presence of the
sexual organs depends the appearance of many of the secondary sexual cha-
racters— characters which apparently are independent of those organs, and yet

REPR OD UCTION. 901

of themselves distinguish the individual as specifically masculine or feminine.
Tiie mode of dynamic reaction of the sexual organs upon the other organs can
at present be little more tiiau hinted at. It is entirely probable that such
reaction is either nervous or chemical, or perhaps it is both combined. Regard-
ing the former little is known. Regarding the latter, recent assertions of the
general invigorating effects of injections of testicular extracts in the adult,
although in most cases not founded upon careful experimentation, are, never-
theless, suggestive, and point to a possible normal and constant contribution
of specific material by the reproductive glands to the blood or lymph, and
thus to the whole body. Such a process is spoken of as internal secreiion, and
in the case of the thymus and thyroid glands its occurrence seems undoubted
(p. 205). As to the reproductive organs, investigation of the subject is yet in
its mere infancy, and it is too early to say with any degree of authority what
the truth of the matter is. Very recently Zoth ^ has shown that daily injec-
tions of testicular extract during one week increased by 50 per cent, the work-
ing power of a man's neuro-muscular system. The increase manifested itself
both by lessened susceptibility to fatigue and, in a still higher degree dur-
ing the periods of rest from labor, by increased power of recovery. What
part of the whole neuro-muscular system is affected by the specific substance
is not decided.

D. The Reproductive Process.

Attention has heretofore been given to the general functions of the repro-
ductive organs. We come now to the special phenomena connected with the
reproductive process itself, and have to trace the history of the spermatozoon,
the ovum, and the embryo. It should be borne clearly in mind that the
essential part of the reproductive process is the fusion of the nuclei of the two
germ-cells. Investigation is making it more and more probable that the
spermatozoon and the ovum, although so different in appearance and general
behavior, are fundamentally and in origin both morphologically and physi-
ologically equivalent cells. In the proc&sses of their growth and maturation
they are secondarily modified, the one into an active locomotive body, the other
into a passive nutritive body. The modifications in both are confined, how-
ever, to the cell-protoplasm (cytoplasm and centrosome) ; the essential parts,
the nuclei, remain unmodified and both morphologically and physiologically
equivalent down to the time of their fusion in the process of fertilization.
The many and complex details of the reproductive process exist for the sole
purpose of bringing together these two minute masses of chromatin.^

Copulation. — Copulation is the act of sexual union, and has for its object
the transference of the semen from the genital passages of the male to those of
the female. It is preceded by erection of the penis and turgidity of the organs
of the vulva. These latter occurrences are in the main vascular phenomena,

' O. Zoth : Pfiiiger's Archivfiir die gesammte. Physiologie, Ixii., 1896.

' Compare Th. Boveri : " Befruchtung," Merkel und Bonnet's Ergebnisse der Anatomie und
Entwickelungsgeschichie, i., 1892.

902 .l.V AMEJRICA^' TEXT-BOOK OF PHYSIOLOGY.

and are brought about by a distention of the cavernous spaces of the erectile
tissues with blood. The vascular phenomena are, however, accompanied by
conijilex nervous and muscular activities. As regards the penis, the arteries
supplying the organ relax and allow blood to flow in quantity to the corpora
cavernosa and the corpus spongiosum. Simultaneous relaxation of the smooth
muscle fibres scattered throughout the trabecular framework of the corpora
increases the capacity of the blood-spaces. Furthermore, the iscMo-cavernosus
(erector penis) and bulbo-cavernosus muscles contract and compress the
proximal or bulbous ends of the corpora and the outgoing veins. The result
of this combined muscular relaxation and contraction is a free entrance of
blood into and a difficult exit from the vascular spaces ; this leads to a swelling
and distention which aid further in compressing the venous outlets and, being
limited by the tough, fibrous tunics of the corpora, result in making the organ
stiff, hard, erect in position, and well adapted to its specific function. During
the process of erection the cresta of the urethra or caput gallinaginis, which is
an elevation extending from the cavity of the bladder into the prostatic por-
tion of the urethra and containing erectile tissue, becomes turgid and, by the
aid of the contraction of the sphincter urethras, effectually closes the passage
into the bladder. Erection is a complex reflex act, the centre of which lies
in the lumbar spinal cord and may be aroused to activity by nervous impulses
coming from different directions. Impulses may originate in the walls of the
ducts of the testis from the pressure of the contained semen or in the penis
from external stimulation of the nerve-endings in the skin, in both cases
passing along the sensory nerves of the organs to the spinal centre ; or they
mav originate in the brain and pass downward through the cord, the impulses
in this case corresponding to sexual emotions. The centrifugal paths for the
arteries are along the nervi erigentes, which are true vaso-dilator nerves, and
in the mammals, where experiment has proved their existence, pass from the
spinal cord along the posterior lumbar (monkey) or anterior sacral (monkey,
dog, cat) nerves to their arterial distribution. The ischio- and bulbo-caverno-
sus muscles are under the control of their motor nerve supply, consisting of
branches of the perineal nerve.

In the female, anatomists recognize the homologues of the male erectile
parts as follows : the clitoris with its corpora cavernosa and glans as the homo-
logue of the penis, the two bulbi vestibuli as that of the bulb of the corpus
spongiosum, the pars intermedia perhaps as that of the corpus spongiosum
itself, and the erector clitoridis muscle as the homologue of the erector penis
{ischio-cavemosus). The mechanism of erection is similar to that in the male,
and the result is a considerable degree of firmness in the external genital
organs.

The sexual excitement attendant upon copulation is usually much greater
in man than in woman, and culminates in the sexual orgasm, when the emis-
sion of semen from the penis into the vagina occurs. It will be remembered
that the prepared semen is stored in the ducts of the testes. The discharge
of the fluid is a muscular act which begins probably in the vasa effereniia

REPRODUCTION. 903

and the canal of the epklldynm, and sweeps along the powerful muscular
walls of the V((s<i dcj'croUia in the form of a scries of peristaltic waves. The
seminal vesicles also contract, and the mixed fluid and spermatozoa are poured
through the ejaculatory ducts into the prostatic portion of the urethra. Tlie
umscles of the prostate expel the prostatic fluid and help to pass the semen
onward. The glands of Cowper possil)ly add their contribution. But the
final urethral discharge is effected especially by powerfid rhythmic contractions
of the already partially contracted striped muscles, viz. the ischio- and bulbo-
cavei'nosi, the conslridov urethrcv, and probably the anal muscles, the result of
the complex series of actions being to expel the semen with some force into
the upper part of the vagina close to the os uteri. Ejaculation is a reflex act.
The centre lies in the lumbar spinal cord ; the centripetal nerves are the sen-
sory nerves of the penis, stimulation of the glans being especially effective;
the centrifugal nerves are the nerves to the various muscles. In the female
during ejaculation the glands of Bartholini pour out a mucous fluid upon the
vulva. There is possibly a downward movement of the uterus, brought about
by contraction of its round ligaments and accompanied perhaps by a contrac-
tion of the uterine walls themselves. But all muscular and erectile activity,
as well as sexual passion, is less pronounced in woman than in man.

Locomotion of the Spermatozoa. — The union of the spermatozoon and the
ovum probably takes place usually in the Fallopian tube not far from its ovarian
end, and to this place the spermatozoa at once proceed. Their mode of entrance
into the uterus is not wholly clear; it is quite generally believed, but without
conclusive experimental proof, that relaxation of the uterus immediately after
copulation exerts a suction upon the fluid which aids in its passage through
the OS and the cervix. It is possible that active contraction of the vaginal
walls assists. However these may be, the main agency in the locomotion of
the spermatozoa through the body of the uterus and the Fallopian tubes, and
probably also from the vagina into the uterus, is the spontaneous movement of
the spermatozoa themselves. By the lashing of their tails they wriggle their
way over the moist surface, being stimulated to lively activity probably by the
opposing ciliary movements in the epithelium lining the passages. Kraft* has
shown in the rabbit that, when spermatozoa in feeble motion are placed upon
the inner surface of the oviduct, not only are they thrown into active contrac-
tions, but they move against the ciliary movement, i. e. up the oviduct. The
capacity of the male cells thus to respond by locomotion in the opposite direc-
tion to the stimulating influence of the ciliary cells over which they have to
pass, is an interesting adaptation. Probably this is the directive agency that
enables the spermatozoa to follow the right path to the ovum, while the ovum,
being in itself ]>assive, is by the same ciliary movement brought toward the
active male cell. The time occupied in the passage of the spermatozoa is un-
known in the human female, but is probably short ; in the rabbit spermatozoa
have been known to reach the ovary within two and three-quarter hours after
copulation. As has been seen, spermatozoa are probably capable of living

' H. Kraft : Pfliiger's Archiv fur die gesammte Physiologic, xlvii., 1890.

904 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

within the genital passages for several days, when, if ovulation has not taken
place, they perish. If, however, an ovum appears, they at once approach and
surround it in great numbers, being apparently attracted to it in some myste-
rious manner. Tiie work of Pfeffer,' who found that in the fertilization of
ferns malic acid within the female organs attracts the spermatozoids to their
vicinity, suggests strongly that also among animals the attraction may be a
ciiemical one, the ovum containing or producing something for which the sper-
matozoon has an affinity. If so, the meeting of the two germ-cells is an illus-
tration of a widespread principle of nature known as chemotropism, or chemo-
iaxis. Experimental evidence upon the subject in animals is wanting.

Fertilization. — It will be remembered that the ovum and the spermatozoon
undergo in their growth the process of maturation, and that this process con-
sists essentially of a loss of one-half of the chromosomes of their nuclei. The
germ-cells thus matured meet, as we have seen, in the distal half of the Fal-
lopian tube and fuse into one cell, the process of fusion being caWed fertilization
or* impregnation. The details of fertilization have not been observed in the
case of the human being, and the following account is generalized from our
knowledge of the process in other mammals and lower animals. In its broad
outlines fertilization is probably the same in all animals, the differences being
confined to details.

The ovum at the time of fertilization is surrounded by the zona radi-
ata alone, the corona radiata having been lost. The spermatozoa swarm
about the 2071a, lashing their tails and attempting to worm their way through
it. Several may succeed in reaching the perivitelline space, but for some
unknown reason in most cases one only penetrates the substance of the ovum ;
the others ultimately perish. In mammalian ova there is no micropyle, and
apparently the successful spermatozoon may enter at any point, the protoplasm
of the egg rising up as a slight protuberance to meet it (Fig. 310, c). In some
animals the tail is left outside to perish ; in others it enters, but then disap-
pears ; in no case does it appear to be of further use. The head and probably
the middle-piece are of vital importance. The head, now known as the sperm-
nucleus or male pronucleus, proceeds by an unknown method of locomotion
toward the centre of the egg, and becomes enlarged by the imbibition of fluid
(Fig. 310, B, s). The matured nucleus of the ovum, ov egg-nucleus {e), remains
in the resting stage from the time of maturation until the entrance of the sperm.
Then, without changing its character, it moves slowly toward the future meet-
ing-place of the two nuclei, which is near the centre of the egg. The sperm-
nucleus finally reaches the egg-nucleus (Fig. 311, c), its chromatin enters into
the latter, and the two fuse together to form a new and complete nucleus,
called the first segmentation nucleus (Fig. 311, d). This body has the con-
ventional nuclear structure — namely, an achromatic network with the chro-
matic reticulum mingled with it — and the whole is covered by a nuclear mem-
brane. The chromatic substance, it will be perceived, is now restored to the
original amount present in either germ-cell before its maturation, one-half of
' W. Pfeffer : Untersuchungen aus dem Botanischen Institvl zu Tiibingen, i., 1884.

BE PROD UCTION.

905

it having come, how-
ever, from the male cell
and oiio-half from the
female cell. On the
com mon ly accepted
theory that this is the
hereditary substance,
the first segmentation
nucleus contains within
itself potentially all the
inherited qualities of
the future individual.

While the head of
the spermatozoon is
making its way through
the substance of the egg
there appears beside it
a minute cytoplasmic

r^j^^- <^

Fig. 310— Stages in the fertilization of the egg (after Wilson). The
drawings were made from sections of the eggs of the sea-urchin, Toxo-
pneu)<teH variegatus, Ag.

A. The surface of the egg has become elevated to form c, the entrance-
cone for the spermatozoon; the head (h) and the middle-piece (m) of the
latter have entered the egg.

B. Five minutes after entrance of the spermatozoon. The head (s),
now the male pronucleus, has rotated 180 degrees, and has travelled
deeper into the ovum. The cytoplasm of the latter has become arranged
in a radiate manner about the middle-piece of the spermatozoon, now the
centrosome, to form the sperm-aster; e, the egg-nucleus, now the fe-
male pronucleus, is approaching the sperm-nucleus ; its chromatin forms
an irregular reticulum ; c, the entrance cone.

Fig. 311.— Stages in the fertilization of the egg (continued from Fig. 310).

c. Ten minutes after entrance of the spermatozoon. The male and the female pronuclei have met
near the centre of the egg and the fusion has begun ; the former has become enlarged and its chromatin
has become loosely reticulated. The sperm-aster has become enormously enlarged. The single centro-
some has been divided into two, which lie upon either side of the sperm-nucleus.

D. The pause thirty minutes after entrance of the spermatozoon. The two pronuclei have fused com-
pletely to form the first segmentation-nucleus, all trace of a distinction between paternal and maternal
chromatin being lost. The sperm-aster has become divided into two asters, which have moved to oppo-
site poles of the nucleus; the astral rays have become shortened. The egg is now ready to .undergo
segmentation.

906

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

1 1 1

'^imr^^f^^^

V

V.

-,5

B

^

s^Cl«^--';rCk'

•./,||r

:.^'^

^r/;'ii'i'

1

§s^--

Fio. 312.— Stages in the segmentation of the egg (after Wilson).
The drawings were made from sections of eggs of the sea-urchin,
Toxopneusles variepatus, Ag.

A. Beginning of the formation of the amphiaster. Tlic nuclear
membrane has disappeared at the two poles of the spindle-shaped
nucleus. Within the nucleus a distinction between the chromatic
and the achromatic substance is being made, the former existing as
irregular rod-shaped bodies lying at the centre, the latter as delicate
filaments extending irregularly from pole to pole. The asters arc well
marked.

B. The nuclear membrane has wholly disappeared. The chro-
mosomes are clearly defined and aggregated in the centre of the
spindle to form the equatorial plate. The achromatic filaments of
the spindle are well marked. The connection of the astral rays with
the cytoplasmic reticulum of the egg is shown.

c. Each chromosome has become split into two, and the latter,
ch, are being pulled toward the poles.

» Th. Boveri : loc. cit. * E. B. Wilson and A. P. Mathews

body, the centrosomc, and
around the latter tlie fila-
ments of the cytoplasm of
the egg arrange themselves
in the form of a star, the
whole body being known
as t\i(i sperm-aster (Y'\g. 310,
b). We have previously
recognized such a structure
in the ovum at^the time of
maturation, and have found
it functional in the forma-
tion of the polar bodies ;
after maturation it disap-
pears. The sperm-aster
accompanies the sperm-nu-
cleus, becomes gradually
enlarged, and finally comes
to lie, a large and promi-
nent body, beside the seg-
mentation nucleus. Its
origin, or, more exactly,
the origin of its centro-
some, has been greatly
disputed, and, at the pres-
ent time, is understood in
few species of animals.
Boveri ^ and Wilson ^ find
in the sea-urchins that the
centrosome is the middle-
piece of the spermatozoon
and is exclusively of male
origin. Several other in-
vestiirators have observed
in other animals its origin
from one germ-cell only,
usually the male, and it is
a question whether its male
origin may not be the com-
mon one. The significance
of this discovery and the
function of the aster will
be explained in the follow-
ing section.
: Journal of Morphology, x., 1 895.

REPR OD UCTION. 907

There results tii»in lortilization, it is juTceivocl, a single cell complete in all
its essential parts. This is the startint^-point of the now individual. A pause
or rostino; p(>riod usually follows fertilization, and then growth begins.

Segmentation. — The process of growth is a complex process of repeated
cell-division, increase in bulk, morphological differentiation, and physiological
division of labor.

Cell-division is largely, if not wholly, indirect or karyokinetic. The term
segmentation, or cleavage, of the ovum is conveniently applied to the first few

/

,^^^^jllI/o. ^^^IjiM^

m

\

\ j ' /

E
Fig. 313.— Stages in the segmentation of the egg (continued from Fig. 312).

D. The divergence of the chromosomes has ceased and the latter have become converted into vesicu-
lar masses beside the eentrosomes. The spindle is becoming resolved into ordinary cytoplasm. The
division of the cytoplasm is beginning with a constriction at the surface of the egg.

E. The vesicular chromatic masses have become converted into two typical resting nuclei, each with
a chromatic network. The single aster, formerly connected with each nuclear mass, has become divided
into two, which have taken positions at opposite poles of the nuclei. The division of the cytoplasm is
complete, and the two resulting cells, or blastomeres, are resting, preparatory to a second division in a
plane at right angles to that of the first.

divisions, although the details of segmentation are not different fundamen-
tally from those manifested later in the division of more specialized cells.
Each division may be resolved into three definite acts, which, however,

908 AN AMERICAN TEXT-BOOK OE PHYSIOLOGY.

overlap each other in time. The first act is characterized by the appear-
ance of two centrosoraes, each with its astral rays, in place of the one
already existing (Fig. 311, c). The two take >ij) positions on opposite sides of
the nucleus (Fig. 311, d) and await the time when tiiey can exert their specific
function. We have spoken of the difference of opinion regarding the origin
of the original ccntrosome of fertilization. The origin of tiie two centrosonies
present in segmentation has likewise been disputed. The question is of consid-
erable theoretical interest in connection with the problem of the physical basis
of inheritance. Certain observers have claimed that the centrosomes have a
double origin, one being derived from the male and one from the female germ-
cell. Upon this theory sexuality is shown by the cytoplasmic centrosomes as
well as by the nuclear chromosomes, and the inference is possible that cytoplasm,
as well as nucleus, transmits hereditary qualities. The observations of Boveri,
Wilson, and others refute this claim by show^ing that the two centrosomes arise
by a splitting of the original centrosome, which is derived from the middle-
piece of the spermatozoon. They are, therefore, not male and female, and
cannot be regarded as bearers of inherited characteristics. These observa-
tions not only allow, but tend to strengthen, the prevailing view of the
exclusive hereditary role of the nucleus. (See below under Heredity,
p. 931).

The second act of segmentation is more complicated than the first, and con-
sists of a halving of the nucleus. The nuclear membrane gradually disap-
pears. The achromatic network resolves itself into long cytoplasmic filaments
arranged in the form of a spindle, and meeting at the two centrosomes (Fig.
312, a). The spindle, centrosomes, and asters form the body known as the am-
phiasfer. The chromatic substance becomes changed into the definite rod-like
chromosomes which are collected in the equatorial zone of the spindle and con-
stitute the equatorial plate (Fig. 312, b). From the observations of Van
Beneden, Riickert,^ ^oj^?^ s»^^ others, it seems probable that the male and
the female chromosomes do not fuse together, but remain distinct from each
other, perhaps throughout all the tissue-cells. Each chromosome proceeds
to split lengthwise, and the two halves are drawn toward the two centro-
somes, being mechanically pulled, it is commonly believed, by contraction
of the spindle-filaments, assisted by the astral rays (Fig. 312, c). The two
halves of the amphiaster, each with its centrosome, are, in fact, commonly
believed to be composed of contractile cytoplasm and to be organs possessing
the definite function of separating the two halves of the nucleus in karyokinesis.
The evidence for this view is not wholly satisfactory. In the process of divis-
ion each nuclear half obtains half of the original male and half of the original
female chromatin, and hence contains inherited potentialities of both parents.
After division each half gradually assumes the structure of a typical resting
nucleus with its accompanying aster.

The third act of segmentation consists of a simple division of the cytoplasm

' J. Riickert: Archiv fur mihroskopische Anatomie, xlv., 1895.
' K. Zoja: Anatomischer Ameiger, xi., 1896.

REPRODUCTION. 909

into two equal parts, the separation taking place along the plane of nuclear
division (Fig. 313, d, e). Each part contains one of the new nuclei, and the
result of the first division is the existence of two cells, two blastomeres, in
place of the one fertilized ovum. The beginning of differentiation is shown
sometimes even as early as this, for, according to Van Beneden, in some mam-
mals at least, one blastomere is often somewhat larger and less granular than
the other.

Each blastomere proceeds now to divide by a similar karyokinetic process
into two, the result being four in all, and by subsequent divisions, eight, six-
teen, and more, the divisions not proceeding, however, with mathematical regu-
larity. By such repeated karyokinetic processes the original fertilized ovum
becomes a mass of small and approximately similar cells, the morula, from
which by continued increase of cells, morphological differentiation, and physi-
ological division of labor, the embryo with all its functions is destined to be

built up.

Polyspermy. — It happens occasionally that two or more spermatozoa enter
the ovum ; such a phenomenon is known as dispenny ov polyspermy, according
to the number of entering sperms. Each sperm with its nucleus and centro-
some becomes a male pronucleus and proceeds to conjugate with the female
pronucleus. In the case of dispermy the one female and the two male pro-
nuclei fuse together ; each centrosome divides as usual into two, making four
in all, which take up a quadrilateral position about the first segmentation
nucleus ; the chromatic figure consists of two crossed spindles ; and the egg
segments at once into four instead of two blastomeres. When three sperma-
tozoa enter, six centrosomes appear and six- blastomeres result from the first
division, and analogous phenomena result from more complex cases of poly-
spermy. Apparently normal larval forms are produced from such double-
or multi-fertilized eggs, but as a rule their development ceases very early and
death occurs.

During cleavage the ovum proceeds, after the manner of the non-fertilized
ovum, slowly along ihe Fallopian tube and enters the uterus. Unlike the non-
fertilized ovum, however, the morula is not cast out of the body, but remains
and undergoes further development. The morphological development of the
embryo in utero does not fall within the scope of the present article. Some
attention may, however, be given to the immediate environment of the develop-
ing child and its relations to the maternal organism.

Decidua Graviditatis. — While the segmentation of the ovum is proceed-
ing within the Fallopian tube, the uterus prepares for the future guest by begin-
ning to undergo a profound change, probably being stimulated to activity re-
fiexly by centripetal impulses originating in the walls of the tube through con-
tact with the ovum. This change comprises an enlargement of the whole uterus
and a great and rapid growth in thickness of its mucosa and its muscular
coat. At first the alterations are not unlike the phenomena of growth pre-
ceding the menstrual flow, but, as they proceed, they become much more pro-

910

AN AMERICAN TEXT-lUKtK OF J'lIYSIOLOGY

IouikI tlmn tliosc. Tlio supply of blood to the walls i.s greatly incroa.sed, the
vessels forming large irregular sinuses within the mucosa. The supply of lymph
is increase<l. The glands become tortuous and dilated into flattened cavernous
spaces, and their walls atrophy, the epithelium breaking down except in their
deepest parts. The mucosa is thus converted into a spongy tissue, the frame-
work of which contains numerous large irregular cells, derived probably from
the original connective tissue and called decidual cells. The musculature is

Ikcidua serotinn.
Chorum frondonum.

— Muscle.
— Uterine glands.
Chorion Iseve.

Mucous plug nithin cenical canal.

Fig. 314.— Diagram of the human uterus at the seventh or eiphth week of pregnancy (modified from
Allen Thompson). The fetal villi are shown growing into the sinuses of the decidua serotina and the
decidua reflexa ; in the latter they are becoming atrophied. They are marked by the black fetal vessels,
which can be traced backward along the umbilical cord to the embryo. The placenta comprises the
decidua serotina and the chorion frondosum.

greatly thickened by an increa.se, partly in number and partly in size, of its
constituent fibres, and the nerve-supply is increased. These general structural
changes proceed through the early part of gestation and are accompanied by
special changes to be discussed later. It is not definitely known how far the
alterations have gone before the advent of the segmented ovum in the uterus.

BEPR OD UCTION. 911

With the latter instead of tlie uiiiinpregnated ovum j)reseiit in the Fallopian
tube, the hv|K rtrophied uterine mucosa does not break away as in menstrua-
tion, but remains, and henceforth is called the daddua graviditath, special
names being given to special parts. Entering the uterus, tlie ovum attaches
itself in an unknown manner to the wall of the womb. The part of the mucous
membrane that forms its bed is henceforth known as the decidua serothia ; as
the seat of the future placenta, it is physiologically the most interesting and
important portion of the uterine mucosa. The surrounding cells and tissues
are stimulated to active proliferation and grow around and over the ovum,
com])letoly covering it with a layer, the decidua refiexa. The remainder of
the uterine liniu"- membrane constitutes the decidua vera. Between the reflexa
and the vera is the uterine cavity. At first thickened, the reflexa later thins
away as the embryo growls, and approaches close to the vera ; finally it touches
the latter, and the original cavity of the body of the uterus becomes oblit-
erated. By the sixth month the reflexa disappears, either coalescing with the
vera or undergoing total degeneration (Minot). During the latter half of
gestation the vera itself thins markedly. This atrophy of the comparatively
unimportant reflexa and vera, in contrast to the placental hypertrophy of the
serotina, is interesting. The arrangement of the parts is well shown in the
accompanying illustration (Fig. 314).

The Fetal Membranes. — The segmented ovum absorbs nutriment at first
directly from its surrounding maternal tissues, and later through the mediation
of the placenta. Its growth and cell-division are active, and it increases in
size and complexity. It early takes the form of a generalized vertebrate em-
bryo, and by the fortieth day begins to assume distinctly human characteristics.
It becomes surrounded early by the fetal membranes, which are two in num-
ber, the amnion and the chonon or, as it is usually called in other vertebrates,
false amnion. The amnion is a thin, transparent, non-vascular membrane imme-
diately siuTounding the embryo (Fig. 314). In origin a derivative of the embry-
onic somatojileure, later it becomes completely separated from the body of the
embryo. The space enclosed by the amnion, the amniotic cavity, within which
the embryo lies, is traversed by the umbilical cord and contains a serous fluid,
the liquor- amnii. This fluid, highly variable in quantity, averages at full
term nearly a liter (If pints). It has in general the composition of a serous
fluid. It contains between 1 and 2 per cent, of solids, consisting of proteids
(0.06-0.7 per cent.), mucin, a minute and variable quantity of urea, and inor-
ganic salts. It is derived perhaps in part by exudation from the fetus, but
doubtless chiefly by transudation from the maternal fluids, as is indicated by
the ready appearance within the amniotic cavity of solutions injected into the
maternal veins. It bathes the entire surface of the embryonic body, and is,
moreover, apparently swallowed at times into the stomach, as the presence of
fetal hairs and epidermal scales within the alimentary canal attests. Its chief
fimctions appear to be those of protecting the fetus from sudden shocks and
from pressure, maintaining a constant temperature, and supplying the fetal
body with water. The proteid possibly confers upon it a slight nutritive

912 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

value, and the minute quantity of urea is perhaps indicative of an unimport-
ant excretory function. As growth proceeds, the amnion expands and becomes
loosely attached to the outer fetal membrane, the chorion.

The chorion (Fig. 314), or false amnion, is formed simultaneously with the
true amnion, and like it from somatopleure. It is a thickened vascular mem-
brane, completely surrounding the amnion witii the contained embryo. Be-
tween it and the amnion there is at first a considerable space, traversed by the
umbilical cord and filled with the chorionic fluid (which is probably of the
same general nature as the amniotic fluid). But later this space is obliterated
by the enlargement of the amnion. Externally the chorion presents, at first,
a shaggy appearance due to the existence of very numerous columnar pro-
cesses, called villi, extending outward in all directions and joining by their
tips the decidua serotina and the decidua reflexa. Later the villi are aborted
except in the region of the serotina, where they become more prominent and
constitute an important part of the placenta. The blood-vessels of the chorion
are fetal vessels coming from the embryonic structure, the allantois. They
comprise the branches and uniting capillaries of the two allantoic or umbilical
arteries, and the one (at first two) allantoic or umbilical vein. They are
especially well developed within the villi. As growth proceeds, the chorion
comes into close contact with the decidua reflexa, and, as the latter disappears^
with the decidua vera ; this portion of it is called chorion Iceve. In the region
of the decidua serotina it enters into the formation of the placenta, and is
here called chorion frondosum.

The Placenta. — The placenta (Fig. 314), or organ of attachment of mother
and fetus, is a disk-shaped body, approximately 20 centimeters (7-8 inches) in
diameter, attached to the inner surface of the uterine wall, usually either upon
the dorsal or the ventral side, more frequently upon the former, and connected
by the umbilical cord with the navel of the fetus. It consists of a maternal
part, the modified decidua serotina, and a fetal part, the modified chorion, inti-
mately united together. The modifications of the serotina consist of a degen-
eration of the superficial layers of the mucosa, especially of the epithelium
and the glands, and the development of very large irregular sinuses at the
surface, into which the uterine arteries and veins appear freely to open. It
should be said that it is a disputed question among histologists whether the
sinuses are maternal or fetal in origin, or really spaces between maternal and
fetal tissues. It is also disputed whether they actually contain blood or only
fluid from the surrounding tissues ; the former has by far the weight of evi-
dence in its favor and is the prevailing view. The modifications of the chorion
consist of a great increase in lengtli and complexity of branching of the villi,
a great development of their contained blood-vessels, and a firm attachment
of their tips to the uneven surface of the serotina, so that their branches come
to float freely within the uterine sinuses and to be bathed in uterine blood
(Fig. 315). The analogy between the mammalian placental villi and the gills
of a fish, also highly vascular and floating in liquid, is striking. We shall
see later that the analogy is not only morphological, but also physiological.

REPROD UCTION.

913

Amnion.

Chorion.

ina.simich as the villi have impctrtant respiratory functions. The bulk of the
placenta is this intravillous portion, of spongy consistence, comprising the
maternal sinuses permeated by the
fetal villi ; this is in contact upon
the fetal side with the thin un-
modified chorion covered within
by the amnion, and upon the
maternal side with the thin rela-
tively unmodified serotina covered
without by the uterine muscle.
The pui-e maternal blood brought
by the uterine arteries moves
slowly through the sinuses and
retires by the uterine veins ; the
fetal blood is propelled by the fe-
tal heart along the umbilical cord
within the allantoic arteries and
through the villous capillaries, and
returns by the allantoic vein. The
two kinds of blood never mix, but
are always separated by the thin
capillary walls and their thin vil-
lous investment of connective tissue
and epithelium. Thus the anatom-
ical conditions for ready diffusion
are present, and this is the chief
means of transfer of nutriment and
oxygen from mother to child, and
of wastes from child to mother.
The physiological role of the pla-
centa is, therefore, an all-important
and complicated one. The placenta is, technically, the nutritive organ of
the embryo.

Nutrition of the Embryo. — We have seen that a fundamental and most
striking difference between the minute human ovum and the large e^^ of the
fowl lies in the relative quantity of food contained in the two. The fowl has
retained the primitive habit of discharging the ovum from the maternal body,
and discharges w'ithin its shell at the same time sufficient food for the needs of
the developing chick. Evolution has endowed the human mother, in common
with other mammals, with the peculiar custom of retaining the offspring within
her body until its embryonic life is completed, and of doling out its nuti'iment
molecularly throughout the period of gestation. The store of nutritive deuto-
plasm with which the egg leaves the ovary is, therefore, only sufBcient for the
early segmentative activities. Within the Fallopian tube absorption from the
surrounding walls doubtless goes on. Arrived in the uterus and imbedded in

58

Fig. 315. — Diagram of the placeuta (Schafer) : s, pla-
cental sinuses, into which project the fetal villi, con-
taining the red fetal vessels ; d. s, decidua serotina ; s.p,
spongy layer, and m, muscular layer, of the uterus ; a,
uterine artery, and v, uterine vein, opening into the
placental sinuses.

914 AN AMERICAN TEXT-BOOK OE PllYSlOLOGY.

its (locidiuil wall, the .segmented ovum eontimies to take nutriment from its
immediate environing cells. It has been suggested, but without much basis
of fact, that the uterine glands, which at this time are greatly dilated, may
furnish a nutritive secretion for the use of the embryo; but, a 'priori, it would
seem more reasonable that, just as the ovum within the Graafian follicle
obtains its food from its surrounding stroma, so within the highly vascular
decidua it absorbs directly from the decidual tissue. But that this source
soon proves insufficient for the rapid growth is indicated by the early develop-
ment of the chorion with its villi and the embryonic vascular system. In
Rei(!hert's ovum, the earliest known human embryo, and believed to be
between twelve and thirteen days old, the villi are already well marked
over an equatorial zone. From this time on\vard throughout gestation the
chorion takes an important part in the embryonic nutrition, becoming, as we
have seen, an integral part of the placenta. The placenta is 'pav exceUenee
the medium of nutritive communication between mother and child.

Let us consider briefly the needs of the embryo. The fetal energies must
be directed almost wholly to the all-important functions of growth and prepa-
ration for the future independent existence. The organism requires, therefore,
an abundance of food containing all the chief kinds of food-stuifs. With the
alimentary canal in its embryonic and functionless state, this food, when it
reaches the embryo, must necessarily be already digested and ready for absorp-
tion by the cells. A supply of oxygen, not necessarily great in quantity, is
also needed. The fetal lungs are not ready for respiration, and the oxygen
must come to the blood by another channel than them. Carbonic acid must
be got rid of, and through other than pulmonary paths. Urea and its fore-
runners and other wastes, probably not in great quantity, must be excreted.
The fetal kidneys and the skin are probably never very active, as is made rea-
sonably certain by the late external opening of the male urethra, the late
development of the cutaneous glands, and the composition of the amniotic
fluid, into which they would naturally pour their secretions. Thus the paths
of income and outgo that are normal to the individual after birth are only
partially open during fetal life; nevertheless, the processes of income and
outgo must be performed. The placenta, with its close relationship but non-
communication of maternal and fetal blood-vessels, has, therefore, been evolved
phylogenetically, and appears early in the course of ontogeny. To it is
brought (m the part of the embryo and discharged into the villous cajiillaries
a mixed blood, comprising venous blood from the various capillary systems
of the body, and containing, therefore, the carbonic acid and other wastes
of venous blood, and a certain i)roportion of ])urified blood that has passed
directly by way of the ductus rcnosus, inferior vena cava, right auricle, /ora-
men ovale, and the left side of the heart to the aorta and the umbilical arte-
ries. To it is brought on the part of the mother and discharged into the
sinuses pure arterial blood, laden with food and with oxygen. Through the
membrane intervening between maternal and fetal vessels there passes from
the fetus carbonic acid and other wastes, and from the mother food and oxy-

R EPROD UCTION. *J 1 5

gen. Back to the fetal liver and heart goes the nutritive and arterialized
blood, and back to the maternal excretory organs the vessels convey the fetal
wastes. The placenta is thus a peculiar organ intermediate between the living
cells of the embryo on the one hand and the digestive organs, lungs, kidneys,
and skin, of the mother on the other. Little is known of the actual details
of the placental process. The structure of the intervening cells indicates that
the interchange may be after a manner analogous to that taking place in the
lungs, rather than to that of a typical secreting gland—?', e. that known physi-
cal processes, such as diffusion and filtration, play a prominent role. It has
been shown by several investigators that the fetus may be poisoned by car-
bonic oxide and strychnine, and may receive other harmless diffusible sub-
stances that are introduced in solution into the maternal circulation. The
mother raav be affected similarly from the fetal circulation. But, as in the
case of the lungs, so the placental membrane can scarcely be regarded as
acting in the same passive way as a lifeless membrane would act (compare
Respiration). As accessory to the main nutritive source it has been sug-
gested that a diapedesis of maternal leucocytes into the fetus may take place.
The uterine glands are thought by some to afford a nutritive secretion to the
sinuses, and to the amniotic fluid has been ascribed a nutritive function.
Theoretically, these various means are not impossible, but true placental diffu-
sion must be regarded as the chief principle at work. The result is that the
mother relieves the child of all the labor of nutrition except that connected
directly with the latter's own cellular and protoplasmic metabolism. The
fetal energies are, therefore, free to be expended in the process of growth,
while gestation profoundly affects the maternal organism.

Physiological Effects of Pregnancy upon the Mother. — As might have
been expected, there is probably not one organic system wdthin the mother's
body that is not more or less altered by pregnancy, often morphologically, but
especially in regard to function. And such normal alterations pass so gradu-
ally and so frequently into genuine pathological conditions that it is sometimes
difficult to draw the line between the two. The most marked changes are
connected with the body of the uterus, and have already been described. The
walls of the cervix ttteri become hypertrophied, though to a less degree than
the body, and their glands secrete a quantity of mucus that forms a plug com-
pletely closing the passage-way of the cervix (Fig. 314). The rest of the
reproductive organs from the uterus outward become involved in the increased
venous hypersemia. The walls of the vagina become infiltrated with serous
fluid. The parts of the vulva partake in the general tumefaction. From the
second month of gestation onward the mammary glands undergo gradual devel-
opment as a preparation for the post-partum lactation. The increase in size of
the laden uterus brings gradually increasing pressure to bear upon the abdom-
inal viscera, and thus mechanically causes functional derangements of the
dio-estive and the urinary organs. The stretching of the abdominal skin
results in localized ruptures of the connective tissue of the cutis, the charac-
teristic scars forming the strice gravidarum, which persist after pregnancy.

916 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Otlier organic changes arc, however, more profound than these mechanical ones.
In accordance with the increased nutritive labor thrown upon tiie mc^ther, the
total quantity of blood in her body is increased, if we can reason from deter-
minations made upon the lower animals.' The condition of the blood is dis-
puted. The old view was that the blood of pregnancy is more watery and
contains less haemoglobin than at other times. This is perhaps true for the
earlier months, but Schroedcr" and others have shown that the ])ro]X)rtion of
hajmoglobin and the number of red corpuscles rise above the normal during
the later stages. The work of the maternal heart is increased during gestation.
It is maintained by some that the heart beats more rapidly — according to
Kehrer,^ over eighty in the minute. It has also been thought, mainly from
the results of percussion and from sphygmographic tracings, that the left ven-
tricle is hypertrophied during pregnancy. Post-mortem examination, although
scanty, cannot be said to confirm this inference. Pregnancy necessarily throws
increased labor upon both the liver and the kidneys, and these organs are prone
to functional disorders. Gastric disturbances are marked by frequent vomit-
ing. A tendency to increased pigmentation in the skin is present. The ner-
vous system is affected, manifesting its alterations both by nutritional disturb-
ances and by mental irritability, depression of spirits, disordered senses, easily
passing into temporary pathological states, and occasionally by feelings of
heightened well-being. The body-weight usually increases independently of
the added weight of the embryo.

Duration of Gestation. — For centuries the duration of gestation in
woman has been commonly regarded as 280 days. The beginning of preg-
nancy, the union of the ovum and the spermatozoon, however, presents no
obvious signs by which it may be recognized, and hence the actual length of
pregnancy in the human female is no moi'e known than in other mammals.
The obstetrician is obliged, therefore, to use artificial schemes in computing its
probable length. Several tables have been publisiied of the time elapsing
between a single coition resulting in pregnancy and the terminal parturition.
Veit,* in collecting 503 such cases reported by several obstetricians, finds the
duration to be from 265 to 280 days in 396 cases, and longer in the remaining
107 cases, the variation thus being marked. It is obvious that the date of the
effective coition can rarely be known. One of the first and most evident signs
of pregnancy is the non-appearance of the menses, and, probably largely from
the long-prevailing idea of the close relation existing between ovulation and
menstruation, it has been customary to regard gestation as dating from the last
menstruation. FoIlo\ving Naegelc, obstetricians estimate the date of parturi-
tion as 280 days from the first day of the last menstruation ; and this simple
but artificial rule is doubtless approximately correct.

In accordance with modern biological theories, it must be supposed that for

' O. Spiegelberg und R. Gscheidelen: Arehivfiir Oiinakologie, iv., 1872.
^ R. Schroeder : Arehivfiir Gyndkoloyie, xxxix., 1890-91.
^ F. A. Kehrer: Ueber die Verdnderungen der Pulscurve im Puerperinm, 1886.
* J. Veil : Midler's Handbuch der GeburtshiUfe, 1, 1888.

RE PR OD UCTION. 917

eac'li species tliero has been developed a gestative period of a length most
favorable to the continuance of the species; this has been a matter of natural
selection. But this ])rinciple does not account for the termination of the period
in any individual case. The proximate cause of the oncoming of birth must
be sought in more specific anatomical or physiological phenomena. This cause
has been sought long, and not wholly successfully. Among the agents sug-
gested may be mentioned the pressure which the uterine tissues, the cervical
ganglion, and the adjacent nerves, receive between the fetal head and the pelvic
wall, the stretching of the uterine wall, the fatty degeneration of the deciduae,
the thrombosis of the placental vessels, the venosity of the fetal blood due to
the growing functional importance of the fetal right ventricle acting as a
stimulus to the placental area, and a gradual increase in irritability of the
uterus as the nerve-supply of the organ increases. Some of these, such as the
fatty degeneration of the deciduae and the placental thrombosis, are not con-
stant phenomena, and the others are not definitely proved to be efficient causes.
It is probable that, with the uterus undoubtedly irritable, in different cases
different stimuli act to inaugurate the process of birth, and a priori the above
causes seem not improbable ones.

Parturition in General. — Parturition, birth, or labor, is the process of
expulsion of the developed embryo, the membranes, and the placenta from the
body of the mother. It is executed by contraction of the muscles of the so-
called wpper segment of the uterus and those of the abdominal walls. The
lower segment of the uterus, comprising approximately that portion of the
body lying below the attachment of the peritoneum, the cervix, the vagina,
and the vulva, are largely, if not wholly, passive in parturition. The obstet-
ricians have found it convenient to divide labor into three stages, although
physiologically these are not sharply differentiated from each other. The first
stage is characterized by the dilatation of the os uteri, the second by the expul-
sion of the fetus, the third by the expulsion of the after-birth. The customary
position of the fetus within the uterus at the end of pregnancy is that in which
the head is downward or nearest the os, the back toward the ventral and left
side of the mother, and the arras and legs folded upon the trunk.

First Stage of Labor. — For several weeks toward the close of pregnancy
there are occasional periods when rhythmic muscular contractions pass over the
uterine walls. These are mostly painless, and apparently are not in themselves
of special functional importance. The first stage of labor is ushered in by
various phenomena, prominent among which are an increase in the intensity
of the contractions, their painfulness, and their frequency and continuance.
In women they are confined practically to the upper segment of the uterus and
its attached ligaments, ceasing at a circular ridge that projects inward and is
called the "contraction ring." For some reason, at present disputed, the
lower segment of the uterus, and the cervix, are passive. The contractions
are probably peristaltic in character, as in lower animals. Schatz^ has graphi-
cally recorded the uterine movements by means of a bladder filled with water
* F. Schatz : Archil fur Gyndkologie, xxvii., 1885-86.

918 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and iiitrcxliiced into tlie uterus. During the earlier part ot" parturition the
contractions grachially increase in intensity up to a maximum which they
then maintain. Their rhythm is somewhat irregular ; the duration of each
contraction averages about one minute, and a })ause, which ensues between suc-
cessive contractions, extends from one and one-half to several minutes. The
relaxation of the muscle-fibres during the period of rest is incomplete, the
result being that the fibres enter gradually into a tonically contracted state.
Each contraction is accompanied by a pain, localized in the early part of labor
in the uterus alone, but later extending outward, upward into the abdomen,
and downward into the thighs. The pains of labor vary greatly in intensity
in individuals, but are usually more intense during the first gestation than
during later ones. They are due chiefly to direct mechanical stimulation of
the sensory uterine and other nerves by compression, tension, and even lacera-
tion.

As a result of the tonic contraction of the uterine walls, gradually increas-
ing with each new peristaltic wave, the uterus becomes gradually narrower in
diameter and longer, and the walls press more and more firmly upon the bag
of amniotic fluid containing the embryo. Schatz finds that the uterine pres-
sure under the uterine contractions rarely reaches and never exceeds 100 milli-
meters of mercury. Tlie direction of least resistance to this pressure lies
along the cervical canal, the walls of which do not take part in the uterine labor.
With each succeeding contraction this canal is forced wider open and the uterine
contents are pressed tightly downward and into the cervix. The head of the
embryo is preceded by a bulging portion of the membrane, filled with fluid
and forming a distinct bladder-like advance guard. This bag a})pears at the
OS uieri, its contents increase under the increasing pressure, and in the majority
of cases, when the os is fully expanded, it bursts and allows the amniotic fluid
to escape to the exterior. In some cases the rupture is delayed until the sec-
ond stage of labor, and rarely the child is born with the membranes intact.

Second Stage of Labor. — The uterine contractions frequently cease for a
period following the rupture of the membrane. They then begin anew with
increased force, and are accompanied by a new feature, namely, analogous
vigorous rhythmic contractions of the muscles of the abdominal walls. These,
following deep inspiration and accompanied by forced attempts at expiration
with a closed glottis, diminish the longitudinal and the lateral diameters of the
abdominal cavity, compress the abdominal organs, and help to augment greatly
the uterine pressure. At the beginning of the second stage the force of the
contractions is expended mainly upon the head of the embryo, which lies like
a plug in the cervical canal. This is squeezed gradually through the os into
the vagina, followed by the more easily passing trunk and limbs. The con-
tractions are frequent, vigorous, and painful, the pains reaching a maximum
as the sensitive vulva is put upon the stretch arKl traversed. The vertex is
usually presented first to the exterior, the head and body following as the suc-
cessive contractions of the maternal muscles develoj) sufficiout power to over-
come the resistance offered to their passage by the surrounding walls. In

RE PR OD UCTION.

919

the human female the vaginal muscles do not appear to engage in the expel-
ling act, the uterine and the abdominal muscles alone sufficing and finally
forcing the child wholly outside the mother's body. In this gradual manner,
painfid and dangerous alike to mother and child, the maternal organism forces
the offspring to forsake its sheltering and nutritive walls and begin its inde-
pendent existence.

Third Stage of Labor.— During the later expulsive contractions of the
second stage the placenta, being greatly folded by the diminution in the uterine
surface of attachment, is loosened from the uterine wall by a rupture takmg
place through the loose tissue in the region of the blood-sinuses. The child,
when born, is joined to the loosened placenta by the umbilical cord, until the
latter is tied and cut by the obstetrician. The muscular contractions, now
almost painless, continue through the third stage, and the placenta is torn
from its attachment, everted, and carried gradually outward. The lining
membrane of the uterus from the placenta outward and for a considerable
depth is gradually torn free from the deeper parts through the spongy layer,
and with the attached chorion and amnion follows the placenta. As a rule,
this after-birth appears at the vulva within fifteen minutes after the expulsion
of the child ; it consists of the placenta, the amnion, the chorion, the decldua
reflexa, and a considerable portion of the decidua vera.

Previous to the third stage slight bleeding from laceration of the passages
occurs. But with the loosening of the placenta and the accompanying rupture
of the placental vessels the maternal blood flows freely and continues to flow
from the uterine wall, chiefly from the placental area, until the after-birth is
discharged. The average loss of blood amounts to about 400 grams. At the
close of the third stage of labor the uterine contractions have so far proceeded
that the organ is compressed into a hard compact mass, the ruptured vessels
are contorted and compressed, and the bleeding is thereby largely stopped.
For several hours, however, slight hemorrhage continues as an accompaniment
to the pod-partum contractions, but finally this ceases with the formation of a
blood-clot over the wounded surface.

The third stage of labor may continue through one or two hours. It is
customary, however, for the obstetrician speedily to put an end to it by assist-
ing the removal of the after-birth.

Nature of Labor. — Our knowledge of the nature of the muscular phe-
nomena of labor is incomplete. The uterine contractions are in part automatic
and in part reflex, but to what extent the former, and to what the latter, is not
known. Nerves reach the uterus partly through the abdominal sympathetic
chain and partly directly from the spinal cord through the sacral plexus.
Rein^ found that in the rabbit after section of all uterine nerves normal
conception, pregnancy, and birth may occur. In some animals uterine move-
ments may continue after removal of the organ from the body. Such and
other observations indicate the existence of an automatic contractile power
resident in the organ itself. Since nerve-cells are not found in its walls, it
' G. Rein : Pfliiger's ArcMv fur die gesammte Physiologic, xxiii., 1880.

920 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

seems probable that the automatism resides in the muscle tissue. The uterus
is, moreover, very sensitive to direct stimulation, even after excision. In ani-
mals higher than rabbits a connection with the lumbar spinal cord seems
essential to normal labor. Goltz ^ obtained in dogs conception, pregnancy, and
delivery after section of" the spinal cord at the height of the first lumbar
vertebra. In jwraplegic women, with conduction in the cord broken in the
dorsal region, delivery is possible. A centre for uterine contraction must
hence be supposed to exist in the lumbar cord. Centripetal and centrifugal
fibres exist in both sympathetic and spinal nerves, and reflex uterine contrac-
tions are readily obtained by stimulation of the central ends of the divided
nerve-trunks. According to von Basch and Hofmann,^ in the dog the sym-
pathetic trunks supply the circular muscular coat of the uterine walls and con-
tain vaso-constrictor fibres, while the spinal trunks supply the longitudinal
coat and contain vaso-dilator fibres. Stimulation of the uterus itself, the
vagina, the vulva, the sciatic and the crural nerves, and various sensory
regions, notably the ni])ples, causes reflex contractions of the uterus. The
same result occurs upon stimulation of various portions of the brain, such as
the medulla oblongata, the cerebellum, the pons, the corpora quadrigemina,
the optic thalamus, the corpus striatum, and even the corpus callosum. In
Moman psychic influences may call forth or inhibit uterine contractions. How
largely the well-known stimulating effects of the blood in asphyxia and of
drugs, like ergot, are due to central, and how largely to direct uterine, influence
is undecided. The regular co-ordinated course of labor and many experi-
mental facts make it probable that, normally, reflex influences constitute a large
part of tlie process, the centripetal impulses arising within the uterus itself.
In fact, it is customary to speak of labor as a complex reflex action. The
undoubted automatism of the uterine muscle-fibres must, however, be taken
into account, and the act should be regarded as composed of both automatic
and reflex elements. AVe have here to deal with that variety of contractility
peculiar to smooth muscle, in which central and peripheral influences work
together to bring about the result. It is perhaps not going too far to regard all
such actions, like that of the heart, as primarily automatic and called out by
direct stimulation, but as modified and controlled by reflex influences. The
parturitive contractions of the striated muscles of the abdominal walls are
probably more generally reflex iu nature, modified, however, by voluntary
efforts.

Multiple Conceptions. — According to the records given by different stat-
isticians, the frequency of twin births varies considerably in different coun-
tries. In 13,000,000 births in Prussia, G. Yeit^ found the number of twins
to be 1.12 per cent., or 1 in 89 births. In the cities of New York and
Philadelphia recent reports give the ratio of twins to single births as 1 : 120,
or 0.83 per cent.

' Fr. Goltz : Pfluger's Archiv fiir die ijesammte Physiolorfie, ix., 1874.

* S. von Bascli und E. Hofmann : Medizinische Jahrbitcber, Wien, 1877.

' G. Veit : Mmatsschrift fiir Geburtskunde und Franenkrankheiten, vi.. 1855.

RKPR OD LCTION. 92 1

Observations of discharged Graafian folli(!les in cases of raultii)le concep-
tions show that twins may arise eitlier from separate eggs or from a single egg.
The presence at birth of a double chorion is commonly regarded as diagnostic
of the former origin, that of a single chorion of the latter. In the former
ease the two ova may come from a single Graafian follicle, or from two folli-
cles situated within one ovary, or from both ovaries, direct observation of the
ovaries themselves being required to determine the origin in any particular
case. The two ova are discharged and fertilized probably at approximately
the same time. There are two distinct amnions. The two placentas may be
either fused into one or wholly separated from each other, and accordingly the
deeidua reflexa may be single or double. The two offspring may be of sep-
arate sexes, and do not necessarily closely resemble each other. In cases
where the two embryos come from a single ovum their origin is little under-
stood. It is conceivable that it may arise from the presence of two nuclei
within the one ovum. It is more probable, however, that it is due to a
mechanical separation of the blastomeres after the first cleavage or later in
segmentation.^ Driesch,^ Wilson,^ Zoja,* and others have shown that in various
invertebrates and the low vertebrate Amphioxus, single blastomeres, isolated
from the rest by shaking or other unusual treatment, are capable of develop-
ing into small but otherwise normal and complete embryos. No reason is
obvious why such an occurrence cannot take place in human development, if
in any accidental manner within the Fallopian tube the blastomeres become
separated. Driesch observed in the sea-urchins and Wilson in Amphioxus
incomplete separation of blastomeres to produce two incomplete organisms
more or less united together. It is not improbable that even in man cases
like the Siamese Twins, and greater monstrosities^ may be similarly accounted
for. In cases of double pregnancy from a single ovum the two amnions are
usually separate, in rare cases a breaking away of their partition wall throwing
them into one ; the two placentas usually fuse more or less into one, the blood-
vessels of the two halves always anastomosing ; and a single deeidua rejiexa
covers both. The two offspring are uniformly of the same sex and their per-
sonal resemblance is always close.

In Veit's statistics of 13,000,000 births in Prussia, triplets occur with a
frequency of 0.012 per cent., or 1 in 7910, and quadruplets 1 in 371,126 births.
There are well-authenticated cases of quintuplets. In all of these cases a
single ovum rarely, if ever, contributes more than two embryos, and these
are characterized, as in the case of twins, by being of similar sex, by pos-
sessing a single chorion, and by close personal resemblance.

The Determination of Sex. — In most, if not all, civilized races more boys
are born than girls. This is shown in the following table : ^

' Cf. Fr. Ahlfeld : Archiv fur Gyndkologie, ix., 1876.

2 H. Driesch: Zeitschrift fiir ivisHenschaftliche Zoologie, liii., 1892*, Iv., 1893; Mittheilungen
cms der Zoologischen Statimi zu Neapel, xi., 1893.

^ E. B. Wilson : Journal of Morphology, viii., 1893.

* R. Zoja : Archiv fur Entwickelungsmechanik der Organismen, ii., 1895.

* Bulletin de I'institut international de slatislique, vii.

922 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Boys born to 1000 Girls born (1887-91).

Italy 1058

Ireland 1056

German Empire 1052

France 1046

England 1036

Connecticut 107'J

Rhode Island 1049

Massachusetts 1046

Tlie proportional birtli-rate ot" tlie two sexes is usually fairly constant from
year to year. This means that constant rej^iilating factors are at work.
What determines sex in any one individual is ill understood. The sexual
oigans in the human embryo are well differentiated at the eighth week of
intra-uterine life, hence the sex of the child must be settled previously to this
time. It is at present quite impossible to say whether it is settled in the
germ-cells previous to their union, in the act of fertilization, or during the
early uterine life. Many facts, both observational and experimental, and
more hypotheses, bearing upon the determination of sex, have been i)rought
forward. The Hofackcr-Sadlcr law (Hofacker, 1828; Sadler, 1830) is well
known, as follows : If the father be older than the mother, more boys than
girls will be born ; if the parents be of equal age, slightly more girls than
boys ; if the mother be older than the father, the probability of girls is still
greater. Since its promulgation this so-called law has received evidence both
confirmatory and contradictory of its truth. Thury in 1863 claimed that the
earlier after its liberation the egg is fertilized, the greater is the tendency to
the production of a female ; the later the fertilization, the greater the prob-
ability of a male. Breeders have made use of this principle apparently with
success — offspring conceived at the beginning of "heat" seem to be more
usually females. Likewise, it is frequently believed that in human beings
conceptions immediately after menstruation produce a larger proportion of
females than later conceptions. Diising ^ accepts Thury's view and extends it
to the male element — the younger the spermatozoon the greater the tendency
toward tlie production of males. Hence among animals the scarcity of one
sex leads to the more frequent exercise of its rejM-oductive function, the em-
ployment of younger germ-cells, and therefore the relative increase of that
sex. Further, the nearer a parent is to the height of his reproductive capacity
the less will be the probability of transmitting his own sex to the oflfspring.
By feeding tadpoles with highly nutritious flesh Yung^ increased the percent-
age of females from 56 to 92. Mrs. Treat ^ showed that the butterflies of
well-fed caterpillars become females, those of starved caterpillars males. Sta-
tistics among mammals and human beings indicate that the ])roportion of male
to female offspring varies inversely with the nutrition of the parents, especially
of the mother. Thus, more boys are born in the country than in the city,
and in poor than in prosperous families; the relative number of boys is said to
vary even with the prices of food. It is contended, moreover, and with some
statistical support, that in the human race an epidemic or a war, either of whicli
affects adversely the well-being of the peo})le, is followed by a relative increase

^ K. Diising: Jenaische Zeitschrift fiir Natunoissenschaft, xvi., 1883, and xvii., 1884.
'■' E. Yung : Comptes rendun de PAcademie des scienceK, Paris, xcii., 1881.
' Mrs. Mary Treat: The American Nataralu<l, vii., 1873.

RE PR on UCTION. 928

of male births. It is claimed that ethnic intermixture causes a decrease in the
relative number ot" males born. This is strongly supported by a recent sta-
tistical study by Ripley ' of the two races inhabiting Belgium, the Walloons,
of the same origin as the Kelts in France, and the Flemish, of German stock.
Where these races are purest, the number of boys born to 1000 girls is 1064;
along the region where the two races come into contact, however, the number
may fall as low as 1043. Maupas "^ found that sex in the rotifer, Hydaiina
senfa, could be controlled by altering the temperature of the medium surround-
ing the egg-laying females. In various experiments at a temperature of 2G°-
28° C, 81-100 per cent, of the eggs gave rise to males, the rest to females ; at
14°-15° C. only 5— 24. per cent, were males, the much larger majority females.
The above considerations are highly interesting and suggestive, but they
have not yet been brought under general laws sufficiently to make their bear-
ing upon the main problem wholly clear. It is probable that numerous
factors are of influence in the determination of sex. The general deduction
from all the facts seems justified that unfavorable nutritive conditions sur-
rounding the parents tend to the production of males, favorable conditions
to the production of females. The experimental results indicate, moreover,
that the conditions surrounding the parents or the developing embryo are
largely responsible for the resulting sex. Watase^ regards the embryo as
neutral as regards sex from the time of fertilization up to a certain stage of
its development ; external conditions act as a stimulus to the sexless proto-
plasm, and the resulting response is a development in the direction of either
raaleness or femaleness according to the nature of the stimulus. How largely
and in what manner this may be true of the human species is wholly unknown.
Diising urges that the various factors determining sex have arisen through
natural selection ; they are conducive to the continuance of the species, and
they act in such a way that sex is in a certain sense self- regulating — the
scarcity of one sex tends to the greater production of individuals of that sex ;
this is instanced by the fact mentioned above that after the destruction of
males by war relatively more males are born than previously.

E. Epochs in the Physiological Life of the Individual.

Fertilization begins, somatic death ends, the physiological life of the indi-
vidual. Between these two events the life-processes go on gradually, and,
with the exception of birth, are marked by few abrupt changes. It is some-
times convenient to divide the individual life into a number of successive
stages, as follows : the embryonic period, the fetal period, infancy, childhood,
youth, or adolescence, maturity, and old age, or senescence. Such a division,
however, is not physiologically exact, the stages are not sharply limited, and
the terms are employed in very different senses by different writers. Between
fertilization and birth the functions originate and are developed gradually.

' W. Z. Ripley : Quarterly Publications of the American Statistical Association, v., March, 1896.
^ E. Maiipas : Comptes rendus de I' Academic des sdences, Paris, cxiii., 1891.
•' S. Watase : Journal of Morphology, vi., 1892.

924 AIV AMERICAN TEXT-BOOK OF PHYSIOLOGY.

At birth tlir eiiviroiinient of the individual is abruptly oliaugcd, or<2:anic'
connection with the mother suddenly ceases, and profound pliysiological
changes occur. At this time, or shortly after it, the individual is capable
of performing all the functions of adult life with the exception of reproduc-
tion, the functions needing, however, to be exercised and improved before
they are at their best. From birth to maturity, therefore, the physiological
history is mainly a history of progressive modifications of function — modi-
fications, indeed, of great importance, but secondary to the primary fact of
function itself. The same may be said of the period of old age, with the dif-
ference that here the modifications of function are retrogressive. In the present
book, devoted mainly to the physiology of the adult at the time of maturity,
little can be said of the origin and development of function in the embryo :
the modifications of function at different periods of life have been discussed in
connection with the various functions themselves; certain topics of special physio-
logical significance have, however, been left for brief treatment in this chapter.

Growth of the Cells, the Tissues, and the Organs. — All growth,
whether of the cells, the tissues, or the organs, is the result of no more than
three processes, viz. multiplication of cells, enlargement of cells, and deposition
of intercellular substance, the first two processes being the most potent of all.
Increase in the number of cells is largely, although not wholly, an embryonic
phenomenon ; increase in the size of cells and deposition of intercellular sui)-
stance are especially important from the later embryonic period through the
time of birth and up to the cessation of the body-growth. The periods of
growth of the several tissues differ ; in view of this it is quite impossible to
designate any period except that of death at which the growth of the tissues
wholly terminates. Detailed statistics of the growth of organs are wanting.

Gro\v1;h of the Body before Birth. — The most obvious result of growth
of the cells, the tissues, and the organs, is growth or increase in size of the
body. Growth of the body continues actively from the beginning of the seg-
mentation of the ovum up to about the age of twenty-five years, and results in
an increase in all dimensions and in weight. In determining the extent of
growth, the two most convenient and most commonly used measurements are
those of length, or height, and weight. For the embryo the following table
has been compiled by Hecker : *

Table showing the Average Length and Weigld of the Human Embryo at

Different Ages.

Month. Length of embryo in centimeters. Weight of embryo in grams.

Third 4 to 9 11

Fourth 10 to 17 57

Fifth 18 to 27 284

Sixth 28 to 34 634

Seventh 35 to 38 1218

Eighth 39 to 41 1569

Ninth 42 to 44 1971

Tenth 45 to 47 2334

' C. Hecker : Monaisachrift fur Oeburtskunde vnd Frauenkrankheiten, xxvii., 1866.

REPROD UCTION.

925

Tilt' length and the weight at birtli vary very greatly. The average measure-
ments, as given for over 450 infants in Great Britain, are, for height, males
19.5 inches, females 19.3 inches; for weight, males 7.1 pounds, females, 6.9
pounds. The weight at birth is said to be greater the nearer the mother's
age is to thirty-five years, the greater the weight of the mother, the greater
the number of ])revious pregnancies, and tlic earlier the appearance of the first
menstruation. Race and climate are also of influence. Minot^ believes that all
of these influences work principally through prolonging or abbreviating the
period of gestation, and that the variations at birth depend partly upon the
duration of gestation and partly upon individual differences of the rate of
growth in the uterus.

Gro"wi;h of the Body after Birth. — In studying the growth of the body
after birth two methods have been employed, named the "generalizing" and

0 A(je. 5 10 15 20 Years. 25

140

l:iO

100

Fig. 316.— Diagram showing increase of stature and weight of both sexes, as determined by the Anthropo-
metric Committee of the British Association.'

the " individualizing " methods. The former consists in deducing the course
of growth by averages or other central values from statistics taken from a
large number of individuals at different ages. It is the method more com-
monly employed ; it shows the cour.se of growth of the typical child, but is
inexact in enabling future growth to be predicted in individual cases. The
individualizing method consists in measuring the actual growth of the same
individual through successive years ; it shows well the relation of the indi-

' C. S. Minot : Human Embryology, 1892.
^ Roberts : Manual of Anthropometry, 1878.

926 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

vicinal to the type throughout the period of" growth. The course of growth
ot" British boys and girls from birth up to the age of twenty-four is graphically
shown in the accompanying diagram (Fig. 316). Growth is here seen to be
rapid during the first five years of life, then slower up to the tenth or
the twelfth year. From thence up to the fifteenth or the seventeenth year
— that is, preceding and including puberty — marked acceleration occurs,
which in turn is followed by slow increase up to the twentieth or the
twenty-fifth year. For from five to ten years thereafter slight increase in
height occurs, while from the accumulation of fat the weight usually rises
markedly up to the fiftieth or the sixtieth year. One of the most interesting
results revealed by statistics is the relative growth of the two sexes. From
birth up to about the age of ten or twelve, boys show a slight and increasing
prej^onderance over girls, but the two curves are nearly parallel. The jirepu-
bertal acceleration of growth in girls, however, precedes that of boys, and is
even accompanied by some check in the male growth, with the result that
between the ages of twelve and fifteen girls are actually heavier and taller
than boys. This fact, first pointed out in 1872 by Bowditch ^ from observa-
tions on several thousand Boston school children, has been abundantly con-
firmed by Pagliani in Italy, Key in Sweden, Schmidt in Germany, Porter in
St. Louis, and others. At about fifteen years boys again take the lead and
maintain it throughout life. Boys grow most rapidly at sixteen, girls at thir-
teen or fourteen, years of age ; the former attain their adult stature approxi-
mately at twenty-three to twenty-five, the latter at twenty to twenty-one years.
The details of growth and the actual measurements vary considerably with
race ; thus the supremacy of the American girl over her brother appears to be
less marked and to cover a shorter period than that of the English, German,
Swedish, or Italian girl. Children of well-to-do families are superior to
others in both weight and stature. Disease may alter the form of the curve
of growth. But the final result seems to depend less upon external condi-
tions than upon race and sex. As an interesting accessor}' fact it was found
by Porter- that well-developed children take a higher rank in school than- less-
developed children of the same age. If the percentage annual increase of
the total weight be computetl, it is found to diminish throughout life, very
rapidly during the first two or three years, later more slowly and with minor
variations of increase and decrease ; that is, as growth proceeds and the powers
of the individual mature, the power to grow becomes rapidly less. This is a
peculiar and most interesting fact and has not been explained. It would seem
to signify that the sum of the vital powers declines from birth onward. Many
facts indicate that the common conception, dating from the time of Aristotle,
of human life as consisting of the three periods of rise, maturity, and decline,
must give way to a more rational idea of a steady decline from birth.

' H. P. Bowditch : Eighth Annual Report of the State Board of Health of Massachusetts, 1877.

* W. T. Porter : " The Physical Basis of Precocity and Dullness," Transactions of the Acad-
emy of Science of St. Louis, vi., No. 7, 1S93. See also "The Growth of St. Louis Children,"
Transactions of the Academy of Science of St. Louis, vi., Xo. 12, 1894.

REPR OD UCTION. 927

Puberty. — By puberty is meant tlie period of sexual maturity, at which
the individual becouies able to reproduce. In the male the exact time of its
onset, characterized primarily by the appearance of fully ripe spermatozoa, is
not well known, but is believed to be about one year later than in the female.
In temperate climates, therefore, it usually appears in boys not before the age
of fifteen ; it is earlier in warmer regions. It is preceded and accompanied by
acceleration in bodily growth, already spoken of. Other bodily changes, such
as general maturation of the functions of the reproductive organs, alterations in
the bodily proportions, increase of strength, and growth of the beard, all of which
are elements of the transformation from boyhood to manhood, either occur at
that time or follow soon after. One of the most obvious external chang-es is
that of the voice. Its tone may fall permanently an octave, and for the time being
become rough, broken, and uncontrollable. This is due to a sudden general
enlargement of the laryngeal cartilages and a lengthening of the vocal cords.

In the girl the oncoming of puberty is marked more exactly than in the
boy by the appearance of menstruation, in the majority of girls in temperate
climates at the age of fourteen to seventeen. But other characteristic anatom-
ical and physiological changes in the body occur. The uterus, the external
reproductive organs, and the breasts become larger, while the ])elvis wndens.
The prepubertal acceleration of growth has been mentioned. Nervous disor-
ders are especially prone to make their appearance at this time. The subcuta-
neous layer of adipose tissue develops and confers upon the outlines the grace-
ful curves characteristic of the woman's body. The mental faculties mature,
and the girl becomes a woman earlier and more rapidly than the boy a man.

Climacteric. — From the sixtieth year the power of producing spermato-
zoa, and, therefore, the reproductive power of man, begins to wane. It con-
tinues, however, in a diminishing degree, even to extreme old age, and there
is no recognized period of ending of the male sexual life.

In woman, on the other hand, the sexual period continues for only thirty
to thirty-five years, and the climacteric, menopause, or change of life, marks a
definite ending of the power of reproduction. In temperate climates it occurs
usually between the ages of forty-four and forty-seven ; in w^armer regions it
comes early, in colder late. It is earlier in the laboring classes, and later
where menstruation has first appeared early. Its most characteristic feature is
the cessation of menstruation, which is a gradual process extending over a
period of two or three years and characterized by irregularity in the oncoming
and the quantity of the flow and by gradual diminution. But the cessation
of the menses is but one phenomenon in a long series of changes that pro-
foundly affect the w^hole organism and endanger life. The reproductive organs
and the breasts diminish in size, and ovulation ceases. The changes in the
pelvic organs are in general the reverse of those occurring at puberty. The
organic functions generally are rendered irregular ; dyspepsia, palpitation,
sweating, and vasomotor changes are frequent ; vertigo, neuralgia, rheuma-
tism, and gout are not rare; a tendency to obesity occurs, though sometimes
the reverse ; irritability, fear, hysteria, and melancholia may be present ; the

Nucleoli observ-

Pigment

Pigment

able in nuclei.

much.

little.

in 53 per cent.

in 5

67 per cent.

33 per cent.

928 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

disposition may be temporarily altered, — all of which changes indicate that
the female organism at this time suffers a profound nervous shock. The loss
of the weighty fimction of reproduction and the adaptation to the new order
of events is not accoinplisheil (piietly.

Senescence. — The progressive diminution in the power of growth from
birth onward throughout life has been mentioned, and may be interpreted as
indicating that the process of senescence begins with the beginning of life.'
Jn the broadest sense this is true, and is confirmed by a study of various
organic functions. In the more restricted sense senescence or old age com-
prises the period from about fifty years (in woman from the climacteric)
onward, during which there is a noticeable progressive waning of the vital
powers. The leading somatic changes accompanying old age are atrophic and
degenerative, but detailed statistics of this period arc almost wholly wanting.
A marked cellular difference between the young and the old, which is shown
by nearly if not (piitc all tissues, is the relatively large nucleus and small
quantity of cytoplasm in the young, the proportions being reversed in the old.
This has recently been pointed out as follows by Hodge ^ in the nerve-cells of
the first cervical spinal ganglion :

Volume of
nucleus.

Fetus (iit birtli) 100 per cent.

Old man (at ninety-two years) 64.2 "

Thus with the progress of age the nuclei become small and irregular in out-
line, and the cytoplasm pigmented, while the nucleoli are often wanting. The
nuclear differences are even more marked in the cerebral ganglia of bees, where,
moreover, aged individuals possess a smaller number of nervc-cclls than the
young. They are in harmony with the growing belief in the function of the
nucleus as the formative centre of the cell. It has been shown that a decrease
in the weight of the whole brain occurs in both men and women, beginning in
the former at about fifty-five years, in the latter at about forty-five years. In
eminent men the decrease begins later. The thickness of the cortex and the
number of tangential fibres in it diminish especially after fifty years, and this
probably signifies a loss of cells. There is a decrease in general brain-power,
in power of origination, in the power to map out new paths of conduction and
association in the central nervous system and thus to form habits. Reaction-
time is lengthened. The delicacy of the sense-organs is noticeably less, and in
the eye the hardening of the crystalline lens and the weakening of the ciliary
muscle diminish the power of accommodation. The muscles atrophy and mus-
cular .strength is reduced. The pineal gland, ligaments, tendons, cartilage, and
the walls of the arteries, show a tendency toward calcification, and the bones
become more brittle. Subcutaneous adipose tissue disappears, but a fatty de-
generation of cells is not uncommon, notably in all varieties of muscle-cells,
in nerve-cells, and probably in gland-cells. The pigment of the hairs disap-

* Cy. C. S. Minot: Journal of Physiology, xii., 1891.

"•C- F. Hodge: AruUomischer Anzeiger, ix., 1894; Journal of Physiology, xvii., 1894.

REPRODUCTION. 929

pears. The size of the muscles, the liver, tlie spleen, the Ij'^mphatic and prob-
ably the (lijjjestive glands, decreases. The heart and the kidneys seem to retain
their adult size. The vital capacity of the lungs, the amounts of carbonic acid
and of urine excreted, diminish. The rate of respiration and of the heart-beat
rises slightly. Ovulation is wanting, and the power of producing spermatozoa
is lessened. The stature undergoes a slight and steady decrease. Boas ' has
shown that in the North American Indian this continues from about thirty
years of age onward. All of these changes, the details of which should be care-
fully studied and reduced to anatomical and physiological exactness, demonstrate
that senescence is characterized by a steady diminution of vitality.

Death. — Sooner or later vitality must cease and the change that is called
death must come. The term " death " is used in two senses, according as it is
applied to the whole organism or to the individual tissues of which the organ-
ism is composed. The former is distinguished as somatic death, or death
simply, the latter as the death of the tissues.

Somatic death occurs when one or more of the organic functions is so dis-
turbed that the harmonious exercise of all the functions becomes impossible.
Thus, if the brain receives a severe concussion, the co-ordination of the organs
may be interrupted ; if the respiration ceases, the necessary oxygen is withheld ;
if the heart fails, the distribution of oxygen and food and the collection of
wastes come to an end ; if the kidneys are diseased, the poisonous urea is
retained within the tissues. A continuation of any one of these profound
abnormal conditions, which may be brought about by accident or disease, or a
simultaneous occurrence of several slight disturbances of function, such as is
not infrequent in aged persons, may prevent the restoration of that concordance
among the organs Avithout which the individual cannot live. The most con-
venient and most certain sign by which somatic death may be recognized is the
absence of the beat of the heart, and in nearly all cases this is the criterion
employed. But it should be borne in mind that the failure of the heart to
beat is but one of the causes, and frequently a very secondary one, the primary
cause being then associated with other functions, It is at present in most cases
quite impossible to trace the course of events by which the derangement of one
function leads to the ultimate cessation of individual life.

Death of the tissues or of the living substance is neither necessarily nor
usually simultaneous with somatic death. Constantly throughout life the mole-
cules of living matter are being disintegrated, and whole cells die and are cast
away ; life and death are concomitants. With the cessation of the individual
life the nervous system dies almost immediately. "With the muscular tissue it
is very diiferent. The stopping of the beat of the heart is a gradual process,
and, as Harvey long ago pointed out, the last portion to beat, the ultimum
moi'iens, is the right auricle. For many minutes after death the heart, if
exposed, will be found to be excitable and to respond by single contractions to
single stimuli. Irritability is said to continue in the smooth muscle of the
stomach and the intestines for forty-five minutes, and considerably later than

' F. Boas : Verhandlungen der Berliner Anthropologischen Gesellschaft, 1895.
59

930 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

this the striated muscles of the limbs can be made to twitch by proper stimuli.
Gland-cells probably die within a few minutes. As to the chemical changes
undergone by the protoplasm in the process of dying, little can be said. The
composition of dead protoplasm is comparatively well known, that of living
protoplasm is at present a blank ; and, although investigation has gone suf-
ficiontly far to offer a basis for several suggestive hypotheses, the latter are too
abstru.se for lucid discussion in the present space. Neither in somatic death
nor in the death of the tissues does the body lose weight. Within fifteen or
twenty hours it cools to the temperature of the surrounding medium. Rigor
mortis, due to the coagulation of the muscle-plasma within the muscle-cells,
begins within a time varying with the cause of death from a half hour to
twenty or thirty hours, and continues upon an average twenty-four to thirty-
six hours. Then the tissues soften, and soon putrefactive changes begin.

Theory of Death. — It has been intimated that all the tissues are destined
to die. An exception must be made in the case of those germ-cells, both male
and female, that arc employed in the production of new individuals. They
pass from one individual, the parent, to another, the offspring, and thus cannot
be said to undergo death. This .is the basis of Weismann's theory of the
orioin and sis>;nificance of death in the organic world.* Accordino- to Weis-
mann, primitive protoplasm was not endowed with the property of death.
As found in the simplest individuals, like the Amoeba, even at the present
day, Avith a continuance of the proper nutritive conditions protoplasm does not
grow old and die; the single individual divides into two and life continues
unceasing, unless accident or other untoward event interferes. With the
progress of evolution, however, the cells of the individual body have become
differentiated into germ-cells and somatic cells, the former subserving the
reproduction of the species, the latter all the other bodily functions. Germ-
cells are passed on from parent to offspring ; they never die, they are immor-
tal. Somatic cells, on the other hand, grow old, and at last perish. Death
was, therefore, in the beginning, not a necessary adjunct to life ; it is not inhe-
rent in primitive protoplasm, but has been acquired along with the differen-
tiation of protoplasm into germ-plasm and somatoplasm, and the introduction
of a sexual method of reproduction. It has been acquired because it is to the
advantage of the species to possess it ; in the simplest cases it should occur at
the close of the reproductive period, and in fact it frequently does occur then.
A superabundance of aged individuals, after they have ceased to be reproduc-
tive, would be detrimental to the race ; it is to the advantage of the species that
they be put out of the way. Death of the individual in order that the species
may survive has, therefore, become an established principle of nature. The
higher animals are better able to protect themselves from destruction than the
lower, and, moreover, they are needed to rear the young ; hence the duration
of life is frequently prolonged beyond the reproductive period.

Weismann's theory has been the cause of much discussion, and the pros
and cons have been set forth by eminent biological authorities. In its appli-
^ A. Weismann : Essays upon Heredity, i., 1889.

REPRODUCTION. 931

cation to the human race it would seem that the factors of social evolution
have brought it about that the aged are protected in the struggle for existence
for k)ni>- after their reproductive usefulness has ceased, and thus the working
of a pitiless biological law has become modified.

F. Heredity.

Biologists are accustomed to recognize two factors as responsible for the
character and actions of the living organism. These are heredity and the
environment. Heredity includes whatever is transmitted, either as actual or
as potential characteristics, by parents to offspring. The environment com-
prises both material and immaterial components, such as food, water, air, or
other substances that surround the organism, and the forces of nature, such as
light, heat, electricity, and gravity, that act as conditions of existence or as
sthnuli to action. The same principles apply to the character and actions of
every cell of a many-celled organism, but here we must include in the envi-
ronniental factor the mysterious influences that are exerted upon the cell by
the other cells of the body. Of these two factors heredity acts from within,
the environment from without the living 'substance. Among unicellular or-
ganisms the individual begins its career when the bit of protoplasm that con-
stitutes its body is separated from the parent bit of protoplasm. Among
hio-her forms, including man, the terra individual may be applied to the fer-
tilized ovum ; the union of the ovum and the spermatozoon inaugurates the
new being. From the inception to the death of the individual, life consists
partly of manifestations of the powers conferred by the germ-cells and partly
of reactions to environmental influences. In considering the details of vital
action we are apt to overlook these fundamental facts and to evolve narrow
and erroneous views as to the causes of vital phenomena. Biologists are
seeking with increasing vigor to determine the relative importance of the parts
played by these two principles in development and in daily life. It is need-
less to say that the problem is a difficult one and is still far from solution.
In previous chapters of this book attention has been directed more especially
to the external than to the hereditary factor. A work upon physiology would
be incomplete, however, if it did not include an examination of the latter,
especially since at the present time heredity is one of the leading subjects of
biological research and discussion. It is proposed, therefore, in this section
to present a brief outline of the focts, the principles, and the attempted ex-
planations of the modes of working of heredity. It should be premised that,
because of the present incomplete state of our knowledge of the facts, the
highly speculative and involved character of most of the theories, and the con-
stant, active shifting of ideas and points of view, such an outline must neces-
sarily be incomplete and in many respects unsatisfactory.

Facts of Inheritance.— It is not proposed in this paragraph to enter into
a discussion of the question as to whether a particular vital phenomenon is a
fact of inheritance or a reaction to external influences. For our present pur-
poses it is sufficient to record the common facts of resemblance to ancestors,

932 J^V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

and tu u.s.sume that such re.semblaiRv, when present, has been inherited.
Resemblances are strongest between child and parents, and appear in a dimin-
ishing ratio backward aloiii; the ancestral line. Galton ' has comijiited that,
of the total heritage t)t' the child, each of the two parents contributes one-
fourth, each of the four grandparents one-sixteenth, and the remaining one-
fourth is handed down by more remote ancestors. The correctness of this
estimate has been disputed by Weismann. The fact must not be overhjoked
that, in addition to and back ol' all the particular individual features that are
inherited, a host of racial characteristics are transmitted — the progeny of a
given species belongs to that species; the human being is the father of the
human child, the child of Caucasian parents is a Caucasian, of negro parents
a negro.

Congenital resemblances may be anatomical, physiological, or psychological,
and in each of these classes they may be normal or pathological. Anatomical
resemblances are the most commonly recognized of all : facial features, stature,
color of eyes and of hair, sujiernumerary digits, excessive hairiness of body,
cleft palate, monstrosities, and various defects of the eye, such as tho.se that
give rise to hypermetropia, myopia, cataract, color-blindness, and strabismus,
are all known examples. Physiological peculiarities that may be transmitted
include the tendency to characteristic gestures, locomotion and other muscular
movements, longevity or short life, tendency to thinness or obesity, handwriting,
voice, hsematophilia or tendency to profuse hemorrhage from slight wounds,
gout, epilepsv, and asthma. Psychological inheritances comprise habits of
mind, talent, artistic and moral qualities, tastes, traits of character, tempera-
ment, ambition, insanity and other mental diseases, and tendencies to crime
and to suicide.

Latent Characters ; Reversion. — Characters that never apjiear in the parent
mav yet be transmitted through him from grandparent to child ; such charac-
ters are called latent. Among the most striking latent characters are those con-
nected with sex. Darwin ^ says : " In every female all the secondary male
characters, and in every male all the secondary female charactei-s, apparently
exist in a latent state, ready to be evolved under certain conditions." Thus, a
girl may inherit female secondary sexual peculiarities of her paternal grand-
mother that are latent in her father, or a boy may inherit from his maternal
grandfather characteristics that never show in his mother. An excellent
example of such transmission, taken from the herbivora, is the common one
of a bull conveying to his female descendants the good milking qualities of
his female ancestors. In the human species hydrocele, necessarily a disease of
the male, has been known to be inherited from the maternal grandfather, and
hence must have been latent in the mother's organism. That in such cases the
character is really potential, though latent in the intermediate ancestor, is
rendered probable by such well-known facts as the appearance of female cha-

' Francis Galton : Xatund Inheritnnce, 1889, p. 134.

- Charles Darwin: The Variation of Animals and Plants under Domeaticntinn, vol. ii.. 2<\ ed.,
1892.

BEPR OD UCriON. 9-^^

rac'teristics in castrated niaks, tiiul of inalo clmractoristics in females with dis-
eased ovaries or after the end of the normal sexual life.

Latency may be offered as the explanation of the numerous eases of
atavism, or reversion, by whieh is meant the appearance in an individual of
peculiarities that were formerly known only in the grandparents or more
remote ancestors, but not in the parents of the individual. This subject is one
of the most important in the whole field of heredity. Almost any character
may reappear even after many generations. In the human species stronger
likeness to grandparents than to parents is a frequent occurrence. The
majority of the frequent anomalies of the dissecting-room arc regarded as
reversions toward the simian ancestors of the human race. The crossing of
two strains develops a strong tendency to reversion, and because of this the prin-
ciple of atavism must constantly be taken into account by breeders of animals
and o-rowers of plants. As an example of reversion after crossing may be
mentioned the well-known one, studied by Darwin, of the frequent appear-
ance of marked stripes upon the legs of the .mule, the mule being a hybrid
from the horse and the ass, both of which are comparatively unstriped but
are undoubtedly descended from a striped zebra-like ancestor. Here the
capacitv of developing stripes is regarded as latent in both the horse and the
ass, but as made evident in the mule by the mysterious influence of crossing.
Darwin thinks likewise that the customary degraded state of half-castes may
be due to reversion to a primitive savage condition which, usually latent in
both civilized and savage races, is rendered manifest in the offspring that
results from the union of the two. Reversionary characters are often more
prominent during youth than during later life — a fact that has been quoted in
favor of their explanation on the theory of latency.

Regeneration. — The facts of regeneration of lost parts must also be taken
into account in a theory of heredity. Such regeneration may be either physi-
ological or pathological. Physiological or normal regeneration has reference
to the reproduction of parts that takes place during the normal life of the
individual, such as the constant growth of the deeper layers of the epidermis
to replace the outer layers that are as constantly being shed. Pathological
regeneration refers to the replacement of parts lost by accident, and presents
the more interesting and striking examples. The power of pathological
regeneration in man and the higher mammals is limited. A denuded surface
raav be re-covered with epitliclium ; the central end of a cut nerve may grow
anew to its termination ; the parts of a broken bone may reunite ; muscle may
reappear ; connective-tissue, blood-corpuscles, and blood-vessels may develop
readilv ; and in the healing of every wound a regeneration of parts takes
place. But in descending the scale of animal life the regenerative power
becomes progressively stronger, and in many plants and low animals it is
marvellous. Thus, the newt may replace a lost leg, the crab a lost claw, the
snail an eyestalk and eye. If an earth-worm be cut in two, one half may
regenerate a new half, complete in all respects. A hydra may be chopped
into fragments and each fragment may re-grow into a complete hydra. From

934 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

a small piece of the leaf of a begonia, planted in moist earth, a new plant
with all its parts may arise. It is evident that the existing parts of an organ-
ism, if not too specialized, possess the power of restoring parts that are lost ;
nnder ordinary circnmstances this power is latent. The growth of tumors is
perhaps allied in nature to regeneration. A study of regeneration shows that
in many cases the process of building anew follows the same course as the
original embryonic growth. It is properly a phenomenon of heredity.

The Inheritance of Acquired Characters. — No topic in heredity has been
more debated during the past fifteen years than that of the possibility of the
transmission to the offspring of characteristics that are acquired by the parents
previous to the discharge of the germ-cells, or, in the case of the mammalian
female, previous to parturition. Obviously, no one denies this possibility in
the unicellular organisms, where reproduction by fission prevails, for there the
protoplasm of the body of one parent becomes the substance of two offspring ;
in the transformation nothing is lost, and hence whatever peculiarities the ances-
tral protoplasm has acquired are transferred bodily to the descendants. But
in multicellular forms, where sexual reproduction exists, the case is very dif-
ferent, for here whatever is transmitted is transmitted through germinal cells,
or germ-plami, as the hereditary substance contained in the germ-cells is now
commonly called. The problem then resolves itself into that of the relation
of the germ-plasm to the protoplasm of the rest of the body, the so-called
somatoplasm; and the question to be answered is this: Are variations in the
parental somatoplasm capable of inducing such changes in the germ-plasm that
somatic peculiarities appear in the offspring similar to those possessed by the
parent? Weismann classifies all somatic variations according to their origin
into three groups — viz. injuries, functional variations, and variations, mainly
climatic, that depend upon the environment. The problem of their inherit-
ance is a far-reaching one, and upon its correct solution depend principles that
are of much wider application than simply to matters of heredity ; for if
acquired characters can be inherited, there is revealed to us a most potent fac-
tor in the transformation of species, and the whole question of the possibility
of use and disuse as factors of evolution is presented. The larger evolutionary
problem need not here be considered.

Regarding the problem of the inheritance of acquired characteristics we may
say at once that it is not yet solved. To the lay mind this may seem strange,
for at first thought it appears self-evident that parents may transmit to their
children peculiarities that they themselves have acquired. Affirmative evidence
seems all about us, as witness the undoubted cases of inheritance of artistic
tastes, of talent, of traits valual)le in professional life, which seem to originate
in the industry of the parent. But scientific analysis by Weismann and others
of popular impressions, popular anecdotes, and hearsay evidence, and accurate
original observation have revealed little that cannot as well be explained on
other hypotheses. Anatomical and functional peculiarities of the body that are
apparently new often reappear in successive generations, but to assume that
they are acquired by the somatoplasm and have become congenital, rather than

REPRODUCTION. 935

that they are geriuiiuil Iroin the; fast, is unwarranted. Direct experiments by
various investigators are ahnost as inconclusive. Weismann ' has removed the
tails of white mice for five successive generations, and yet of 901 young every
individual was born with a tail normal in length and in other respects. Bos^
has experimented similarly upon rats for ten generations without observing any
diminution of the tails. The practice of circumcision for centuries has resulted
in no reduction of the prepuce. The binding of the feet of Chinese girls has
not resulted in any congenital malformation of the Chinese foot. Brown-
S6quard,^ and later Obersteiner/ have artificially produced epilepsy in guinea-
pigs by various operations upon the central nervous system and the peripheral
nerves, and the offspring of such parents have been epileptic. At first this
would seem to amount to proof of the actual hereditary transmission of mutila-
tions, yet in these cases the mutilation itself was not transmitted ; the offspring
were weak and sickly and exhibited a variety of abnormal nervous and nutri-
tional symptoms, among which was a tendency toward epileptiform convulsions,
the cause of which is still to be explained. Evidence from palaeontology
regarding the apparent gradual accumulation of the effects of use and disuse
throughout a long-continued animal series seems to require the assumption of
such a principle as the inheritance of acquired characters, but even here the
principle of natural selection may perhaps be equally explanatory.

The Inheritance of Diseases. — The question of the inheritance of diseases
has also been much discussed. The same general principles apply here as in
the inheritance of normal characteristics. The fact has been mentioned above
that pathological characters, whether anatomical, physiological, or psycholog-
ical, are capable of transmission. If, however, a pathological character has
been acquired by the parent and is not inherent in his own germ-cells, it
is extremely doubtful whether it can be passed on to the child. A diseased
parent, on the other hand, may produce offspring that are constitutionally
weak or that are even predisposed toward the parental disease, and such off"-
spring may develop the parent's ailment. In such cases constitutional weakness
or predisposition, and not actual disease, is inherited ; the disease itself later
attacks the weak or predisposed body. Proneness to mildness or severity of,
and immunity toward, certain diseases seem to be transmissible. These sub-
jects, however, are so little understood, and the real meaning of such terms as
predisposition, inherited constitutional weakness, and inherited immunity, is so
little known, that it is idle to discuss them here.

Considerable experimental work has been performed recently upon the
transmissibility of infectious diseases. Undoubtedly infectious diseases cling
to a particular family for generations. The transmitted factor is probably fre-
quently, if not usually, simple predisposition. But in an increasing number
of cases there appears to be transmission of a specific micro-organism. Such

* A. Weismann : Essays upon Heredity, vol. i., 1889, p. 432.
^ .J. E. Bos : Biologisches Ceniralblatt, xi., 1891, p. 734.

' E. Brown-S^quard : Researches on Epilepsy, etc., Boston, 1857 ; also various later papers.

* H. Obersteiner : Medizinische Jahrbikher, Wien, 1875, p. 179.

936 .l.V AMERICAN TEXT- HOOK OF PllYSIOLOGY.

transmission is called germbud when the niiero-organisui is conveyed in the
ovum or the semen, and placental or intra-uterine when the micro-organism
reaches the fetns after nterinc development has begnn, and chieHy throngh the
circulation. Of germinal infections syphilis seems undoubtedly caj)able of
transmission within either the ovum or the semen. The possibility of germinal
transmission of tuberculosis has been maintained, but is not fully proven. Of
intni-nterine infections there have been observed in human beings apj)arently
undoubted cases of typhoid fever, relapsing fever, scarlatina, small-pox,
measles, croupous pneumonia, anthrax, and possibly tuberculosis, syphilis, and
Asiatic cholera. It is obvious that neither germinal nor placental iidieritance,
both taking place through the medium of a specific mi(;rt)-organism, and not
through the modification of germ-plasm, is comparable to inheritance in the
customary sense.

Theories of Inheritance. — From early historical times theories of inher-
itance have iiot been wanting. Physical and metaphysical, materialistic and
spiritualistic theories have had their day. Previous to the discovery of the
spermatozoon (Hamm, Leeuwenhoek, 1677) all theories were necessarily
fantastic, and for nearly two hundred years later they were crude. The
theories that are now rife may be said to date from 1864, when Herbert
Spencer published his Principles of Biology. Since that date they have
become numerous. Even the modern theories are highly speculative ; none
can be regarded as being accepted to the exclusion of all others by a large
majority of scientific workers, and the excuse for introducing them into a
text-book of physiology is the hope that a brief discussion of them may jjrove
suggestive, stimuhiting, and productive of investigation.

Germ-plasm. — Germinal substance, germ-plasm (Weismann), or, as it is
sometimes called, idioplasm (Nageli), must lie at the basis of all scientific
theories of heredity. The father and the mother contribute to the child the
spermatozoon and the ovum respectively, and within these two bits of proto-
plasm there must be contained potentially the qualities of the two parents.
There is much evidence in favor of the prevailing view that the nucleus alone
of each germ-cell is essentially hereditary, or, more exactly, that the chromatic
substance of the nucleus is the sole actual germinal substance. We have seen
that the tail of the spermatozoon is a locomotive organ, and that the body of
the ovum is nutritive matter. We have seen also that the essence of the
whole process of fertilization is a fusion of the male and the female nuclei, or,
more exactlv, a mingling of male and female chromosomes. Hence most
physiologists agree with Stra,sburger and Hertwig that the chromatic substance
of the nuclei of the germ-cells transmits the hereditary qualities.

As to the origin of the germ-plasm, two hypotheses have been suggested.
Spencer, Darwin, Galton, and Brooks have argued in favor of a production
of germ-plasm within each individual by a collocation within the reproductive
organs of minute elementary vital particles — " physiological units " (Spencer),
"gemmules" (Darwin) — that come from all parts of the body; hence each
part of the body has its representative within every germ-cell. This hypothesis

REPRODUCTION. 937

affords a rciuly ox})laiuiti()n of miiiRToiis facts, but its highly speculative cha-
racter, the entire absence of direct observational or experimental ])roof of its
tnitli, and the demand that its conception makes upon human credulity, mili-
tate against its general acceptance. Weisnaann, the j)romulgator of the second
hypothesis, denies altogether tlie formation of the germ-plasm from the body-
tissues of the individual, and maintains its sole origin from the germ-plasm of
the parent of the individual. Through the ])arent it comes from the grand-
parent, thence from the great-grandparent, and so may be traced backward
through families and tribes and races to its origin in simple unicellular
oro-anisms. According to Weismann, therefore, germ-plasm is very ancient
and is directly continuous from one individual to another; the parts of an
individual body are derivatives of it, but they do not return to it tlieir rei)re-
sentatives in the form of minute particles. The general truth of Weismann's
conception can hardly be denied.

As to the morphological nature of germ-plasm, two views likewise are held.
One school, led by His and Weismann, holds that germ-plasm ])ossesses a
complicated architecture; that the fertilized ovum contains within its structure
the rudiments or primary constituents of the various cells, tissues, and organs
of which the body is destined to be composed ; and that growth is a develop-
ment of these already existing germs and largely independent of surrounding
influences. In accordance with this idea, segmentation of the ovum is specifi-
<3allv a qualitative process, one blastomere representing one portion of the
future adult, another blastomere another portion, and so on. This theory
recalls in a refined form the crude theory of Preformation that was advocated
during the seventeenth and eighteenth centuries by Haller, Botmet, and many
others, according to which the germ-cell was believed to contain a minute but
perfectly formed model of the adult, which needed only to be enlarged and
unfolded in growth. The other modern school, in which Oscar Hertwig is
prominent, maintains that the fertilized e^g is isotropous — that is, that one
part is essentially like another part — that the architecture of the egg is rela-
tively simple, and that growth is largely a reaction of the living substance to
external influences. The idea of isotropy is based largely upon the experi-
mental results of Pfluger, Chabry, Driesch, Wilson, Boveri, and the brotliers
Hertwig, who by various methods and in various animals have found that
single blastomeres of a segmenting ovum, when separated from the others, will
develop into normal but dwarfed larvse ; that is, a portion of the original germ-
plasm is capable of giving rise to all parts of the animal. These results are
interpreted to signify that segmentation, instead of being qualitative, is quanti-
tative, each blastomere being like all the others. The second theory, like the
first, resembles in some degree a theory of the past two centuries, advocated
by Wolff and Harvey, and known as the theory of Epigenesis. According to
this there was no preformation in the germ-cells, but rather a lack of organi-
zation which during growth, under guidance of a mysterious power supposed
to be resident in the living substance, gave place to differentiation and the
appearance of definite parts.

938 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Modern microscopes have revealed no miniature of the adult in the egg,
nor has modern physiology found necessary an assumption of extra-physical
forces within living matter. With the increase of knowledge the old and
crude preformation of Haller and Bonnet and the speculative epigenesis of
"Wolff and Harvey have given ])lace to the new preformation and epigenesis
of the present time, and all modern theories of heredity may be classed in
the one or the other category or as intermediate between them. The mod-
ern advocates of preformation explain hereditary resemblance by the supposed
similarity of all germ-plasm in any one line of descent. The modern advocates
of epigenesis, while allowing the necessity of a material basis of germ-plasm,
ascribe hereditary resemblance to similarity of environment during develop-
ment.

Variation. — It is a commonplace in observation that, however close hereditary
resemblance may be, it is never absolute ; the child is never the exact image
of the parent either physically or mentally. Variations from the parental type
may be either acquired by the offspring subsequent to fertilization or to birth,
and hence are to be traced to the action of the environment ; or they may be
congenital, that is, inherent in the germ-plasm. Although it is not always
easy in the case of any one variation to determine to which class it belongs,
yet the fact remains that the two classes exist ; and a complete theory of
heredity must recognize and explain congenital variation as fully as congenital
resemblance. It is unnecessary to say that the origin of congenital variation
is one of the much discussed and still unsettled questions. At least two causes
of congenital variations are commonly recognized, although opinions differ as
to the relative importance of the role played by each. These causes are differ-
ences in the nutrition of the germ-plasm, and sexual reproduction. As to the
former, it is evident that the germ-plasm in no tAvo individuals, even father
and son, has exactly identical nutritional opportunities. Since the life of one
individual is not the exact counterpart of the life of another, the germ-plasm
of one individual has a different nutrition from that of another. It would
hence be strange, even although we regard the germ-plasm as relatively stable,
if with succeeding generations there did not appear variations that are sufficient
to give rise to unlikeness in relatives. Differences in the nutrition of the germ-
plasm in different individuals are, therefore, a true cause of variations. As
regards sexual reproduction, it must be remembered that a new individual is
the product of two individuals, that the two individuals have descended along
different genealogical lines, and hence that the two conjugating masses of germ-
plasm are different in nature. It is only to be expected, therefore, that the
resulting individual shall be different from the two contributing parents. Thus
sexual reproduction is a true cause of variations.

Having outlined the main facts and principles of heredity, let us now review
a few of the specific theories that have been of value in clearing the clouded
atmosphere.

Darwin's Theory of Pangenesis. — Darwin's " Provisional Hypothesis of
Pangenesis" was published in 1868 as chapter xxvii. of his work on The Vari-

REPRODUCTION. 939

ations of Animals and Plants under Domestication. It was the first of the
modern theories to attempt to cover the whole ground of heredity ; it was
accompanied by a most exhaustive presentation and analysis of facts, and it
stimulated abundant discussion and investij^ation. In Darwin's own words
the hypothesis was formulated as follows : " It is universally admitted that the
cells or units of the body increase by cell-division or proliferation, retaining
the same nature, and that they ultimately become converted into the various
tissues and substances of the body. But besides this means of increase I assume
that the units [cells] throw off minute granules which are dispersed throughout
the whole system ; that these, when supplied with proper nutriment, multiply
by self-division, and are ultimately developed into units like those from which
they were originally derived. These granules may be called gemmules. They
are collected from all parts of the system to constitute the sexual elements, and
their developnient in the next generation forms a new being ; but they are
likewise capable of transmission in a dormant state to future generations, and
may then be developed. Their development depends on their union with other
partially developed or nascent cells which precede them in the regular course

of growth Gemmules are supposed to be thrown off by every unit,

not only during the adult state, but during each stage of development of
every organism ; but not necessarily during the continued existence of the
same unit. Lastly, I assume that the gemmules in their dormant state have a
mutual affinity for each other, leading to their aggregation into buds or into
the sexual elements. Hence, it is not the reproductive organs or buds which
generate new organisms, but the units of which each individual is composed.
These assumptions constitute the provisional hypothesis which I have called
Pangenesis."

Since the cells of the body are represented by gemmules within the germ-
cells, Darwin's theory is a theory of Preformation. It explains the facts of
the regeneration of lost parts by the assumption that the gemmules of the part
in question are disseminated throughout the body and have only to unite with
the nascent cells at the point of new growth. Pangenesis explains reversion,
since gemmules may lie dormant in one generation and develop in the next.
It explains congenital variation, since the mixture of maternal and paternal
gemmules is plainly different from the two kinds taken separately. It explains
how acquired variations may become congenital, since an altered part throws
off altered gemmules, and by the collocation of these in the germ-cells the
alteration may be transmitted. It thus allows the transmission of acquired
characters.

Darwin's assumptions of gemmules and their behavior are pure assump-
tions, for which subsequent investigation has not provided a basis of facts.
As we have seen, also, the inheritance of acquired characters is greatly in
doubt, and, if they are heritable at all, they can be so only comparatively
feebly. Besides these objections it was early found that, w'ith the increase
of knowledge of the facts of heredity, it was necessary to modify very mate-
rially the theory of Pangenesis. This has been ably done successively by

940 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

G:ilt(»n,' Brooks,^ and de Vrios.^ But neither the ()ri<;iiial theory nor its
nioditiciitions have been generally aceej)ted.

Weismann's Theory. — Since 1880, Professor Weismann*of Freiburg has
published numerous essays upon heredity and allied subjects, in which, besides
reviewing the views of others, he has developed in detail a new and elaborate
theory of his own, that is the most ambitious attempt yet made to solve the
problem of inheritance. In the course of their development Wcismann's
ideas have undergone some modification. Their leading features are as
follows :

The essential hereditary substance, or germ-plasm, is the chromatin of the
luicleus of the germ-cells. One of the fundamental tenets of Wcismann's
system is expressed by his own phrase, "the continuity of germ-plasm." By
this is meant that the germ-plasm of one individual, instead of arising de novo
in the individual by the collocation of multitudinous "gcmmules" derived
from the body-cells, originates directly from the germ-plasm of the parent,
thence from that of the grandparent, and so oji backward through all genera-
tions to the origin of all germ-])lasms that took place simultaneously with the
origin of sex — germ-plasm is continuous from individual to individual along
any one line of descent. Weismann draws u sharp line between germ-plasm
and Hoiiiatoplasm, or body-plasm, which latter comprises all protoplasm that
the body contains except the germ-plasm. Germ-plasm once originated con-
tinues from generation to generation ; somatoplasm develops anew in each gen-
eration from germ-plasm by growth and differentiation, resulting in a loss of its
specific germinal character. Germ-plasm is stable in composition ; somatoplasm
is variable. Germ-plasm, being passed on from parent to offspring, is immortal ;
somatoplasm dies when the individual dies. Weismann believes that "the
germ-plasm ]iossesses a fixed architecture, which has been transmitted histori-
callv " and which represents the parts of the future organism. It consists of
material particles or hereditary units called determinants, each of which has a
definite localized position within the germ-plasm. The determinants are sug-
gestive of Darwin's gemmules, yet they arc not the same, for, while gcmmules
were supposed to represent individual cells, determinants are representatives
of cells or groups of cells that are variable from the germ onward. Deter-
minants consist of definite combinations of simpler units, or biophors, which
are the smallest particles that can exhibit vital phenomena. Below biophors
there come in order of simplicity of material structure the molecules and
the atoms of the physicist. Above biophors and determinants Weismann
finds it necessary to assume the existence of higher units, named in order ?V/.s'
and idants, the former being groups of determinants, and actually visible as
granules of chromatin, the latter being the chromosomes of the nucleus. Each

' Francis (xalton: "A Theory of Heredity," Journal of the Anthropological Inxtttiite, 1875.

2 W. K. Brooks: Tlie X«w'« of Heredity, 1883.

' H. de Vries: Die Intro celluldre Pangenesis, 1889.

* August Weismann: Essays upon Heredity and Kindred Biological Problems, authorized
translation, vol. i., 1889; vol. ii., 1892; The Germ-plasm, authorized translation, 1893; Tlie
Effect of External Influences upon Development, the Konianes Lecture, 1894.

REPRODUCTION. 941

one of these various units is possessed of the fundamental vital properties of
growth and uuiltiplieation by division. Such a complex system is Preforma-
tion in an extreme form. In fertilization idants of the sperm join with idauts
of the ovum, and the resulting segmentation nucleus consists of a mixture of
paternal and maternal determinants. Within this mixture there exist in a
potential state the primary constituents of a considerable number of forms
wiiich the future individual may assume. In ontogeny, or development of
the individual, these primary constituents take two paths: some of the ids
remain inactive and enter the germ-cells of the embryo for the production of
future generations ; otiier ids disintegrate into determinants, the determinants
enter the embryonic cells that result from segmentation, and there themselves
disintegrate and set free into the cytoplasm their constituent biophors ; thus
they determine the future character of the cells of the organism. Tiie division
of primary constituents into those that shall remain latent and those tliat siiall
become active is effected largely by the stimulation of external influences ;
hence, given several potential formations in the germ, external influences
decide which one shall become the actual structure in the adult organism.
Once set free and having become somatoplasm, neither the biophors nor the
determinants are able to return to the germ-cells. In the adult, germ-plasm is
never capable of reflecting in any way the characteristics of the somatoplasm
which surrounds it on all sides. With its ancient ancestry it leads a charmed
existence, largely independent of environmental changes. It follows that
characters acquired by the adult are incapable of acquisition by the germ-
plasm, and hence may not be transmitted. The non-inhet^itance of acquived
characters is thus another of the fundamental tenets of Weismann's theory,
and one about which he is most positive.

If these two principles of continuity of stable germ-plasm and non-inheri-
tance of acquired characters be true, why are not all individuals in any one
line of descent exactly like each other? Ho\v is congenital variation possible?
In the first place, Weismann allows that germ-plasm, while eminently stable,
is not absolutely so ; it is subject to slight continual changes of composition
resulting from inequalities in nutrition ; and " these very minute fluctuations,
which are imperceptible to us, are the primary cause of the greater deviations
in the determinants which we finally observe in the form of individual varia-
tions." The accumulation of minute deviations may be aided greatly by sex-
ual reproduction, or, to use Weismann's more exact term, which is equally
applicable to the combination of sexual elements in sexual organisms and to
the process of conjugation in the asexual forms, amphimixis. Given the in-
finitesimal beginning of a variation, the mingling of two lines of descent, with
different past surroundings, may be a most powerful factor in strengthening
the deviation and bringing it into recognition as a new character. Moreover,
natural selection becomes here also potent as soon as the variation has assumed
sufficient proportions to be seized upon by this important factor of evolution.
In cases of reversion Weismann supposes the determinants to remain inactive
in the germ-plasm for one or more generations and later to develop. The

942 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

tlieorv accounts fur tlic regeneration of lost parts by the assunij)tion that the
colls in the vicinity of the wound, by the proliferation of which the new })art
grows, contain, besides tlie active determinants that have given them their
specific character, other determinants that are latent until the o])portunity for
regeneration arrives. Some cells do not possess such latent determinants, and
hence some parts of a body are incapable of reproducing lost parts.

Such are the main features of Weismann's theory — a germ-plasm of highly
complex architecture and independent of somatoplasm ; continuity of germ-
j)lasm and non-inheritance of acquired somatic characters tending to preserve
the uniformity of the species ; slight nutritional variation of germ-plasm and
sexual reproduction tending to destroy that uniformity ; the result is inherited
resemblance and congenital variation. The theory is now being most actively
discussed.

Theory of Epigcnesis. — Among epigenesists no one theory may be said to
be pre-eminent. The main features of the epigenetic conception, already
referred to, may be summarized as follows : The fertilized ovum is isotropous,
i. e. all parts are essentially alike; germ-plasm probably consists of minute
particles, but these particles do not represent definite cells or groups of cells
of the adult; segmentation is a quantitative process; the early blastomeres
are essentially alike, and any one of them, if isolated from the rest, may
give rise to a whole organism, although under ordinary circumstances they
react upon each other in bringing about the resultant individual ; there is
no predetermination, either in the germ-cells or in the segmenting ovum,
of the ultimate form or function of the various constituent parts ; morpho-
logical differentiation and physiological specialization are phenomena of
comparatively late embryonic life, and the prospective character of any one
cell, wiiether it is to be a muscle-cell, gland-cell, nerve-cell, or germ-cell, is
determined by the influence of the surrounding cells and the surrounding
physical and chemical conditions — " the prospective character of each cell is a
function of its location." Extreme epigenetic views are not so numerous as
those of preformation.'

The more moderate thinkers of the present time recognize truth in both
preformation and epigcnesis, and are endeavoring l)y cx})ori mental methods to
determine how much share in the production of the characteristics of the off-
spring is to be ascribed to the original qualities of the germ-plasm and how
much to the physical, chemical, and physiological phenomena of the immediate
environment of the developing embryo. Such experimental work is per-
formed at present upon the simpler and lower animals, mostly marine inverte-
brates, and has reference to the effect of changes in the composition of the water
surrounding the embryo, the effects of various salts, of changes in temperature,
of pressure, of electricity, etc., etc. Such work is now in its infancy, but it is
doubtless destined to yield results of the highest value in an understanding of
the true nature of horodity.

* The best statement of a moderate epigenetic theory is to be found in Zcil- unci Streiifragen
der Biologic : I. Pr&Jorvmtion oder Epigcnesis f O. Hertwig, 1894.

XIV. THE CHEMISTRY OF THE ANIMAL BODY.

Introduction. — T^iving matter contain.s hydrogen, oxygen, sulphur, clilo-
rine, Huorine, nitrogen, phosphorus, carbon, siHcon, potassium, sodium, calcium,
magnesium, and iron. Abstraction of one of these elements means death to
the organization. The compounds occurring in living matter may for the
most part be isolated in the laboratory, but they do not then exhibit the prop-
erties of animate matter. In the living cell the smallest particles of matter
are arranged in such a manner that the phenomena of life are possible. Such
an arrangement of materials is called protoplmm, and anything which disturbs
this arrangement results in sickness or in death. Somatic death may result
from physical shock to the cell ; or it may be due to the inability of the cell or
the organism to remove from itself poisonous products which are retained in
the body so affecting the smallest particles that functional activity is impossible.
Pure chemistry adds much to our knowledge of phy.siology, but it mu.st alw^ays
be remembered that the conditions present in the beaker glass are not the con-
ditions present in the living cell, physical and chemical results being dependent
on surrounding conditions ; hence the necessity and value of animal experimen-
tation. From chemical changes, the physical activities, i. e. the motions cha-
racteristic of life, result. Hence the chemistry of protoplasm is the corner-stone
of biology. The plan of this section is designed to consider the substances
concerned in life in the order usually followed by chemical text-books.

The Non-metallic Elements.
Hydrogen, H = 1.

This gas is found as a constant product of the putrefaction of animal
matter, and is therefore present in the intestinal tract. It is found in the
expired air of the rabbit and other herbivorous animals, and in traces in the ex-
pired air of carnivorous animals, having first been absorbed by the blood from
the intestinal tract. By far the greater amount of hydrogen in the animal
and vegetable worlds, as well as in the world at large, occurs combined in the
form of water, and it will be shown that the proteids, carbohydrates, and fats,
characteristic of the organism, all contain hydrogen originally derived from
water. In the atmosphere is found ammonia in traces, which holds hydrogen
in combination, and this is a second source of hydrogen, especially for the con-
struction of the proteid molecule.

Preparation. — (1) Through the electrolysis of water, by which one volume

943

it44 .l.V AMERICAX TEXT- BOOK OP PHYSIOLOGY.

of oxvnren is evolved on the })ositive pole and two volumes of" liydrogeu on the-
Degative.

(2) Throiigli the aetion of zinc on sulphuric acid/

Zn + H^SO, - ZnSO, + Hj.

(3) Throuixh putrefaction (hy which is understood the change effected in-
organic matter through certain lower organisms, bacterid) hydrogen is liberated
in tlie intestinal canal from proteid matter, and especially from the fermenta-
tion of carbohydrates :

CeH. A = QHA + 2CO, + 2H,.

Sugar. Butyric acid.

In putrefaction in the presence of oxygen the hydrogen formed immediately
unites with oxygen, producing \vater ; hence, notwithstanding the enormous
amount of putreiaction in the world, there is no accumulation of hydrogei>
in the atmosphere.

Both bacteria and an enzyme can liberate hydrogen by acting on calcium formate,
Ca (CHO.,)^ -:- H.,0 = CaCOs + CO, - 2H„
and this same reaction may be brought about by the action of metallic iridium, rhodium,,
or ruthenium on formic acid. An enzyme is a substance probably of proteid nature capa-
ble of producing change in other substances without itself undergoing apparent change
(example, pepsin). Bunge * calls attention to the fact that the above reaction may be brought
about by living cells (bacteria), by an organic substance (enz>Tne). and by an inorganic
metal. Tiiis similarity of action between organized and unorganized material, between
living and dead substances, is shown more and more conspicuously as science advances.

Properties. — Hydrogen burns in the air, forming water, and if two volumes
of hydrogen and one of oxygen be ignited, they unite with a loud explosion.
Hydrogen will not support respiration, but, mixed with oxygen, may be
respired, probably being dissolved in the fluids of the body as an inert gas^
without effect u|)on the organism. Hydrogen may jmss through the intes-
tinal tissues into the blood-vessels, according to the laws of diffusion, in ex-
change for some other gas, and may then be given off in the lungs. Xascent
hydrogen — that is to say, hydrogen at the moment of generation — is a powerful
reducing agent, uniting readily with oxygen (see p. 952).

Oxygen, O = 16.
Oxygen is found free in the atmosphere to the amount of al)out 21 per
cent, bv volume, and is found dissolved in water and chemically combined in
arterial blood. It is swallowed with the food and may be present in the stom-
ach, but it entirely disappears in the intestinal canal, being absorbed by respir-
atory exchange through the mucous membrane. It occurs chemically com-
bined with metals so that it forms one-half the weight of the earth's crust ;
it likewise occurs combined in water and in mo.st of the materials forming
animal and vegetable organisms. It is found in the blood in loo.se chemical

1 It is not within the scope of this work to give more than typical metho(is of hihoratory
preparation. For greater detail the reader is referred to works on genenil chemistry.
» Physiologische Chemie, 2d ed., 1889, p. 167.

THE CHEMISTRY OF THE ANIMAL liODY. 945

coiubiuatiun as oxylitcinoglobin. It is present dissolved in the saliva, so great
is the amount of o.\y«2;en furnished by the blood to the salivary gland ; it
is, however, not found in the urine or in the bile,

l\rp<tr<ttlt)ii. — (I) Thruujih the elcctrnlysis of wuter (sec Hydrogen).

(2) IJy lieutiiig auuigiiiicse dioxide with sulijhuric iicid,

2MnO, + H,SO, = 2M11SO4 + 211,0 + 0,.

(3) By licatiiig potassium chlorate,

2KC10, = 2KCl+30,.

(4) By the aetion of a vacuum, or an atmosphere containing no oxygen, on
a solution of oxyhsemoglobin,

Hb-O^^Hb + O^.

This latter is the method occurring in the higher animals. Any oxygen present
in a cell in the body combines with the decomposition products formed there,
consequently entailing in such a cell an oxygen vcwtium, which now acts upon
the oxyhaemoglobin of the blood-corpuscles in an adjacent capillary, dissociating
it into oxvgen and haemoglobin.

(5) By the action of sunlight on the leaf of the plant, transforming the
carbonic oxide and water of the air into sugar, and setting oxygen free,

6CO2 + 6H2O = CgHiA + 6O2.

Properties. — All the elements except fluorine unite with oxygen, and the
products are known as oxides, the process being called oxidation. It is usually
accompanied by the evolution of energy in the form of heat, and often the
energy liberated is sufficiently great to cause the production of light. The
light of a candle comes from vibrating particles of carbon in the flame, which
particles collect as lampblack on a cold plate. In pure oxygen combustion is
more violent than in the air; thus, iron burns brilliantly in pure oxygen, while
in damp air it is only very slowly converted into oxide (rust). This latter
process is called slow combustion, and animal metabolism is in the nature of a
slow combustion. In the burning candle has been noted the liberation of heat,
and motion of the smallest particles : in the cell there is likewise oxidation, with
dependent liberation of heat and motion of the smallest particles in virtue of
which the cell is active. Phenomena of life are phenomena of motion, and
the energy supplying this motion comes from chemical decomposition. The
amount of oxidation in the animal is not increased in an atmosphere of pure
oxygen, nor, wathin wide limits, is it affected by variations in atmospheric
pressure, for oxygen is not the cause of decomposition. In putrefaction it is
known that bacteria cause decomposition, and the products subsequently unite
with oxygen. But the cause of the decomposition in the cell remains unsolved,
it being only known that the decomposition-products after being formed unite
with oxygen. So the quantity of oxygen absorbed by the body depends on the
decomposition going on, not the decomposition on the absorption of oxygen.
This distinction is fundamental (see further under Ozone and Peroxide of
Hydrogen).

60

946 AX AMJ:UJrAX TEXT-BOOK OF PHYSIOLOGY.

By reduction in its sim])lost sense is meant the removal of oxv<;en wholly
or in })art from the molecule. Example : reduced h;emo<^lobin from oxy-
hremoglobin, iron from oxide of iron (FegOs)- Reduction may likewise be
accomplished hy simj)le addition of hydrogen to the molecule, or by the sub-
stitution of hydrogen for oxygen. These two processes may be represented
respectively by the reactions :

CiyilO +H2 =CH3CH/)H.

Ktliyl iil.U'hyde. Ktlivl alc^)liol.

CH.Ci )( )H + 2II2 = C'HgCH/)!! + HgO.

Acetic acid. Ethyl alcohol.

Ozone, O.j. — Ozone is a second form of oxygen possessing more active oxi-
dizing properties than common oxygen. It is found in neighborhoods where
large quantities of w^ater evaporate, and after a thunder-storm.

Preparation. — (1) An induction current in an oxygen atmospliere breaks up some of
the molecules jjresent into atoms of nascent or "active" oxygen — 0 — , the powerful
affinities of whose free bonds enter into combination with oxj'gen, 0 = 0 to form

O
ozone, /^\^

(2) Through the slow oxidation of phosphorus,

P., I 3IL0 -r 20, = 2H3PO3 + (-0-).

(-0-) + 0, = 03.

(3) On the positive pole in the electrolysis of water.

In each of the above eases ozone is formed by the action of nascent oxygen on oxj'gcn.

Properties. — Ozone is a colorless gas, hardly soluble in water, and having
the peculiar smell noted in the air after thunder-storms. Ozone has powerful
oxidizing properties due to its third unstable atom of oxygen, oxidizing silver,
which oxygen of itself does not. But ozone is not as oxidizing as nascent or
"active" oxygen, which may convert carbon monoxide into dioxide, and
nitrogen into nitrous acid. Ozone cannot occur in the cell, as any nascent
oxygen formed would naturally unite not with oxygen, but with the more
readily oxidizable materials of the cell itself. Ozone acts on an alcoholic solu-
tion of guaiacum, turning it blue ; blood-corpuscles give the same reaction
with guaiacum, hence it was thought that haemoglobin converted oxygen into
ozone. However, this test is not a test for ozone, but for " active " atomic
oxygen, which is produced from the ozone and in the decomposing yood-cor-
puscle (see theory of Traube below, and that of Ho}>pe-Seyler under Peroxide
of Hydrogen). Ozone converts oxyhsemoglobin into metha^moglobin.

Theory of Traube ctf^ to the Cause of O.vidation in the Bodi/. — Indigo-blue
dissolved in a sugar-solution gives np oxygen in the atomic state for the oxida-
tion of sugar, and the solution becomes white. If shaken in the air the blue
coloration reappears, owing to the absorption of oxygen by the indigo. Hence
indigo has the power of splitting oxygen into atoms, and acts as an "oxygen-
carrier" between the air and the sugar. Traube is of the opinion that an
" oxygen-carrier " exists in the blood-corpuscles. Sugar is destroyed by stand-
ing in fresh defibrinated blood ; scrum alone does not effect this, nor does a
solution of oxyhsemoglobin, but it may take place in the extract obtained by

THE CHEMISTRY OF THE ANIMAL BODY. 947

the action of a 0.6 per cent, sodiiiiii-cliloi-ide solution on blood-corpuscles.'
The action here has been described as that of ca/a/y.s/.s, that is, an action in
Avhich some substance effects decomposition in another substance without per-
manent change in itself. In this case the substance in the blood-corpuscle,
whatever it may be, is defined as an "oxygen-carrier," tjdving molectilcs of
oxygen from oxyhaemoglobin and giving atomic oxygen for the oxidation of
the sugar.

01(1 turpentine is highly oxidizing. Tills action was once believed to be due to absorbed
ozone. If old turpentine be mixed with water and filtered, the aqueous extract has the
same properties, due to the fact that an oxidized product which is soluble in water, gives
off', under favorable conditions, atomic oxj'gen.*

Di'tirtnut. — Moist strips of filter-paper soaked in starch-paste containing potassium
iodide turn blue when exposed to the action of ozone, due to the liberation of free iodine,
which colors the starch :

2KT + H.,0 + 03 = 2K0II + 0, + 21.
This liberation of iodine is likewise accomplished by chlorine, bromine, some nitrous oxides,
and peroxide of hydrogen."

Water, HoO. — Water is found on the earth in large quantities, and its
vapor is a constant constituent of the atmosj)here. It is a product of the
combustion of animal matter, and occurs in expired air almost to the point of
saturation. It is furthermore given off by the kidneys and by the skin. It
is a necessary constituent of a living cell, and forms 67.6 per cent, of the
weight of the human body (Moleschott). Removal of 5 to 6 per cent, of
water from the body, as for example in cholera, causes the blood to become
very viscid and to flow slowly, no urine is excreted, the nerves become excess-
ively irritable, and violent convulsions result.'^

Pveparatim. — (1) By passing an electric spark through a mixture of one volume of
oxj'gen and two volumes of hydrogen.

(2) By the combustion of a food — as, for example,

C^HiA + 120 = 6CO, + 6H2O.

Sugar.
(3) Distilled loater is made in quantity by boiling ordinary water and condensing the
vapors formed in another vessel.

Properties. — Water is an odorless, tasteless fluid of neutral reaction, colorless
in small quantities, but bluish when seen in large masses. It is a bad conductor
of heat and electricity. It conducts electricity better when it contains salts.
It is nearly non-compressible and non-expansible; thus in plant-life, through
evaporation on the surface of the leaf, sap is continuously attracted from the
roots of the tree. The solvent properties of Avater give to the blood many of
its uses, soluble foods being carried to the tissues and soluble products of
decomposition to the proper organs for elimination.

When water is absorbed by any substance the process is called hydration,
as an example of which may be cited the change of calcium oxide into

1 Read W. Spitzer : PJluger's Arckiv, 1895, Bd. 60, p. 307.

'^ N. Kowalewsky: Centralblatt filr die medicinische Wissenschaft, 1889, p. 113,

' C. Voit: Hermann's Handbuch, 1881, Bd. vi., 1, p. 349.

948 ^l.Y AMERICAN TEXT-BOOK OF rilVSIOLOGY.

liydroxide when thrown into water. When a substance breaks down into
simpler bodies throiigli absorption of water the process is called In/droli/fii.s or
hifdrolytlc cleavaf/e. Thus caiu'-siigar may take up water and be roolvcd into
a mixture of dextrose and levnlose, which are called c/cardf/c-prodKcts. 80,
likewise, starch and proteid are resolved into series of simpler b(;dies through
hydrolytic cleavage — changes which take place in intestinal digestion. All
forms of fermentation and puticfaction are (jharacterizcd i)y hydrolysis (exam-
ples, p. 94-1), and hence complete drying prevents such j)roccsse.s. Alcoholic,
butyric, and lactic fermentatiou are apparent though not real exceptions to the
above. Alcoholic fermentation, for example, is usually represented by tin?
reaction, (.'6^1,206 = 202115011 + 200,, but the CO2 is in fact united Mith
water, and hence the true reaction should read,

CgHiaOg + 2H2O = 2C2H5OH + 2112003.

Sugar. Alcohol.

Driiikincj-watcr contains salts and air dissolved, giving it an agreeable taste.
One does not willingly take distilled water on account of its tastelessness.
Drinking large quantities of water produces a slight increa.se in the decom-
position of proteid in the body.

Dry animal membranes and cells aksorb water in quantities varj'ing with the concentra-
tion and the quality of salts in the solution in wliicli they are suspended (Liebig). This is
called imbibition. Membranes will absorb a solution of potassium salts in greater quantity
than of sodium salts, and so the potassium salts are found predominating in the cells, the
sodium salts in the fluids of the body. A blood-corpuscle treated with distilled water
swells because it can hold more distilled water than it can salt-containing ])lasma. A cor-
puscle i)laceil in a ().f>5 percent, solution of sodium chloride (the ])hysiological salt-solution)
remains unchanged, for this corresponds in concentration to the plasma of the blood. If
the cor])Uscle be placed in a strong solution of a salt it shrivels, because it cannot hold as
much of that solution as it can one having the strength of the salts of the i^lasma. Oysters
are often planted at the mouths of fresh-water rivers, since they imbibe more of the weaker
solution and appear fatter. If salt be ])laccd on meat and left to itself a brine is formed
around the meat, not on account of the hygroscopic projicrties of the salt, but because
salt penetrates the tissues, which can then hold less water than they could before, and
so water is forced out from the meat.

Different bodies require different quantities of heat to warm them to the same extent.
The amount of heat required to raise the temperature of water is greater than that for any
other substance. A caloric or heat-unit is the amount of heat required to raise 1 cubic
centimeter of water from 0° to 1° C. The specific heat of the human body— that is, the
amount of heat required to raise I gram 1° C— is about 0.8 that of water. On the trans-
formation of a substance from the solid to the liquid state, a certain amount of heat is
absorbed, known as latent heat. To melt 1 gram of ice producing J gram of water at 0°.
7'.» calories are required, or sufficient to raise 1 gram of water from 0° to 79°. Upon the
basis of these facts a determination may Ije made by means of the icc-cnloriineter of tlie
number of heat-units produced in the combustion. For exami)le, 1 gram of sugar (dex-
trose) burned in an ice-chamber, melts 49. S6 grams of ice. Since each gram required
79 calories to melt it, 3939 calories must have been produced altogether. If 1 gram of
sugar be burned in the body, the heat produced is identically the same, and may be meas-
ured with great accuracy.'

In the transformation of water at 100° to steam at 100° there is a further absorption of

' M. Kubner: Zeilschrift fur Bioloyk, 1893, Bd. 30, p. 73.

THE CHEMISTRY OF THE AXIMAL BODY. 049

heat, tlio huont lioat of stoaiii. For I jrraiii ol' water this alisorptiuii amounts to 536.5
cjilories. Tliis projierty of water is of jrreat vahie to life, lor through tlie heat al)Sorbed in
the evaporation of sweat the tenijierature of the body is in part ref,'ulated.

Peroxide of Hydrogen, ll20^, is found in very small quantities in the air,
in rain, f^now, and sleet, and where there is oxidation of organic matter.
rrcjutnifioii. — (!) By the action ol' sulphurie acid on peroxide of barium,
BaO, i II, SO, BaSO«+II,(),.

(2) Peroxide of hyfh'ogen is a product of the oxidation of phosplionis, and L^'iierally
exists wherever ozone is produced.

(3) Peroxide of hydrogen exists wlierevcr nascent hydrogen acts on oxygen.
It is therefore found mixed with hydrogen evolved at the negative pole in the
electrolysis of water. This action happens in putrefaction, where the na.scent
hydrogen unites with any oxygen pi-esent, and the residting H.JO^ strongly
oxidizes the organic matter through the free — O — atom liberated.'

Properties. — Peroxide of hy(h"ogen is a colorless, odorless, bitter-tasting
fluid, which decomposes slowly at 20° F., and with great violence at higher
temperatures. It oxidizes where ordinary oxygen is ineffective ; it is a powerful
bleaching agent, and is used to produce blonde hair. It destroys bacteria. Bk)od-
corpnscles brought into a solution of H^02 bring about its ra})id decomposition
into water and atomic oxygeji, whereby oxygen is evolved and oxyhaeinoglobin
is converted into methfemoglobin. If oxyhsemoglobiu be brought into a
putrefying fluid, the nascent hydrogen withdraws oxygen from combination
to form HgOo, and then the atomic oxygen reacts on haemoglobin to form
methaemoglobin.^ The formula for the peroxide is probably H — O — O — H.
In certain cases peroxide of hydrogen has a reducing action.

Tlieori/ of Hoppe-Seykr^ to account for the Oxidation in the Body. — This
maintains that, as in putrefaction, hydrogen is produced in the decomposition
of the cell, and acting on the oxygen present converts it into peroxide with
its unstable atom, which then splits off as active oxygen and effects the oxida-
tion of the substances in the cell. This theory is easier to reconcile with the
fact that oxidation is dependent on the amount of decomposition (see p. 945)
than is the theory of Traube.

Detection. — Solutions of H2O2 do not liberate iodine from ])otassium iodide imme-
diately, but only on the addition of blood-corpuscles or of ferrous sujpliate, which cause
liberation of — 0 — , and then any starch present may be colored blue (see p. 947).
Guaiacum is not affected by H.^O, unless blood-corpuscles or ferrous sulphate be added
which make the oxygen active.

Sulphur, S = 32.

Sulphur is built in the proteid molecide of the plant from the sulphates
taken from the grotnid. It is found in albuminoids, especially in keratin. As
taurin it occurs in muscle and in bile, as iron and alkaline sulphide in the

^ Hoppe-Seyler : Zeilscfirift fiir physioloyiscfie Chemie, 1878, Bd. 2, p. 22.
^ Hoppe-Seyler, Op. cit., p. 26.

■* Pfl'dger's Arctiiv, Bd. 12, p. 16, 1876. See also Bericfite der deutsctien chanisctien Geselhctiafty
Bd. 22, p. 2215.

950 AiY AMERICAN TEXT-BOOK OF PHYSIOLOGY.

feces, as sulphuretted liydrogcn iu the intestiual gas, as sulphate and other
unknown compounds in the urine.

Detection. — If a sulphur compound be fused with sodium carbonate on charcoal, the
sulphur will be reduced to sodium sulphide. The melted mass if placed with a drop of
water on a silver coin leaves a black spot of silver sulphide.

Sulphuretted Hydrogen, H.,^. — This gas is found iu the intestines, and

pathologically in the urine.

Preparation. — (1) Action of hydrochloric or sulphuric acid on ferrous

sulphide,

^ FeS + H2SO, = FeSO, + H.S.

This same reaction takes place by treating feces (which contain FeSj M'ith acid.

(2) From the putrefaction of proteids, and by boiling proteid with mineral
acid.

Proijerties. — Sulphuretted hydrogen unites readily with the alkalies and
with iron salts, forming sulphide ; hence little HgS is found in the intestinal
tract. It is a strong poison when respired. It has been shown in frogs to
enter into combination with oxyhsemoglobin to form sulph-hsemoglobin,
and likewise rapidly kills the nerves.* Sulphuretted hydrogen diluted
with hydrogen and introduced into the rectum of a dog produces symptoms
of poisoning in one to two minutes (Planer). It has an offensive odor similar
to Ibul eggs.

Detection. — If a piece of filter-paper soaked in acetate of lead be brought in contact
with Ha8, it turns black, owing to the formation of sulphide of lead (PbS). Soluble sul-
phides in alkaline solution give with sodium nitro-prussiate, Na2Fe(CN)5NO + 2H2O, an
intense violet color, given also bj^ acetone and aceto-acetic acid.

Sulphurous Acid, H2SO3. — This acid has been found in the urine of cats and dogs,
and has been detected bj' Striimpell in human urine in a case of typhoid fever.

Sulphuric Acid, H2SO4. — This acid is found in the urine in combination
with alkali (preformed sulphate), and with indol, skatol, cresol, and phenol
(ethereal sulphates). It is found in the saliva of various gastropods.

Preparation. — (1) By oxidation of sulphur with nitric acid,

S + 2HNO3 = H2SO, + 2NO.

(2) By oxidation of sulphur-containing proteid.

Properties. — Sulphuric acid is a very powerful acid. It is produced in the
body by the burning of the proteids (which contain 0.5 to 1.5 per cent. S),
80 per cent, or more being oxidized to acid, while tlie remainder appears iathe
urine in the unoxiuized condition tqi'uied neutral sulphur. When proteid, fat,
and starch free from ash is fed to dogs, they live only half as long as they
would were they starving,^ for, according to Bunge,^ the sulphuric acid formed
abstracts necessary salts from the tissue. (For further discussion of this see
pp. 956 and 969).

Detection. — If 100 cubic centimeters of urine be treated with 5 cubic centimeters of

' Ilarnack : Archir fiir erpei-imentelle Palholof/ie nnd Pbarmukologie, 1894, Bd. 34, p. 156.
2 J. Foster: Ze.itschrift fiir Biologic, 1873, Bd. 9, p. 297.
» Physiologische Chemie, 2d ed., 1889, p. 104.

THE CHEMISTRY OF THE ANIMAL BODY. 951

hydrochloric acid and barium cliloride be added, the preformed sulphuric acid iw precip-
itated as barium sulpliato (BaS(^4), which may be washed, dried, and weij^died. If 100
cubic centimeters of urine be mixed with an equal volume of a solution containin.i^ barium
chloride and hydrate, filtered, and one-half the filtrate ( =50 cubic centimeters of urine,
now free o^ preformed sulphate) be stronjrly acidified with hydrochloric acid and boiled, the
ethereal sulphates will be broken up, and the resulting precipitate of barium sulphate will
correspond to the ethereal sulphuric acid. To determine the neittrol sulj)hur, evaporate
the urine to dryness, fuse the residue with potassium nitrate (KNO3), which oxidizes all
the sulphur to sulphate, take uj) with water and hydrochloric acid, add barium chloride,
and the precipitate (BaS04) represents the total sulphur present. Deduct the amount
belonging to sulphuric acid, previously determined, and the remainder represents the
neutral sulphur.

Metabolism of Sulphur. — The total amount of sulphur in the urine
runs proportionally parallel with the amount of nitrogen ; that is to say, the
amomit is proportional to the amount of proteid destroyed. The amount of
ethereal sulphate is dependent upon the putrefactive production of indol,
skatol, phenol, and cresol in the intestinal caiial, which on absorption form a
synthetical combination with the traces of sulphate in the blood. Concerning
neutral sulphur it is known that taurin is one source of it. If taurin be fed
directly, the amount of neutral sulphur in the urine increases (Salkowski), and
in a dog with a biliary fistula the neutral sulphur decreases but does not en-
tirely disappear.* In a well-fed dog with a biliary fistula Voit^ foimd the
quantity of sulphur in the bile to be about 10 to 13 per cent, of that in the
urine. This biliary sulphur (taurin) is normally reabsorbed, as the quantity
of sulphur in the feces (FeS, NaaS) is small and derived principally from pro-
teid putrefaction. The amount of neutral sulphur in the urine is greatest
under a meat diet, least when fat or gelatin is fed ; the sulphur of gelatin
burns apparently to sulphuric acid.^ The neutral sulphur of the urine includes
potassium sulphocyanide (originally derived from the saliva), likewise a sub-
stance which on treatment with calcium hydrate yields ethyl sulphide,
(03115)28,* and there are present other unknown compounds. When an
animal eats proteid and neither gains nor lo.ses the same in his body, the
amount of sulphur ingested is equal to the sum of that found in the urine
and feces. If sulphur be eaten it partially appears as sulphate in the urine.
Sulphates eaten pass out through the urine. They play no part in the life of
tlie cell.

Chlorine, CI = 35.5.

Free chlorine is not found in the organization, and when breathed it vigor-
ously attacks the respiratory mucous membranes. Chlorine is found combined
in the body as sodium, potassium, and calcium chloride, as hydrochloric acid,
and it is said to belong to the constitution of pepsin.*

^ Kunkel : Archiv fur die gesammte Physiologie, 1877, Bd. 14, p. 353.
^ Zeitschrift fiir Biologie, 1894, Bd. 30, p. 554. ^ Voit, Op. cit., p. 537.

* J. J. Abel : Zeitschrift fiir physiologische Chemie, 1 894, Bd. 20, p. 253.

5 E. O. Sehoumow-Simanowski : Archiv fiir exper. Pathologie und Fharmakologie, 1894, Bd.
33, p. 336.

952 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Hydrochloric Acid, HCl, is IouikI to a small extent in the gastric juice.

Preparation. — (1) If sunlight acts on a mixture of equal volumes of chlorine and
hydroirei), they unite with a loud ex])losion.

(2) By the action of strong sulphuric acid on common salt,

2NaCl + HjSO, = Na,SO, + 2HC1.

(3) By the action of primary acid phosphate of sodinm on common salt,

XaH^PO, + NaCl = Na^HPO, + HCl.

This, according to Maly, represents the process in the cells of the gastric glands.
Properties. — Hydrochloric acid readily unites with most metals, forming
chlorides. It causes a gelatinization of the proteids and seems to unite with
them ciiemically. Such gelatinization is a necessary forerunner of peptic di-
gestion. The cleavage products of peptic digestion (peptones, ])roteoses, etc.)
combine with more hydrochloric acid than the original more complex proteid.'
Hydrochloric acid of the strength of the gastric juice (0.2 per cent.) inverts
cane-sugar at the temperature of the body, and inhibits the action of bacteria.
Hydrocidoric acid is indis[)utably derived from decomposition of chlorides in
the secreting cells of the stomach. It has been shown that the excretion of
common salt in the urine is decreased during those hours that the stomach is
active, while the alkalinity of the urine increases. If, in a dog with a gastric
fistula, the mucous membrane of the stomach be stimulated and the gastric
juice be removed as soon as formed, the urine becomes strongly alkaline with
sodium carbonate (the excess of Na liberated taking this form) while the chlo-
rides may entirely disappear from the urine.^ Respiration in an atmos])here
containing 0.5 per cent. HCl gas becomes very uncomfortable after twelve
minutes.^

Detection. — Hydrochloric acid and the chlorides give with silver nitrate a white itrecipi-
tate of silver chloride, insoluble in nitric acid, very soluble in ammonia. If the bases
(K, Na, Ca, Mg, Fe) of gastric juice and then the acid radicals (01 and P.-Oj) be deter-
mined, after uniting by calculation phosphoric atdiydride with the proper bases, then chlo-
rine with the rest of the bases, there still remains an excess of chlorine which could only
have belonged to hydrochloric acid present. To detect free hydrochloric acid, put three or
four drops of a saturated alcoholic solution of tropaeolin (10 in a small white iiorcelain
cover, add to this an equal quantity of gastric juice, evaporate slowly, and tlie presence
of hydrochloric acid is shown by a beautiful violet color, not given by any organic acid.*
Giinzburg's reagent con.sisting (5f pliloroglucin and vanillin in alcoholic solution, warmed
(as above) with gastric juice containing free hydrochloric acid, gives a carmine-red
mirror on the porcelain, not given by an organic acid.*

Chlorine in the body is ingested as chloride, and leaves the body as
such, principally in the urine, likewise through the sweat and tears, and in
traces in the feces.

^ Chittenden: Carturighi Lecture-^ on Digestive Proteolm-'^, 1895, p. 52.

" E. O. Schoiimow-Simanowski : Arehiv fiir erper. Pathotoyie und Pharmakologif, 1894, Bd.
33, p. 336.

■* Lehmann: Archie far Hygiene, Bd. 5, p. 1.

* Boas: Deutsche medicinische Wochenschrift, 1887, No. 39-

* Giinzburg : Centralblatt fiir klinische Medicin, 1887, No. 40.

THE CHEMISTRY OF THE ANIMAL BODY. 953

Bromine, \^Y = 80.

Salts of bromine are found in marine plants and animals, but their physiological im-
portance has not been established. Bromine is a fluid of intensely disagreeable odor,
whose vapors strongly attack the skin, turning it brown, and likewise the mucous mem-
lirancs of tlie respiratory passages.

Hydrobromic Acid, 11 Br, may be jirepared by the action of water on phosphorus

tri bromide,

PBr^ + 311,0 = 3HBr -r ll.l^Oa-

It is a colorless gas of penetrating odor. If sodium bromide be given to a dog in the
place of sodium chloride, fifty per cent, and more of the hydrochloric acid may be sup-
I>lanted by hydrobromic acid in the gastric juice.'

Iodine, I = 127.

Like bromine, the salts of iodine are found in many marine plants and animals, espe-
cially in the alga'. It is found in the thjToid gland. Iodine is prepared in metallic-looking
plates, almost insoluble in water, but soluble in alcohol (tincture of iodine). Iodine is still
more strongly corrosive in its action on animal tissue than is chlorine or bromine, and is an
antiseptic and disinfectant. A slight trace of free iodine turns starch blue.

Hydriodic Acid, HI, is prepared like hydrobromic acid, by the action of water on
tri-iodide of phosphorus. An aqueous solution of hydriodic acid introduced into the
stomach is absorbed, and shortly afterward iodine, as alkaline iodide, may be detected
in the urine. On administration of sodium iodide to a dog with his food, only very
little hydriodic acid appears in the gastric juice. ^

Circulation in the Body. — Iodine or iodides given are rapidly eliminated in the
urine, in smaller amounts in saliva, gastric juice, sweat, milk. etc. It is noticed that for
weeks after the administration of the last dose of potassium iodide, traces of iodine are
found in the saliva, and none in the urine. The explanation lies in the presumption that
iodine has been united with proteid to a certain extent, and appears in such secretions as
sahva, which contains materials derived from proteid through glandular manufacture.'
A similar explanation avails in the case of Drechsel's* discovery that, in patients who
have been treated with iodides, iodine may be detected in the hair (the keratin of hair
being derived from other proteid bodies.) Baumann* has recently announced the dis-
covery of an organic compound of iodine occurring in the thyroid gland and containing as
much as 9. 3 per cent, of iodine. This tliyro-iodin is the effective principle, or at least one
of the effective principles, of the thyroid gland. "^ Whether free iodine or hydriodic acid
is liberated in the tissues from ingested iodides is a disputed point.

Fluorine, F = 19.

Fluorine i.s found in the bones and teeth, in muscle, brain, blood, and in

all iuve.stigated tissues of the body, though in .small quantities. In one liter

of milk 0.0003 gram of fluorine have been detected.^ Fluorine is found in

])lants, and in soil without fluorine plants do not flourish. It seems to be a

necessary constituent of protoplasm. Free fluorine is a gas which cannot be

preserved, as it unites with any vessel in Avhich it is prepared.

^ Xencki and Schoiimow-Siinanowski : Archiv fiir exper. Pathologic und Fharmakologie, 1895,
B(l. 34, p. 320. ^ Nencki and Schouniow-Simanowski, loc. cit.

* Schmiedeberg : Grundri.is der Arzneiiniltellehre, 2d ed., 1888, p. 197.

♦ Centmlblatt fur Physiologie, 1896, Bd. 9, p. 704.

^ Zeit.<chriJI fiir phi/niologische Cheinie, 1895, Bd. 21, p. 319.

« See Dreclisel : Cenlralblatt fiir Physiologie, 1896, Bd. 9, p. 705.

' G. Tammann : Zeitschrift fiir physiologische Chemie, 1888, Bd. 12, p. 322.

954 AX AMERICAN TEXT-BOOK OF PHYSTOLOGY.

Hydrofluoric Acid, IIF, is prepared by heating a fluoride' with coiieeiitrated sul-
phuric acid, in a platinum or lead dish,

CaF, + H,S04 = CaSO* + 2HR

Prnpertu's.—\\yi\vo^\iov\c acid is a colorless pas, so powerfully corrosive that breathing

its fumes results fatally. Its aqueous solutions are stable, but can be kept only in vessels

of platinum, gold, lead, or india-rubber. It etches glass, uniting to form volatile silicon

fluoride,

Si02 + 4HF = SiF, + 2H.A

Detection. — If silicon be absent from the substance to be tested, the above reaction maybe
used, and if the glass be etched, after treating the substance with sulphuric acid, fluorine
is present. In the organism silicon is found, and the method of detection is different.
The principle of the method depends on the flict that SiF^ in contact with water forms
silicic acid (HiSiOJ, and hydrofluor-silicic acid (HjSiFg). If the ash of the organ be
mixed with powdered silica (Si02), transferred to a flask, mixed with concentrated sul-
phuric acid, then heated, and if a current of dry air remove the SiF4 from the flask
through a tube into water, the slightest trace of fluorine is proven by the appearance
of a whitish cloud of silicic acid at that part of the tube where SiF^ first comes in con-
tact with moisture. This may be noted when 0.0001 gram of fluorine is present.^

Circulation in the Body. — Tappeiner and Brand! ^ have shown, on
feeding sodium fluoride (XaF) to a dog in doses varying between 0.1 and
1 gram daily, that the fluorine fed was not all recoverable in the urine and
feces, but was partially stored in the body. On subsequently killing the dog,
fluorine was found in all the organs investigated, and was especially found in
the dry skeletal ash to the extent of 5.19 per cent, reckoned as sodium fluoride.
From the microscopic appearance of the crystals seen deposited in the bone, the
presence of calcium fluoride was concluded. In this form it normally occurs
in bones and teeth.

NiTEOGEN, X = ] 4.

Free nitrogen constitutes 79 per cent, of the volume of atmospheric air. It
is found dissolved in the fluids and tissues of the body to about the same extent
as distilled water would dissolve it. It is swallowed with the food, may par-
tially diffuse through the mucous membrane of the intestinal tract, but forms
a considerable constituent of any final intestinal gas. It is found in the atmos-
phere combined as ammonium nitrate and nitrite, which are nsefid in furnish-
ing the roots of the plant with material from which to build up proteid.
Bacteria upon the roots of certain vegetables combine and assimilate the free
nitrogen of the air (Hellriegel and Willforth). Cultures of alga do the same.^

Preparation.— {\) By abstraction of oxygen from air through burning phosphorus in
a bell jar over water, pentoxide of phosphorus being formed, which dissolves in the water
and almost pure nitrogen remains.

(2) By heating nitrite of ammonium,

NH.NO., = 2N -f 211,0.
Properties. — Nitrogen is especially distinguished by the absence of chemical
affinity for other elements. It does not support combustion, and in it both a

* Tammann, he. cit. * Zeitschrifl fiir Biologic, 1892, Bd. 28, p. 518.

^ P. Kossowitch : Bolanische Zeitung, 1894, Jahrg. 50, p. 97.

THE CHEMISTRY OF THE ANIMAL BODY. 955

flame and animal life are extinguisiied, owing to lack of oxygen. It acts as
a diluent of atmospheric oxygen, thereby retarding combustion, but on higher
animal life it is certainly without direct influence.

Ammonia, NII3, is ibund in the atmosphere as nitrate and nitrite to the
extent of one part in one million. It is found in the urine in small quantities,
is a constant product of the putrefaction of animal matter, and is a product of
trypsin proteolysis.

Preparation,— {}) Through the action of nascent hydrogen on nascent
nitrogen. This may be -brought about by dissolving zinc in nitric acid,

3Zn + 6HNO3 = 3Zn(X03)2 + 6H.

lOH + 2HNO3 = 6H2O + 2N.

N + 3H = NH3.

Ammonia is produced in a similar way in the dry distillation of nitro-
genous organic substances in absence of oxygen, being therefore a by-product
in the manufacture of coal-gas. In putrefaction nascent hydrogen acts on
nascent nitrogen, producing ammonia, which in the presence of oxygen becomes
oxidized to nitrate and nitrite, or in the presence of carbonic oxide is con-
verted into ammonium carbonate. Ammonium nitrite is likewise formed on
burning a nitrogenous body in the air, in the evaporation of water, and on the
discharge of electricity in moist air,

2N + 2H2O = XH.XO^.

At the same time a small amount of nitrate is formed in the above three

processes,

2N + 2H2O + O - NH,N03.

Hence these substances find their way into every water and soil, and furnish
nitrogen to the plant. The value of decaying organic matter as a fertilizer is
likewise obvious.

Properties. — Ammonia is a colorless gas of pungent odor. It readily dis-
solves in water and in acids, entering into chemical combination, the radical
NH4 appearing to act like a metal with properties like the alkalies, and its
salts will be described with them. Very small amounts of ammonia instantly
kill a nerve, but upon muscular substance it acts first as a stimulant, provok-
ing contractions.

Detection. — On Marming an ammonium salt with sodium hydrate, ammonia
is set free, recognizable by its smell, by the fact that it turns turmeric paper
brown, and that even in smallest traces it gives a yellow coloration, or, in
greater amounts, a reddish precipitate in Xessler's reagent (mercuric iodide dis-
solved in potassium iodide and potassium hydrate).

Ammonia in the Body.— If it be agreed with Hoppe-Seyler that normal
decomposition in the tissues is analogous to putrefiiction, then nascent hydrogen
acting on nascent nitrogen in the cell produces ammonia, which in the presence
of carbonic acid becomes ammonium carbonate, and in turn may be converted
into urea by the liver. If acids (HCl) be fed to carnivora (dogs) the amount

956 ^.V AMERICA X TEXT-BOOK OF PHYSIOLOGY.

of ammonia present in the nrine is increased, which indicates that an amount
of ammonia usually converted into urea has been taken for the neutralization
of tiie acid.^ In a similar manner acids formed from decomposing proteid
may be neutralized (see ])p. 950 and 993).

[ The ammoniacal fn-mentdtion of the urine consists in the decomposition ol' urea into
I ammonium carbonate by the micrococcus ?/?•<««% the urine becoming alkaline.

Compounds of Nitrogen with Oxygen. — There are various oxides of nitrogen, the
hiiiluT (iiu's being pdWeit'iilly cdrrusivt-. uiul some of these unite with water to form acids,
of which nitric acid (HNO3) is the strongest. Only nitrous and nitric oxides are of phj'si-
ological interest.

Nitrous Oxide, N^O, likewise called ''laughing-gas," is prepared by heating ammo-
nium nitrate,

NH,N03 = N20-r2H.A

It supports ordinary combustion almost as well as pure oxygen, but it will not sustain life.
Mixed with oxygen it may be respired, producing a state of unconsciousness preceded by
hysterical laughter.

Nitric Oxide, NO, is prepared by dissolving copper in nitric acid,

.3Cu + 8HNO3 = 3Cu(N03)2 + 4H.,0 -T 2N0.

•

Contact with oxygen converts it into peroxide of nitrogen (NO.,), which is an imtating
irrespirable gas of reddish color. Nitric oxide in blood first unites with the oxj'gen of
oxyha^moglobin, forming the peroxide (NO,)- and then the nitric oxide combines with
hfemoglobin, forming a highly stable compound, nitric-oxide haemoglobin (Hb-NO).

XiTROGEX IX THE BoDY. — Nitrogen is taken into the body combined in
the great group of proteid substances, which are normally completely absorber!
bv the intestinal tract. It pas.ses from the body in the form of simple decom-
position-products, in larger part through the urine, but likewise through the
juices which pour into the intestinal canal. The uuabsorbed residues of these
latter juices, mixed with intestinal epithelia constitute in greater part the/«?ces.^
An almost insignificant amount of nitrogen is further lost to the body through
the hair, nails, and epidermis, but, generally speaking, the .sum of the nitrogen
in the urine and feces corresponds to the proteid decomposition for the .same
time (1 gram X = 6.25 grams proteid). When the nitrogen of the proteid eaten
is equal in quantity to the sum of that in the urine and feces, the body is said
to be in niirogenons equUibr'nim. When the ingested nitrogen has been larger
than that given off, proteid has been added to the substance of the body ; when
smaller, proteid has been lost. Tliese propositions were established by Carl
Voit.

A small amount of urea and other nitrogenous substances may be excreted in profuse
sweating. Proteid nitrogen never leaves the body in the form of free nitrogen or of
auiinonia. That ammonia is not given off by the lungs may be demonstrated by perform-
ing tracheotomy on a rabbit, and passing the expired air first through pure potassium
hydrate (to absorb CO2) and then through Nessler's reagent. The experiment maybe
continued for hours with negative result.'

' Fr. Walther: Archiv fiir exper. Pathologk und Pharmakologie, 1877, Bd. 7, p. 164.
■^ Menichanti and Prausnitz : ZeilAchrift ftir Biologic, 1894, Bd. 30, p. 353.
' Bachl : Zeitgchrifl fur Biologic, 1869, Bd. 5. p. 61.

THE CHEMISTRY OF THE ANIMAL BODY. 957

Piiosi'iioiius, P =-32.

Phosphorus is found combined as phosphate in the soil ; it is necessary to
the developiucnt of phints. As phospliate it is present in hirge quantity in
the hones, and is found also in all the cells, tissues, and fluids of the body,
probably in loose eheniieal combination with the proteid molecule. It is pres-
ent in nuclein, protagon, and lecithin.

Preparation. — Phosphorus was first prepared by igniting evaporated urine,
SNaH.PO^ + 5C = 3H,0 + 5C0 + 2P + NusPO,.

In a similar way it may be obtained y)y chemical treatment of bones. The vapors of
phosphorus may be condensed by passing them under water, where at a temperature of
44.4° it melts and may be cast into sticks.

Properties. — Phosphorus is a yellow, crystalline substance, soluble in oils and carbon
disulphide. It is insoluble in water, in which it is kept, since in moist air it gives off" a
feeble glowing light, accompanied by white fumes of phosphorous acid (II3PO3) and small
amotuits of ammonium nitrate, peroxide of hydrogen, and ozone, to which latter the
peculiar odor is ascribed. Phosphorus ignites spontaneously at a temperature of 60°, and
tliis may be produced by mere handling, the resulting burns being severe and dangerous.
This form of phosphorus is poisonous, but if it be heated to 250° in a neutral gas (nitrogen)
it is changed into red phosphorus, which has different properties and is not poisonous.

Phosphorus-pokoning. — On injecting })hosphorus dissolved in oil into the
jugular vein, embolisms are produced by the oil in the capillaries of tlie lungs,
the expired air contains fumes of phosphorous acid, and the lungs glow when
cut out (Magendie). If the phosphorus oil be injected in the form of a fine
emulsion, embolism is avoided,' and the fine particles of phosphorus are generally
distributed throughout the circulation. On autopsy of a rabbit after such injec-
tion in the femoral vein, all the organs and blood-vessels glow on exposure to
the air.^ If two portions of arterial blood be taken, and one of them be mixed
with phosphorus oil, and they be let stand, both portions become venous in the
same time.^ Hence phosphorus in blood, as in water, is not readily oxidized.
Persons breathing vajior of phosphorus acquire phosphorus- jioisoning. AMiat
the direct action of j)hosphorus is, is unknosvn, but the results are most inter-
esting. To understand the results it mu.st be made clear that proteid in decom-
posing in the body splits up into a nitrogeneom portion which finds its exit
through the urine and feces, and a non-nitrogenous portion which is resolved
into carbonic oxide and water, just as are the sugars and the fats. This car-
bonic acid is given off, for the most part, through the lungs. Now if a .starv-
ing dog, which lives on his own flesh and fat, be poisoned with phosphoru.s,
the proteid decomposition as indicated by the nitrogen in the urine is largely
increased, while the amount of carbonic acid given off and oxygen ab.sorbed
are largely decreased ; on post-mortem examination the organs are found to
contain excessive quantities of fat. We have here presumptive evidence that a
part of the proteid molecule usually completely oxidized has not been burned,

1 L. Hermann: Pfliiger's Archiv, 1870, Bd. 3, p. 1.

* H. Meyer : Archiv fiir exper. Pathologie und Pharmnfcoiogie, 1881, Bd. 14, p. 327.

' Meyer, Op. cit., p. 329.

958 .l.V AMERICAN TEXT-BOOK OE ElIYSJOLOGY.

hut has hoen converted into fat.' Similar resnUs are cliaraoteristic of areenic
and antimony poi.soning, and of yellow atrophy of the liver.

Dctt'ctinn. — If any organ containing phosphorus he boiled with water in a flask with a
long ui>right tube, a ring of luminous phosphorus will condense at a certain point of
the tuV)e.

Compounds of Phosphorus -with Oxygen. — Of these corapound.s three
oxides and several acids exist, but only meta- and orthophosphoric acid need
attention here.

Phosphorus Peroxide, V.f)^, is a white ])o\vder, which rapidly absorbs
moisture; it is produced by burning phosphorus in dry air.

Metaphosphoric Acid, HPO3, is said to occur combined in nucleiu.

rreparation, — (1) By dissolving P2O5 in cold water,

P205 + H20 = 2HP03.

(2) By fusing phosphoric acid,

H3PO, = HP03 + H20.

It is converted slowly in the cold, rapidly on heating, into phosphoric acid.
Crystalline it forms ordinary glacial phosphoric acid. Metaphosphoric acid
precipitates proteid from solution, yielding a body having the properties of
nuclein,'^ but this has been denied.^

Orthophosphoric Acid, H3PO4. — Salts of this acid constitute all the in-
organic compounds of phosphorus in the body, and are called phosphates.

Preparation. — (1) By heating solutions of metaphosphoric acid,

HP03 + H20 = H3PO,.

(2) By treating bone-ash with sulphuric acid,

Ca3(PO,)2 + SH^SO, == SCaSO, + 2H3PO,.

Properties. — On evaporation of the liquors obtained above, the acid separates in color-
less hygroscopic crystals.

Phosi)horic acid forms different salts according as one, two, or three atoms of hydrogen
are supplanted by a metal. Thus there exist primary sodium or calcium phosphates,

Nall.PO, and Ca<j|-'pQ'; the secondary phosphates, Na,HPO, and CaHPO^ ; and the

tertiary phosphates, Na^POi and CaglPOi)^. On account of their reaction to litmus
these salts have been falsely called acid, neutral, and basic, but the secondary salts are,
chemically speaking, acid salts.

The bones contain a large quantity of tertiary phosphate of calcium ; the
fluids and cells of the body contain likewise the jirimarv and secondary pho.s-
phates, while to primary sodium phosphate carnivorous urine mainly owes its
acid reaction.

In speaking of the ash of proto])lasm, Xencki * advocates the idea of .separate
combinations of the base and acid radicles with the proteid molecule, as, for

' J. Bauer: Zeitschrift fiir Biologie, 1871, Bd. 7, p. 63.

■^ L. Lieberraann : Berichte der deutschen cheml.tchen Gesellschaft, Bd. 22, p. 598.

' Salkowski : PflugeT>s Archir, 1094, Bd. 59, p. 245.

* Archiv fiir exper. Pathologie und Pharmakologie, 1894, Bd. 34, p. 334.

THE CHEMISTRY OF THE ANIMAL BODY. 959

example, the separate uiiiuii of" potassium witli piott-id and of j)hosplioric acid
with proteid, iu tlie functionally active cell. However combined, phosphoric
acid is necessary for the organism.

Ddection. — A solution of phoy])hate treated with a magnesium salt dissolved in am-
monia containing ainmitiiium chloride, gives a fine cr.vstalline precipitate of magnesium-
ammonium j)hosphatc, which on ignition loses ammonia and is converted into magnesium
pyrophosphate.

Phosphorus in the Body. — The principal source of supply is derived
from the phosphates of the alkalies and alkaline earths in the foods; it may be
absorbed in organic combinations in nucleiu, casein, and caseoses ; and it may
further be absorbed as glycerin phosphoric acid, which is an intestinal decompo-
sition product of lecithin ^ and probably also of protagon. Phosphorus leaves
the body almost entirely in the form of inorganic ])liosphate, the only exception
being glycerin phosphoric acid, which has been detected in traces in the urine.
In man and carnivora the soluble primary and secondary phosphates of the
alkalies are found in the urine, together with much smaller amounts of the
less soluble primary and secondary phosphates of the alkaline earths. There
is likewise, even during hunger, a continuous excretion of tertiary phosphate
of calcium, magnesium, and iron in the intestinal tract. In herbivora the ex-
cretion is normally into the intestinal tract, and no phosphates occur in the
urine. This is because herbivora eat large quantities of calcium salts which
bind the phosphate in the blood, and they likewise eat organic salts of the
alkalies, which become converted into carbonate and appear in the urine as
acid carbonates; such a urine has no solvent action on calcium phosphate.^
In a similar manner a great reduction of phosphate in the urine of man may
be effected by feeding alkaline citrate and calcium carbonate, the first to furnish
the more alkaline reaction to blood and urine, the second to bind the phosphate
in the blood. The more alkaline reaction itself is insufficient to prevent the
appearance of phosphates in the urine.^ On the other hand, starving herbiv-
ora, or herbivora fed with animal food, give urines acid from primary phos-
phate.*

Excreted phosphates may be originally derived froiu the phosphates of the
bones, or from phosphates arising from the oxidation of nuclein, protagon, and
lecithin, but by far the greater quantit}' is derived from the food, or from pro-
teid metabolism. In a starving dog, which feeds on its own proteid, it was
found that a ratio existed between nitrogen and phosphoric acid in the urine as
6.4:1, w^hicli approximates that in muscle, i.e. 7.6:1. On feeding meat till
nitrogenous equilibrium was established, the ratio became 8.1 :1.^ On addi-
tion of proteid to the body, a proportionate amount of phosphoric acid is re-
tained for the new protoplasm, Mobile on destruction of proteid the phosphoric
acid corresponding to it is eliminated. The larger excretion of phosphoric acid

^ Bokay : Zeitschrift fiir physialogisehe Ckemie, 1877-78, Bd. 1, p. 157.

* J. Bertram : Zeitschrift fiir Biologic, 1878, Bd. 14, p. 354. ^ Op. eit., p. 354.

* Weiske: Ibid., 1872, Bd. 8, p. 246.

5 E. Bbchoff: Ibid., 1867, Bd. 3, p. 309.

960 yl.Y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

during hunger shown in the ratio above, has been ascribed to the decomposi-
tion of tiie bones.^ Thus Munk found on Cetti, wiio lived many days without
footl, a ratio as low as 4.5:1. In starvation the brain and nerves do not
decrease in weight, so the })rotagon can hardly yield any great amount of phos-
phoric acid (Voit). Casein and other nucleo-albumins, when fed, are oxidized
and furnish phosphoric acid for the urine.

Carbon, C = 12.

This element is found combined in every organism, and in many decom-
position-products of organized matter. Elementary carbon occurs as lanij)-
black, diamond, and graphite, the two latter having tiieir origin from the action
of high heat on coal. Carbon occurs combined in coal, petroleum, and natural
gas, which are all products of the decomposition of wood out of contact with the
air. Further it is found in vast masses, principally consisting of calcium car-
bonate, having their origin from sea-shells. Tiie maintenance of life depends, as
will be shown, on the small percentage of carbon dioxide which is contained in the
atmosphere. Lavoisier believed that compounds of carbon were all products
of life, formed under the influence of a " vital force," which was a property
of the cell. It is now known that almost every constituent of the cell may be
prej)arcd from its elements in the laboratory without the aid of any '' vital
force" whatever. Notwithstanding its loss of strict scientific significance, the
old term "organic" for a carbon compound is still in vogue, and conveniently
describes a large number of bodies which are treated under the head of " or-
ganic chemistry," while the term "inorganic" is applied to the rest of the
chemical world.

Elementary Carbon. — This burns only at a high heat. It is unaffected
by the intestinal tract. This is shown by the fact that diamonds have been
stolen by swallowing them, and that finely divided jiarticles of lampblack pass
unchanged and unabsorbed to the feces, coloring them black (proof that the
intestinal canal does not absorb solid particles). If lampblack be eaten with a
meal its appearance in the feces may be used as a demarcation line between the
feces belonging to the period before the meal, and the ]x>riod subsequent to it.
Carbon unites directly with hydrogen, oxygen, and sulphur only.

Carbon Monoxide, CO. — Tiiis gas is a product of tlie incomplete combus-
tion of carbon, is present in illuminating gas, and burns on ignition to carbon
dioxide. It is usually prepared by heating oxalic acid with sulphuric acid,

COOH

I ^H.,0-f CO.,+CO,

COOH

the carbon dioxide being removed by passing through calcium iiydroxide.

Properties. — A colorless, odorless gas. Inspired, it unites with the blood
to form a carbon-monoxide haemoglobin (Ilb-CO). This is a very stable
bright-red compound which may even be boiled without decomposing. Ani-
^ See Voit : Hermann's Handbuch, 1881, vi. 1, p. 79.

THE CHEMISTRY OF THE ANIMAL BODY.

9G1

luals poisoned with VO die from want of oxygen, since the latter cannot dis-
place the carbon nionoxiile from combination with haemoglobin.

Carbon Dioxide, CO.,.— This is the highest oxidation compound of carbon,
the product of its complete combustion. It is present in the air to the extent
of 0.04 per cent. It is formed in all living cells, and in higher animals is
collected by the blood and brought to the lungs and skin for excretion ; it is
also a product of putrefaction ; it gives an acid reaction to herbivorous urine.
It is found dissolved in all natural waters, and is present combined in sea
shells. It is found in the blood principally combined with sodium in the
serum, and is likewise combined with calcium and magnesium in the bones.

Preparation.— {}) By burning carbon or a carbon-containing substance,

C^H, A + 120 = 6CO2 + mf>.

Sugar.

(2) By heating a carbonate,

CaC03=CaO + C02.

(3) By the action of an acid on a carbonate,

Na^COa + 2HC1 = 2NaCl + CO^ + Hp.

In the blood, haemoglobin and, to a less extent, serum-albumin and primaiy
sodium phosphate act like acids. If the gases be extracted from fresh defib-
rinated blood in a vacuum, all the CO2 is removed. If sodium carbonate be
added to blood, the carbonic acid belonging to this is likewise given up in a
vacuum, while a simple aqueous solution of sodium carbonate is not affected.
If serum be extracted in vacuo, only a little more than half the carbonic acid
contained in it is dis.sociated from combination, indicating that in the previous
experiment hsemoglobin had acted like an acid. If a solution of bicarbonate
of sodium (NaHCOj) be exhausted under the air-pump, just one-half of the
CO2 is given off, sodium carbonate (NajCOj) remaining. In the serum more
than one-half of the CO2 is obtained in vacuo, because the serum-albumin,
like the hsemoglobin, though less effectively, acts like an acid in fixing the
alkali and liberating fhe gas. There is likewise present the action of pri-
mary phosphate on the acid carbonate,

NaH^PO, -f NaHCOs = Na^HPO, + H^O -f CO^.

Through these agencies the tension of carbonic acid is kept high in the blood,
and its escape through the walls of the alveolar capillary is not unlike the
escape of gas on uncorking a bottle of carbonated water.

After drinking a carbonated water, carbonic oxide may be detected dissolved
in the urine.

Properties. — A colorless, odorless gas. It is poisonous, its accumulation at
first stimulating and afterwards paralyzing the nervous centres. It affects the
irritability — not, however, the conducting power — of the nerves. A solution
of carbonic oxide in water forms carbonic acid, HoCOj, and from this are derived
two series of salts, primary or acid salts, MHCO3, and secondary or neutral
salts, M2CO3.

962 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Detection. — If exj)irecl air, or air I'roiii a bag enclosing any part of the skin^
be passed through a solution of calcium or barium hydrate, a precipitate of
white insoluble carbonate will be thrown down.

ISIetabolism of Carbon. — It will be remembered that there is a union of
chlorine and hydrogen on exposure to sunlight. In a similar manner the chloro-
plivll-containing leaf of the plant, through the medium of the energy of the sun's
rays, brings the molecules of water and carbonic oxide derived from the air in
such a j)osition with regard to each other that they unite to form sugar with the
elimination of oxygen (reaction on p. 945). This process is called synthesis —
the construction of a more complicated body from simpler ones. The active or
" kinetic " energy from the sun required to build up the compound is stored,
becoming " potential " energy in that compound, and is liberated again in
exactly the same quantity on the resolution of the substance into its original
constituents. So the amount of energy liberated in the decomposition of a
food in the body is exactly equal to the energy needed to build it up from
its excreted constituents,^ and this liberated energy appears in the body as
heat, work, and electric currents.

The plant has the power of converting sugar into starch and cellulose, and
likewise into fat. Further the sugar undoubtedly unites with certain nitrogen-
containing bodies, and the synthesis of proteids results. Plants containing this
mixture of food-stuffs become the sustaining basis of animal life. The animal
devours these substances and either adds them to his body, or burns them to
prevent destruction of his own substance : such are the objects of food. In
contradistinction to synthesis in plants, animal life is said to be characterized by
analysis, i. e., the resolution of a complicated substance into simpler ones. This
classification is not entirely accurate, many exceptions occurring on both sides;
for example, animals may convert sugar into fat, which is synthesis. The
animal expires its carbon partly as carbonic acid, and partly in the form of
more complex organic compounds such as urea and uric acid. Since these
latter after leaving the body eventually become oxidized, and the carbon
becomes completely changed to carbon dioxide, it follows that all animal carbon
is finally restored to the air in the form of carbon dioxide. Thus is established
the revolution of the carbon atom, made possible by the energy of the sun,
between air, plants, animals, and back to air again. Burning coal, lime-kilns,
volcanoes, give carbonic acid to the air. Rain water receives carbonic acid
from the atmosphere, from putrefying organic matter in the soil and from the
roots of trees, and ultimately much of this combines with mineral matter, or
contributes to form shells in marine life.

Silicon, Si = 28.

Silicon is found in the ash of plants, and in traces in the cells and tissues of
animals, being a constant constituent of hen's eggs. It appears in traces in the
human urine, and in considerable quantity in herbivorous urine. It is especially-
present in hair and feathers. It does not seem to be of great importance to the
' See Rubner, Zeitschrift fiir Biologic, 1893, Bd. 30, p. 73.

THE CHEMISTRY OF THE ANIMAL BODY, 963

life of the plant, i'ov if corn-stalks, whose ash usually contains 20 per cent, of
silica (SiOa), be grown in a soil free from it, the plant flourishes though only
0.7 per cent, of silica is found in the ash, this having been derived from the
vessel holding the soil.

Silicon Dioxide, or Silica, SiOa- — This is the oxide of the element, and is found in
quartz and sand, but nut in the organism.

Silicic Acids. — The ortho-silicic acid (IliSiOJ is formed by the action of an acid on a

metallic silicate,

Ca^SiO* + 2H2CO3 = 2CaC03 + H.SiO,.

This reaction takes place in the soil, and the silicic acid so obtained is soluble in water and
is a colloid — that is to say, is of gelatinous consistence, will not crystallize, and does not
osmose through vegetable and animal membranes. However, it is in this form or in the
form of vsoluble alkaline silicate that it is probably received by the root of the plant.'

Metasilicic acid has the formula IlaSiO;,, while the polysilicic acids (H2Si05,H6Si.207, etc. )
are numerous, and constitute the acid radicals of most mineral silicates. If silicic acid be
evaporated and dried, it leaves a gritty residue of silica.

The Metallic Elements.
The metals in the body are the alkalies potassium and sodium, the alkaline
earths calcium and magnesium, and the heavy metal iron.

Potassium, K = 39.

Potassium salts are found predominating in all animal cells (see p. 943),
and in the milk which is manufactured from the disintegration of such cells.
They are found in the blood -corpuscle to the almost complete exclusion of
sodium salts. Only to a small extent do they occur in the fluids of the body
and in the blood plasma (K2O = 0.02 per cent, in plasma). They are excreted
in the urine. Potassium salts are retained on the surface of the ground for the
use of vegetation, and occur in the plant not only as inorganic but also as
organic salts (tartrate, citrate, etc.).

Potassium Chloride, KCl. — Potassium chloride is a constant constituent
of all animal cells and tissues, and may be absorbed with the food or be pro-
duced in the body after eating potassium carbonate or phosphate, since these salts
may react with the sodium chloride. If fed, it is ordinarily balanced by its ex-
cretion, but if 0.1 gram be introduced into the jugular vein of a medium-sized
dog, immediately paralysis of the heart ensues. It is a powerful poison for nerves
and nervous centres. It melts when heated to a low red heat, and volatilizes
at a higher heat.

Potassium Phosphates. — The primary (KH2PO4) and secondary (KgHPO^)
phosphate of potassium are the principal salts of the cells of the body, and are
likewise present in the urine, and to a very small extent in the blood-plasma.
They are undoubtedly intimately connected with the functional activity of proto-
plasm. Presence of carbonic acid causes the conversion of the secondary phos-
phate into the primary salt, and this occurs in the blood-corpuscle as well as in the

plasma :

^ K^HPO, + CO, + HP = KH^PO, + KHCO3.

' Bunge: Physiologische Chemie, 3d ed., 1894, p. 25.

964 ^l.V AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Priinarv acid jihospliate of potassium contributes to the acid reaction of the
urine, tliougli in presence of sodium chloride there is a tendency to the forma-
tion of primary sodium phosphate and potassium chloride. It is the cause of
the acid reaction in muscle in rigor mortis (see j). 989).

Potassium Carbonates, — The priniary and secondary carbonates exist
in the body only in trifling quantities. They may be j)roduced as above de-
scribed by the action of carbonic acid on the phosphates, tluy may be ingested
with the food, or they may result in the body froin tlie combustion of an organic
salt of potassium, according to the same reaction as would take place by burn-
ing it in the laboratory,

KX\H A + 'iO = K2CO3 + 3CO2 + 2H2O,

K tartrate.

Feeding potassium carbonate or an organic salt of potassium makes the urine
alkaline owing to the excretion of potassium carbonate.

Potassium salts are poisonous if introduced into the blood in too large quantities. In
concentrated solutions in the stomach they ijroduoe ffostn'tis, even with quickly fatal
results. '

Zuntz believes that potassium is combined with haemoglobin in the blood-corpuscle, and
may_ be dissociated from it by the action of carbonic oxide.*

Potassium in the Body, — The various salts of j)otassium are received
with the food in the manner described ; the pho.sphate may be retained for
new tissue, but the other salts are removed in the urine. They are all quite
completely absorbed in the intestinal tract. In starvation, or in fever, where
there is high tissue-metabolism, the body suffers greater lo.ss of the potassium
phosphate-containing tissue than it does of the sodium-rich blood, and j)otas-
sium exceeds sodium in the urine (reverse of the usual proportion), lounge ^
has noted an important influence of potassium salts. If a potassium .<alt be in
solution together with sodium chloride, the two partially react on each other,
with formation of potassium chloride. If now potassium carbonate, for example,
be eaten, the same reaction occurs in the body,

K2CO3 H- 2NaCl = 2KC1 + Na^COj.

The kidney has the power of removing soluble substances which do not belong
to the blood or are pre.'^ent in it to excels, and con.^equently the two salts
formed as above are excreted. Hence potassium carbonate has caused a direct
loss of sodium and chlorine. For this reason, if potatoes and vegetables very
rich in potassium salts are eaten, sodiimi chloride must be added to the food to
compensate for the loss. Nations living on rice do not need salt, for here the
potassium content is low. Tribes living solely on moat or fish do not use
salt, but care is taken that the animals slaughtered for food shall not lose the
blood, rich in sodium salts, and strips of meat dipped in blood are, by some
races, considered a delicacy.*

* Biinge: Pkyniologische Chemie, 3d ed., 1894, p. 136.

* A. Loewy und N. Zuntz: Pflilger's Archiv, 1894, Bd. 58, p. 522.

' ^p. cit., p. 108. * Bunge, Op.cit., p. 116.

THE CHEMISTRY OE THE ANIMAL BODY. 9(j5

Sodium, Na = 23.

Sodium salts belong particularly to the fluids of" the boily (see p. 948),
blood-plasnia containing 0.4 per cent, calculated to NagO.

Sodiura chloride, NaCl, is found in all the fluids of the body. It is found
in blootl and lynij)h to an extent of about O.Go j)er cent., in the saliva, gastric
juice, milk, sweat, urine, etc. Sodium chloride, like potassium chloride, melts
at a low red heat, hence the fluids of the body yield a fluid asii, with the single
exception of milk, which contains a high percentage of infusible calcium phos-
phate. Sodium chloride is very readily soluble. In the blood it acts as a
solvent on serum-globulin and other proteids, and its inert presence in proper
concentration affords a medium in which the functional activity of cells and
ti&sues is maintained. (For "physiological salt-solution" see p. 948.) From
sodium chloride the hydrochloric acid of the gastric juice is prepared (see p.
952) ; it is also a necessary addition to every food where potassium salts are
in great preponderance (see p. 964), but it is taken by most races in amounts
far above these physiological necessities.

If a mixture of necessary food-stuffs — proteid, fats, starch, salts, and water — in proper
proportion, but without flavor, be set before a dog, he will starve rather than touch it. A
raan will attempt its digestion, but the permanent support of life is impossible. A food
to support life must be a well-tasting mixture of food-stufFs, for, through the action of the
flavor on the mucous membrane of the mouth and stomach there is established reflexly a
nervous influence causing a proper flow of the various digestive juices. Hence salt,
pepper, mustard, beer, wine, and other condiments are taken with the food. What the
change is, when a substance acts on the taste-buds of the tongue, for example, start-
ing a motion such as is afterwards interpreted in the brain as flavor, is unknown.
Chemical constitution gives no hint how a body will taste or smell.

In carnivora every trace of sodiura chloride is absorbed by the villi from
the intestinal tract. This is a proof that absorption does not depend on simple
physical osmosis, in which case the intestinal contents would tend to have the
same percentage composition as the blood, but upon the selective capacity of the
exposed protoplasm of the villi. Sodium chloride is the principal solid con-
stituent of sweat and of tears. Usually, however, it is lost to the body
through the urine, of whose ash it forms the chief constituent. The quantity
of salt in the urine is decreased during gastric digestion (see p. 952). Sodium
chloride does not pa.ss to the urine as soon as it rises above a certain quantity
in the blood, but the tissues retain or give it up according to circum,stances.
Experiments ^ have been made on a man who ate normally 27 grams of salt
daily; on reducing this to 1.4 grams the following daily excretions occurred
in the urine: 9.9, 6.5, 3.8, 4.1, 3.2, 2.9, 2.9, 2.5. Then, on returning to 27
grams daily: 3.4, 7.9, 11.2, 15.8, 17.4. Experiments of abstention have never
been carried so far as to produce vital disturbances, but the physiological min-
imum is probably very low. A dog weighing 35 kilograms may live on 0.6
gram of salt daily.'^ Sodium chloride, fed, produces of itself alone an increase

' Klein und Verron : Sitzungsberichte der Wiener Academie, Mathematisch-physikalische Classe, ■
1867, iv. (2), p. 622.

* Voit: Hermann's Handbuch, 1881, vi. 1, p. 367.

i'OG Ay AMEIilCAX TEXT-BOOK OF PHYiSIOLOUY.

of water and of urea in the urine.* The increase of urea means increase in
proteid metabolism, and is prothiced by all sidts; it is to be explained by the
increased motion of water from the cell, the same eifect being seen on drinking
large (juantitics of water (see p. 948).

Sodium sulphate, 'S'a.^O^ called " Glauber's s:ilt," is found together with
potassium sulphate in the urine in the condition of preformed sulphuric acid
(see p. 951). If fed, it reappeare in the urine. It acts on the epithelial cells
of the intestines, preventing the absorption of water, consequently causing diar-
rhoea. Other laxatives act in the same way.

Sodium Phosphates. — The primary (XaHgPO^) and the secondary
(NaoHPOJ salts are found to a small extent in the blood-])lasnia and other
fluids, and in the urine. As with the jiotassium ph()S|»liates, carbonic oxide
acts when in certain excess to convert the secondary phosphate into NalloPO^
and XaHC03. These two, however, may react on one another to drive ulf car-
bonic acid (see p. 961). Carnivorous urine owes its acid reaction principally
to primary sodium phosphate. If a mixture of XaHjPO^ and Xa2HPO^ be
permitted to diffuse through membranes, the XaHoPO^ passes through in
greater quantity, and this process may take place in the kidney." Secondary
sodium phosphate dissolves uric acid on warming, forming sodium acid urate
and primary phosphate, which solution reacts acid (Voit). Urine standing in
the cold precipitates uric acid with the formation of secondary phosphates,
while the reverse reaction with return of original acidity takes place on warm-
ing the urine.

Sodium Carbonates. — Of these there are two, the primary, XaHCOg, and
the neutral, Xa.X'Oj. The organization owes its alkaline reaction, and also its
])ower of combining with carbonic acid, almost entirely to sodium carbonate.
Saliva, pancreatic and intestinal juice are strongly alkaline with sixliuin carbonate,
as are also blood, lymph, and other fluids. If the organization be acidified, by
feeding acid to a rabbit, for example, death occurs even before complete loss
of the blood's alkalinity, while venous injections of sodium carbonate at the
proper time restore the animal. Carbonic oxide cannot be remtn-ed from the
tissues in the acidified blood. Sodium carbonate treated with carbonic acid
becomes acid sodium carbonate, and this change is effected in the internal res-
piration, where the cells give COo to the blood. Treated with acids, both car-
l)onates liberate carbonic oxide — a reaction which takes place in the blood
(see p. 961). Bunge suggests that the acid chyme of the stomach, into whose
finest particles the alkaline intestinal juice diffuses, is especially penetrable by
the latter's enzymes, because liberated carbonic oxide has separated the j)articles
of chyme from each other. The same principle would hold true of a morsel
well mixed with saliva, which, as is well known, is more easily penetrable by
gastric juice than one not so mixed. Sodium carbonate mav be obtained for
the body either directly from the food by absorption, or indirectly through

1 Voit : Op. ciL, p. 160.

^ Soubiranski: Archiv fiir exper. Pathologic und Pharmakologie, 1895, Bd. 35, p. 178.

THE CHEMISTRY OF THE ANIMAL BODY. 967

combustion of siKliuiu organic salts. Ingested in sufficiently large quantities,
it makes the urine alkaline.

Sodium salts are undoubtedly united witii serum-albumin in the pla.sma,
forming a combination which may be dissociated by carbonic oxide.

Detection. — Sodium gives a yellow coloration to a colorless flame, and a distinctive
bright line in the j-ellow ot" the spectroscope.

SoDU'M IN THE BuDY. — This suhject has been discussed under the diflerent salts, and
likewise under potassium and hydrochloric acid ; repetition here is therefore needless.

Ammonium, XH^.

Ammonia, NH.v has already been described (p. 955).

Sodium- Ammonium Phosphate, NaNH^HPOi, is an insoluble salt formed in the
urine durinu ammoniacal fermentation.

Ammonium Carbonate, (XHJgCOg, is formed by the union of carbonic
oxide and ammonia in the presence of water, and is therefore a usual product
of putrefaction. If introduced into the blood, it is converted into urea by the
liver. In uremia urea passes from the blood into the stomach and is there
converted into ammonium carbonate, which produces vomiting through irrita-
tion of the mucous membrane. (See further discussion under Carbamic Acid
and Urea.)

Calcium, Ca = 40.

Calcium is by far the most abundant metallic element in the body, and, as
has been found in the dog, 99.5 per cent, belongs to the composition of the
bones.^ Outside the bones it occurs most abundantly in blood-plasma. It is
found in all the cells and fluids of the body, probably loosely combined with
proteid. Calcium is always accompanied by magnesium.

Calcium Chloride, CaCl,, is found in small quantities in the bones.

Calcium Fluoride, CaFj, a salt insoluble in water, is found in bone, den-
tine, and enamel (see p. 954).

Calcium Sulphate, CaSO^, is found in small quantities in bones and rarely
as part of the sediment in strongly acid urine.

Calcium Phosphates. — Of these there are three — primary, CaH^(POJ2,
secondary, CaHPO^, and tertiaiy, Ca3(P04)2- The tertiary phosphate is insol-
uble in water, the secondary only very slightly soluble, but the primary salt is
soluble. The tertiary and secondary phosphates are insoluble in alkali, but
soluble in mineral acids and in acetic acid. The tertiar\^ phosphate forms the
largest mineral constituent of the bones (83.89 per cent., Zalesky) and of den-
tine and enamel. Tertiary phosphate of calcium likewise occurs in the blood;
how it is held in solution it is difficult to say, though it is probably loosely
combined with proteid. In a similar way it is combined with the protoplasm
of the cell. It is largely found in the ash of milk, having been in previous
chemical combination with casein. Tertiary phosphate of calcium is continu-
ously excreted into the intestinal tract. It is present in the acid gastric juice,
but only in traces in the alkaline saliva, pancreatic juice, and in the nearly
1 Heiss : Zeitschrift fiir Biologie, 1876, Bd. 12, p. 165.

968 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

neutral bile. Tertiary phosphates never occur in the urine, except as a sedi-
ment after the urine has attained an alkaline reaction, being formed from the
acid phosphates. In carnivorous urine the calcium jiresent occurs as primary
and secondary phosphate, the sokition of the latter being aided by the primary
alkali phosphate and sodium cldoride. Occasionally a coat is noticed on the
surface of the urine, an appearance once thought to be. a sign of pregnancy.
Tins coat is now known to consist chiefly of secondary phosphate of calcium,
which may crystallize out on the urine becoming alkaline. Calcium dues not
occur as phosphate in an alkaline urine (see p. 959).

Calcium Carbonates. — Of these there are two, the primary or acid,
CaH2(C03)2, and the secondary or neutral carbonate, CaCOa. Neutral calcium
carbonate is the substance of which sea shells, coral, egg-shell, and otoliths
consist. It is found in the ash of bones to the extent of 13.032 per cent.
(Zalesky). Ajuitite is a mineral having the formula CaioF2(P04)6, and Hoppe-
Seyler, using Zalesky's figures, believes that bone has a composition repre-
sented by Cai,C03(PO,)6, or 3Ca3(P0,)2,CaC03, in which CO3 has the position
of F2 in apatite. In the wasting of the mineral matter of bones in osteoma-
lacia this formula of composition remains constant, • one molecule of calcium
carbonate always being removed for every three molecules of the phosphate.
Neutral calcium carbonate is insoluble in water or alkali, but dissolves in
water containing carbonic oxide to form the soluble acid carbonate, CaH2(C03)2,
This is found in blood and lymph, and in minute quantities in all the tissues.
It is found in herbivorous urine, which contains carbonic acid in excess, but it
is soon deposited as neutral carbonate as the carbonic oxide diffuses into the
air. It occurs in all alkaline and neutral urines, though to a less extent than
calcium phosphate in acid urines. It is found in pancreatic juice and in the
saliva, from which latter is derived the calcic carbonate which, mixed with
bacteria and other organic matter, is deposited as tartar on the teeth.

The ferment rennet does not act in the absence of calcium salts. The
coagulation of the blood requires the presence of calcium salts,'-^ and fibrin
always contains calcium. If ten parts of blood be drawn into one part of a
1 per cent, solution of potassium oxalate, thus precipitating the calcium, no
coagulation takes place, but on the addition of calcium chloride a typical fibrin
forms. A solution of sodium oxalate passed through a beating excised heart
causes it to cease beating' and nerves and muscles lose their irritability when
calcium salts are abstracted from them with sodium oxalate.* These facts
illustrate the intimate relation between calcium salts and the functional activity
of protoplasm.

Detection. — Ammonium oxalate in neutral or alkaline solutions of calcium
salts gives a precipitate of calcium oxalate — a white powder, insoluble in acetic
or oxalic acid.

1 M. Levey: Zeitschrift fiir phijsiolofjische Chemie, 1894, Bd. 19, p. 239.
" Arthus et Paget: Archives de Physiologie, vlo. ii. p. 739.
' Howell and Cooke : Journal of Phy.volofjy, 1893, vol. 14, p. 219, note.
* Howell : Journal 0/ Physiology, 1894, vol. 16, p. 476.

THE CHEMISTRY OF THE ANEMAL BODY. 969

Calcium in tiik Body. — Calcium salts arc especially needed in childliood for the
growth of the bones. It lias been estimated that the human suckling retjuires 0.32 gram
CaO dail}', and in the milk for that time is contained 0.55 gram to 2.37 grams, so that
there may easily be lack of CaO when absorption is unfavorable. In children with rickets
the bones contain too little calcium, and are abnormally weak and flexible. This same con-
diti(m may be reproduced in young growing dogs by feeding them entirely on meat and I'at,
which contain too little calcium lor j)roper skeletal devel()|)ment. ' Such dogs iivovf rapidly
in size, especially around the thorax, while the pelvis remains ludicrously small, the extrem-
ities become bent and finally incapable of supporting the weight of the body. A puppy
of the same litter fed on the same food but with the addition of bones grows normally. In
certain cases even when children are fed with sufficient calcium they still have the rickets.
This might be due to a lack of ability to absorb the salts, but this Riidel ^ has disproved.
To a child having rickets he administered a calcium salt, and confirmed its absorption
by the increase in the calcium contents of the urine, the result being the same as with
a normal child. (Example: Normal da}% 0.0196 gram CaO in urine; after I'eeding
1.4 grams CaO dissolved in acetic acid the amount in the urine rises to 0.0396 gram for
the twenty-four hours. ) Riidel therefore concludes that the cause of rickets may be in a
local change of the bones themselves, whereby calcium salts are not deposited in the normal
manner.

In osteomalacia there occurs a solution of the salts of the bones in adult life, called
softening of the bones. In osteoporosis, which is a simple atrophy of the bones, similar
effects are produced. Voit ' fed a pigeon for a year on washed wheat and distilled water,
at the end of which time the pigeon apparently did not diff'er from the normal bird. A
few months later a wing was broken, and the autopsy discovered osteoporosis in high
degree, the skull being especially attacked. Weiske * has shown that rabbits ultimately
die when fed on oats which are poor in calcium ; the oats yield an acid ash and produce an
acid urine. On autopsy osteoporosis is found. This does not take place when calcium
carbonate is added to the food. Whether the loss of salts to the bone is due to a normal
metabolism, or to solution due to the production of acids in the metabolism of proteid,
is an unanswered problem (see pp. 950, 955) the discussion of which lack of space forbids.*
In such experiments as the above, the percentage of ash is always diminished, while the
percentage of organic matter always rises, whereas the actual percentage composition of the
ash itself remains the same. This is a strong argument in favor of the view that bone is
a mineral of definite chemical composition. The mineral matter of bone is believed by
some to be loosely combined with the organic material, principally ossein, but of this there
is no proof.

The exact amount of calcium salt necessary to keep up the supply in the adult body is
unknown, but it must be exceedingly small. A dog of 3.8 kilograms eating with his food
0.043 gram CaO maintains his calcium equilibrium (Heiss).

Regarding the absorption of calcium salts, it has long been questioned
whether inorganic salts can be absorbed, since, it was argued, insoluble
phosphate would immediately be precipitated in the blood. It has, however,
been conclusively shown that such .salts when eaten produce an increase in the
calcium of the urine® and it is known that blood has a special capability for
carrying calcium phosphate. Calcium carbonate and chloride are capable of

' E. Voit: Zeitschrift fur Biologie, 1880, Bd. 16, p. 70.
' Archiv fiir exper. Pathologie und Pltarm-akologie, 1893, Bd. 33, p. 90.
' Hermann's Handbuch, 1881, vi. 1, p. 379.
* Zeitschrift fiir Biologie, 1894, Bd. 3],p. 421.

5 See Weiske, loc. cit. ; Bunge, Physlologische C'hemie, 3d ed., 1894, p. 104; V. Noorden, Path-
ologie der Stoffwechsels, 1893, pp. 48 and 413. ^ Riidel, Op. at., p. 79.

970 ^l.V AMERICAN TEXT-BOOK OF rilY^IOLOGY.

absorption, while al)sorj)tioii of the phuspliate may be consitlerod as still in
doubt. If calcium chloride be given, a little of the calcium appears in the
urine, and all of the chlorine, this being due to the conversion in the intes-
tine of calcium chloride into calcium carbonate and sodium chloride, which
latter is completely absorbed. Organic salts of calcium such as the acetate are
absorbable, as are probably proteid combinations with calcium such as casein.
Milk and egg-yolk are the foods richest in calcium salts, cow's milk containing
more calcium to the liter than does lime-water.'

The excretion of calcium takes place in major part as triple phosphate from
the wall of the intestine, in minor part through the urine (for the latter see pp.
959 and 968). It is excreted during starvation, and is the principal constituent
of starvation feces (Yoit). The secretions of the intestines, according to Fr.
MUller," hardly contain enough calcium to account for that found in the feces,,
so that it is probably excreted by the epithelial cells of the villus. In starva-
tion the source of excreted calcium is principally from the breaking down of tis-
sue, but partially from the metabolism of the bones. The excretion is
never large. On subcutaneous injection of small amounts of calcium acetate
in dogs,^ the calcium excretion may be raised for several days. On venous
injection of 0.8 gram CaO as acetate, after one hour but 0.3 gram could be
found above the normal in the blood, and analysis of the liver, kidney, spleen,
and intestinal wall failed to reveal more than the usual minimal amounts of
calcium. As it is never rapidly excreted it must have been temporarily depos-
ited in some unknown part of the body. Rey * believes the large intestine to
be the principal organ of calcium-excretion, while F. Voit ^ attributes this
function to thfe small intestine.

Strontium, Sr == 87.5.

Cremer® has shown, on adding strontium phosphate to almost calcium-free food of young
growing dogs, that the strontium line could be detected in the subsequent spectral anab'sis
of their bones. Weiske,' on feeding j'oung rabbits with food nearly free from calcium,
and with addition of strontium carbonate, found the ash in some of the bones to contain,
in the place of CaO, as high as 4.09 per cent, of SrO. In both of the above experiments
the skeleton remained very undeveloped in comparison with the normal, so that strontium
cannot be considered a physiological substitute for calcium.

Magnesium, Mg = 24.3.

This is the second in importance of the alkaline earths. It is present
wherever calcium is found, but in comparison with calcium it has been little
investigated. It occurs principally as pho.sphate, but is found as carbonate
in herbivorous urine. Of the total quantity of magnesium in the dog, Heiss

^ Bnnge: Physiologiache Chemie, 3d ed., 1894, p. 101.
' Zeitschrift fUr Biologie, 1894, Bd. 20, p. 356.

' Rey: Archiv fur exper. Pathologic und Phorrhokologie, 1895, Bd. 35, p. 298.
* Rey, loc. cit. * Zeitschrift fiir Biologie, 1893, Bd. 29, p. 325.

® Sitzungsberichie der Gesellschaft fiir Morphologic und Physiologic in MUnchen, 1891, Bd. 7,
p. 124.

^ Zeitschrift fiir Biologie, 1894, Bd. 31, p. 437.

THE CHEMISTRY OF THE ANIMAL BODY. 971

found that 71 per cent, belonged to the boue.s. It is found decidedly pre-
dominating over calcium in muscle, but is less in quantity than calcium in
the blood.

Magnesium Phosphates. — Magnesium tertiary phos[)hate, Mg2(P04)3, is
found in the ash of bones to the extent of about 1 per cent., is present in blood
and especially in muscle, probably in combination with proteid, and contrib-
utes to the functional activity of protoplasm. It is continuously excreted
by the walls of the intestinal canal. The primary and secondary phosphates
of magnesium are found in carnivorous urine, solution of the latter being
aided by the presence of primary alkali phosphate and sodium chloride.
Tertiary phosphate of magnesium is insoluble in water, the secondary very
slightly so, the primary quite soluble ; but all are soluble in acids. In the am-
moniacal fermentation of the urine, ammonium magnesium phosphate, MgXIT^-
PO4, is precipitated as a fine crystalline powder insoluble in alkalies. When-
ever this fermentation takes placed, whether in the bladder or, by similar
reaction, in the intestines (herbivora especially), stones are formed.

Magnesium Carbonates. — The neutral carbonate, MgCOg, is insoluble in
water, but soluble in water containing carbonic oxide, forming secondary or acid
carbonate, MgH2(C03)2. This latter occurs in herbivorous urine.

Detection. — A mixture of sodium phosphate and ammonia containing an
ammonium salt (NH^Cl) precipitates from magnesium solutions magnesium
ammonium phosphate.

Magnesium in the Body. — Considerations regarding the absorption of
calcium apply likewise to magnesium. It is absorbed by the intestine as inor-
ganic and probably as organic combinations. If growing rabbits be fed on
a diet poor in calcium salts, but containing magnesium carbonate, the bones
may be brought to contain double the normal quantity of magnesium, but the
skeletal development remains far behind that of a normal rabbit, and there-
fore magnesium can in no sense be considered a substitute for calcium.^ The
magnesium salts, whether phosphate or carbonate, being more soluble than the
calcium salts, occur in the urine in greater abundance. Indeed, in carniv-
orous urine the major part of excreted magnesium is found in the urine, the
balance being given oif through the intestinal wall to the feces. In starvation
the source of the excreted magnesium is from the bones, and especially from
destruction of its combination in proteid metabolism.

Iron, Fe = 56.

This is the one heavy metal which is an absolute necessity for the organ-
ism. About three grams occurs in the average man. It has been demon-
strated of certain bacteria that they will not develop in the absence of iron,
and this is believed to be true of all protoplasm. Iron is found through-
out the body, and is especially an ingredient of haemoglobin (0.4 per cent.),
which carries oxygen to the tissues. It is found deposited in the liver and
the spleen as ferratin, hepatin, and other less investigated organic compounds.
1 Weiske : Zeitschrift fur Biologie, 1894, Bd. 31, p. 437.

972 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

It is found in muscle washed free from blood. Iron appears in urine and in
milk as organic compounds, and in the bile, gastric juice, and intestines as
phosphate, in the feces as sulphide. Iron occurs in two forms, the ferro- and
ferri- compounds, in which it has respectively two and three bonds.

Ferrosulphide, FeS. — This is found in the feces and is the ])rotluct of
the action of sulphuretted hydrogen or alkaline sulphide on both inorganic
iron and likewise, more slowly, on organic iron-containing com])ounds (fer-
ratin, haematogen, etc.). Ammonium sulphide acts in a similar manner, and,
in all cases, ferric salts are reduced to ferrous :

2FeCl3 + 3(NH,)2S = 2FeS + 6XH,C1 + S.

Ferric chloride.

Ferric Phosphate, FePO^. — This is found in the gastric juice, bile, and
probably in the intestinal juice ;^ it is not, as many have believed, given off
by the epithelia of the intestines. It is soluble in mineral acids, but insoluble
in water, alkalies, or acetic acid.

Detection. — Ammonium sulphide gives a black precipitate of ferrous sulphide in all
iron solutions. Ferrocj-anide of potassium gives a deep blue coloration (Berlin-blue) to
solutions of ferric salt. Ferricj'anide of potassium gives TurnbuU's blue, very similar
to Berlin-blue, with solutions of ferrous salts.

Irox in the Body. — The amount of iron in the urine is very small,
amounting daily in a large starving dog to 0.0013-0.0049 gram.' Feeding
iron compounds does not increase the amount of iron in the urine. Forster'
fed a dog of 26 kilograms for thirty-eight days with washed meat containing
0.93 grams of iron, and in the feces were found 3.59 grams belonging to the
same period. Here there was a loss of 2.66 grams * of iron from the body,
and the necessity of iron as a food was established.

Concerning the method and the amount of iron-absorption, considerable difficulty has
been encountered owing to the fact that both absorj^tive and secretive organs lie in the
intestinal canal. On feeding a dog for thirteen days with meat containing 0. ISO gram Fe,
there were found in urine and feces for the same time 0.1765 gram Fe ; then to the same
food for a similar length of time were added 0.441 gram Fe (as sulphate), making in all
0.636 gram Fe, and of this 0.6084 gram were recovered in the excreta.^ This experiment
proves only that such absorption as may take jjlace is pretty nearly balanced by the excre-
tion. After eating blood the feces are found to contain much lutimatin, and it is believed
that iron cannot be absorbed in that way. Bunge® has sought for one oi' the antecedents
of haemoglobin in egg-yolk, and has described it as an iron-containing nucleo-albumin,
which he names hfematogen. That and similar nueleo-albumins existing in plants he con-
ceives to be the source of absorbable iron, while inoriranic salts of iron aid only indirectly
by forming iron sulphide, thus i>reve!iting the same formation from organic iron (see above).
IMarfori^ has jncparcd a substance from i)roteid and iron salts, called fcrratin, which con-
tains 4 to s ]HT cent, of iron : it is a coiiiiiound unaffected by gastric juice or by boiling ; it

' Macallum : Journal of Phyxioloyy, 1894, vol. 15, p. 268.

^ Forster: Zeilschrift fur Biologie, 187.3, Bd. 9, p. 297. '' Loc. cit.

* This figure is probably too high, but the principle itself is fundamental. See Voit,
Hermann'ii Handbook, 1881, vi. 1, p. 385.

^Hantburger: Zeiischrift filr phynioloffij^rhe Chemie, 187S, l?d. 2. p. 191.

* Zelt.frlirit't filr physiologiiicJie Ckeiiiie. 1884, Bd. 9, p. 49.

' Archil- fiir ejrper. Pathologic und Pharmakologie, 1891, Bd. 29, p. 212.

THE CHEMISTRY OF THE ANIMAL BODY. 97'J

is soluble in thealkaliiio iiiti'stini', wlicic it is l)iit slowly affected by alkaline sulphide. Now
this same forratin is louiid in tlu; body itscU", esijccially in \.\ni liver/ althoui-di not the only
iron-containing substance of the liver. '^ If ferratin be fed, the (juantity of it incirease.s in
the liver. If a dog be fed on milk, which is alway.s poor in iron, and he be bled from
time to time, the ferratin disappears from the liver, being used for the formation of new
red blood-corpuscles.^ Such a liver does not change color when placed in dilute ammo-
nium sulphide, while one containing ferratin or other iron compounds gradually turns black
from iron sulphide. As it is not decomposed by boiling, i'crratin is found in the usual
cooked moat. Concerning the influence of inorganic salts, Schmiedcberg agrees with Bunge
that the formation of iron sulphide protects the ierratin Irom attack.

The insolubility of iron salts in alkaline solutions has raised the question of their
absorption by the blood. If inorganic iron salts be injected into a vein, the iron reappears
chiefly in the intestines, with only 3 to 4 per cent, in the urine (Jakobj) : in too great
quantities they have jiowerful to.xic properties. Gottlieb* administered 0.1 gram of iron
as sodium iron tartrate subcutaneously to a dog during a period of nine days ; twenty-eight
days after the first injection 0.0969 gram Fe had been removed in the excreta over and
above the normal excretion calculated for the same time. It was shown that this iron was
especially stored in the liver. It may be argued that such iron, being foreign to the organ-
ization, was deposited in the liver and gradually excreted through the bile, as other heavy
metals, mercury, copper, lead, would be. Kunkel* fed mice and to the food of half their
number added a solution of oxychloride of iron (FeCl:„4Fe(OII)3, liquor ferri oxychlorati) :
in the livers of those fed with iron, iron was present to a greater extent than in the others ;
but here, again, the surplus can be attributed to the sulphide-forming protective power of
the added salts, which Kunkel admits, though maintaining the contrary ground. The only
proof of the absorption of inorganic salts emanates from Macallum,® who showed, after
feeding chloride, phosphate, and sulphate to guinea-pigs, that the epithelial cells and the
subepithelial leucocytes of the intestines gave a strong microchemical reaction for iron
with ammonium sulphide. With small doses this was observed only near the pylorus, for
iron is soon precipitated by the alkali of the intestines, but where the iron salt was in suf-
ficient quantity to neutralize the intestinal alkali it could be absorbed the whole length of
the small intestines. Whether inorganic iron unites with proteid before absorption or not
is unknown.

Regarding the transformation of iron compounds after absorption into haemoglobin,
little is known except that the necessary synthesis takes place in the spleen, in the bone-
marrow, and probably in the liver. On the destruction of red blood-corpuscles, proteid
bodies holding iron in combination are deposited in the cells of the liver and spleen, this
being noticeable in pernicious anaemia. On the production of icterus with arseniuretted
hydrogen, similar iron compounds are noted in the liver, being cleavage products of h;«mo-
globin in its transformation to biliary coloring matter. The amount of iron normally
excreted from the body is far less than the corresponding biliary coloring matter (see
Haemochromogen), showing that the rest of the iron is retained for further use in con-
structing new haemoglobin.

Iron is excreted as phosphate in the gastric juice, in bile (in considerable quantity), and,
according to Macallum,^ in the intestinal juice. In the urine it is present as an unknown
organic compound.

A newborn child or animal has, proportionately to its weight, far more iron than at any

^ Maifori, loc. cit., and Schmiedeberg, Arckiv fur exper. Pathologie und Pharmakologie, 1894,
Bd. 33, p. 101.

^ Vay: ZeitMchrift fur phyniologische Chemie, 1895, Bd. 20, p. 398.
^ Schmiedeberg, Op. cit, p. 110.

* Zeitschrift fiir phyi^iologische Chemie, 1891, Bd. 15, p. 371.

* Pflugers Archiv, 1891, Bd. 50, p. 11. " Journal of Physiology, 1894, vol. 16, p. 268.
' Op. cit., p. 278.

974

AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

other time of its lil'c. This iron is lost only very slowly, lu'iu-e the very small (jtiantity of
iron in the milk answers all necessities. The other salts of the milk arc in the same pro-
portion to one another as are the salts in the newborn animal.

Tables representing generally accejjtetl analyses of the mineral constituents of the more
important fluids and cells of the body are subjoined. Only very i)ronounced differences
are to be taken into consideration in drawing conclusions, for analyses of animals of dif-
i'orent species, or of the same species, or even of the same animal at different times, show
wide variations. The tables rejjresent parts in 1000 of fresh substance :

I.

KsS04.

KCl.

NaCl.

NajCOa.

CaCOa.

CajPO^.

MgCOj.

Mg3(P04)j.

FePO«.

Saliva 1 (dog) ....
Pancreas *•' (dog) . .
Gastric juiced (dog).
Fresh bile< (dog) . .

0.209

6.022

0.940

0.93

1.125

1.546
2.53

2.507
0.185

0.940
3.30(NaaO)

0.056

0.150

0'.624(CaOj)
0.030

0.113
0.07
1.729
0.039

O.Ol(MgO)
0.007(MgO)

0.01
0.226

0.082
0.021

11.

Blood-scrum s (dog) . .
Blood-corpuscles 0 (pig)
Blood-serum fi (pig) . .

Muscle " (ox)

Milk 8 (cow)

KjO.

NajO.

CaO.

MgO.

FeaOg,

0.202

4.341

0.176

0.041

0.01

5.543

0

0

0.158

0.273

4.272

0.136

0.038

4.654

0.770

0.086

0.412

0.057

1.67

1.05

1.51

0.20

0.003

CI.

3.%1
1.504
3.611
0.672
1.86

PA-

0.489
2.067
0.188
4.644
1.60

THE CHEMISTRY OP THE COMPOUNDS OF CARBON.

Derivatives of Methane.

The complicated structure aud the great variety of the compounds of car-
bon are due to the fact that carbon-atoms have a greater power for union
with one another than liave tlie atoms of otlier elements.

Saturated Hydrocarbons or Paraffins (formula, CuHgn + ^ ). —

Methane, CH^, gas. Pentane, C5H12, liquid at 38°.

Ethane, CHe, " Hexane, CoHu: " '1°-

Propane, C3H,, " Heptane, CH.e, " 98°.

Butane, C4Hio, " etc.

These are the constituents of petroleum and natural cas, and are formed by the action
of low heat on coal under pressure in the absence of oxygen, and are probably derived
from fossil animal fat, since it has been shown that the paraffins may be obtained in large

' Herter: Hoppe-Seyler's Phijsiologmhe Chemie, p. 192.

* Kroner : Quoted liy Halliburton, Chenmtry, Phyxiological and Pathological, p. 656.
' liidder and Scliniidt: Quoted by Halliburton, Op. ciL, p. 638.

* Hoppe-Seyler : Physiolof/ische Chemie, p. 302.

* Bunge: Ibid., 3d ed., p. 2G5.

* Op. cit., p. 222 (Bunge finds NajO exceeds K^O in the blood-corpuscles of cattle).
' Bunge: Zeitschrifl Jilr phisiologb^che Chemie, 1885, Bd. 9, p. 00.

* Bunge : Physiologische Chemie, 3d ed., p. 100.

THE CHEMISTRY OF THE ANIMAL BODY. 975

quantity by heating fish oil at u pressure of fen atmospheres.' The i)araffins may all be
formed synthetically from methane by the action of sodium on halogen compounds of the
group :

2CII3I + 2Na - C,He + 2NaI.

0,115! + Cir,l + 2Na = CJIs + 2NaI.

'i'lii.s may be continued to ronii a theoretically endless number of compounds. Paraffins are
notably resistant to chemical reagents, not being affected })y either concentrated nitri(; or
sii]i)huric acids. Vaseline contains a mixture of paraffins melting between 30° and 40°.
By massage vix^ivVmc may be absorbed by the skin, through tbe epithelial cells of the seba-
ceous glands. In rabbits and dogs, directly after such treatment, it may be detected de-
posited especially in muscle, but it is for the greater part destroyed in the body.*

MoNATOMic Alcohol Radicals.

These are radicals which may be considered as paraffins less one atom of hydrogen, and
therefore having one free bond. They ibrm the basis of homologous series of alcohols
and acids.

Monatomic Alcohols (general formula, C„H2„ + lOH). —

Methyl alcohol, CII3OH. Amyl alcohol, CaHnOH.

Ethyl alcohol, C^HjOH. Hexyl alcohol, CV,Hi,OH.

Propyl alcohol, CH^OH. Heptyl alcohol, C^H.^OH.
Butyl alcohol, C4H9OH. etc.

General Reactions for Primary Alcohols. — (1) Alcohols treated with sulphuric acid
give ethers (see Ethyl ether) :

2CH3OH -f H.,S04 = ch;>^ + ^^^ + ^*^^*-

Methyl ether.

(2) Alcohols oxidized give first aldehyde and then acid :

CH3OH + 0 = HC ^g + H,0.

Methyl aldehyde.

CH,0-fO = HC<gjj

Formic acid.

(3) Primary alcohols may be prepared'' by reduction of the aldehyde with nascent
hydrogen,

CH3CHO + H, = CHgCH-^OH

Ethyl aldehyde. Ethyl alcohol.

and similarly by reduction of the acid.

Secondaiy Alcohols. — From propyl alcohol upward there are alcohols isomeric with the
primary alcohols, but in which the grouping R — CHOH — R is characteristic. These are
secondary alcohols, and may be produced by the action of nascent hydrogen on ketones :

CH3 - CO - CH3 + H, = CH3 - CHOH - CH3.

Acetone. Isopropyl alcohol.

Tertiary Alcohols. — These have the general formula R3 — COH.

^ Engler : Berichte der deutschen chemischen Gesellsehaft, 1S88, Bd. 21, p. 1816.

' Soubiranski : Archivfur exper. Pathologie und Pharmakologie, 1893, Bd. 31, p. 329.

' Again attention is called to the fact that the list of these reactions is in no wise complete,
but only intended to be suggestive of what should be mastered from a text-book on general
chemistry.

976 AX AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Monobasic Acids — The Fatty Acids (fbnniila, CllonOg). —

Formic acid, II COOII. Capric acid, CsH.sCOOH.

Acetic acid. CH.rOOII. Laurie acid, C„H.^COOH.

Propionic acid, CJIjCOOH. Myristie acid, C,3H,;C00H.

Butyric acid, C3H,C00H. Palmitic acid, C.sHs.COOH.

Valerianic acid, C^HsCOOH. Stearic acid, CnHo/JOOH.

Caproic acid, CsHuCOOH. Arjichidic acid, CsII^^COOH.

(Enanthylic acid, CJI^COOH. Cerotic acid, C^sHmCOOH.

Caprylic acid, CjH.sCOOH. Melissic acid, C29H59COOH.

These are organic compounds of acid reaction in which one atom of h}'dro«ren is replace-
able by a metal or an organic radical. Combined with glycerin the higher members of the
series (from C4 up) form the neutral fats of the organization. By distillation of a fatty
acid with alkaline hydrate, a hydrocarbon is obtained containing one carbon atom less than

the acid used.

CH3C00Na + NaOH = CH, + Na^CO,.

Preparation. — [a) Through oxidation of alcohols or of aldehydes,

CHjOH + 0, = CH3COOH + H3O.

(h) Through the action of carbon dioxide on the sodium compound of alcohol radicals,

CHjNa + CO2 = CH3C00Na.

Compounds of Methyl.
Methane, or Marsh-gas, CH^. — This ga.s is produced by intestinal putre-
faction, and is the only hydrocarbon found in the body. It is formed in largest
quantities from the fermentation of cellulose, which takes place, according to
Hoppe-Seyler, thus :

C,H,oO,H-H,0 = CeH,A-
CeHi206 = 3CH,H-3C02.

Tappeiner ^ finds that less CH^ than CO^ is prcKluced in cellulose fermenta-
tion in the intestine, and that the lower fatty acids (acetic to valerianic) are
also formed. This putrefaction is especially great in the ccscum of herbivora.
Methane is also a product of putrefiictiou of proteid (but not of casein, since
it is not present when milk is fed). Through the putrefaction of cholin, a
decomposition product of lecithin, methane is likewise evolved in small
quantity.^ Further, methane may be produced from the putrefaction of metal-
lic acetates :

CaC\HA + 2H2O = CaCOj H- CO^ + H^O + 2CH,.

PropeHies. — A colorles.s, odorless gas which burns with a didl flame. It is
absorbed by the blood, and in the herbivora is given off by the lungs often in
laro-er quantity than from the rectum.^ In man only little is produced. Methane
is not oxidized in the body, and is harmless when respired, even when 10 or 20
per cent, in volume is present.*

• Zeitschrifl fur Bioloffie, 1884, Bd. 20, p. 84.

' Hasebroek : Zeitschnft fur physiologi.tche Chemie, 1888, Bd. 12, p. 148.
' B. Tacke: Quoted by Bimge, Phynologuoche Chemie, 3d ed., 1894, p. 284.

* Paul Bert: Comptes rendus de la Societe de Biologic, 1885, p. 523. Abstract in Maly'a
Jahre-fbericht Uber Thierchemie, 1886, Bd. 16, p. 364.

THE CHEMISTRY OF THE ANIMAL BODY. 977

Trichlormethane, or Chloroform, CHCI3. — This temporarily paralyzes nerves and
nerve centres. It is principally removed as vapur through the lun.Lrs, but is ))artially
burned, thereby increasing the inorganic chlorides in the urine.' After giving chloroform
it may itself occur in the urine, and likewise a substance which reduces Fehling's solu-
tion, glycuronie acid (which see).

Methyl Aldehyde, or Formic Aldehyde, ll.CllO. — Tlii.s may be pro-
duced synthetically by pa.ssing vapor of inetiiyl alcohol mixed with air over
an ignited platinum spiral,

CH3OH + O = H.CHO + H2O.

On cooling the vapor, the aldehyde is found dis.solvecl in the alcohol. On
evaporation of the alcohol, the aldehyde, through condensation of three of
its molecules, forms a crystalline body having the composition (HCHO)^ and
• called paraformic aldehyde. This latter treated with calcium or magnesium
hydrate again suffers condensation with the production o^ formose, CgHijOg, a
sweet-tasting sugar (Butlerow, Loew) identical with i-fructose (Fischer).
Baeyer ^ first suggested that the sugar synthesis in the plant was analogous
to the above process. He conceived the reduction of carbon dioxide to
carbon monoxide, which united with chlorophyll, and afterward through
hydrogen addition became formic aldehyde ; then in upward stages became
metaformic aldehyde, sugar, starch, and cellulose. Reinke^ has shown the
presence of formic aldehyde in chlorophyll leaves, and believes its produc-
tion due to the reduction of carbonic acid through the power of the sun
on the leaf, thus :

H2CO3 = HCHO + O2.

Bach * states that carbonic acid and water in the presence of uranium acetate
yield formic aldehyde and nascent oxygen when placed in the sun. According
to Stocklasa,^ 400 grams of fresh leaves (128 grams dry) of the sugar beet
form synthetically and send to the beet root 31 grams of cane-sugar in
thirty days.

General Behavior of Aldehydes. — They act as reducing agents, being readily oxidized
to the corresponding acid. With nascent hydrogen they are reduced to alcohols. A dis-
tinctive reaction of aldehydes and ketones is their union with phenyl hydrazin, CgHj —
NH — NH.,, giving hydrazones :

CH3CHO -f CeHsNHNH^ = CH3.CH:N.NH.C6H5 + H.,0.

I^eparation. — By distillation of the salt of an acid with a salt of formic acid :

CHaCOONa + HCOONa = Na^COa + CH3CHO.

Aceto-aldehyde.

Methyl Mercaptan, CH3SH. — This is a product of bacterial action on
proteid,^ and is found with HgS in the intestine. It is, furthermore,

' A. Zeller : Zeitschrift fur physioloffische Chemie, 1883, Bd. 8, p. 74.
^ Berichte der deutschen chemischen Gesellschaft, 1870, Bd. 3, p. 67.
3 Ibid., 1881, Bd. 14, p. 2144.

* Ibid., 1894, Bd. 26, pp. 502 and 689.

' Stocklasa: Zeitschrift fiir physiologische Chemie, 1895, Bd. 21, p. 83.

• M. Nencki : Archivfiir exper. Pathologic und Pharmnkologie, 1891, Bd. 28, p. 206.

62

978 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

given off* on fusing proteid with potash.' Mctiiyl niercapttin boils at 5°,
and has a strong odor. It is found in the urine, especially after eating
asparagus, giving to it a peculiar sniell.^ According to Ilubner^ the smell of
cooked cabbage, ctmliflower, and the like, is due to methyl niercaptan.

Methyl Telluride, (CUsl^Te. — A f?as of penetrating odor found in all excreta of an
animal after feeding salts of telluric, H2Te04, or tellurious, HjTeOa, acid. The salt is re-
duced to metallic tellurium in the body, which unites with a methyl group in some way
liberated in the cells/ 3Ictallic tellurium may be microscopically seen deposited in various
cells, and the odor of (CII^l.Te may be detected for months after the last dose has been
given to a dog.^

Methyl Selenide, (CH:j).^Se. — This is very similar to the last-named substance, but
more poisonous.

Formic Acid, HCOOH. — Found in ants, and obtained by distilling them
with water. Present likewise in stinging-nettles and in the sting of honey--
bees, wasps, and hornets. Its salts are found in minute quantities in normal
urine, and are present especially in both blood and urine in such diseases as
include an abnormal proteid decomposition — such as leucocythsemia, fever,
diabetes.^ Formic acid may be obtained from the oxidation of methyl alcohol,
of sugar, and of starch, but not from the latter two in the body. - Likewise
by heating oxalic acid,

COOH

60011 = »c««« + ^°=-

It is found in the urine after feeding methyl alcohol and other methyl deriv-
atives, such as oxymethyl-sulfouic acid, or formic aldehyde. Ethyl alcohol, on
the contrary, does not yield it.^ It is the lowest member of the fatty-acid series,
the most volatile, and the least readily oxidized in the body. If formates be
fed they apjiear readily in tlie urine. It has a penetrating odor, acts as a
reducing agent ( HCOOH + O = COg + II2O), and therefore precipitates
Fehling's solution. Outside of the body it readily undergoes oxidation to
water and carbonic acid. It produces inflammation of the skin. A 7 per
cent, solution given to a rabbit per os has a most powerful corrosive action and
results fatally, formic acid being found in the urine.

Ethyl Compounds.
Ethyl Hydroxide, or Ethyl Alcohol, CgH.pH. — This has been detected
in minute quantity in the normal muscle of rabbits, horses, and cattle.^ It is
formed by the fermentation of dextrose, the process taking place in the yeast-
cell itself, alcohol and carbonic acid being the chief excretory products ; like-
wise, to a very small extent, the higher alcohols, propyl, isobutyl, amyl, the

1 M. Riibner : Archiv fur Hygiene, 1893. * Nencki, loc. cit. ' Loc cU.

* Hofmeister : Archiv fiir erper. Patholnpie nvd Pharmakologie, 1894, Bd. 33, p. 198.

* Beyer : Archiv fiir Physiologie, Jahrgang 1895, p. 225.

' See R. Jaksch : Zeiti^chrift fiir 'physiologiache Chemie, 1886, Bd. 10, p. 537.
' Pohl : Archiv fiir exper. Physiologic und Pharmakologie, 1893, Bd. 31, p. 298.
8 Rajewsky: Ffliiger's Archiv, 1875, Bd. 11, p. 122.

THE CHEMISTRY OF THE ANIMAL BODY. 979

estei*s of the fatty acids (fusel oils), jrjycerin, and succinic acid are ])r()duced.
Such fermentation may to a small extent take place in the intestine,' and like-
wise iu the bladder (occurrence in diabetic urine). Pure alcohol is a colorless,
almost odorless li(|uid, havinsji; a burning taste. It is a valuable solvent of
resins, fats, volatile oils, bromine, iodine, and many medicaments.

Tincturex arc alcoliolic solutions of various druirs and salts.

Liqwurs arc nianufaclurcd I'roin alcohol i)roi)crly diluted, and treated with sugar and
characteristic ethereal oils and aroniatics.

JJistilled liquors are ohtained bj' the distillation of the fermentative products of various
substances, whiskey from corn and rye, rum from molasses, brandy from wine. The cha-
racterizing taste dejiends on the different ethereal and fusel oils.

Wines are jiroduced from the natural fermentation of grape-juice. Sherry, madeira,
and port are fortified by the further adchtion of alcohol and sugar.

Beer is made by converting the starch of barley into maltose and dextrin throutrh
diastase. To an aqueous solution of the above hops are added, and the whole is boiled.
After the settling of precipitated proteid, etc., the clear supernatant fluid is drawn off and
treated with yeast, with ultimate conversion into beer. The taste is furnished by the hops.

Alcohol in the Body. — Alcohol in the stomach at first prevents the
gelatinization necessary in proteid for peptic digestion, but this difficulty is of
no great moment because the absorption of alcohol is rapid and complete.
It makes the mucous membrane hyperaeraic, promotes the absorption of
accompanying substances (sugar, peptone, potassium iodide), and stimulates
the flow of the gastric jiiice.^ In this matter it acts as do other condiments
(salt, pepper, mustard, peppermint),^ but if there be too great an irritation
on the mucous membrane there is less activity (dyspepsia). The rapid
absorption gives to alcohol its quick recuperative efiect after collapse, and
its value in administering drugs, especially antidotes. Alcoholic beverages
combining alcohol and flavor promote gastric digestion and absorption, but
often stimulate the appetite in excess of normal requirement. Alcohol is
burned in the body, but may also be found in the breath, perspiration, urine,
and milk. Alcohol has no effect on proteid decomposition, but acts to spare
fat from combustion.* The addition of 50 to 80 grams of alcohol to the
food has no apparent effect on the nitrogenous equilibrium.^ Alcohol in the
body acts as a paralyzant on certain portions of the brain, destroying the more
delicate degrees of attention, judgment, and reflective thought, diminishing the
.sense of weariness (use after great exertion — furnished to armies in the last
hours of battle) and raising the self-esteem ; it paralyzes the vaso-constrictor
nerves, producing turgescence of the skin with accompanying feeling of warmth
and thereby indirectly aiding the heart." The higher alcohols, propyl, butyl,
amyl (see p. 983) are more })oisonous as the series ascends,^ and are less vol-

' Macfadyen, Nencki, and Sieber : Archiv fiir exper. Pathologie imd Pharmakologie, 1891,
Bd. 28, p. 347.

- Brand! : Zeitsrhriff fiir Biologie, 1892, Bd. 29, p. 277. ' Brandl, Op. cit., p. 292.

* See V. Noorden : Pathologie des Stojfwechsels, 1893, p. 227.

'" Strom : Abstract in CeniralblaU fiir Physiologic, 1894, Bd. 8, p. 582.

^ Schmiedeberg : Grundriss der Arzneimiflellekre, 2d ed., 1888.

' Gibbs and Reichert : Archiv fiir Physiologie, 1893, Suppl. Bd. p. 201.

980 ^iV^ AMERICAN TEXT-BOOK OF PHYSIOLOGY.

atile, less easily burned, and therefore more tenaciously retained by the body,
with more pernicious results.

Ethyl Ether, CjHj.O.CjHj. — This is formed hy Ihe action of sulphuric acid on
alcohol, thus :

C2H5OH + H,SO, = CHjHSO^ + H,0.

C,H,HSO, + CH^OH =(C,H5),0 + H,SO,.

Ether is a solvent for fats, resins, and ethereal oils. Respired with air its action is like that
of chloroform, producing temjiorary paralysis of the nerves and nervous centres. Since it
boils at 35.5° its tension in the blood is always high, and it is probably not burned in the
body to any great extent, but when present is eliminated through the breath.

Ethera in general are neutral and very stable bodies, and may be considered oxides of
organic radicles. They may all be prepared by boiling the corresponding alcohol with sul-
phuric acid. Mixed ethers, in which the radicles are different, are prepared by boiling two
different alcohols with sulphuric acid :

CH3HSO, + C^HjOH = CHaOC,!!, -f H.SO^.

Methyl-ethyl ether.

Chloral Hydrate, CCL.CHO + H.O or CClsCHCOH).,.— This is the hydrated form of
trichlor-ethyl aldehyde, CCI3CHO, and is used as an anaasthetic. It is an interesting fact
that when fed it partially reappears in the urine as urochlordlic acid, which consists of
trichlor-ethyl alcohol, CCljCH./JH, combined with glycuronic acid (which see). This is a
notable illustration of reduction in the body, the change from an aldehyde to an alcohol.

Acetic Acid, CH3COOH. — Acetic acid, the second of the fatty-acid series,
is found in the intestinal tract and in the feces, being a product of putrefaction
(see p. 988). It is more easily burned than formic acid, and when aksorbed is
resolved * into COg and water. It is found in traces in the urine, the total
amount of fatty acids normally present being 0.008 gram })er day.^ Like
formic acid, and accompanied further by the higher acids of the series, it is
present in the blood, sweat, and urine whenever there is an abnormal proteid
decomposition (leucocythaemia, diabetes).

Acetic acid is the product of the oxidation of alcohol. This may be
brought about through the presence of sj)ongy platinum, or through the action
of bacteria {Mycoderma aceti) on dilute alcohol (})reparation of vinegar, sour-
ing of wine : for reaction see p. 976). Acetic acid, as well as other higher fatty
acids, is one of the products derived from proteid through its putrefaction, its dry
distillation, its fusion with potash, and its digestion with baryta water in sealed
tubes. Formic, acetic, and propionic acids are products of dry distillation of
sugar (formation of caramel). These facts are of importance in their rela-
tion to the question of the production of fat in the body. Acetic and the
higher fatty acids are, further, products of the dry distillation of wood and
of the fermentation of cellulose (see p. 976). Putrefaction of acetates may
take place in the intestines, the reaction being as follows:

2CH3COONa + 2H2O = ISa.CO, + 2CH, + H^O -f CO..

These products are similar to those in the marsh-gas fermentation of cellulose.
Vinegar, whose acidity is due to acetic acid, is used as a condiment.

Acetyl-acetic Acid, or Aceto-acetic Acid, CH3.CO.CH2.CX^OH. — This
' V. .Taksch : Zeitschrij't fur physiologische Chemie, 1886, Bd. 10, p. 536.

THE CHEMISTRY OF THE ANIMAL BODY. 981

may be eoiisitlerod as acetic acid in which one H atom is replaced by acetyl,
CH3CO — ; or as /9-keto-butyric acid. Treated with hydrogen it is reduced
to /?-oxybutyric acid (CH3.CHOH.Cir2.COOIl), which in turn nmy be oxi-
(\\7An\ to the original substance. Aceto-aceticacid readily breaks up into acetone
and carbonic acid :

CHgCOCH.COOH = CH3COCH3 + CO„.

Aoeto-acctic; acid, acetone, and /i-oxybutyric acid are found in the urine sometimes singly,
sometimes together, but only as the result of a metabolism of the body's oriianized protcid
(lencocythii3mia, diabetes, fever, inanition), not of that of the proteid ingested. Indeed,
these substances under the above circumstances seem to appear in the urine in direct pro-
l)ortion to the nitrogen present — in other words, to the protcid decomposition.' From their
chemical relations already mentioned they may be regarded as of common origin, coming
from the proteid molecule under peculiar conditions of metabolism, and in contirmation of
this, Araki '^ has shown that on feeding /?-oxybutyric acid it is oxidized and aceto-acetic
acid and acetone may be detected in tlie urine. The production of the two acids seems to
further a gradual neutralization of the blood, ultimately causing coma.^ In the i)resence
of these substances ammonia runs high in the urine, and in amounts proportional to their
excretion* (compare p. 993).

Aceto-acetic acid gives to urine in the absence of phosphates a red coloration
with ferric chloride (j)rinciple of the reaction of Gerhardt).

Amido-acetic Acid, or GlycocoU, CHg.NHg.COOH. — This is a substance
obtained by boiling gelatin with acids or alkalies. It is found in human bile
and in that of other animals combined with eholic acid and called glycocholic
acid. Chittenden^ has found glycocoU in the muscles of Peden irradians.
It is found in the urine combined with benzoic acid as hippuric acid after
feeding benzoic acid or compoinids which the body converts into benzoic acid.
In a similar manner phenaceturic acid is found in the urine from the grouping
together of glycocoU and j^henyl acetic acid. GlycocoU and urea are to be
obtained by the decomposition of uric acid through hydriodic acid. GlycocoU
forms colorless crystals, soluble in water and having a sweet taste.

GlycocoU in the Body. — If glycocoU be fed it is absorbed and appears as
urea in the urine. The fact that dogs, whose bile never contains glycocholic
acid, nevertheless excrete hippuric acid after being fed with benzoic acid, indi-
cates that glycocoU may be considered a normal nitrogenous decomposition
product of proteid. Its easy cleavage from gelatin, a product manufactured
from proteid in the body, confirms this.

Amido' Acids in General. — These acids, such as glycocoU. aspartic acid, glutamic acid,
leucin, and tyrosin are found as putrefactive products of albumin and gelatin. In these
acids the amido- group is very stable, and cannot be removed by boiling with KOH. They
are all converted in the body into the amide of carbonic acid (urea). Amido- acids may in
general be synthetically formed by heating mono-halogen compounds of the fatty acids with
ammonia :

CH5CICOOH + NH3 = CH.NH^COOH + HCl.

* Wright : Grocers' Research Scholarship Lecture, London, 1891 ; V. Noorden : Pathologic des
Stoffwechsels, 1893, p. 178.

' Zeitechrijt fiir physiologische Chemie, 1893, Bd. 18, p. 6.

•* Miinzer and Strasser : Archiv fiir exper. Pathologic und Pharmakologie, 1893, Bd. 32, p. 372.

* Loc. cit. 5 Annalen der Chemie und Pharmakologie, 1875, Bd. 178, p. 266.

982 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Methyl Amido-acetic Acid, or Sarcosin, CII5.NII.CII2.COOII. — This is not found
in the liotly, but is derived from ereatin, theobroniin, and cafiein by heating with barium
hj'droxidc.

Propyl Compounds.

Normal or Primary Propyl Alcohol, CII3CH2CH2OH. — This is one of
the higlier aleohols foi'ined in the ienueutation of sugar, and on oxidation
yiekls projnd ahh-hyde and propionie acid.

Propionic Acid, CII3CH2COOH. — Combined with glycerin this iorras the
simplest fat ; salts of this acid feel fatty to the touch. Propionic acid is a
product of the dry distillation of sugar, of the butyric-acid fermentation of
milk-sugar, and of the putrefaction of proteid. It is said to be present in the
sweat, in the bile, and sometimes in the contents of the stomach. Like others
of the lower fatty acids, it may partially escape oxidation and appear in traces in
the urine (see p. 980).

/3-Acetyl Propionic Acid, or Levulic Acid, CIIsCOCH.CHjCOOH.— This is the next
higher honiologue to aceto-acetic acid. It lias been obtained only by boiling sugars, espe-
cially levulose, with acid and alkalies, and since Kossel and Neumann ' found that it is
yielded by some nucleins they conclude that this indicates the presence of the carbo-
hydrate radical in these nucleins.

Dimethyl Ketone, or Acetone, CH3COCH3. — This is found normally in
the blood and urine, and in especially large quantities in patients suft'ering
from an abnormal decomposition of organized proteid (see p. 981). During
the first day of starvation by Cetti, the starvation artist, the amount of acetone
in the urine rose to forty-eight times that of the day previous.^ It may like-
wise appear in the breath, giving a characteristic odor. Acetone is a product
of the dry distillation of tartaric and citric acids, of woofl, and of sugar. Its
occurrence in the urine, in diabetes, however, is not proportional in any way
to sugar-metabolism or non-metabolism (.see p. 981). Oxidized, acetone yields
acetic and formic acids, whereas, treated with hydrogen, it is resolved into sec-
ondarv propyl alcohol. When acetone is in the urine it is al^^o found in the in-
testinal canal and in the feces, ]>robably by passage through the intestinal wall.

Butyl Compounds.

Normal Butyric Acid, CHgCHgCHjCOOH. — Butyric acid was first found
in butter, combined with glycerin. When free it gives the rancid odor to
butter, and likewise contributes to the odor of sweat. It has been detected in
the spleen, in the blood, and in the urine, but usually only in traces. As a pro-
duct of putrefaction of proteid, and especially of carbohydrates, it is found in
the intestines and in the stomach when the acidity is insufficient to be bacteri-
cidal. It contributes to the unpleasant taste after indigestion, through the
return of a small portion of the chyme to the mouth. In cheese it is a
product of the putrefaction of casein.

If starch, sugar, or dextrin be treated with water, calcium carbonate, and

^ Verhandlung der Berliner physiologischen Gesellscliaft, Archivfur Physiologic, 1894, p. 536.
* Fr. Miiller : Berliner klinische Wochemchrift, 1887, p. 428.

THE CHEMISTin' OF TlIK ANIMAL BODY. 983

foul cheese, tlie earl )oliy(l rates are slowly eoiivertetl into a mass of calcium
lactate. On further stiinding the lactic acid is resolved into butyric acid :
2CH3CI1()II( 'OOI I Cy I/'(K)TI + 4H + CO..

Ijictic nt'id.

Calcium salts are foiuid to putrefy more readily than others, and the carbon-
ate is added above to neutralize any acids formed in the putrefactive process
which mii^ht inhibit the action of the spores. This same fermentation takes
place in the intestinal tract.

Iso-butyl Alcohol, (CHa)^ : CH.CH,OH.— This is found in fusel oil.
Iso-butyric Acid, (CHj)^: CH.COOIL— This is a product of protcid putrefaction
and is I'ound in the feces.

Pentyl Compounds.

Iso-pentyl Alcohol, or Amyl Alcohol, (CH3)2CHCH,CH20H.— This is the principal
constituent of fusel oil, prodiu-in.ir the after-effects of distilled-liquor intoxication. The
poisonous dose in the dog per kiloirrum for the different alcohols has been found to be — for
ethyl alcohol 5-6 grams, for propyl alcohol 3 grams, for butyl alcohol 1.7 grams, for amyl
alcohol 1.5 grams' (see p. 979).

Iso-pentoic or Iso-valerianic Acid, (CH3)2CHCH2COOH. — This is found
in cheese, in the sweat of the foot, likewise in the urine in sfnall-pox, in typhus,
and in acute atrophy of the liver. It is a product of proteid putrefaction, and
has a most unplea.sant odor.

Alcohols containing More than Five Carbon Atoms.

Of tliese, cetyl alcohol C16H35OH, is found combined with palmitic acid in spermaceti ;
cerotyl alcohol, C27H55(OH), is found as an ester in Chinese wax; and melicyl alcohol^
CaoHfiiOH, is combined with palmitic acid in beeswax.

Acids containing More than Five Carbon Atoms.

Caproic Acid, CsHjjCOOH. — This is formed from the putrefaction of
proteid, being found in cheese and in feces; it may likewise be detected in the
sweat. United wnth glycerin it occurs in butter-fat.

Iso-butyl Amido-acetic Acid, or Leucin, (CHa), : CH.CHo.CHNH^.
COOH. — This substance is a constant product of proteid })utrefaction, is there-
fore found in cheese, and may likewi.se be obtained by boiling proteid or gelatin
with sulphuric acid or with alkali. When fed it is converted into urea. When
fed to birds the tissues decompose it with elimination of ammonia, which latter
may be converted into uric acid by the liver.^ It is said to occur in pancreatic
juice. According to Kiihne it is produced in trypsin proteolysis to the extent
of 9.1 per cent, of the proteid used. Since this weakly alkaline medium in
pancreatic digestion is especially favorable to bacterial activity, Kiihne added
antiseptic salicylate of sodium and still found leucin (and tyrosin). The sam6
results are obtained with thymol. It is generally accepted that leucin (and
tyro.sin) are normal products of tryptic digestion. In certain diseases of the liver

' Dnjardin-Beauraetz et Audig^ : Comptes rendus, vol 81, p. 19.

* Minkowski : Archiv fur exper. Pathologic und Pharmakologie, 1886, Bd. 21, p. 85.

984 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

leucin (and tyrosin) appear in tho urint', which may he interjireted to mean that
thi-se siihstance.s, normally produeed Ironi proteid metalK)li.sni in the tissues, are
not normally burned but accumulate within the body, and are excreted (.see
below).

Another view, advanced by Von Noorden * and ba.sed on the unconfirmed experiments of
Harris and Tooth.* claim.s that leucin and tyro.sin are not luund in tryptic dige.stion if bac-
teria be excluded. Leucin and tyrosin are found in yellow atrni)hy of the liver both in the
urine and in the liver it.self. under conditions indicating tlieir production by bacteria and
their non-combustion after production. In phosphorus-poisoning and acute annc^mia leucin
and t\Tosin occur in the urine, but apparently without good ground for considering them
of V)acterial origin, ^'on Noorden argues that, as in yellow atrophy of the liver, the tissue-
cells have become incapable of decomposing leucin and tyrosin, and tliese substances
absorbed as products t)f intestinal putrefaction cannot be burned but are eliminated by the
urine. That leucin is a product of proteid metabolism in the tissues has never been shown.

Leucin crystallizes in characteristic ball-shaped crystals. It was formerly supposed to
be amido-caproic acid, but Schulze' has shown its true composition. Inactive leucin con-
sists of a mixture of d- and Meucin, and may be obtained by treating conglutin with
BalOHij. The two leucins maybe separated by fermentation of (Z-leucin with PenidUium
gJancnm. Cleavage of proteid by acids and by putrefaction seems to yield c?-leucin.*

Caprylic, CjHjpOo. and Capric, ' CioHjoOj, Acids. — The.«e are found as
glveerin esters in milk-fat. They are likewise present in sweat and in cheese.

Palmitic, C,6H3202, and Stearic, CigHg^O,, Acids. — As glycerin esters
these two acids are found in the ordinary fat of adipose tissue, and in the fat
of milk. The acids may occur in the feces, and are found combined with
calcium in adipocere (p. 1002). "Wool-fat consists in the cholesterin esters of
thase acids.

The bile contains palmitic, .stearic, and oleic acids,^ and to these have been
attributed its very slight acid reaction.®

Compounds of the Alcohol Radicals with Nitrogen.

Amines. — ^These are bodies in which either one. two. or three of the hydrogen atoms
in ammonia are replaced by an alcohol radical, and are termed respectively primar>', second-
ary, and tertiary amines. Methyl, ethyl, and propyl amine bases are the jiroducts of pro-
teid putrefaction. Tliey resemble ammonia in their basic properties.

Methylamine, NHjlCH,,).— This is found in herring-brine. It has the fishy smell
noted in decaying fish. It is a product of the distillation of wood and of animal matter.
Feeding methylamine hydrochloride is said to cause the apj)earance of methylated urea in
a rabbit's urine ' (analogous to the formation of urea from ammonia salts! :
21101. NH,(CH3) + C0,= 0C(NHCH3), + 2HCI + H,0.
According to Schiffcr.* the body, probably through intestinal putrefiiction. has the power
of partially converting creatin into oxalic acid, ammonia, carbonic acid, and methylamine,
which last is finally excreted as methylated urea in the urine.

» Paihnlogie des Stoffu-echseh, 1893, p. 296. ' Journal of P/it/.sio/o.T?/, 1SS8, vol. 9, p. 220.

» Berichte der deutschen chemkchen Ge,«elkchaft. 1891, Bd. 24, i>. 669; also, Gmelin : Zeilschri/I fur
physfiologi^che Chemie, 1893, Bd. 18, p. 38.

* rrmelin : Zeitschrifi fur phyaiologische Chemie, 1893, Bd. 18, p. 28.

* Lassar-Cohn : Ibid., 1894, Bd. 19, p. 571.

« .Idles: Pfiiiger's Archiv, 1894, Bd. 57, p. 13.

' Schiffer: ZeiUchnft fiir physiologische Chemie, 1880, Bd. 4, p. 245. " Loc. cit

THE CHEMISTRY OF THE ANIMAL BODY. 985

Ethylamine, C.^lIjNIIj, when fed as eurbonule appears in part as ethylated urea in the
urine.'

Trimethylamine, NiCH,),. — Like ethyhiuiine. this is found in herrinp-brine and
ainonir the pnKhicis dT proteid putrefaetion ami distiUation. In the putrefaction of meat
the first ptomaine ajipearini: is elioHn, wliich certainly is derive<l from lecithin; the cholin
(sue p. 986) gradually disappears, and in its jilace trimethylamine may Ijc detected.'

Compounds with Cyanogen.

The radicle NC — forms a scries of bodies not unlike the halogen com-
pounds. Owing to the mobility of the cyanogen group, Pfliiger' has sought
to attribute the proj)ertie.-; of living proteid to its presence in the niolecide,
whereas in the dead proteid of the blood-})lasma, for example, he imagines that
the nitrogen is contained in an amido- group. When the cyanogen radical
occurs in a comjiound in the form of N=:C — the body is called a nitril, when

in the form of C :N — an iso-nitril.

Cyanogen Gas, NC — CX. — A very poisonous gas.

Hydrocyanic Acid, IICN. — This is likewise a strong poison. Amygdalin is a glucoside
oc-eurring in cherry-pits, in bitter almonds, etc.. together with a ferment called emulsin,
which latter has the powerof transforming amygdalin into dextrose, benzaldehyde, and hN'dro-
cyanic acid. Hydrocyanic acid, therefore, gives its taste to oil of bitter almonds, and it
may likewise be detected in diem* brandy.

Potassium Cyanide, KCN. — Tliis and all other soluble cyanides are fatal poi.sons.

Acetonitril, or Methyl Cyanide, CII3CX. — This and its higher homologous nitrils
are violent poisons. After feeding acetonitril in small doses, formic acid (see p. 978) and
thiocyanic acid (see below) appear in the urine, the thiocyanic acid being a sjiithetic prod-
uct of the inge.sted cyanogen radical, and the HS — group of decomposing proteid.* After
feeding higher homologues of acetonitril or hydrocyanic acid, thiocyanide likewise appears
in the urine. Since the amount of thiocyanide in the urine is normally very small, there
i.s no reason for believing that cyanogen radicals similar to those described above are ever,
to any great extent, cleavage-products of proteid.' Through intravenous injections of
sodium sulphide, and especially of sodium thiosulphate, poisonous cyanogen compounds
may be administered much beyond the dose ordinarily fatal:®

XaCX - SO, < ^^ 4- 0 = NCSNa + Na^SO^.

Cyanamide, NC.NHj. — This is a laboratory decomposition-product of creatin, but does
nut occur in the body. It is poisonous when administered. When boiled with dilute
sulphuric or nitric acids it is converted into urea :

NCNH2 + H2O = H^XX'ONHj.
It is to be remembered that creatin in the body is not converted into urea.

Ammonitim Cyanate, OCN(NH^). — Boiling ammonium cyanate converts it into
urea. This was shown by Wohler in 1828, and was the first authoritative laboratory
production of a body characteristic of living organisms :

OCN(NHJ=OC(NH,),.
This reaction illu.strates Pfliiger's idea of the transformation of the c.vanogen radical in
living proteid into the amido- compound in the dead substance. According to Hoppe-

' Schmiedeberg : ArchivfUr erper. Pnlhologie und Pharmakologie, 1877, Bd. 8, p. 5.
' Brieger : Abstract in Jnhn'sbericht iiber Thierchemie, 1885, p. 101.
' PAuger's Archiv, 1875, Bd. 10, p. 251.

* Lang : Archiv fiir exper. Pathologie und Pharmaiologie, 1894, Bd. 34, p. 247.
-' Op. cit., p. 256.

* Lang : Archiv fiir exper. Pathologie vnd Pharmakologie, 1895, Bd. 36, p. 75.

l»cSO AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Sevier the urea-formation in the body is as indicated in the above reaction, but that no
cyanic acid or aninioiiiuin cyaiuite is to be detected on account of their extreme instabihty.
Potassium Thiocyanide, NCSK. — This substance is usually found in human saliva
and ill the urine. Since it contains nitrogen and sulphur its oriirinal source must be I'rom
proteid. The amount in the urine is probably wholly and ((uaiititatively derived i'roni that
in the saliva.' If thiocyanides be fed, they appear quickly in the urine without change.
Thiocyanides are less poisonous than the simple cyanides (see discussion under Acetonitril
above). Thiocyanides give a red color with ferric chloride in acid solution.

Diatomic Alcohol Radicals.
Thus far only derivatives of monatoniic radicals have been disciis.sed ; next
in order follow diatomic alcohol radicals, represented by the formula CnHgn, and
including; the bodies ethylene, HgC = CH2, j^^'opyleiie, CH3 — HC = CHo, etc.
This set of hydrocarbons is called the defines. The first series of compounds
which are of physiological interest are the amines of the olefines.

Amines of the Olefines.

These include the group of ptomaines — basic substances which are formed
from proteid through bacterial putrefaction. Those which arc jwi.^^onous are
called toxines. These bodies are diamines of the olefines, and have been
investigated especially by Brieger.^

Tetramethylene-diamin, or Putrescin, H2N.CH.,.CH,.CH,.CH,,.NHo.— This com-
pound is found in putrefying proteid, and has been detected in the urine and feces in
cystitis.

Pentamethylene-diamin, or Cadaverin, HjN.CiHjo.NHj.— This is found with
putrescine wherever produced. They are both found in cultivations of Koch's cholera bacil-
lus and in cholera feces. In cystitis they are a result of special infection of the intestinal
tract, are principally excreted in the feces, but are partially absorbed, and prevent, perhaps
through chemical union, the burning of cystein normally produced.^ Diamines are not
normally present in the urine.

Neuridin and Saprin. — These are isomers of cadaverin and are produced by the same
putrefactive processes.

Cholin.— This is trimethyl oxyethyl ammonium hydroxide,

and has its source in lecithin decomposition, and putrefaction (see p. 1001).

Musearin, or Oxycholin.— This is a violent heart-poison, and may be obtained by
treating cholin with nitric acid.

Neurin.— This is trimethyl-vinyl ammonium hydroxide, (€113)3 ^ N < ^jj _ qjj

and is derived from lecithin. Theoretically it may be considered as derived from cholin,
with the elimination of a molecule of water, but it has never been shown that bacteria
make this conversion. It is a powerful poison.

Dertyattves of Diatomic Ai>coiioi^.
Taurin, or Amido-ethyl Sulphonic Acid, H2N.CH2.CH2.SO3H. — This
has been detected in muscle,* in the spleen, and in the suprarenal capsules.

' Gscheldlen : Pfluger's Archiv, 1877, Bd. 14. p. 411.
^ Abstract, Jahreahericht iiber Thierchemie, 1885, p. 101.

3 Baumann und Udranszky : ZeUschrift fur physiologische Chemie, 1889, Bd. 13, p. 562, and
1891, Bd. 15, p. 77.

* Reed, Kiinkenberg, and Wagner: Zeitschri/tfur Biologie, 1885, Bd. 21, p. 30.

THE CHEMISTRY OF THE ANIMAL BODY. 987

It is likewise a usual constituent of" tlio liuniau bile in combination with
eholic acid, the salt present being known as sodium taurocholate. Taurin
is of proteid orii;in as is shown by its nitrogen and sulphur content. Little
is known regarding its fate in the body, except as it indicated through the
behavior of its sulphur atom (see p. 951).

The BUim-ji Salts. — Taui'in and glycocoll are found in the bile of cattle in
combination with eholic acid {t\^ll^JJ^). In human bile, according to Lassar-
Cohn,^ there is more fellic acid (CgjH^OJ present than eholic, and there is
likewise present some choleic acid, (C24H^(,02). These acids are of similar chemi-
cal structure, though what the structure is, is unknown. Still other acids
occur in the bile of pigs, geese, etc. Taurin and glycocoll form compounds
with these acids, the sodium salts of which usually make up the major part of
the solids of the bile. It has been shown that glycocoll and taurin are found
in various parts of the body. Cholic, fellic, etc. acids are only found as products
of hepatic activity. In a dog with a biliary fistula the solids of the bile increase
on feeding much meat, but the hourly record of the solids compared with
the nitrogen in the urine shows that the great production of biliary salts con-
tinues after the nitrogen in the urine has begun to decrease." The experiments
of Feder^ have shown that the greater part of the nitrogen in proteid eaten by
a dog leaves the body within the first fourteen hours, whereas the excretion of
the non-nitrogenous moiety is more evenly distributed over twenty-four hours.
It may be fairly concluded that cholic and fellic acids are produced from the
non-nitrogenous portion, or from sugar or fat/ Furthermore Tappeiner ' has
8hown that cholic acid on oxidation yields fatty acids. A synthesis may there-
fore be effected in the liver between the non-nitrogenous cholic acid formed in
the liver from fat or materials convertible into fat, and glycocoll and taurin
formed from proteids, whether the latter be produced in the liver or brought to
it from the tissues by the blood. That the liver is the place for the synthesis
is shown by the fact that the biliary salts do not colkct in the body after extir-
pation of the liver.

In the intestine either the acid of the gastric juice or bacteria may split up
the biliary salt through hydrolysis :

Glycocholic acid. Glycocoll. Cholic acid.

Taurin and glycocoll may be absorbed, while cholic acid is precipitated if in
an acid medium, but may be dissolved and absorbed in an alkaline intestine.
Hence cholic acid, fellic acid, etc., may often be found in the feces. Meco-
nium, that is, the fecal matter of the fetus, contains quantities of the biliary
.salts, but unaltered, since putrefaction is absent in the fetus. Kiihne has de-
scribed dyslysin as a putrefactive product of cholic acid, but its existence is
denied by Hoppe-Seyler and Yoit. In icterus (jaundice), a condition in

^ Zeitschrift fiir physiologiscbe Chemie, 1894, Bd. 19, p. 570.

» Voit : Zeitschriftfur Blologie, 1894, Bd. 30, p. 545. ' Ihid., 1881, Bd. 17, p. 531.

* Voit, Op. cit, p. 556. * Zeitschriftfur Biologie, 1876, Bd. 12, p. 60.

988 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

which the biliary sah^? return to the blood from the liver, they are burned in
the body, sometimes so completely that none appear in the urine. They have
the power of dissolving liaMuoglobin from the blood-corpuscles, and in con-
sequence the urine may be highly colored, perhaps from bilirubin.'

Pettenkofer, experimenting once on the conversion of sugar into fat, warmed together
cane-sugar, bile, and concentrated sulj)huric acid. He obtained no fat, but a strong violet
coloration. This is " Pettenkofer' s test'' for biliary acids (cholic acid, fellic acid, etc.).
This coloration is likewise given by i)roteid, oleic acid, and other bodies. The test of Neu-
konim, however, is said to be absolutely characteristic. Here a drop of a substance con-
taining biliary acids is placed on a small white porcelain cover, with a drop of dilute
cane-sugar solution, and one of dilute sulphuric acid ; the mixture is then very carefully
evaporated over a flame and leaves a brilliant violet stain.

OxY- Fatty Acids, Lactic-acid Group.

These are diatomic monobasic acids of the glycols. A glycol is a diatomic
alcohol. The oxy- fatty acids have the general formula CnHjnOg, and include :

Carbonic acid, CHgOg. Oxy-butyric acid, C4H^03.

GlycoUic acid, CgH^Oj. Oxy- valerianic acid, C5H,o03.

Lactic acid, C3Hg03. etc.

Carbonic Acid, or Oxy-formic Acid, HO.CO.OH. — This is, in reality,
a dibasic acid on account of the symmetric structure of the two — OH radicals.
It has already been considered (see p. 1003).

Lactic Acids, or Oxy-propionic Acids. — Of these there are two isomeres,
which vary in the position of their — OH group, the a- and /9- lactic acids.
Physiology is concerned only with the first.

a-Lactic Acid, or Ethidene Lactic Acid, CH3.CHOH.COOH. — Tiiis
is called fennentation lactic acid, being a product of the fermentation of carbo-
hydrates (see p. 982) :

CeH,A = 2C3HA.
On lactic fermentation of milk-sugar depends the souring of milk. This fer-
mentation does not take place in tiie presence of sufficiently acid gastric juice,
but it is very active in the more nearly neutral (or alkaline) intestine. After
a meal which includes carbohydrates the intestinal contents may remain quite
distinctly acid down to the ileo-csecal valve, due to acetic and lactic acid pro-
duction, to such an extent even that proteid putrefaction is inhibited, as indicated
bv the total absence of Icucin and tyrosin.^ It has been noticed that the fecal
excrements after a carbohydrate diet react acid, after proteid diet alkaline.
The acid reaction is due chiefly if not wholly to acetic acid, since lactic acid,
being the stronger acid, is first neutralized by the intestinal alkali. Lactic
acid, when absorbed, is completely burned in the body. Lactic-acid fermenta-
tion between the teeth dissolves the enamel, and gives bacteria access to the
interior. The fermentation lactic acid is inactive to polarized light, and, since

^ HoppeSeyler : Physiolofjische Chemie, 1877, p. 476.

* Macfadyen, Nencki, und Sieber : Archiv fiir exper. Pathologic und Phavmakologie, 1891,
Bd. 28, p. 347

THE CHEMISTRY OF THE ANIMAL BODY. 989

it has in its lorimiiu an asynuuctrii' carbon atom,' it is necessary to assume that
it consists of an equal mixture of right and left ethidene lactic acid. On
standing with Pcnicllliuni f/hmcum tlie left lactic a(ud is destroyed more freely
than is the right, and the solution rotates polarized light to the right.^

The right ethidene lactic acid, CiiUed also sareo- or para-lactic acid, is that
which is found in muscle, blood, in various blood-glands, in the pericardial
fluid, and in the aqueous humor. Likewise it is found in the urine after
streiuious physical effort, after CO-poisoniug, in yellow atrophy of the liver,
in phosphorus-poisoning, in trichinosis, and in birds (geese and ducks) after
the liver has been extirpated. It is sometimes present in diabetic urine. Para-
lactic acid is a normal constituent of the blood and increases in amount after
work or tetanus. It accunudates in the dying muscle {rigor mortis), causing
the formation of KH2PO4, whicii gives the acid reaction and causes coagula-
tion.^ Some believe that free lactic acid itself is present and aids in the coag-
ulation. Regarding its origin it has been shown that it increases in amount in
the dying muscle without simultaneous decrease in the amount of glycogen.*
On extirpation of the liver in geese,^ ammonia and lactic acid replace the cus-
tomary uric acid in the excreta, and previous ingestion of carbohydrates or of
urea will not increase the amount of lactic acid. The lactic acid excreted is
proportional in amount to the proteid destroyed and to the ammonia present.
It may fairly be concluded that it owes its origin to proteid.

Hoppe-Seyler ® says that lactic acid appears in the urine only when there is insufficient
oxidation in the body, and attributes its derivation to the decomposition of glycogen. In
CO-poisoning Araki ' finds as much as 2 per cent, of lactic acid (reckoned as zinc lactate) in
a rabbit's urine. Minkowski,** on the other hand, denies the insufficient-oxidation theory,
and maintains that the destruction of lactic acid depends on a specific property of the

' An asymmetric carbon atom is one in wliich the four atoms, or groups of atoms, united to

CH3

■ . I

it are all different. In lactic acid we find the following grouping, H — C — OH. The central

COOH.
carbon represents the asymmetric atom. Such an arrangement is always optically active. One
is able to conceive the arrangement of the atoms in space, according to the above grouping, or
CH3

as follows: HO— C— H. This latter represents a different configuration. The two arrange-

I
COOH

ments are optically antagonistic. A mixture of the two is optically inactive. The reader is

referred to a text-book on general chemistry for the suggestive illustrations of the tetrahedral

space pictures.

'•^ BericMe der deutschen ehemischen Geselhchaft, Bd. 16, p. 2720.

^ Astaschewski : Zeitschrift fiir physioloffische Chemk, 1880, Bd. 4, p. 403; Irisawa, Ibid.,
1893, Bd. 17, p. 351.

* Boehm : Pfluger's Archiv, 1880, Bd. 23, p. 44.

' Minkowski : Archiv fur exper. Pathologie und Phamiakologie, 1886, Bd. 21, p. 41.

* Festschrift zu R. Virchmv's 70. Geburtstarj.

^ Zeitschrift fiir phyaiologische Cheniie, 1894, Bd. 19, p. 42ti.

^Loc. cit., and Archiv fiir exper. Pathologie und Pharmakoloyie, 1893, Bd. 31, p. 214.

{){)() .I.Y AMERICAN TEXT-BOOK OE PTTYSIOLOGY.

liver, the normal action bein^ cither ilcstruction in the liver itscll" or in other organs
through the medium of a substance (enzyme ?) produced in the liver.

One may inter|)ret Araki's experiment as showing that consideral)le (juantities of lactic
acid are constantly produced in metabolism, but are normally swept away and burned; the
C'()-pt»isoning would prevent the normal combustion. 'I'hc accumulation in mu.scle after
stoppage of blood-current [rigor mortis) woidd then be oidy a continuation of the normal
process of decomposition.

Cystein, a-Araido-a-thiopropionic Acid. — This substance has the formula
Nil,

OH3 — C — COOH. It is a product of proteid metabolism and is normally

SH

destroyed in the body. On the introduction of a halogen derivative of benzol
into the body, compounds are formed with cystein, called mercapturic acids,
which appear in the urine :

NH, NH,

I I

CH3-C— COOH + CgH^Br + O - CH3— C— COOH + H^O.

I I

SH SCgH.Br.

Bromophenyl-mercapturic acid.

This proves that cystein (like glycocoll, for example) is at lea.st an intermediary and
possibly a primary product of proteid metabolism (.see p. 951). If cy.'^tein be fed,
the greater part (two- thirds) of the sulphur appears in the urine as sulphuric acid,
the rest as neutral sulphur. Thiolactic acid has been found ^ as a decomposition
product of horn. Baiunann ^ demonstrates the reduction of cy.stein to thiolactic
acid, i^hows that the latter yields an odor of ethyl sulj)hide on evaporation,
and asks if thiolactic acid be not the mother substance of Abel's compound
(see p. 951) :

NH,
CH3— C— COOH + H2 = CH3CH(SH)COOH + NH3.

I Thiolactic acid.

SH

Cystein itself is never directly detected in the urine or in the body.

Cystin, Dithio-diamido-ethidene Lactic Acid. — Cystein is converted by
atmospheric oxygen into cystin :

NH,

2CH,— C— COOH + 20 =

CH3— CSNH2— COOH
CH3— CSNH2— COOH*

oil ("y.stiii.

Cystin is very insoluble in water. In particular cases it appears in considerable

' Ruter: Zeitschrift filr physiohgische Chemie, 1895, Bd. 20, p. 564.
^ Baumann : Ibid., 1895, Bd. 20, p. 583.

THE CHEMISTRY OF THE ANIMAL BODY. 991

quantities as a urinary sediment, still more rarely as a stone in the bladder
(see p. 986). It is hevo-rotatoi-y.

It is reported' that bodies having; the conipositioii C — S — H (thio- acids, mercaptaris)
may form sulphuric acid, while most of those having the composition ~C — S — C—
(ethyl sulphide) are not oxidized in the body.

/3-Oxybutyric Acid, CHsCIiOIlCIIaCOOlI.— A Itevo-rotatory aeid (see
p. 981).

Amido- Derivatives of Carbonic Acid.
^'"^OH ^'"^OH '^'^^NH;

Carbonic acid. Carbamic acid. Carbamide.

Carbamic Acid. — This is not known free, but its calcium salts have been
found, especially in herbivorous urine, and its presence in the blood as ammo-
nium carbamate is maintained.^ The latter has been obtained by DrechseP by
oxidizing glycocoll and leucin in ammoniacal solution, and he has converted it
into urea by electrolysis. From these facts he concludes that ammonium car-
bamate is the antecedent of urea.

Ammonium carbamate is formed by the direct union of ammonia with car-
bonic oxide in their nascent states, and is therefore found in commercial ammo-
nium carbonate and as the product of the oxidation of the amido- compounds
above mentioned :

2NH3 + C0.3=OC<g^|j^-

Water converts it into ammonium carbonate :

Carbamide, or Urea, OC(NH2)2. — This is the principal end-product of the
nitrogenous portion of proteid in all mammals, being found in considerable
concentration in the urine. It may be detected in the blood in traces, in
lymph, and in the liver, but Liebig could find no trace of it in muscle. In
ursemia it may collect in all tissues of the body, and may then be excreted
in slight amount by the gastric and intestinal juices. It is given off in profuse
sweating, though only in small proportion to that lost in the urine.

Preparotion. — (1) Like other amides, by heating ammonium carbonate ;
further, by the electrolysis of, or by heating, ammonium carbamate :

oc<8nS: = of^<IS: + 2HP.

OC<™k, = OC<^W= + H,0.

> W. J. Smith : PJluger's Archiv, 1894, Bd, 55, p. 542, and 1894, Bd. 57, p. 418.
' Drechsel: Ludwig's Arbeitm, 1875, p. 172; Drechsel und Abel, Archiv fiir Physiologie, 1891,
p. 242.

* Loc cit.

992 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

(2) Through the union of ammonia with carhonyl chloride :

OCCI2 + 2NH3 - OC(NH,)2 + 2IIC1.

(3) By evaporating an aqueous soKition of ammonium cyanate:

0:C:N.NH, = OqNHj,.

This was Wohler's notable preparation in 1828 of an "organic" compound,
a product of life, without the aid of a " vital force."

(4) As a decomposition ])rodiict of guanin, xanthin, crcatin, uric acid, etc.

(5) From proteid, through hydrolytic cleavage' (see p. 994). This origin
has not as yet been confiriuod.

Properiiea. — Urea is a weak base, of great stability when within the alka-
line fluids and tissues of the body. It is soluble in water in all proportions,
very soluble in hot, less so in cold alcohol, whence it crystallizes in needle-like
forms. It melts at 132° and recrvstallizes on cooling. Heated higher it is
converted into biuret, a substance which giv&s a violet color with dilute cupric
sulphate in a sodium-hydrate solution (called the biuret reaction) :

NH,

Heating urea with water over 100° in sealed tubes, boiling it with alkalies
or acids, bacterial action (see p. 956), all convert it through hydrolysis into
carbonic oxide and ammonia. Such decomposition may take place in the
stomach in uraemia.^ Nitrous oxide breaks up urea, thus:

OC(NH2)2 + 2HNO, = CO2 -^ 3H2O + 4N,

and hypobromite of soda acts in like manner in the presence of alkali :

OaNH^)^ + SNaBrO = CO^ + 2H,0 + 2N + 3NaBr.

The alkali present absorbs the CO^i and the volumes of N afford a measure tor the
amount of urea present (method of Hiifner, apparatus by Doremus).

Urea combines with nitric acid to form urea nitrate, ()C(NH2)2.HN03,
which is insoluble in nitric acid. Urea oxalate, which is formed in similar
manner by the combination of urea with oxalic acid, is insoluble in water.
Many combinations with metallic salts have been prepared, of which one with
mercuric nitrate, of uncertain formula, is the ba«?is of Liebig's method of titra-
tion for urea.

Urea in the Body. — This subject has l)een discussed under Nutrition.
It can only be briefly considered here. When urea is fed it is i-aj>idly excreted
in the urine. The excreted nitrogen of proteid appears in mammalia in greater
part as urea. Amido- products of proteid decomposition, glycocoll, leucin,
aspartic acid, uric acid, when ^ad are converted by the body into urea. So like-
wise are ammonium carbonate, lactate, and tartrate. Ammonium chloride, on

' Drechsel : Archiv fiir Physiologle, 1891, p. 2fil.
' Voit: Zeitachrift fur Bidogk, 1.%S, VA. 4, p. 150.

THE CHEMISTliY OF Till': ANIMAL BODY.

993

acooimt of tho ^{vimv^ ac-id radical, passes tlin.tiuh can.ivora unclian^^od, but in
herbivora, the blood of which is more stron};ly alkaline, a certain part of tiie
ammonia is converted first into carbonate and then into urea. This conversion
of ammonium carbonate into urea is of striking interest. Artificial irrij,^ation
of a liver with blood containing annnouium carbonate increases the urea in
the blood, while similar treatment of muscle or kidney shows no such results.'
In other experiments it has been shown that annnouium salts appear in the
urine after feeding acids to carnivora, and that in disease in which acids are
produced (lactic, aceto-acetic, oxybutyric acids) ammonia accompanying them
is found in the urine, in all ca.ses representing that ordinarily converted into
urea. In disease of the liver (cirrhosis, phosphorus-poisoning) ammonia is
found in the urine above the normal. Admitting the fact that ammonium
ciirbonate (and carbamate likewise) may be converted into urea by the liver,
there is no ground for believing that this is the normal process for the produc-
tion of the whole amount of urea, nor is there at present any measure of the
amount of ammonium-salts produced in the body. The liver may be very
completely destroyed by disease, and large quantities of urea still be excreted.^
In getse extirpation of the liver has no effect on the urea excreted, therefore in
geese it is formed elsewhere.' For aught that is known, therefore, urea may
be formed in other organs than the liver, and it is not at all improbable that
it is formed in all organs where proteid decomposition is progressing. The
greater part of urea from proteid is eliminated in the dog fourteen hours after
his meal (see p. 987).

Guanidin, HN: C< ^Jg'. This is the imide of urea, and has been obtained by the
oxidation of guanin. It iinites with alcohol and acid radicals— forming, for example,
methyl guanidin, HNC < NHCH3' ^"*^ guanidin acetic acid, HN < NHCH^COOH.

NH

Creatin, or Methyl Guanidin Acetic Acid, HNC < ts^^/qjj \qy{ COOH.

Creatin is a product of proteid decomposition and found in muscle to the ex-
tent of 0.3 per cent., in traces in the blood, and in varying amounts in the
urine. It is the principal constituent of meat-extracts (liiebig's). Creatin
may be formed synthetically by the union of cyanamide w^ith sarcosin, and it
may be broken up into these constituents by boiling with barium hydrate, but
the cyanamide is immediately converted into urea through the addition of
water :

H,N.CN + HN(CH3)CH,COOH = HN :C < ^T(ck)3CH,C00H.

Cyanamide. Sarcosin. Creatin.

Creatin, however, is not converted into urea in the body if fed, but is ex-
creted in the urine as creatinin.* The amount of creatinin found in the urine

> Von Scliroeder : Archivfur exper. Pathohgie und Pharmakologie, 1882, Bd. 15, p. 364.
' Marfort : Ibid., 1894, Bd. 33, p. 71.
» Minkowski: Ibid., 1886, Bd. 21, p. 62.
♦ Volt : Zeitschrift fur Bioloffie, 1868, Bd. 4, p. 114.
63

994 AJV AMKlilCAy TEXT-BOOK OF PHYSIOLOGY.

corresponds normally to the amount of creatin contained in tlic meat food ; in
starvation urine it is proportional in amount to the proteid (muscle) destroyed,
being present even on the thirtieth day (experiment on Succi^); and it is
]>resent only in traces, or not at all, in the urine of milk-fed children (ci-eat in-
free food). In convalescence creatin is said to be retained, possibly for the
building of new muscle.^ There is no reason for believing that much creatin
is ever formed in the body.

Creatin gives its flavor to meat. If .trently heated it gives the odor of roasting beef.
Creatinin in the urine reduces alkaline solutions of copper salts (care must be taken, there-
fore, in making the sugar test after using meat extracts). The action of creatin is simply that
of a ]ileasant-tasting. pleasant-smelling substance, which prepares the stomach for food
but has no nourishing value /)<"/• ac. It is considered by some to be a nerve-stimulant.

Creatinin, or Glycolyl Methyl Guanidin. — Heating creatin Avith acids
changes it into creatinin with loss of water, and having the formula

NH — CO
HX:C!^ I . Warming at 60° with phosphoric acid causes this

\N(CH3)CH,
conversion. In like manner when the kidney prepares an acid urine, creatin
becomes creatinin : if tlu; acid reaction be effaced through feeding alkaline
salts the creatin is excreted unchanged.' Creatinin with chloride of zinc
forms a characteristic very insoluble white powder of creatinin zinc chloride,
(C,H7N30)2.ZnCl2.

Lysatin, C,;H,3X202, and Lysatinin, C|.H,,N302. — These substances are
obtained, like lysiu (see below), from the hydrolytic cleavage of proteid, as for
example from casein or conglutin heated with hydrochloric acid and zinc
chloride; they are probably likewise produced in trypsin digestion.*

According to Drech.sel^ they are homologues of creatin and creatinin, and
therefore should yield urea on heating with barium hydroxide. This is
Drechsel's method of direct production of urea from proteid by hydrolytic
cleavage.

Diamido- Fatty Acids. — Of these four have been described :

Diamido-acetic Acid, CH(NH..,)2C00II. — This was found byDrechsel® among other
compounds after lieating casein in sealed tubes with concentrated hydrochloric acid at 140°-
J)lnmido-i[)r(qvonic acid has not l)een found in the body.

Diamido-valeric Acid, or Ornithin, C4H7(NH2)2COOII.— This has been detected by
Jatfe in the urine and excrements of fowls.

a-e-Diamido-caproic Acid, or Lysin, CH2NH2CH2CH2CH2CHNH2-
COOH. — This is a hydrolytic cleavage product of casein after boiling with
hydrochloric acid, or baryta water,'^ and may be similarly obtained from gela-

' Luciani : Dan Hnngei'v, Leipzig, ]S00, p. 144.
^ Von Noorden : Patltolor/ie des Stoffuechseh, 1 893, p. 1 69.
3 Voit : Zeitschrift fur Binlogie, 1868, Bd. 4, p. 150.

* See Drechsel, and his pupils Fisher, Siegfried, and Hedin : Archivfiir rin/siologie, 1891, p.
248 et seq.

^ Op. cit., p. 261. * Abstract in Maly's Jahrcsbericht liber Thierchemie, 1892, p. 9.

' Drechsel : Archivfiir Physiolof/ie, 1891, p. 248.

THE CHEMISTRY OF THE ANIMAL BODY. 995

tin, from vegetable proteid (conglutin), and from tlie pancreatic digestion of
fibrin.'

Alloxuric Bodies and Bases.

The alloxuric bodies comprise those containing in combination two radicals,
one of aUoxan, OC < ^{^ ~ ^ > CO, the other of urea. The skeletal struc-
ture of all alloxuric bodies may be written thus :

N— C

C C — N.

N— C — N-^

Alloxan. Urea.

These bodies fall into three groups, that of hypoxanthin, of xanthin, and of
uric acid. Bodies belonging to the first two groups are called alloxuric bases,
or more commonly xanthin bases, or nudein bases, because they are derived
from nuclein. The strong family analogy of the three groups is shown by
the following reactions — results of heating with hydrochloric acid in sealed
tubes at 180° to 200°:'^

CsH.N.O + 7H2O = 3XH3 + C2H5NO2 + CO2 + 2CH A-

Hypoxanthin. Glycocoll. Formic acid.

C^H.XP^ + 6HP - 3NH3 + C^H.NO^ + 2CO, + CH A-

Xanthin.

CsH.N A + 5H,0 = 3NH3 + C2H5NO2 + 3CO2.

Uric acid.

Reference to the formulae below will show that the molecules of COg given
oft* correspond to the number of CO radicals in the alloxuric body, while the
molecules of formic acid correspond to the number of CH groups.

(a) Hypoxanthin Bases.

XH — C — H

/ II

Hypoxanthin, or Sarcin, HC C — NHv

^ I > CO.— This is found in

N — C=N /

small amounts in the tissues and fluids of the body and in the urine. The
action of water or dilute acids on nuclein yields hypoxanthin.^

NH— C— H

/ II

Adenin, or Imidosarcin, HC C — NHv

vv I >CNH.— This is found

N — C=N /

» For literature on these diamido- fatty acids see Klebs : Zeitschrift fur lyhysiologische Cheniie,
1895, Bd. 19, p. 301.

2 Kriiger: Ibifl., 1894, Bd. 18, p. 463. ^ Kossel : Tbid., 1881, Bd. 5, p. 268.

996 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

in the tissues and fluids of the body and in the urine. It is, like hypoxan-
thin, a decomposition product of nuclei.' It is convertetl into hypoxanthin
through the action of nitrous acid.

{b) Xantiiin Bases.

NH— C— H

/ II

Xanthin, OC C— NH.

\ I J>CO. — This substance, like the two last

NH— C-N /

named, is found in the tissues and the fluids of the body, and is a decomposi-
tion product of niiclein. Occasionally it occurs in the form of a urinary cal-
culus, as a stone of exce])tional hardness.

Monomethyl Xanthin, or Heteroxanthin, C'gHgN/X- — This has likewise
been detected in the urine (see Cafl'ein).

Theobromin, Dimethyl Xanthin, or Paraxanthin. —

XCH3— C— H

/ II

0 = C C— XCH3.

XH — C = N ^

This is the principal alkaloid in cacao (chocolate). When fed it is in part
excreted as monomethyl xanthin in the urine (see Caff'ein). Its silver com-
pound treated with methyl-iodide yields caffein.
NCH3-C-H

Theophyllin, 0=r^ ('-NIK ^. . ,.

\ I /CO. — This is found in tea and uiav be

>X'H,— C = N /

converted into caffein through the addition of a third methyl group.^

XX^H,— C— H

Caffein, Thein, Trimethyl Xanthin, 0 = C C — NCHjv

\ I y CO.

This is the alkaloid of coflee, tea, guarana, and the cola nut, imparting the
nerve-stimulating proj)erties to each. A cup of coflee contains 0.1 gram of
cafleiu. If caffein be fed it a})pcars in part as methyl xanthin in the urine.*
That the compounds theobromin and caffein may be demethylated in the tissue
is an interesting commentary on the methylation of tellurium, selenium, and
pyridin by the tissues.

Guanin, Imido -xanthin, C.H^XpXH. — This is found, like hypoxanthin,
adenin, and xanthin, in tissues rich in nuclei, and in the blood.* It is a decom-

* Kossel : Zeitschrift Jiir physiobgische Chemie, 1886, Bd. 7, p. 250.

* Jbid., 1889, Bd. 13, p. 298.

' Boudzynski iind Gottlieb : Archlvfur eiper. Palholofjif und. Pharmakoloyie, 1895, Bd. 36, p. 45.

* Kossel : Zeitschri/l fiir physiologische Chemie, 1884, Bd. 8, p. 404.

THE CHEMISTRY OF THE AMMAL BODY. 997

position product o^ miclcin. Combined with calciuni it gives tiie brilliant
iridescence to fish-scales.' It is found in the fresher layers of deposited guano,
according to Voit being very probably derived from the fish eaten by the
\vater-fowl.

(c) Uric Acids.

NH— C = O

/ I

Uric Acid. O = C C— NH

\ II >CO. — This acid is found in the nor-

NH— C— NH

mal urine in small amounts, and may be detected in the blood and tissues,
esi)ecially in gout. It is the principal excrement of birds and snakes, that of
the latter being almost pure ammonium urate.

Preparation. — (1) By heating glycocoU with urea at 200° :

C2H5XO2 + 3CO(NH2)2 = QH.X.Oj + 3NH3 + 2H2O.

(2) By heating the amide of trichlorlactic acid with urea :

CCI3CHOH.CO.NH2 -f 2CO(NH2)2 - CsH.NA + 3HC1 + NH3 + H^O.

Properties. — Uric acid may be deposited in white hard crystals, which are
tasteless, odorless, and almost insoluble in water, alcohol, or ether. (For its
solution in the urine see p. 966.) Presence of urea adds to its solubility.^ Its
most soluble salts are those of lithium and piperaziu. Uric acid is dibasic —
that is, two of its hydrogen atoms may be replaced by monad elements.

(1) Nitric acid in the cold converts uric acid into urea and alloxan :

C5H,NA+ 0 + H,0 = OC<5jgZco>^^ + OC(NH,),.

Alloxan.

(2) Whereas, if the hot acid acts, it produces parabanic acid :

/NH — CO. /NH — CO

0C< >CO + 0-OC< J +C0,.

\NH-CO/ \NH — CO

Parabanic acid.

(3) Throujrh water addition parabanic acid becomes oxaluric acid:

/NH — C = 0 /NH, ■

0C< I +H.,0 = OC<

\NH — C = 0 \NH.CO.COOH

Oxaluric acid.

(4) And still another molecule of water added produces oxalic acid and urea : *

/NH, COOH

0C< +H.,0= I +OC(NH.J,.

\NH.C0.C00H COOH

Oxalic acid.

The above reactions lead up to the constitutional formula of uric acid, and show its
decomposition into urea and oxalic acid through oxidation and hydrolysis. It is known
that uric acid when fed increases the amount of urea in the urine, and it is possible that
the oxalic acid in the urine may have the same source.

* Voit : Zeitsehrift fur tvissemchaflliche Zoologie, Bd. 15, p. 515.

^ G. Riidel: Archiv fiir exper. Pathologie und Pharmakologie, 1893, Bd. 30, p. 469.

^ See Bunge : Physiologische Chemie, 1894, p. 312.

998 ^l.V AM Kill C A. \ TEXT- BOOK OF PHYSIOLOGY.

Uric iiciil oxidized witli iit'rmaiiiraiiatc of i)ota.s]i is converted into aUdtitoin, CiHgN^O,,
a substance which is found in the allantoic fluid, and in the urine of jire^'nant women and
of newborn children.

If uric acid be carefully evaporated with nitric acid on a small white porcelain cover,
a reddish residue remains, which moistened with ammonia gives a brilliant purple color
due to the formation of mnrexid, CgHjlNHilNsOg; subsequent addition of alkali gives
a red coloration. This is known as the mnrexid test and is very delicate.

Carnin, or Dimethyl Uric Acid. — The formula is unknown. Carnin i.s
found in tissue, aud has been detected in extracts of meat and in the urine.
A synthetic dimetiiyl uric acid of the following formula,

NCH3— c = o

/ 1

OC C— NHv

\ II >co,

NCH3— C— NH'^

when fused with oxalic acid is converted into theophyllin.^ This is the only
transformation between the uric-acid group and the xanthin buses known in the
laboratory.

The Alloxuric Acids and Bases in the Body — To the definitely
determined facts belong (1) that these substances when fed are generally con-
verted into urea ; (2) that some nucleins under proper chemical treatment
break up as follows :

Nuclein.
I

Proteid. Nucleic acid.

Phosphoric acid. Adenin.

Guanin.

Xanthin.
Hypoxanthin.

(3) that these last named substances have been obtained from no j)roteid other
than nuclein (see Nuclein). The idea that the alloxuric bodies in mammals were
metabolic products of nuclein, the uric acid being derived from oxidation of the
bases, was especially emphasized by Horbaczewski.- His statement that uric
acid and the bases are increased in the urine after feeding nuclein has been con-
firmed.^ The increase of alloxuric bodies in the urine in leucocytha?niia has long
been known, and is now explained by the increa.-ed nuclein-metabolism following
the destruction of the white blood-corpuscles. An interesting investigation of a
case of leucocvthsemia * has shown that ingested theobromin is burned as in the
normal person ; the explanation is offered that the alloxuric bodies produced

' Fischer and Acht: Berichte der Berliner Acad^mk, 1895, p. 259.

^ Sitzungsberichte der Wiener Akademie der Wvisenschaften, 1891, Bd. C. Abtli. iii. p. 13.

' Weintraud : Verhandlung der Berliner physiologische Gesellschaft, Arrhiv filr Physioloyie,
1895, p. .382.

* Boudzynski and Gottlieb: Archiv fUr exper. Pathologic und Pharmakologie, 1895, Bd. 36,
p. 127.

THE CHEMISTRY OF THE ANIMAL BODY. 999

iu the body in some way have lesser opjwrt unities for oxidation than those
introduced into it. Experiments on this kuuc case have shown tliat, though
the pro[)ortion of daily uric-acid nitrogen to total nitrogen in the urine may
vary considerably (1 : 63 to 1 : 88), the proi)ortiou of the nitrogen of uric acid
plus the bases to total nitrogen is quite constant (1 : 48.3 to 1 : 40.8) ; from
this may be interred that there is greater or less production of uric acid through
oxidation of the bases on different days. This may be interpreted as affording
the missing link in explanation of the conversion of the ba.>es into uric acid.
If xanthin itself be fed, it is not converted into uric acid. According to
Horbaczewski/ uric acid is produced from nuclein by digesting putrid extract
of the spleen with blood.

Ximthin fed to birds is converted into uric acid. In birds the formation of uric acid
depends on a synthetic union of ammonia and lactic acid in the liver, since on extirpation
of the liver tlie last two substances appear in the urine in amounts proportional to the
normaljj' formed uric acid (see p. 989).

The literature on the subject of gout is enormous. It is sufficient to re-
mark here that it is not even known whether gout is due to an increased for-
mation or an increased retention of uric acid. The amount of uric acid in the
blood is certainly increased. The normal amount of uric acid in the daily
urine is put at 0.7 gram, that of the alloxuric bases at 0.1325.^ The amount
of the bases may be quadruplet! in leucoeythsemia.'' Whether all the alloxuric
bodies produced in the organism are eliminated, or whether they are partially
burned, is a matter of controversy.

Diatomic Dibasic Acids, CJ^on-iO^.

COOH
Oxalic Acid, | . — This is found as calcium oxalate in the urine, and

COOH
is present in most plants. Its possible origin from uric acid has been men-
tioned. It is a product of boiling proteid with barium hydrate. It may be
obtained .synthetically by heating sodium formate :

COONa
2HCOONa= | +2H.

COONa

Oxalic acid and its alkaline .^^alts are very soluble in water. Its calcium salts
are insoluble in water and dilute acetic acid, but are soluble in the acid phos-
phates of the urine.

If oxalic acid be given subcutaneously it appears unchanged in the urine.^
Given per os it undoubtedly unites with the calcium salts of the gastric and
other juices, and is therefore but partially absorbed. After feeding a man
with meat alone, or with meat, fat, and sugar, Bunge* could find no oxalates

' Loc. cit. 2 Kruger and Wulff : ZeUschrift fur physidogische Chemie, 1895, Bd. 20, p. 184.
^ Boudzynski and Gottlieb, Op. cit., p. 132.

* Gaglia: Archiv fur exper. Pathologie und Pharmakologie, 1887, Bd. 22, p. 246.

* Physiologische Chemie, 1894, p. 340.

1000 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

in tlic iirino. ]Ie therefore concludes that the oxalic acid in the urine is
derived from the oxalates of the food and not from metabolism in the body.
Stones in the bladtler are sometimes composed of calcium oxalate, as are also
urinary sediments when formed in consequence of aramoniacal fermentation.

Succinic Acid, HOOC.CgH^.COOH. — This has been detected in the
spleen, thymus, thyroid, in echinococcus fluid, and often in hydrocele fluid. It
is a product of alcoholic fermentation, and of proteid putrefaction. It is often
found in plants.

Amido-succinic Acid, or Aspartic Acid, nOOC.CJl3NIl2.C'OOH.
This is a product of boiling proteid with acid or alkalies, and it is also formed
under the influence of tryj)siu in proteid digestion.

Monamide of Amido-succinic Acid, or Asparagin, H,^NOC.C2H3NH2.COOH.

— This is found widely distributed in plants, especially in the germinating seed. If a plant
be placed in the dark its proteid nitrogen decreases, whereas the non-i)roteid nitrogen
increases,' the cause of tliis being attributed to proteid metabolism with tlie produCTion of
amido- acids, i. c. aspartic and glutamic acids, leucin, and tyrosin. In the sunlight, it
is believed, these bodies are later reconverted into proteid. One view regarding the for-
mation of asparagin is based theoretically on the production of succinic acid from carbo-
hydrates (as in alcoholic fermentation) and the subsequent formation of oxymccinic acid
(or malic acid, IIOOC.C,H:tOII.rOOII), which the inorganic nitrogenous salts change
to asparagin.^ At any rate asparagin in the plant has the ])0wer of being constructed into
proteid. Since proteid in the animal body may yield 45 per cent, of dextrose in its
decomposition, as will be shown, it seems fair to surmise that the synthesis of proteid in
the plant may in part depend upon the union of asparagin or similar amido- compounds
with the carbohydrates present. Asparagin if fed is converted into urea. It forms no
proteid synthesis in the animal, and has only a very small effect as a food-stuff.'

Glutamic acid, H00C.CIINH2.CH,.CH,.C00n.— This is found as a cleavage-
product of tryi)tio digestion in the intestinal canal. GJntamin, its amido- compound, is, like
asparagin, widely distributed in the vegetable kingdom and in considerable amounts. It
probably jilays the same role as asi)aragin in the plant. Glutamin is more soluble than
asparagin and is therefore less easily detected.

Compounds of Triatomic Alcohol Radicals.
Glycerin, or Propenyl Alcohol, CTI2OH.CHOH.CH2OIT. The glycerin
esters of the fatty acids form the basis of all animal and vegetable fats.
Glycerin is furthermore formed in small quantities in alcoholic fermentation.

Preparation.— {I) Through the action of an alkali on a fat, glycerin and a
soap are formed, a process called saponification:

2C3H,(C,8H3,02)3 + 6NaOH = 2C3H,(OH)3 + 6NaC,8H3,02.

stearin. Sodium stcarate.

(2) Fats may be decomposed into glycerin and fatty acid by superheated
steam, and likewi.se by the fat-splitting ferment in the pancreatic juice. Thu.s,
if a thoroughly washed butter-ball, consisting of pure neutral fat, be colored
with blue litmus, and a drop of pancreatic juice be placed upon it, the mass

' Schulze and Kisser : Lamlmrthschatfliche Versuchs-Slation, 1889, Bd. 36, p. 1.

2 MUller: Ibid., 1886, Bd. 33, p. 326.

' See Voit : Zeitschrift fur Biologic, 1892, Bd. 29, p. 125.

THE CHKMISTny OF TTTE AMMAL BODY. 1001

will gradually grow rrd in virtue of tlic fatty acid liberated from its glycerin
couibiiiation. This reaction takes place to some extent in the intestine.

If lattv acid be led, the chyle in the thoracic duct is ibund to contain much
neutral fat.' This synthesis indicates the presence of glycerin in the body —
perhaps, in this case, in the villus of the intestine: the source of this glycerin,
whether from proteid or carbohydrates, is problematical. If glycerin be fed,
only little is absorbed (since diarrhoea ensues), and of that little some apjjcars
in the urine. In its pure form, therefore, it seems to be oxidized with dif-
ficulty in the body.

Glycerin Aldehyde, IIOCH.,.CIIOH.CHO, and Dioxyacetone, IIOCII,.CO.Cn,
OIL— These sul. stances arc formed by tlie careful oxidation of t,dycerin with nitric acid,
and together are termed glycerose. They have a sweet taste and are the lowest known
members of the glycose (sugar) series — i. c. substances which are characterized by the
presence of either aldehyde-alcohol, — CHOH— CHO, or ketone-alcohol, — CO— (;il,0ll,
radicals. The constituents of glycerose, from the number of their carbon atoms, are
called trioscs. On boiling glycerose with barium hydrate the two constituents readily
unite to form i-fructose (levulose).

Glycerin Phosphoric Acid, (HO)AH5.H2P04.— This is the only ethe-
real phosphoric acid in the urine. It is found in mere traces, its source being
the lecithin decomposed in the body.^

^(C„H2„_i02)2'

Lecithin. CsH,^^ p^^^^^^^^^^^.^^,^^^^Qjj _-^^^,.^j^.^ .^ ^^^^^^^

in every cell, animal or vegetable, and especially in the brain and nerves.
It is found in egg-yolk, in muscles, in blood-corpuscles, in lymph, pus-cells,
in bile, and in milk. On boiling lecithin with acids or alkalies, or through
putrefaction in the intestinal canal, it breaks up into its constituents, fatty
acids, glycerin phosphoric acid, and cholin (see p. 986), substances which the
intestine may absorb. The fatty acids may be stearic, palmitic, or oleic, two
molecules of different fatty acids sometimes uniting in one molecule of
lecithin : hence there are varieties of lecithins. Through further putrefaction
cholin breaks up into carbonic oxide, methane, and ammonia.^ Lecithin
treated with distilled water swells, furnishing the reason for the " myelin
forms" of nervous tissue. Lecithin is readily soluble in alcohol and ether.
It feels waxy to the touch. Protagon, which has been obtained especially
from the brain, is a crystalline body containing lecithin and cerebrin — which
is a glucoside (a body separable into proteid and a sugar). The chemical
identity of protagon is shown in that ether and alcohol will not extract lecithin
from it.* Protagon readily breaks up into its constituents. While protagon
seems to be regarded as the principal form in which lecithin occurs in the
brain, simple lecithin is believed to be present in the nerves and other organs.
This subject has not been i)roperly worked out. Regarding the synthesis of

» Munk: Virchovfs Archiv, 1880. Bd. 80, p. 17.

* Sotnitschewsky : ZeiU^chrift fiir physiohr/ische Chemie, 1880, Bd. 4, p. 214.
3 Hasebroek : Ibid., 1888, Bd. 12. p. 148.

* Gamgee and Blankenhorn: Journal of Physiology, 1881, vol. ii. p. 113.

I(K)2 AX AMERICAN TEXT-BOOK OF PIIVSIOLOOY.

lecithin in the hody, or the physiologieal importance of the substance, abso-
lutely nothin«^ is known.

Fat in tiik Body. — Animal and vegetabh; fats consist principally of
a mixture of the triglycerides of })ahnitic, stearic, and oleic acids. In the
intestines the fat-splitting ferments convert a small portion of fat into glycerin
and tatty acid ; the fatty acid unites with alkali to form a soap, in the presence
of which the fat breaks up into fine globules called an emulsion; if now the
fine globules and the intestinal wall be wet with bile, fat is absorbed, and may
be burned in the cells or deposited in the adipose tissue.

Fat may likewise be derived from ingested carbohydrates. The chemical
derivation of fatty acid from carbohydrates has already been mcntionetl in
the case of formic, acetic, propionic (see p. 980), and butyric acids. The fatty
acids of fusel oils are likewise formed from carbohydrates in fermentation.
The laboratory synthesis of sugar from glycerin has been already related.
These reactions, however, furnish only the smallest indication of the large
transformation of carbohydrates into fiit possible in the body.

If geese be fed with rice in large quantitj', and the excreta and air respired be ana-
lyzed, it may be shown that carbon is retained in large amount by the body, in amount
too great to be entirely due to the formation of glycogen, and must therefore have been
deposited in the form of fat.' 8uch fattening of geese produces the delicate 2)d(4 de foie
gras. The principle has been established in the case of the dog as well.^

The formation of fat from proteid (fatty degeneration) has been established
with all certainty in pathological cases (see p. 957). Recollection of the fact
that proteid may yield 45 per cent, of sugar aids in the comprehension of this
problem.

. Other usually cited proofs of the formation of fat from proteid include the conversion
of casein into fat incident to the ripening of cheese ; and the transformation of muscle in
a damp locality into a cheese-like mass called adipocere, which is probably effected by
bacteria.* Adipocere contains double the original quantity of fatty acid, occurring as cal-
cium, and sometimes as annnonium salts.

Experiments of C. Voit show that on feeding large quantities of proteid. not all the
carbonic acid is expired that belongs to the proteid destroyed as indicated by the nitrogen
in the urine and feces. The conclusion follows that a non-nitrogenous substance has been
stored in the bod}'. Too much carbon is retained to be present only in the form of glyco-
gen; fat from proteid must therefore have been stored.* The formation of fat normally
from proteid has been violently combated by Pfliiger, it would seem without proper founda-
tion. For behavior of fat in the cell see p. 999.

Oleic Acid, CisHg^O,. — This acid belongs to the series of fatty acids hav-
ing the formula CDH2n_202. Its glyceride solidifies only as low as +4° C. It is
the principal compound of liquid oils. Pure stearin is solid at the body's
temperature, but mixed with olei'n the melting-point of the mixture is reduced
below the temperature of the body aiM its absorption is thereby rendered possi-
ble. The fat in the body is all in a fluid condition, due to the presence of olein.

' Voit: Abstract in Jahresbericht iiber Thierchemie, 1885, Bd. 15, p. 51.
' Kiibner : Zeitschrift filr Biologie, 1886, Bd. 22, p. 272.

* Read Lehmann: Abstract in Jahresbericht iiber Thierchemie, 1889, Bd. 19, p. 516.

* Erwin Voit : Miinchener rrudieinische Wochenschrift, No. 26, 1892 ; abstract in Jahresbericht
iiber Thierchemie, 1892, p. 34.

THE CIIEMISTRV OF THE ANIMAL BODY. 1003

Carbohydrates.

The important sugar of (he 1)100(1 and the tissues is dextrose. It is
derived from the hydration of starchy loods, and from protcid metabolism.
From dextrose the laetie glands manufaeture another carbohydrate, milk-
sugar. Cane-sugar forms an article highly prized as a food. The study of
the various sugars or carbohydrates is of especial interest because their chemi-
cal nature is now well known.

Carbohydrates were formerly defined as bodies which, like the sugars and
substances of allied constitution, contain carbon, hydrogen, and oxygen, the
carbon atoms being present to the number of six or multiples thereof, the
hydrogen and oxygen being present in a proportion to form water. Glycoses
include the monosaccharides like dextrose, CgHjgOg ; disaccharides include,
for example, cane-sugar, CigHjoOn, which breaks up into dextrose and levu-
lose, while jwlysacchdvides comprise such bodies as starch and dextrins, which
have the formula (CgHjoOs)^.

In recent years the term glycose has been extended to cover bodies having
three to nine carbon atoms and possessing either the constitution of an
aldehyde-alcohol, — CII(OH)CHO, called aldoses, or of a ketone-alcohol,
— COCH^OH, called ketoses. These bodies also have hydrogen and oxygen
present in a proportion to form water, and the number of carbon atoms always
equals in number those of oxygen. According to their number of carbon
atoms they are termed trioses, tetroses, pentoses, hexoses, heptoses, octoses, and
nonoses.

It has been shown (foot-note, p. 989) how from the asjiiiinetric carbon atom in lactic
acid two configurations are derived. If a body (such as trioxybutyric acid) contains two
asymmetric carbon atoms, four configurations are possible,

CH.OH CH^OH CH,OH CH.OH

HCOH OHCH OHCH HCOH

HCOH OHCH HCOH OHCH

COOH COOH COOH COOH

Similarly among the glycose-aldoses, a triose has two modifications ; a tetrose, four ; a pen-
tose, eight : a hexose, sixteen, etc. Thus in the following formula by the variations of H
and OH on the four asymmetric carbon atoms, sixteen possible hexoses may be obtained.

CH^OH
-C—

— C—

— c-
-c- .

CHO

The carbohydrates have well-defined optical properties, rotating polarized light to the
right or left, and are therefore designated as d- (dextro-) and I- (laevo-) respectively. An
inactive («'-) form consists in an equal mixture of the two others. Where the OH group
is attached on the right it may be indicated by the sign -f , on the left by — , or the 4- OH
may be written below, the — OH above.

H H OH H
or CH.OH C C C C CHO
OH OH H OH

CHO

CHO

HCOH

C-f

OHCH

c- ,

HCOH

c-f '

HCOH

c +

CH.OH

CH,OH

d-Glucose.

1004 ^iV' AMERICAN TEXT-BOOK OF PHYSIOLOGY.

The Glycoses.

The triose called glycerose has already been described.

A tetrose called erythrose, which is the aldose of erythrite, C4He(OH)^, a
tetratoniic alcohol, is known.

Of the possible pentoses, arabinose, xylose, and rhamnose (raethyl-arabinose)
occur in the vegetable kingdoms in considerable quantity. They may be
absorbed by the intestinal canal. ^

Hexoses, or Glucoses. — Through the oxidation of hexatomic alcohols
there may be obtained, first, glucoses, tiien monocarbonic acids, and lastly
saccharic acid, or its isomer mucic acid :

C6H6(OH)3CH20H. QH6(OH),CHO. C5H6(OH)5COOH.

Mannite. Mannose Mannonic acid,

(and levulose).

C,H,(OH),(COOH),.

Saccharic acid.

Mannose and levulose are respectively the aldose and ketose of mannite,
galactose is the aldose of dulcite, whereas glucose is probably the aldose of
sorbite — dulcite and sorbite being, like mannite, hexatomic alcohols.

Properties. — (1) The hexoses are converted into their respective alcohols on
reduction with sodium amalgam.

(2) The hexoses act as reducing agents, converting alkaline solutions of
cuprous oxide salts (obtained through presence of tartrate) into red cnprous
oxide, which precipitates out (Trommer's test). Levulic acid is among the
products formed (see p. 982). Of the higher saccharides only maltose and
milk-sugar give this reaction.

(3) Strongly characteristic are the insoluble crystalline compounds formed
by all glycoses with phenylhydrazin, called osazones (see p. 977) :

QH, A + 2H2N.NH(CeH,) = C6HioO,(:N.NH.C,H,)2 + m.O + H,.

Levulose. Phenylhydrazin. Glycosazone.

Levulose, dextrose, and mannose give the same glycosazone. The glycos-
azones are decomposed into osones by fuming hydrochloric acid :

CeH,A(:^^NH.CfiH,)2 + 2H2O = QH,A + 2H2N.NH.C6H5.

Glycosone.
Osones are converted into sugar by nascent hydrogen. The osone de-
rived from levulose, dextrose, and mannose yields levulose by this treatment,
and the transformation of dextrose and mannose into levulose is therefore
demonstrated.

(4) Only trioses, hexoses, and nonoses are capable of alcoholic fermenta-
tion.

Synthesis of the Glucoses. — Formose may be purified by means of phenyl-
hydrazin as above, so that pure /-fructose is obtained ; this treated with sodium
amalgam yields i-mannite, which on oxidation is converted into /-mannonic
acid ; this last is separated by a strychnin salt into its two components ; the
^ "NVeiske : Zeitschrift fur physioloyische Chemie, 1895, Bd. 20, p. 489.

THE CHEMISTRY OF THE ANIMAL BODY. 1005

d-mannonic acid is divideil and one ptirt treated witli hydrogen, with resulting

d-raauno.se, which, as has been showu above, is convertible into tZ-fructose

or ordinary fruit-sugar ; the second part of the d-mannonic acid treated with

chinolin is transformed throngh change in configuration into its isomer,

tZ-gluconic acid, which on reduction yields rZ-glucose, or ordinary dextrose.

This shows the preparation of the common sugars from their elements. The

transformation of levulose into dextrose is especially to be noted, since it takes

place in the body.

^ H H OHH

(7-Glucose, Dextrose, Grape-sugar, CHgOH C C C C CHO. —

OH OHH OH

This is the sugar of the body. It is found in the blood and other fluids and in
the tissues to the extent of 0.1 per cent, and more, even during starvation. The
principal source of the dextrose of the blood is that derived from the digestion
of starch, and also of cane-sugar, in the intestinal tract. Dextrose is likewise pro-
duced from proteid, for a diabetic patient fed solely on proteid may still excrete
sugar in the urine. Minkowski^ finds that in starving dogs after extirpation
of the pancreas the proportion of sugar to nitrogen is 2.8 : 1. The same ratio
has been shown to exist in phlorizin diabetes in rabbits^ when the drug is
administered in a certain way.

In calculating this production of glucose from proteid, it is discovered to i)e
a process of oxidation, in which 45 grams of dextrose are formed from eveiy
100 grams of proteid decomposed.^ The sugar so formed contains 44 per cent,
of the physiologically available energy of the proteid consumed. The pancreas
may perhaps manufacture a ferment which, supplied to the tissues, becomes the
first cause of the decomposition of dextrose, and in whose absence diabetes
ensues. Excess of dextrose in the body is stored up, especially in the liver-
cells, as glycogen, which is the anhydride of dextrose ; the glycogen may be
afterwards reconverted into dextrose. The presence of sugar in the body in
starvation, even when little urea may be detected there, shows the readier excre-
tion of the nitrogenous radical of proteid. Traces of dextrose are found in
normal urine.

Dextrose is a sweet-tasting crystalline substance ; its solutions rotate polar-
ized light to the right.

^ H H OH

(i-Fnictose, Levulose, Fruit-sugar, CHjOH C C C COCHgOH.—

OH OHH
This occurs in many fruits and in honey. It is sweeter than dextrose, and
rotates polarized light to the left. It is a product of the decomposition of
cane-sugar in the intestinal canal. If levulose be fed, any excess in the blood
may be converted into glycogen, and through the glycogen into dextrose. It
is possible thus to convert 50 per cent, of the levulose fed into dextiose.*

' Archiv fur Physiologie und Pharmakologie, 1893, Bd. 31, p. 85.

* Lusk: Paper read before the American Society of Physiology, Philadelphia, 1895.
' Weintraud and Laues: Zeilschrift fiir physiolcgische Chemie, 1894, Bd. 19, p. 632.

♦ Minkowski : Archiv fur Pathologie und Pharmakologie, 1893, Bd. 31, p. 157.

1006 AN AMERICAN TEXT- BOOK OF PHYSIOLOGY.

Wliou levulose is fed to a diabetic i)atieiit, it may be burned, though j)o\ver to
burn dextrose has been lost.^

H OHOHH
(/-Galactose, CHjOH C C C C CHO.— This is found combined

OHH H OH
■with proteid in the brain, forming the ghicoside cerebriu. It is produced
together with dextrose in tiie hydrolytic decomposition of milk-sugar. It does
not undergo alcoholic fermentation, at least not with Saccharomyces apicidatus.
WJien fed it is not converted directly into glycogen, but through its burning
it spares the decomposition of some of the dextrose produced from proteid,
"which latter may of course be converted into glycogen.^

The Disacch abides, CigHojOu.

These are di-multiple sugars in ether-like combination. To cane-sugar and
milk-sugar, Fisher has ascribed the following formuh« : *

Cane-sugar. Milk-sugar.

€H-^^__^ CHPH CH3OH CHO

^/ CHOH ^\C CHOH CHOH

^\CHOH /CHOH CH CHOH

CH 0\CHOH ^/CHOH CHOH

CHOH ^CH ^\CHOH CHOH
CH2OH CH2OH CH — O— CH2

Dextrose group. Levulose group. Galactose group. Dextrose group.

Cane-sugar, or Saccharose. — Cane-sugar, obtained from the sugar-cane
and the beet-root, is largely used to flavor the food, and likewise assumes
importance as a food-stuff. On boiling with dilute acids, cane-sugar is con-
verted through hydrolysis into a mixture of levulose and dextrose. The same
result is obtained by warming with 0.2 per cent, hydrochloric acid at the
temperature of the body. This inversion, therefore, takes place in the stomach.
In the inte.'^tinal canal the inversion is accomplished through the action of a
ferment present in the intestinal juice. Subcutaneous injection of cane-sugar
shows that it is not directly converted into glycogen, but that in burning it
spares some dextrose coming from proteid decomposition, and this latter is
converted into glycogen and may be found in the liver and muscles. But fed
per OS, cane-sugar is the cause of a large glycogen storage, in virtue of its
srreater or le.^^s conversion into dextrose and levulose in the intestines.

Milk-sugar, or Lactose. — This is found in the milk and in the amniotic
fluid. It is probably manufactured from dextrose in the mammary glands,
for the blood does not contain it. It is sometimes present in the urine during
the last days of pregnancy, and almost always during the first days of lactation.
It readily undergoes lactic fermentation, producing lactic acid, which then
causes clotting of the milk. This fermentation may take place in the intestinal
tract. Boiling with dilute acids splits up milk-sugar into galactose and dextrose.

1 Loc cU. » C. Voit : Zeiischrift fitr Binlogie, 1S91, Bd. 28, p. 245.

* Benchte der deutschen chemischen Gesellschaft, 1894, Bd.26, p. 2400.

THE CHEMISTRY OF THE ANIMAL BODY. 1007

This decomposition probably does not take i)la<e in the stomach. Neither
does the intestinal juice cause tliis transformation.' Milk-sugar is probal)ly
absorbed unchanged, and is not a glycogen-producer except indirectly in the
sense of sparing i)roteid dextrose which may become glycogen.'' The contrary
view, /. e. that milk-sugar is converted into dextrose and galactose, is held by
^rinkowski"* and others. The question is not definitely settled.

Isomaltose.— This is the only disaccharide which has been synthetically
obtained, having been produced by boiling dextrose with hydrochloric acid.
It ferments with difficulty and forms an osazone which melts at 150°-153°.
It, wnth dextrin, is a product of the action of diastase and of the diastatic
enzymes found in saliva, pancreatic juice, intestinal juice, and blood upon
starch and glycogen. Through further action of the same ferments isomaltose
is converted into maltose.

Maltose.— ]Maltose (and dextrin) are the end-products of the action of
diastase on starch and glycogen, the process being one of hydrolysis :

Maltose. Dextrin.

It is likewise a product of the diastatic action of ptyalin (saliva), amylopsin
(pancreatic juice), and of ferments in the intestinal juice and in the blood.
Maltose readily undergoes alcoholic fermentation and forms an osazone which
melts at 206°. It is converted into dextrose by boiling with acids. Certain
ferments convert maltose (and dextrin) into dextrose (see Starch).

Cellulose Group, (CgHioOs)^.

Cellulose.— This is a highb' polymerized anhydride of dextrose, perhaps also of uian-
nose. It forms the cell-wall in the plant. It undergoes putrefaction in the intestinal
canal, especially in herbivora (see p. 976), and owing to the production of fatty acids it may
have value as a food. In man only young and tender cellulose is digested, such as occurs
in lettuce and celery. The bulk of herbivorous fecal matter consi.sts of cellulose. Cellulose
is only with difficulty attacked by acids and alkalies. Tunicin, found among the tunicates,
is identical with cellulose, so that the substance is not solely characteristic of the vegetable
kingdom.

Starch, (C6Hio05)2o.— This substance on boiling with dilute acids breaks
down by hydrolysis principally to dextrose. It is found in plants, and
may be manufactured by them from cane-sugar, dextrose, levulose, and from
other sugars. It forms a reserve food-stuff, being converted into sugar as the
plant requires it— in winter, for example. Starch gives a blue color with
iodine. According to recent investigations * starch is said to be broken up by
diastase into five successive hydrolytic cleavage-products as follow^s : (1) Amylo-
dcvtrin (C22H2oOio)54, a substance giving a deep-blue color with iodine. This
is next changed to (2) Erythrodextrin, (Ci2H2oOio)i8 + HgO, or (Ci2ll2oO,o)i7.

1 Pregl : Pflugei's Archiv, 1895, Bd. 61, p. 359. ' C. Voit, Op. cit., p. 260 et seq.

^ Archiv fur exper. Pathologic und Pharviakologie, 1893, B<1. 31, p. Kil ; Kausch and Socin, ibid.,
1893, Bd. 31, p. 398.

* Lintner and Diill : Berichte der deulschen cJiemi^chen Gctellschajt, 1893, Bd. 26, p. 2533.

1008 AN A mi: RICA jY TEXT-JiOOK OF PHYSTOLOGY.

(CiJIjaO,,), ^vlli(•ll is roailily suluble in water ami givc-s with iodine a reildi.sh-
hrown eolor. Erythrodextrin is converted into (3) Adiroodexirin, {^\nyi^Oy^^
+ HgO, or (C,2Tl2uO,u)5.Ci2H220ji, wliioh is likewise very soluble, tastes slightly
sweet, but gives no coloration with iodine. Achroodcxtrin now breaks up
into (4) I.s(»nalios(', which through change in configuration is transformed to its
isomere (5) Maltose.

Products similar to these are formed by the various diastatic ferments in
the body, and in addition also some dextrose. Ptyalin ^ acts rapidly on starch,
producing dextrin antl maltose, but very little dextrose. Amylopsin, from the
pancreas, acts still more rapidly than ptyalin, and with the production of con-
siderable dextrose. The diastatic ferment of intestinal juice acts very slowly
on starch, forming dextrin, maltose, and a little dextrose, while the ferment in
blood-scrum likewise acts slowly but with complete transformation of all the
maltose and dextrin formed, into dextrose.

The above facts lead Hamburger to suggest that the diastatic ferments of the body
consist of mixtures, in different proportions, of diastase, which forms dextrin and maltose
from starch, and of glucase, which converts these into dextrose. This, however, is merely
an hypothesis, and glucase has never been prepared. The vegetable diastase is not iden-
tical with that found in the body. Thus ptyalin, like cmulsin, breaks up salicin into sali-
cylic alcohol and dextrose, of which action vegetable diastase is incapable. But ptyalin,
again, is not identical with emulsin, for it will not act on amygdalin.

Glycog-en, or Animal Starch. — Recent investigations have shown that in
all the juu'ticulars of diastatic decomposition glycogen is identical with vege-
table starch.^ Glycogen is soluble in water, giving an opalescent fluid. The
blood has a normal composition which does not greatly vary. After a hearty
meal excess of fat is deposited in fatty tissue, excess of proteid in the nui.scular
tissue, while excess of sugar is stored in the muscles and especially in the liver-
cells in the less combustible and less diffusible form of glycogen. About one-
half of the total quantity of glycogen is found in the muscles, the remainder
in the liver, where it may even amount to 40 per cent, of the dry solids.
When the blood becomes poor in sugar, the store of glycogen is drawn upon to
such an extent that in hunger the body becomes glycogen-free. Muscular work
likewise causes the rapid conversion of glycogen into sugar. The sources of
glycogen are certain ingested carbohydrates, and also the dextrose derived from
proteid. If large quantities of proteid be fed, glycogen may be stored. If
milk-sugar and galactose be burned in the cells of an otherwise starving animal,
the dextrose from proteid is economized and glycogen is found. If dextrose
or levulose (or anything which produces dextrose, e. g. cane-sugar, maltose) be
fed, there is a direct conversion of the sugar into glycogen. Voit' has called
attention to the fact that only directly fermentable sugars are convertible into
glycogen, Cremer * shows that yeast-cells contain nmch glycogen when cul-
tivated in media which they ferment, not, however, when cultivated in milk-

» See Hamburger: Pflilger'a Archiv, 1895, Bd. 60, p. 573.
' Kulz and Vogel ; Zeitschrift fur Biologie, 1895, Bd. 31, p. 108.
» Zeitschrift fur Biologie, 1891, Bd. 28, p. 270.
* Ibid., 1895, Bd. 31, p. 188.

THE CHEMISTRY OF THE ANIMAL BODY. 1009

sugar, for example. So perhaps, in Icvulose-fennentation the first step may
be conversion into glycioj^en or the anhydride of" dextrose. Cremer maintains
that the pentoses are burned in the body, but are oidy indirectly glycogen-
producers.

Dextrins. — These have been described under starch.

H H Oil II
(^-Glucuronic Acid, or Glycuronic Acid, HOOC C C C C CIIO.

OHOHH OH

— Obtained by reducing- (/-saccharic acid with nascent hydrogen. After feed-
ing chloral hydrate, naphthalin, camphor, terpentine, ])lienol, ortho-nitrotoluol,
and other bodies, they appear in the urine (usually having been first converted
into alcohol) in combination with glycuronic acid. Urochloralic acid, naphthol-
glycuronic acid, campho-glycuronic acid, terpene-glycuronic acid, etc., all rotate
polarized light to the left. It seems that these ingested substances unite in the
body with the aldehyde group of dextrose, at the same time protecting all but
one group of the dextrose molecule from further oxidation (Fischer). Glycu-
ronic acid, which is easily separated by hydrolysis from its aromatic combina-
tion, itself rotates polarized light to the right, reduces alkaline copper solutions,
and might be confounded with dextrose except that it d(jes not ferment with
yeast. Glycuronic acid is likewise found in the urine after administration of
curare, morphine, and after chloroform-narcosis, perhaps paired with aromatic
bodies formed in the organization.

Combustion in the Cell, in General. — Experiments^ show that taking
the proteid decomposition in the starving dog as 1, it is necessary to feed three
to four times that amount of proteid taken alone in order to attain nitrogenous
equilibrium, 1.6 to 2.1 times that amount of proteid when fed with fat, and 1 to
1.2 times that amount when fed with carbohydrates. The physiological proteid
minimum is in these cases never less than the amount required in starvation.
Only after feeding gelatin with proteid may the proteid fed be below the
amount decomposed in starvation. The above shows what is well known, that
sugar spares proteid from decomposition more than fat does. E. Voit ^ states
these two propositions: (1) The part played by these several food-stuffs in the
total metabolism depends on the composition of the fluid feeding the cell.
The greater the amount of one of these food-stuffs, the greater its decompo-
sition and the less the decomposition of the others, so long as the total decom-
position suffers no change. (2) The several food-stuffs do not act wholly on
account of their quantity in the fluid surrounding the cell, but especially accord-
ing to the chemical affinity of the cell-substance for them individually. First
in this regard comes proteid, then carbohydrates, and lastly fat.

The excessive proteid decomposition in diabetes is due to the non-combus-
tion of the proteid protecting sugars^ and the same is true in fever where a
small supply of carbohydrates reaches the blood.^

* E. Voit and Korknnoff: Zeitsehrift fur Biologk, 1895. Bd. 32, p. 117.

^ Op. cit., pp. 128 and 135. =• Lusk: Zeitsehrift fur Biologic, 1890, Bd. 27, p. 459.

* May : Ibid., 1894, Bd. 30, p. 1.

1010 AN AMERICAN TEXT-BOOK OF PHYSIOLOGY.

For further discussion of carbohydrates in the body see under the indi-
vidual sugars, and under Fat in the liudy.

Benzol Derivatives or Aromatic Compounds.
The aromatic compouuds are characterized by a configuration in which six
atoms of carbon are linked together in a circle called the benzol ring. The
type of this is benzol, a hydrocarbon found in coal-tar and having the formula,

{!

H— C C— H

H— C C— H

\ //

3

C 4

H

The hvdroiren atoms mav be substituted for others, substitution of one OH

group, for example, forming phenol, CgHg — OH. If, however, two OH

groups are substituted, three different bodies, corresponding to the different

arrangements on the ring, become possible. If the two OH groups occupy

the positions 1 and 2 the substance is orf/io-dioxybenzol ; if 1 and 3, meta-

dioxybenzol ; and if 1 and 4, para-dioxybenzol.

It is possible to convert bodies of the fatty series into those of the aro-
matic. Acetylene passed through red-hot tubes yields benzol. On the other
hand, aromatic bodies may be converted into those of the fatty series. If
phenol in aqueous solution be subjected to electrolysis by an alternating cur-
rent under which circumstances hydrogen and oxygen are alternately liberated
on the same pole, the effect of this intermittent oxidation and reduction is to
break up the phenol into caproic acid, and finally, after passing through acids
of lower carbon contents, into carbonic acid and water.

The aromatic compounds found in the urine are normally exclusively
derived from the products of proteid putrefaction in the intestines. It is
admitted that neither fats nor carbohydrates play any part in their formation.

Benzol, CfiHg.— This body if fed is absorbed and afterward converted into oxybenzol
or phenol, with subsequent behavior similar to phenol.

Phenol (Carbolic Acid, Oxybenzol, Phenyl-hydroxide), CgHpH. —
This is an aromatic alcohol. A 5 per cent, solution precipitates proteid, and a
ranch weaker solution produces irritation of the tissues, and especially those
of the kidney, M'here its excretion takes place. It is strange that a strong
antiseptic like j)henol should be a normal product of proteid putrefaction.
Phenol is obtainable from tyrosin, by processes of cleavage and oxidation (see
Tyrosin), and in the intestinal canal is probably derived from tyrosin. A
small amount of the phenol ordinarily absorbed is converted by the organism
into pyrocatechin, a dioxybenzol. These two substances are found in normal
urine in ethereal combination with sulphuric acid, CgH^O.SOj.OH (or as an
alkaline ethereal sulphate). This synthesis, accomplished by the union of the

THE CHEMISTRY OF THE ANIMAL BODY. 1011

phenol and .sulphuric at'i<l with loss of water, has heen obtained by electrolysis,
using alt('rnatint»; electric currents.' [f phenol be administered in more than
a very small amount, hydroqiiinone likewise a})pears in the urine, paired like
the others with sulphuric acid, and should the plienol administered exceed at
any time the available sulphate, it forms to a certain extent -a synthesis with
glycuronic acid, and so combined appears in the urine.

Phenol ffivcs with jMillon's rea.ireiit (niorcuric nitrate in nitric acid with some nitrous
acid) a brilliant red coloration. This is given by all bodies liaving an hydroxyl group on the
benzol ring, of which substance tyrosin may be mentioned as an example. It is likewise
given by proteid, slowly in the cold, more rapidly on warming, and this fact together
with the cleavage putrefactive products has given foundation to the belief that the oxy-
benzol ring exists preformed in the proteid molecule.

Pyrocatechin, C6H4(OH)2. — This is ortho-dioxybenzol. For its forma-
\'\(^\\ see under Phenol.

Hydroquinone, C6H4(OH)2. — Para-dioxy benzol. Found in the urine
especially in cases of carbolic-acid poisonuig (see Phenol). If such urine be
shaken in the air, it is turned black, owing to the oxidation of hydroquinone

to quinone, CgH/ | .

p-Cresol, CgH^.OH.CHs. — This is a product of intestinal putrefaction, and is
derived from tyrosin (which see). It is found in the urine as an ethereal sulphate.

Benzoic Acid, CgHsCOOH. — Salts of this acid and analogous bodies
are found especially in plants. In the urine of herbivora therefore is found a
considerable amount of hijppurie acid, COOH.CHg.NH.CO.CgHg, the com-
bination of benzoic acid and glycocoU (see Glycocoll, p. 981). On feeding
jjhenifl-acetie acid, CgHsCHgCOOH, phenaceturic acid, COOH.CHg. ISTH.-
CO.CHj.CgHj, appears in the urine, while the higher benzyl acids, such as
phenyl-propionic acid, suffer the oxidation of the side chain in the body, and
ordinary hippuric acid is formed. After eating apple-parings and other vege-
table substances, hippuric acid is found in human urine. It is further stated
that j)henyl-acetic acid and phenyl-propionic acids are normal products of
proteid putrefaction, though in very small quantities ; hippuric acid and phen-
aceturic acid must therefore be constantly present in traces in human urine.
Hippuric acid is split into its constituents by hydrolysis through the action of
the Micrococcus urccv.

p-Oxyphenyl-acetic Acid, C6H4.OH.CH2COOH. — This is a product of
the intestinal putrefaction of proteid and of tyrosin (which see). It occurs
in the urine either paired with sulphuric acid or as an alkaline salt of oxyphenyl-
acetic acid.^

j^-Hydrocumaric Acid, CgH4.0H.C2ll4COOII. — This second oxy- acid is
likewise derived from proteid and tyrosin (which see) putrefaction. Its occur-
rence in the urine is similar to the above oxy- acid.

Tyrosin, Amido-hydrocumaric Acid, p-Oxyphenyl-amido-propionic

^ Drechsel : Journal Jar praktische Cliemie, Bd. 29, p. 229 ; abstr. Jtihresbericht ilber Thierchemief
1884, p. 77. ' Baumann : Zeitschrijl fur physiologische Chemie, 1886, Bd. 10, p. 125.

1012 A.X AMERICAA' TEXT-BOOK OF PHYSIOLOGY.

Acid, (.'eH^.OH.CsHsNHaCOOlI.— Tyri)sin is a coiistant product ol'tlic putre-
iiu^tion of all proteid bodies (except gelatin), and is therefore found in cheese.
It may be formed in large quantities by boiling horn-shavings with sul-
phuric acid. Leucin is always formed whenever tyrosin is. Tyrosin forms
characteristic sheaf-shaped bundles of crystals. All the aromatic bodies thus
far described have been eliminated in the urine with their benzol nucleus
intact. Tyrosin, however, may be completely burned in the body. This
seems to be because of the presence of the aniido- group on the side chain, for
phenyl-amido-propionic acid is likewise destroyed. Tyrosin is found in the
urine in vellow atrophy of the liver, in phosphorus-poisoning, etc. (see Leucin,
p. 1)83). Through cleavage, oxidation, or reduction, the following reactions
take place, phenol being the final product.^ The substances not found in intes-
tinal putrefaction are named in italics :

CcH,.0H.C,H3NH,C00H + H^ = C6H,.0II.C,H,C00H + NH3

jj-IIydrocumaric acid.

C6H,.0n.aH,C0()H = C«H,.0H.aH5 + CO,

p-Ethyl[)henol.

C6H,.OH.C.,H5 + 30 = CeH.OH.CH^COOH + H,0

p-Oxyphenyl-acetic acid.

CeH^.OH.CH.COOH = C«H,.OH.CII:, + CO^

p-Crcsol.

C6H,.OH.CH3 + 30 = C«H,OH COOH + H,0

p-Oxybeiizoic acid.

CeH^.OH.COOH = CsH.OH + CO,

Phenol.

It has never been shown that tyrosin is a normal product of proteid metabolism
within the tissues. With leucin it is said to be a normal product of pancreatic di-
gestion (see p. 983), being derived only from hemipeptone (Kiihne, Chittenden).

Pyridin.— This body has the accompanying formula, one of the CH groups in benzol
H
C

^\
HC CH .,,,.,.

bein<' substituted by N: I II • When pyridin is fed, met hyl-pyndm ammonium
HC CH

V

hydroxide, OH.CH3.NC5HS, is excreted in the urine.'^ This is another case, besides those
of selenium and tellurium, of methylation in the body.

H H

C C

HC C CH

Chinolin.— The accompanying formula I II I illustrates the composition

HC C CH

N C
H
of this body. Several of the methyl-chinolins burn readily in the body.'

' Bauraann: Berichle da- deutschen chemischen GeselMinfl, 1879, Bd. 12, p. 1450.
- His: Archil' fiir exper. Pathologie und Plumnakolorjie, 1S87, Bd. 22, p. 253.
^ Cohn : Zeitschrift Jur physiologisehe Chemie, 1894, Bd. 20, p. 210.

THE CHEMISTRY OF THE ANIMAL BODY. 1013

Cynurenic Acid, (-.jH5N.OH.COOH. — This is oxychinolin carbonic acid ; it is found
normally in iloir's urine, beins derived from proteid metabolism. This form of the chinolin
prouj) is therefore not burned in the body.

Indol, or Benzopyrol, CgH^N. — The source of iiulol i.s surely from
proteid putrefaction ; it may also be obtained by melting proteid with potash.

H H

C C

^ \ /\ //\ /\

HC C CH HC C COH

I II II I II II

HC C CH HC C CH

% /\/ % /\/

C N C N

H H H H

Indol. Indoxyl.

After its absorption it receives an oxy- group just as benzol does, and like
benzol pairs with sulphuric acid with the loss of a molecule of water, and
appears as ethereal sulphate in the urine. In preparing indol from feces the
fecal odor clings to it. Pure indol, however, has no smell. An alcoholic
solution of indol mixed with hydrochloric acid colors fir-wood cherry-red.
If urine be mixed with an equal volume of hydrochloric acid, chloroform
added, and then gradually an oxidizing agent (chloride of lime), any indoxyl-
sulphuric acid present will be oxidized to indigo-blue, which gives a blue color
to the chloroform in which it dissolves.

Skatoi; or /3-Methyl Indol, CgHjCHaNH.— The history of skatol,

H

C
^ \ /\
HC C CCH3
I II II ,

HC C CH
^ /\/
C N
H H

Skatol.

is the same as that of indol. Its source is from proteid putrefaction ; after ab-
sorption it unites with an oxy- group, and the skatoxyl thus produced pairs with
sulphuric acid, and appears in the urine as ethereal skatoxyl-sulphuric acid.

Aromatic Bodie.s in the Urine. — There have been named above as
appearing in normal human urine the ethereal sulphates of phenol, p-cresol,
pyrocatechin, indoxyl, skatoxyl, hydroparacu marie acid, and oxyphenyl-acetic
acid, of which, however, the last two appear likewise as their salts without
being combined with sulphuric acid.^ These, are derived from proteid putre-
factive products formed almost entirely in the large intestine (see p. 988),
which are partially absorbed and partially pass into the feces. The amount
' Baiiniann : Zeitschrift fur pkysiologische Chemie, 1886, Bd. 10, p. 125.

1014 .LV AAfl'JRICAN TEXT-BOOK OF PHYSIOLOGY.

of etlieroal sulphate in tlie urine ^ivcs an indication of the amount of intes-
tinal putrciac'tion. It does not disappear in starvation, mucin and nucleo-
proteitl of bile and intestinal juice furnishing material.* If the intestinal
tract be treated so as to make it antiseptic, the ethereal sulphates disa])pear
from the urine.^ Diarrluea likewise decreases their amount, obviously from
the short time given for putrefaction.

Inosit.— This is the hexatomic jjhenol of hexahydrobenzol, 0,;Hg(OH)g.
It was long mistaken for a carbohydrate. It has been found in muscle, liver,
spleen, suprarenals, lungs, brain, and testicles; likewise in plants, in unripe
peas and beans. After drinking nnich water it may be washed out in the
urine, and perhaps for this reason is often found in the voluminous urine of
the diabetic. When fed it is burned ; also by the diabetic. ^ Its origin is
unknown.

Substances of Unknown Composition.

Coloring Matters in the Body.

Haemoglobin, C-iJIii.joN.^uFeSjO^^ (Ziiioffsky's forimila for lisemojrlobin in horse's
blood). — Ibcuioglobin is found in the red blood-corpuscle. United with oxygen it forms
oxyhemoglobin, which gives the scarlet color to arterial blood ; h;«moglobin itself is darker,
more bluish, and therefore venous blood is of a less brilliant red. Methods for i)reparing
oxyhacmoglobin crystals are numerous, but all depend on getting the haemoglobin into solu-
tion. If the corpuscles in cruor be washed with physiological salt-solution, then treated
with distilled water, the HbO will be dissolved ; on shaking with a little etiier the stroma
will likewise dissolve ; after decantation and evaporation of the ether, at the room's tem-
perature, the solution is cooled to — 10° and a one-fi)urth volume of alcohol at the same
temperature added ; after a few days rhombic crystals of oxyhgemoglobin may be collected,
redissolved in water, and reprecipitated for purification. The crystals may be dried m
vacuo over sulpliuric acid. Once dry they may be heated to 100° without decomposition,
but in aqueous solution they are decomjiosed at 70° into a globulin and hacmatin, the latter
having a brown color. This difference in color gives the divStinction between "rare " and
"well-done " roast-beef Gastric and pancreatic digestion likewise convert oxyhajmoglobin
into a globulin, which may be absorbed, and haematin, which passes into the feces. Hjemo-
globin is without doubt formed in the body from simple proteids by a synthetic process.
(For further information see pp. 973 a!id 101,'"), and likewise under the section on Blood.)
CO-Hsemoglobin (see p. 960).
NO-Hsemoglobin (see p. 956).

Methaemoglobin.— This has the same composition as oxyhaemoglobin. It is found
in blood-stains, and may be considered as oxyhfemoglobin which has undergone a chemical
change whereby its oxygen is more firmly bound in the molecule.

Haematin, C.TiH:,.,N,04Fe.— This is a cleavage-product of haemoglobin in the presence
of oxygen. (See above, under Haemoglobin). It is not itself a constituent of the body.
It is insoluble in dilute acids, alcohol, ether, or chloroform, but is soKible in alkalies or in
acidified alcohol or ether, showing characteristic absorption-l)ands. If a little dry blood
be placed on a microscope slide with NaCl and moistened with glacial acetic acid, and
warmed, characteristic brown microscopic crystals ofhcpmin, C;«H3oN4Fe03.H('l, crystallize
out. If these crystals and the spectroscopic test be obtained, one can be absolutely posi-
tive of the presence of blood.

Haemochromogen, (>„n;,fiN4Fe05.— If reduced haemoglobin be heated in sealed tubes
with dilute acids or alkali in absence of oxygen, a i)uri)le-red comjiound is i)roduced called
1 Von Noorden : Patholocjie des Stoffwechsela, 1893, p. 163. '■' Baumann, Op. cit., p. 129.

Tifi': ciiEMisTin' or tiik animal body. 1015

hjeniochroni()i,u-ii, which is a crystallizuldo cleavage-product of hncmoglobin. According
to lloppo Soyk'r the ()xy.ii:cMi inox.vha'inoirlohin is bound to the hiuniochronioiren irroup.
HiXMnuchromogou treated with a .stroiii; dehydratinjr agent is converted, with ehmination
of iron, into hcrmafoporphi/rin, C^iJlmN^Oo, an isomer of biHniltin. ILx'uiatoporijhyrin
is said to occur in normal urine/ Iljcmatoporphyrin treated with nascent hydrogen is
converted into a body believed to be identical with hydro- or urobilirubin. Analogous to
this is the work of the liver in the body, manufacturing the biliary coloring matter from
haMnoglobiii, and retaining the separated iron for tlie synthesis of fresh hemoglobin
(see p. 073). I/iniKifoidin, found in old blood-stains, is believed to be identical with
bilirubin.

The Bile-pigments.— The ordinary coloring matter of yellow human bile is hilirubin,
C3.,HsbN406. The next higher oxidation-product is the green biUcerdin, CajHssN^Ob,
which is the usual dominant color in the bile of herbivora. In gall-stones have been found
the following coloring matters, to which have been ascribed the accompanying formulae :

Bilirubin (red), C.^H^eNA ;

Biliverdin (green), QiiHsBN^Og;

Bilifuscin (brown), . C3.2H4oN408;

Biliprasin (green), Q^HuN^Oia ;
Bilihumin (brown), ?

Bilicyanin (blue), ?

Choletelin (black), C32H3BN4O12.

If nitric acid containing a little nitrous acid be added to a solution of bilirubin, a play of
colors is observed at the juncture of the two fluids, undoubtedly depending upon various
stages of oxidation. Above is a ring of green (biliverdin), then blue and violet (bilicya-
nin), red, yellowish-brown (choletelin). Cholotelin is the highest oxidation-product. The
above is known as Gmcliiis tesf.'^

If bilirubin or biliverdin is subjected to the action either of nascent hydrogen or
of putrefaction it is reduced to hydrobilirubin, C32H44N4O7. This substance is therefore
formed in the intestinal tract, is in part absorbed, and appears in the urine, where it is
called urobilin, though the two are identical. Urobilin gives a yellowish coloration to the
urine. Injection into the blood-vessels of distilled water, ether, chloroform, the biliary
salts, or arsenuretted hydrogen, produces a solution of the red blood-corpuscles and conver-
sion of haemoglobin into biliary coloring matters which are thrown out in the urine (see
p. 988). Bilirubin, biliverdin, and bihcyanin give characteristic spectra.

Melanins. — Under this name are classed the pigments of the skin, of the retina, and
of the iris. They contain iron, and their source has been attributed to haemoglobin. In
n>elanosis and kindred diseases they are deposited in black granules. There are melanins
of different composition. In a case of melanotic sarcoma the haemoglobin was one quar-
ter, the number of blood-corpuscles one-half, the normal, indicating perhaps the source
of melanin.'

Tryptophan. — This is said to be a cleavage-product of hemipeptone in tryptic diges-
tion ; * it gives a red color with chlorine and a violet color with bromine, due to halogen-
addition compounds.

Lipochromes. — These include Infein, the yellow pigment of the corpus luteum, of
blood-plasma, butter, egg-yolk, and of fat ; likewise viswd jntrple of the retina, which is
bleached by light. Solutions of the pure visual purple from rabbits or dogs become clear
as water on exposure to light.*

1 Garrod : Journal of Physioloyy, 1894, vol. 17, p. 348.

"^ For a delicate modification of tliis test see Jolles : Zeitschrift fur physioloffische Chemie, 1895>
Bd. 20, p. 461.

3 Brandl und Pfeiffer : Zeitschrift fur Biologic, 1890, Bd. 26, p. 348.

* Stadelmann : Ibid., 1890, Bd. 26, p. 491. * Kubne : Ibid., 1895, Bd. 32, p. 26.

1016 ^l^V AMERICAN TKXT-liOOK OF PHYSIOLOGY.

Cholesterin.

Cholesterin, CafiH4:,0n. — Tliis is I'oiind in all animal and vegetable cells and in the
milk.' It is es|)ecially present in nervous tissue, in blood-cdriiuseles. and in the bile. It may
be prepared by dissolvinjr ^'all-stones in alcohol, from which solution the cholesterin crys-
tallizes on coolinsr in characteristic plates. It is insoluble in water or acids, but soluble
in the biliary salts, alcohol, and ether. It is probably excreted unabsorbed in the feces,
("holesterin feels like a fat to the touch, but is in reality a monatomic alcohol. With con-
centrated sulphuric acid it yields a hydrocarbon, cholesferilin , C2eH4„ coloring the sul-
jdiuric acid red (Salkowski's reaction). Iso-cholesterin. an isomere, is found combined as
an ester with fatty acid in wool-fat or lanolin. The physiological importance of cholesterin
is unknown.

The Proteids.

Consideration of the proteids from a purely chemical standpoint is impos-
sible, for their composition is unknown. There exist only the indices of cora-
po.sition furnished bv tlie jn'oducts of cleavage and di.^integration. Bodies at
present classed as individuals may .sometimes be sho\vn to be identical, \vith
characterizing impurities. It remains for the chemist to do for the proteid
o-rouji what Emil Fischer with phenyl-hydrazin has accomplished for the
sugars.

As a characteristic proteid, egg-albumin may be mentioned. Proteid forms
(after water) the largest part of the organized cell, and i.-j found in all the
fluids of the body except in urine, sweat, and bile. Proteid contains carbon,
hydrogen, nitrogen, oxygen, sulphur, sometimes phosphorus and iron.

General Reactions. — A neutral solution of proteid (with the exception of
the jieptones and proteoses) is partially precipitated on boiling, and is quite
completely precipitated on careful addition of an acid (acetic) to the boiling
solution. Proteids are precipitated, in the cold by nitric and the other com-
mon mineral acids, by metaphosphoric but not by orthophosphoric acid.
Metallic salts, such as lead acetate, copper sulphate, and mercuric chloride,
precipitate proteid ; as do ferro- and ferricyanide of potassium in acetic-acid
solution. Further, saturation of acid solutions of proteid with neutral salts
(XaCl, Na2S04, (NHJ2SOJ precipitates them, as does likewise alcohol in
neutral or acid solutions. Proteid is also precipitated by tannic acid in acetic-
acid solutions, by phospho-tungstic and phospho-molybdic acids in the presence
of free mineral acids, by picric acid in solutions acidified by organic acids.^

Of the color-reactions the action of ^Slillon's reagent has been described
(see p. 992). Soluble proteids give the biuret test (see p. 1011). With concen-
trated sulphuric acid and a little cane-sugar a pink color is given when proteid
is present (.see p. 988). Proteid heated with moderately concentratcxl nitric
acid gives yellow flakes, changing to orange-yellow on addition of alkalies
(xaiitho-proteid reaction). Proteid in a mixture of one part of concentrated
suli)huric acid and two parts of glacial acetic acid gives a rwldish-vioiet color
(Adamkiewicz), a reaction accelerated by heating. Finally, proteid dissolves

' Schmidt-Muhlheim : Pfluger's Archiv, 1888, Bd. 30, p. 384.

■^ The above list is given bv Hammai-sten, Physiological Chemistry, translated by Mandel,
p. 18.

THE CHEMISTRY OF THE ANIMAL BODY. 1017

after heating with concentrated hydrochloric acid, forming a violet-colored
solution (Licborniann).

The following, taken in part from Chittenden/ is submitted as a general
classification of the proteids :

SiMPi.E Proteids.
r Serum-albumin ;

I Egg-albumin ;

Albumins ^ t * n

Lacto-albunnn;

GhbnJin.s

Myo-albumin.

Scrum-globulin ;

Fibrinogen ;

Myosin ;

Myo-globulin ;

Paramyosinogen ;

^ Cell-globulin.

. ,, . , f Acid-albumin ;
Albuminates { , ,, ,. „ .
(. Alkali-albumm.

Proteoses and Peptones.

Coagulated Proteids < _ , ' , , . ,

I Other coagulated proteids.

Combined Proteids.

r Haemoglobin ;

Histo-haematins ;
Chromo-proteids ^ Chlorocruorin ;

Hsemerythrin ;

^ Hsemocyanin.

x^, . • 7 r Mucins

{jrlyGo-proteids

Mucoids.

{Casein ;
Pyin ;
i.yui:ito-proieta>i <. Vitellin.

'^ 2. Those yielding true nuclein < ^ „ , . '
^ t Cell-nuciem.

Phospho-glyco-proieids. Hel i co-pro teid.

Albuminoids.
Collagen (gelatin).
Elastin.
Keratin and Neurokeratin. ^

Albumins.— Bodies of this group are soluble in water and precipitated by boiling, or
on standing with alcohol. Serum-albumin is the principal proteid constituent of blood-
plasma, while lacto-albumin and myo-albumin are similar bodies found respectively in
milk and muscle.

* " Digestive Proteolysis," Oartwright Lectures, 1895, p. 30

1018 ^.Y AMERICAN TEXT-BOOK OF PHYSIOLOGY.

Globulins. — These are insoluble in water, but soluble in dilute salt-solutions. They
are coagulated on heating. If blood-serum be dialyzed with distilled water to remove the
salts present, seruui-globulin formerly held in solution separates in flakes. Fibrinogen and
serum-globulin are in blood-plasma and the lymph. Myosin is the principal constituent
of dead muscles ; in the living muscle myosin is said to be present in the form of myosin-
ogen. jMyoglobulin in muscle is akin to serum-globulin in plasma. I'aramyosinogen in
muscle is characterized by the low temperature at which it coagulates (+47°). Cell-
globulin is also found in the animal cell.

The globulins of vegetable cells are interesting as having been obtained in well-deflned
crystalline form and in great purity of composition.^ These are not generally coagulable
by heat, and indeed vegetable proteids show many points of divergence from those of the
animal.

Albuminates. — If any of the above native animal proteids or any coagulated proteid
be treated with an alkaline solution, alkali albuminate is formed. In this way the alkali
of the intestine acts upon proteid. If hydrochloric acid acts on proteid, there is a gelatin-
ization and slow conversion into acid albuminate, a process accelerated by the presence
of pepsin. This takes place in the stomach. Both alkali and acid albuminates are in-
soluble in water, but both are soluble in dilute acid or alkali, without loss of individual
identity.

Proteoses and Peptones. — These are bodies obtained from the digestion of proteids,
through a process of hydrolysis. They are non-coagulable by heat. If a mixture of pro-
teoses and peptones be saturated with ammonium sulphate the proteoses are said to be
precipitated, while true peptone remains in solution. The chemical identity of this true
peptone is still, however, to be established. In gastric digestion are said to exist four
varieties of proteoses: (1) Dysproteose, insoluble in water and dilute NaCl solutions, (2)
hetero-proteose, insoluble in water and soluble in NaCl solution, (3) proto-proteose, soluble
in water and in NaCl solution, (4) deutero-proteose, which is also soluble in water and in
NaCl solution, but is distinguished by the fact that w'hile the first-named three are pre-
cipitated by saturating the neutral solution with NaCl, deutero-proteose is only partly
precipitated, the rest coming down on addition of an acid. Proteoses are converted into
amphopeptones, a mixture of hemi- and antipeptone. According to Kiihne proteid con-
sists of a hemi- and an anti- group, which separate into distinct hemi- and anti- bodies in
proteolysis. Of the final products, hemi- and antipeptone, only the former jdelds leucin
and tjTosin in tryptic proteolysis. This is the only radical difference between the two
peptones, hence hemipeptone has never been isolated.

Coagulated Proteids. —These are insoluble in water, salt-solutions, alcohol, dilute
acids and alkalies, but soluble in strong acids and alkalies, pepsin-hydrochloric acid,
and alkaline solutions of trypsin. The chemical or physical change which is efiected in
coagulation of proteid is imknown.

Combined Proteids. — These consist of proteid united to non-proteid bodies such as
haemochromogen. carbohydrates, and nucleic acid.

Chromo-proteids. — These are compounds of proteid with an iron- or copper-contain-
ing pigment, like hoemoglobin, which has already been described. IIistoli(V)nat!ns are
iron-containing pigments found especially in muscle. That which is found in muscle is
called myohfematin, and resembles h.nemochromogen somewhat in its spectroscopic appear-
ance, and is believed to be present in two forms corresponding to htemoglobin and oxyhaemo-
globin. It has been regarded as an oxygen-carrier to the tissues. Among the inverte-
brates the blood often contains only white corpuscles with sometimes a colored plasma.
Thus the blood-serum of the common earth-worm contains dissolved haemoglobin, that
of some other invertebrates a green respiratory pigment, chlorocruorin, whose charac-
terizing component seems similar to haematin ; hcemo-ythnn occurs in the pinkish corpus-

' Osborne: Journal of American Chemical Society, 1894, vol. xvi., Xos. 9, 10; and other arti-
cles in the same journal by the same author.

THE CHEMISTRY OF THE ANUTAL BODY. 1019

cles of SipH)icult(s, wliile the bloutl of crabs, snails, and other animals (mollusks and
arthropods) is colored blue by a pigment, hcenwcyanin, which contains copper instead of
iron.

Glyco-proteids. — Those consist of protcids conibiiic(l with a carbohydrate. They are
insoliililc ill water, but soluble in very weak alkalies. On boiling with dilute mineral acids
they yield a reducing substance.

Mucins are found in mucous glands, goblet cells, in the cement substance of epithelium
and in the connective tissues. Of the nearly related mucoids maybe named colloid., a sub-
stance appearing like a gelatinous glue in certain tumors; pacndo-mucoicl., the slimy body
which gives its chai-actcr to the liquid in ovarian cysts ; and chondro-mucoid, found as a
constituent of cartilage. On boiling chondro-mucoid with dilute sulphuric acid it yields
acid-albuminate, a peptone substance, and chondroitic acid. The last is a nitrogenous
ethereal sulphuric acid, yielding a carboh3'drate on decomposition, and found preformed in
every cartilage' and in the amyloid livci'.'^ It is, of course, not a proteid.

Nucleo-proteids, or Nucleo-albumins.'— These are compounds of proteid with
nuclein, which latter yields phosphoric acid on decomposition. If nucleo-proteid, which
is found in every cell, be digested with pepsin-hydrochloric acid, there remains a residue
of insoluble nuclein, likewise insoluble in water but soluble in alkalies. If this nuclein
yields xanthin bases on further decomposition it is called true nuclein, if it fails to yield
these bases it is called paranuclein.* Nucleo-proteids yielding proteid and paranuclein on
decomposition include the casein of milk, pyin of the pleural cavity, vitellin of the Qgii.,
Bunge's* iron-containing h?ematogen of the eg§, as well as nucleo-proteids found in all
protoplasm. They all contain iron. Paranuclein is probably absorbable (see p. 958).
It is considered by Liebermann to be a combination of proteid and metaphosphoric acid
(see p. 958).

A second group of nucleo-proteids yields true nuclein on decomposition. This group
includes the various nucleo-proteids which are constituents of different cell-nuclei. The
nuclein here obtained yields on decomposition nucleic acid, from which xanthin bases are
always to be derived. These xanthin bases vary in proportion and kind in the different
nucleic acids. Nucleic acid of yeast nuclein yields guanin and adenin, that of a bull's
testicle adenin, hypoxanthin, and xanthin, that of the thymus adenin alone. Kossel®
calls this latter "adenylic acid," and speaks likewise of "guanj'lic," "xanthylic,"' etc.,
acids, as provisional names for separate nucleic acids. Each one of this family of acids is
capable of combining with any soluble proteid to form nuclein, hence it is readily seen
that nucleins may exist in great variety. Another constituent of nucleic acid Kossel finds
to be thymin (a body derived from paranucleic acid, which latter, according to Kossel, is a
component of paranuclein). Some nucleic acids, such as those derived from j'east, pan-
creas, and the lactic glands, yield a reducing carbohydrate, while others (calf's thymus)
show the presence of the carbohydrate group only in the production of levulic acid after
very thorough decomposition, and still others (fish-sperm) fail to indicate any carbohydrate
radical as being present. A clearer idea of these relations is afforded by the following
schematic view of the decomposition of the nucleohiston, the constituent of blood-plates
and of the nuclei of leucocytes.'

^ Morner : Zeitschrift fiir physiologische Chemie, 1895, Bd. 20, p. 357.

^ Oddi: Archil' fiir exper. Pathologie und Phnrmakologie, 1894, Bd. 33, p. 376.

^ These two terms are used here as synonymous, though Hammarsten would confine the
term nucleo-albumin to those proteids which yield paranuclein. It is difficult to give a definite
classification of these bodies, as the whole subject at present is in a transition stage.

* Kossel : Yerhandlungen der Berliner physiologischen Gesellschaft, Archivjur Physiologie,
1894, p. 194.

^ Physiologische Chemie, 3d ed., 1894 p. 92. * Loc. cit.

' Lilienfeld : Zeitschrift fiir physiologische Chemie, 1895, Bd. 20, p. 106.

1020 .l.V AMERICAN TEXT-BOOK OF PHYSIOLOOY.

Nucleoht'ston, soluble in H.^0,
decomposed by HCl or BalOH)^ into

Jfiston, a [)rolci(l. LeuconucUin, an acid ;

decomposed by strong alkali into

Proteid. Adenylic acid (nucleic acid), which on lieating

with mineral acids yields adenin, thymin,
levulic acid, and phosphoric acid.

( For the respective offices of histon and leuconuclein in the coagulation of the blood,
see section on the Blood. )

In the sperm of salmon is found only i'ree nucleic acid uncombined with proteid.
According to Kossel other nuclei may at times contain free nucleic acids.

Phospho-glyco-proteids. — This class is represented by Hammarsten's hch'co-proteid,
which yields paranucleiu, and, unlike other nucleo-proteids of the paranuclein class, it
yields a reducing carbohydrate on boiling with acids.

The Albuminoids. — These are bodies derived from true i)roteid in the body, but not
themselves convertible into proteid. They are resistant to the ordinary jnoteid solvents,
and as a rule exist in the solid state when in the body.

Collagen. — This is the chief constituent of the fibres of connective tissue, of the
organic matter of bone (ossein) and is likewise one of the constituents of cartilage. Col-
lagen is insolul)le in water, dilute acids and alkalies. On boiling with water it forms
gelatin through hydration, which is soluble in hot water, but gelatinizes on cooling (as in
bouillon). Dry gelatin swells when brought into cold water. By continuous boiling or by
gastric or tryptic digestion further hydration takes place with the formation of soluble
gelatin peptone. Gelatin fed will not take the place of proteid, but, like sugar, only more
effectively, it may prevent proteid waste by being burned in its stead. ^ Gelatin yields leucin
and glycocoll on decomposition, but no tyrosin. It therefore gives the biuret reaction, but
none with Millon's reagent. It contains but little sulphur. It yields about the same
ami<l()- acids as ordinary proteid.

Elastin. — This is very insoluble in almost all reagents and in boiling water. On
decomposition it yields leucin, tyrosin, glycocoll, and lysatin. It is slowly hydrated by
boiling with dilute acids, and by pepsin hydrochloric acid. It contains very little sulphur,
and gives IMillon's teat. It is found in various connective tissues, and especially in the
cervical ligament.

Keratin and Neuro-keratin. — These arc insoluble in water, dilute acids and alkalies ;
insoluble in i)epsin hydrochloric acid, and alkaline solutions of trypsin. Keratin is found
in all horny structures, in epidermis, hair, wool, nails, hoofs, horn, feathers, tortoise-shell,
whalebone, etc. Neuro-keratin has been discovered in the brain, and in the medullary
sheath of nerve-fibres.'' On decomposition with hydrochloric acid keratin yields all the
l)roducts given Ijy simple proteids. It contains more sulphur than simple jiroteid and
yields more tyrosin. DrechseP believes that it is transfonncd from simi)le proteid by the
substitution of sulphur for some of the oxygen and of tyrosin for leucin or other amido-
acid. Part of the sulphur is loosely combined, and a lead comb turns hair black, due to
the formation of lead sulphide. There are different keratins, and their sulphur content
varies greatly.

General Remarks on the Proteids. — It has been impo.-^sible within
the limits set to more than glance at tlie proteid bodies. Many facts concern-
ing the behavior of proteids have been mentioned throughout the text, and

' Voit: Zeitschrift fur Bioloc/ie, 1872, Bd. 8, p. 297.

■^ Kiihne and Chittenden : Zeitschrift fiiv Biologie, 1890, Kd. 2(3, p. 291.

' Ladenburg's Handwbrlerbuch der Chemie, 1885, Bd. 3, p. 571.

THE CHEMISTRY OF THE ANIMAL BODY. 1021

cannot be classified here. A list of the priiicipal products of the digestion
and putrefaction of proteid may not b(; out of place. It iuchidcs albunioses,
peptones, leucin, tyrosin, lysin and lysatinin, aspartic acid, glutamic acid, amido-
valerianic acid, volatile fatty acids ; ph('nyl-pro[)ionic, phenyl-acetic, ^j-oxy-
phenyl-acetic, and p-hydrocumaric acids ; /j-cresol, phenol, indol, skatol ; and
the gases, ammonia, carbonic oxide, sulphuretted hydrogen, nictiiyl mercaptan,
hydrogen, and methane

The size of the proteid molecule must be very great, and one computation
shows the following figures:^

Egg-albumin. Proteid from heemoglobin (dog).

It is well, perhaps, finally, to speak of experiments which, however incom-
plete, at least throw some light on the possibilities of the problem of the syn-
thesis of proteid. Lilienfeld - through the condensation of the ethyl-ester of
glycocoU has obtained a body insoluble in water, but swelling in it, forming a
gelatinous mass. The substance gives the biuret reaction, is insoluble in
alcohol and dilute hydrochloric acid, but dissolves in pepsin-hydrochloric
acid. These reactions show its kinship to gelatin. Lilienfeld likewise de-
scribes a synthetically formed peptone and a coagulable proteid,^ the peptone
formed principally through condensation of the above-described product with
the ethyl-esters of the amido- bodies, leucin and tyrosin, the proteid from the
same with addition of formic aldehyde. Griraaux likewise has produced,
with other reagents, colloids which resemble proteids. Probably none of
these substances are native proteids, but they furnish indications of lines of
attack for the future mastery which in time is sure.

^ Bunge : Physiologische Cheniie, 3d ed., 1893, p. 56.

'^ Verhandlungen der Berliner physiologischen Gesellschaft, Archiv fiir Phydologie, 1894,
p. 383.

^ Ibid., p. 555. ^

INDEX.

Aberration. 760, 761
Absorption, 250-259

bile ill, physiological importance of, 265, 266

by diti'iisiou and osmosis, 250

in the large intestine, 2o4

in the small intestine, 253

in the stomach, 252

of fats, 257

of proteids, 255

of sugars, 257

of water and salts, 258

phenomena of, 27

spectra. See Spectrum.
Accommodation. See Eye.
Acetone, 982
Acetonitril, 985
Achroodextrin, 223, 1008
Acid, acetic, 980

aceto-acetic, 980

acetyl-acetic, 980

amido-acetic, 981

amido-ethyl sulphonic, 986

amido-hydrocumaric, 1011

amido-succinic, 1000
monamide of, 1000

«-amido-a-thiopropionic, 990

a-lactic, 988

a-€-diamido-caproic, 994

aspartic, 1000

p-oxybutyric, 991

benzoic, 1011

butyric, normal, 245, 982

capric, 984

caproic, 983

caprylic, 984

carbamic, 991

carbolic, 1010

carbonic, 988
amido-derivatives of, 991

choleic, 987

cholic, 987

cynurenic, 1013

f?-glucuronic, 1009

diamido-acetic, 994

diamido-valeric, 994

dithio-diamido-ethidene lactic, 990

fellic, 987

formic, 978

glutamic, 1000

glycerin phosphoric, 1001

glycurtmic, 1009

hippuric, 1.54. 279, 1011

hydriodic, 9.53

hydrobromic, 953

hydrochloric, 952

hydrocyanic, 985

hydrofluoric, 954

iso-butyl amido-acetic, 983

iso-butyric, 983

iso-pentoic, 983

iso-valerianic, 983

lactic, ethidene, 988
of gastric juice, 226, 227
production of, 234

Acid, lactic, sarco- or para-, 989
source of, 148

levulic, 982

malic, 1000

metaphosphoric, 958

metasilicic, 963

methyl amido-acetic, 982
guanidin acetic, 993

oleic, 1002

orthophosphoric, 958
detection of, 959

oxalic, 999

oxy-formic, 988

oxy-succinic, 1000

palmitic, 984

phenaceturic, 1011

phenyl-acetic, 1011

jj-hydrocumaric, 1011

^-oxyphenyl-acetic, 1011

jj-oxyphenyl-amido-propionic, 1011

propionic, 982
I /3-acetyl, 982

stearic, 984

succinic, 1000

sulphuric, 950

sulphurous, 950

taurocholic, 263

thiolactic, 990

uric, 277, 278. 997
dimethyl, 998
murexid test for, 998
preparation and properties, 997

urochloralic, 980
Acids, action of, in promoting pancreatic secre-
tion, 177

amido, in general. 981

biliary, Xeukomm's test, 988
Pettenkofer's test, 988

containing more than five carbon atoms, 983

dibasic, diatomic, 999

fatty, 976
diamido-, 994

lactic, 988

mercapturic. 990

monobasic. 970

oxy-, fatty, 988

oxy-propionic. 988

polysilicic. 963

silicic, 963

uric, 997. 998
Acini. 1.53
Adenin, 995
Adipocere. 1002

Adrenal bodies, internal secretions of, 210
Adult, body-temperature of female, 577
male, variations in, 577

heat-production in the, estimates of, 589
After-birth, the. 919
Agamogenesis. 878

Age, changes in the nervous system dependent
upon. 715

increase in brain-weight with. 724

intluence of, on heat-dissipation, .592
on heat-production, 590

1023

1024

INDEX.

Age, iiifluenco of. on tlie respiratory rate, 533
on till' resjiiratory tnu-t, olfi
old, atrophy of I he hrain in, 7~0, 726
decrease in hniin-weijiht in, 742
metabolism in the eerebellum in, 743
in the eneephalon in, 743
in the nerve-cells in, 742
recovery of vision in, 7()0
the period of, t»2>s
Air, amount of, in adult human lungs, 517
dry and moist, exposure to, physiological

effect of, .'".78, .'■>i)3, 59.-)
expired, ))roj)ortions of O and COa in, 518
quantity of N iu, 518

of watery vapor given oft' by, 518
temperature of, 518
volume of. 51!)
inspired and alveolar, pressure of gases in,
.521
constituents of, 518

eflFect of, on the respiratory quotient, .547
efl'ects of alterations of. on the absorption

and elimination of gases, 543
influence of alteration iu composition of,
upon the respiratory rate, .534
proportions of O, CO2, and N iu atmospheric,

521, 523
rarefied and compressed, respiration of, effects

of, on the circulation, 559
respired, quantity of, .534, .536
Air-capacity, alveolar, of the lungs, 535
of the trachea aud bronchi, 535
vital, .535, .536
Air-passages, obstruction of the, effects of, on

the circulation, 555)
Air-vitiatiou of inhabited rooius, 547
Air-volumes, respiratory, Hutchinson's classifi-
cation, 534, 535
— complemental air, 535
— residual, 535
— stationary air, 535
— supplemental or reserve air, 535
Albumin, acid-, 230

serum-, 349
Albuminates, 1018
Albuminoids, 215, 1020
action of gastric .juice on the, 235

of trypsin on the, 243
chemistry of the, 215
nutritive value of, to the body, 215, 288
Albuminous glands. Sec Glands.
Albumins, 1017
Albumose, defined, 230, n.
Alcohol, amyl, 983
butvl, poisonous dose of, 983
cerotvl, 983
cetvl, 983
ethyl, 978

poisonous dose of, 983
excessive use of, effect of, 298
in the body, 979
iso-pentyl,'983
melicyl, 983

physiological effect of, 297
propenyl, 1000
propyl, normal or primary, 982

poisonous dose of, 983
radicals, compounds of the, with nitrogen, 984
diatomic, derivatives of, 986
monatomic, 975
triatomic, 1000
Alcohols containing more than five carbon
atoms, 983
primary general reactions for, 975
secondary. 975
tertiary, 975
Aldehyde, formic (methyl), 977

Aldehyde, glycerin, 1001
nietiiyl, '.)~7
paraforniic, 977
Aldehydes, behavior and preparation of, 977
Alimentar.v canal, bacteria of the, 248

digestive processes in the, object of, 213
movements of the, 307-325
— defecation, .324
—deglutition, 310
— masticatiou, 310
— movements, intestinal, 320
^movements of the stomach, 315
— vomiting, 325
osmosis of tlie, 2.52
Alkalies, action of. in promoting pancreatic se-
cretion, 177
AUantoin, 998
Allochiria, 844
Altitude, influence of, on the number of red

cor])Uscles in blood, 344
Alveoli and the blood, iuterchange of C and
CO.' lietween, 522-527
of resting mammary gland, epithelial cells of,

202
of the lungs, number aud size of, 504
of the pancreas, 172
of the sebaceous glands, 197
secretory, of mammary gland, incompletel.v
formed before pregnancy, 201, 204
Amines, the, 984

of the olefines, 986
Ammonia, 955
Ammonium, 967
carbonate, 218, 967
cyanate. 98,5
Amnion, the, 911
Amcrba, 33, 34
Amphibia, removal of cerebral hemispheres of,

efiect of, 706-709
Ampho-iiei)tones, 231, 241
Amygdalin, 985
AmVlodextrin, 223, 1007
Amylopsin, 243, 1008
end-i)roducts of, 243
s]iecific reaction of, 243
Anabolism defined, 19
Analysis, chemical, defined, 962
Anatomy of the ear, 807-824
physiological, of the central nervous system,
644
Anelectrotonus, 69
Animal "starch," 266

Animals, cold-blooded, bod.v-tenii)erature of, .575
class of, 57.5

retentiou of vitality of, after death, 39
heat-production in various, .590
human physiolog.v founded ui)on experimen-
tation on lower, .30
nerve-cells iu different, size of. 609
neurons in diflerent, size of, 609
reflex action of central nervous system of, 704
removal of cerebral hemispheres of, result of,

compared, 705-710
reproduction in, periods of desire and power

of, 898
sense of smell in lower, 851
warm-blooded, bod.v-temperature of, 575
class of, .575
Anode, electrical, 44

])hysical and i)hysiological, defined, 62
Antalbuniid, 231, n.
Antipei)toue, 231, 241
Anti-peristalsis. 317, 320
Antrum pylori, 315
Apex-beat" of tile heart, 409
Aphasia, 697
Apua'a, 548, 549

INDEX.

1025

Apparatus, electric, 43-4")
Area, visual, cortical subdivisious of, 712.
Areas, cortical. See Bruin.
Arteries and heart, {leneral changes in, 404
blood-speed in tiie, iSMH

coronary, closnre oC the, ehanjj;es in the heart-
beat from, IT.'S
excilinji cause of ventricular arrest from,

474
frequency and results of ventricular ar-
rest from, 473
in the do;;, 471
terminal nature of, 472
great, ciianges in the, in the open chest, 407
Articulation, defined, 874
Articulations, the, 85.")

of the auditorj' ossicles, 812
Asparagin, l(KH)
Asphyxia defined, 548

stages of, 552, 553
As.similation. See Nutrition.
Astigmatism, 763-7(i5
Atavism, 933
Atropiu, action of, upon the salivary glands and

their secretions, 170
Auditory meatus, external, 807
ossicles, HIO

sensation, tjieory of, 824
Auricle a feeble force-pump, 427
are the venous openings into the, closed during

its systole? 430
changes in the, from vagus excitation, 455
connections of the, 426
function of the, 428
is the, emptied by its systole? 430
pressure of the systole of the, 427
withiu the, negative, 429
Auricles, beating, changes in size of, 404, 405
changes in the, in the open chest, 407
color of the, 407

functions of the, 426. See also Heart.
Auricular cycle, relations of time of the, 413
Auscultation, inventor of, 410
Automatism, muscle, defined, 35
Axilla, temperature of the, mean, 577
Axis-cylinder of nerve, 36, 151

Bacteria, intestinal, 248-250
pathogenic, destruction of, by the leucocytes
of the blood, 346
Basilar membrane, cochlear, 821, 824

fibres of the, number of, 824
Basophiles, 345

Baths, influence of hot and cold, on body-tem-
perature, 579
Beats in notes or tones, production of, 830
Benzol, 1010
Benzopyrol, 1013
Bidder's ganglion, 440
Bile, 261
absorption spectrum of, 262
analysis of, chemical, 261
anti.septic properties of, 266
circulation of the, 263
color of, 185, 186, 262
constituents of, 186, 261-265
— bile-acids, 263
— bile-pigments, 262
— cholesterin, 264
—fats, 265
—lecithin, 265
— nucleo-albuniin, 265
ejection of, from the gall-bladder, process of,
188
normal mechanism of, 189
formation of, action of secretory nerve-fibres
upon the, 188

Bile, formation of, during the digestive process,
189
not controlled by the nervous system, 185
function of, 1.54

importance of, physiological, 265
inlliiiiicc (if, in th<' eniulsidcatiou of fats, 246
in llie l)lood, action of the presence of, 187
method of obtaining, 261
quantity of, secreted, 186, 261
reaction and specific gravity of, 262
Bile-acids, 2(i3, 2()4

Bile-capillaries, relations of the, to the liver-
cells, 185
Bile-duct, complete occlusion of the, effect of,

189
Bile-ducts, lining epithelium of, relationship be-
tween the liver-cells and the, 185
Bile-pigments, 262, 1015

Gmelin's test for, 262, 1015
reabsorption of, 265
relationship of hajmoglobin to, 343
Bile-salts, 1.54

Bile-secretion, conditions influencing the amount
of, 187 ■
digestive function of, 265
normal mechanism of, 189
quantity of, 186

relation of, to the blood-flow in the liver,
187
Bile-vessels, motor nerves of the, 188
Bilirubin, 262, 1015
Biliverdin, 262, 1015
Birth. See Parturition.
body-growth before and after, 924, 925
length and weight of fetal body at, 925
Birth-rate, relative, of the two sexes, 922, 923
Births, multiple, 920, 921

periods of largest number of, 899, n.
Bladder, changes in size of the, from reflex
stimulation, 329
contraction of the, influence of the force of,

upon the urinary stream, 328
contractions of the, physiological mechanism

of, 329
mechanism of the, nervous, 330

of urinary injection into the, 327
movements of the, 328
nerve-fibres of the, sensory and motor, 330
nerves of the, vaso-motor, 500
"Blind spot," retinal, 774
Blood, absorption-coefficient of, for O, 523
alkalinity of, degree of and test for, 332
ammonia carbamate of the, 276
appearance of, in asphyxiation, .553
arterial, gases of, alterations in the, 519
per cent, of, of various animals, 519
proportions of O and CO2 in, 519
pulmonary, color of, 519
speed ancf pressure of, compared, .393
bile in the, pre.sence of, action of the, 187
capillary, speed and pressure of, compared, 393
CO2 in the, influence of the quantity of, 551
composition of, chemical, 347
gaseous, effects of, on the respiratory move-
ments, .548
importance of, ui)on the respirations, 566
defibrinated, 331, 332
defibrination of, 3.52, .3.53
functions of the, 73, 331
gases in the, alterations in the, 519

extraction of, 528
haemoglobin in, amount of, 336
in the body, distribution of, .sto, 361

quantity of, 360
in the central system, 734-736
" laky," 3:53
menstrual, amount of, discharged, 896

1026

INDEX.

Bloud. nu'ii8triial, ihaiacter of the, 896
uiovt'iuLMit of (lie, ill i'!i]ii Maries, uiiuute arte-
ries and veins, 371-377
of preKiiaiicy, i'KJ

of various animals, nutritive value of, 482
of tile niaininalian heart, 482
jieptoiU'S and jiroti'oses in, 'I'-AS
jiroperties of tiie, general, 331-347
reaetion of, 33'J

regeneration of, after hemorrhage, 361
solutions of, isotonic. .334
sjieeilie gravity of, 332
sjieetra of. absorj)tion, 338
structure of, histological. 331
sugar of the. form of. 2r)7
tenijierature of the, 577

time spent by the, in a systemic capillary, 395
transfusion t)f, 3(i'2
urea present in the, amount of, 275
venous, iiroportions of () and COa in, 519, 520
speed and jiressure of. compared, 393, 394
Blood and the alveoli, interchange of C aud CO2
between the. .522-.527
and the tissues, interchange of O and CO2 be-
tween the, .527
Hlood-circulation. See CirculKtion.
Hlood-clottiug. See Coiujulniion.
Blood-cor])uscles. See Corpusclex.
Blood-tlovv, cai)illary, 372
causes of the, 369
course of the, 368
ill the small ves.sels, direct observation of,

372
sumniary of, 377
through the kidneys, 195

the lungs, 395
venous, subsidiary forces assisting the, 387
Blood-li'ucocytes. See Leucoq/tes.
Blood-jiassages in the frog's heart, 471
Blood-path, circle of the, 368

jmlmonary, .370
Blood-plasma. See PlaKma.
Bluod-iilates, 347
Blood-pressure, aortic, 377-383

arterial, capiJlarv, and venous. 377-383
causes of, .383-389
causation of, 383, 385
arterial and venous, manometric and
graphic, method of studying, .377-380
manometric trace of, 381, 382
<-apillary, 376, 438

why pulseless? 387
cardiac, eflect of stimulation of cardiac

nerve-fibres on the, 46.3-467
changes in, from stimulation of the brain,

due to reflex action, 494
effects of resj)iratory movements on, .5.55
intracranial, 735, 7.36

symptoms of bleeding in relation to, 383
the mean arterial, ca]tillary, and venous, 382
venous, causation of. ;i86
Blood-pressures within the ventricles, 416
Blood-proteids of Ivmph, 363
JMood-serum, .331-334

action of, bactericidal, 334
globulicidal, 334
Blood-s[)ced and ])ressure compared, 393

in arteries, capillaries, and veins, 390-395
in large vessels, measurement of, 390, 392
in the arteries, .393
in tlic caiiillaries. .393
in the minute vessels, .375
in the veins, 393

varies inversely as the collective sectional
area of its ])ath, 394
Blood-stream, evidence of the more rapid move-
ment of the central part of, 373

Blood-stream, iiulmonary, 3i(5, 3f)6
Blood-supjily and heartbeat, relation of, in the
coronary circulation, 477
eHect of the, on nerve and muscle, 73
importance of the, ujioii the respirations, .566
inliuence of the, 011 bodv-tenipcrature, 579
of the brain, 723. 734-7:i(>
Blood-vessels, chorionic, 912

clotting within the, production of, 3.58
condition of the, due to asphyxiation, .553
contractility of the, early experimental

deuKMist rations of. 482-486
innervation of the, 482-.")01
large, sjieed of the blood in, 390-392
minute. s]>eed of the blood in, .375
lilacental, 912
retinal. 767

small, How in the, direct observation of, 372
why blood does not clot within the, 359.
See Arterie.1, Ciipilldries, ]'eins.
Body, chemistry of the, 943-1021
equilibrium, dynamic, 833, 843, 845-849

static. 849
locomotion of the, 860
" Body of Aranzi," 404
Bodv-activitv, influence of, on heat-productiou,

592
Body-fat, origin of, theories of, 290, 291
Body-heat. See Heat, also Temperature.
chemic production of, 302
specific. 948
Body-growth before and after birth. 924, 925
diminution of, progressive. 926, 928
influence of race upon, 926
ra])iditvof, relative, in both sexes. 926
Body-metabolism, 282-302
Bodv-stirface in relation to heat-dissipation,

594, .5!)5
Bodv-tenii)erature. See Temperature.
Body-weight in death, 9.30

influence of, on heat-production, 590
loss of, from starvation, .301
relations between weight of centi'al nervous
system and the, 719
Bone a mineral, 969

Bones, action of muscles upon the, method of,
8.57
in human skeleton, number of, 855
muscles of, contraction and reaction of, 107
of the skull, conduction of sound-sensation

through the, 815
union of. See Articulations.
" Border cells," 178

Brain, atroi)hy of the, in old age, 720, 726
blood-supiily of the, 7.34
frontal lol)es of, effect of removal of, 703
growth of the, 724

hemis|)lien's of the, effect of injury to the
two, ()99, 700
nervous pathways within the, 696-702
nerves of the, vaso-motor, 494
relations of the, to vaso-motor centres, 493
removal of the, in animals, result of, 705-715
sensory and motor regions of the, 684-687
specific gravity of the, 716
"speech-centre " of the. 698. 702
water in the. })ercentage of, 7](>
weighing the, method of, 718, 719
white matter of. composition of, 150. See also
Eiici'phitlon.
Brain-weight among the insane, 722
at birth, 726
comparative, 718, 719

of eminent men. Manouvrier's table, 721
decrease in, in old age, 742, 928
differences in, conditions determining, 718
increase in, with age, 724

INDEX.

1027

IJiaiii-weight, iiillufiice of social enviroumeut
on, 7J1
interpretation of, 720
of i-riniinals, 7'^"J
of (liircriMit races, 722

variations in, acoiirdinK to age, sex and stat-
ure, 7 IS, 71!», 720
llrain-weijiiit and weight of the pia and fluid,
71(i
of tlie s|iinal cord, 715-724
IJreathing. Sei- liespi ration.

nasal, value of, 517
Hroniine, 9515
" BuUy coat," :}53

Hulbus arteriosus, action on the, from vagus ex-
citation, 455
Huliniia, K((j
Butyl compounds, 98

Cadaverin, 986
Catlein, 99(i
(.■alcium, 967

carbonates, 968

chloride, 967

detection of. 968

fluoride, 967

in the body. 969

phos)>hates, 967

sulphate, 967
Calorie, or heat unit, 584, 948
Calorimeter, Eeichert's, 586
Calorimeters, classes of, 585
Cane-sugar, 218, 247, 1006

chemical action of invertiu on, 220

inversion of. 257

relation of, to glycogen-formation, 267, 268
Cai)illaries, blood-flow of the, .377, 379

blood in the, movement of, 371

blood-pressure of the, 376

blood-speed in the, 393

calibre of the, 371, 376

characters of the, .371

of the lungs, .504

red corpuscles of the, behavior of, 373
deformity of, 373

"systemic," 369
Capillary, structure of the, histological, 372

systemic, time spent by the blood in a, 395
Capsules, suprarenal, removal of the, symptoms

preceding death from, 210
Carbamate of ammonia, derivation of urea from,

275, 276
Carbamide, 991
Carbohydrates, 215, 861, 1003

absorption of the, 257

action of gastric juice on, 235
of intestinal secretion on, 247

combustion equivalents of, 303

effect of, on the amount of glycogen in the
liver, 267

nutritive importance of, to the body, 215, 292

oxidation of, 292

potential energy of, determination of, 303

production of fat by the, 291

]iroper regulation of, to the tissues, essential
to health, 269
Carbon, 960

atom, asymmetric, 989

compounds, chemistrv of, 974

dioxide, 961

detection of. 962

elementary, 960

equilibrium defined, 284

metabolism of, 962

monoxide, 960
Carbonate, ammonium, 967
Carbonates, calcium, 968

Carlxinates, magnesium, 971
potassium, !)ili
sodium. !lii6
Cardia<' centre, augmentor, localization of, 469
inliibitory, localization of, 467, 468
cycle. <leliii"ed, :5!»6, 414

relations in time of the main events of, 413
cycles, brevity and varialjility of each, 414

freciuency of the. 412
excitation-wave, 443
fibres, inhil)itory, origin of, 468
"impulse," 405,409
nerve-centres, 467-470
nerves, 450
Cardiogram, the, 409
Cardiometer. the, 398
Cardio-pneumatic movements, 520
Carnin, 998

Caitilages of the larynx, 865
— of Santorini, 865
—of Wrisberg, 865
— the arytenoid, 865
— tlie cricoid, 865
— the thyroid, 865
Casein, 234
Caseinogen, 2.34
Castration, pbvsiological changes due to, 871,

872. 900, 933
Cataleptic rigor, 145
Catalysis of enzymes, 220, 947
Cell, combustion in tlie, in general, 1009
death of the. somatic, 943
the, the unit of structure of living organisms,
20
Cell-bodies, nerve, change in, resulting from
stimulation, 629-633
relation of in the cerebral cortex, 729, 730
Cell-diflTerentiation, 22, 37
Cell-division, 20
Cell-granules, 157
Cell-groups, localization of, in cerebral cortex,

682-696
Cell-protoplasm, conductivity of, 81

irritability of, conditions determining
the, 65
Cell-reproduction, asexual, 879
Cells, auditory, classes of, 818
"border," function of, 178, 179
capillary, 372
daughter-, 20
dineuric, defined. 607
embryonic, growth of, 924

■epithelial, glomerular, influence of the, in
urinary secretion, 193, 194
influence of, in the secretorv processes, 154,

155
of resting mammary gland, 202
erythroblastic, of red marrow, formation of
red blood-corpuscles by the, 343, 344
ganglion-, iiitracardiac, 440
gland-, sebaceous, 197
goblet, secretorv, 157

hair-, auditory,' of Corti, 818, 822, 824, 825
hepatic, relations of the, to the ducts, 184, 185
mononeuric, defined, 607
mucous (secretory), 157
muscle-tissue, of alimentary canal, 307
nerve-, classes of, defined, 641
gustatory, 851
tactile, 8.53
vaso-motor, 488. 489
of Langerhans, 172

of mucous gland, appearance of, after stimu-
lation. 169
in a resting state, 169
of pancreas, appearance of. during fasting, 174
during the stages of digestion, 175

1028

INDEX.

Cells of pancreas, histological changes in, during
activity. 174
characters of, 172
of parotid, appearance of, after stimulation,
l(i8
in a fresh state, IfiS
in a restin;r condition, l(i7
of tuhules of kidney, secretory functions of,

definite. 1!)2. 1!«
of the cortex. .See Cortex.
of the gastric glands, histological changes in,
during secretion, 1S"J
histological characteristics of, 178
of the intestinal glands. 184
olfactory, 8o0
"oxyntic." 178
"parietal," 178, 179

secretory, appearances of, histological, 157
lumen of the, 101
of sweat-glands, 198
spindle-shaped, of j)lain muscle-tissue, 307
sustentacular, auditory, 818
" wandering,'' 346
Cellulose, 1C)07

Centre of gravity of the human body, 859
Centres, nerve-, cardiac, 407-470
of the cortex. See Cortex.
thermogenic, 598, 600. 601
tiicrmo-inhibitory. .599, 601
vaso-motor. 489-49.'5
Centrosome, 20. 22, 908
Cephalization defined, 703
Cerebellum, changes in the, in old age, 743

removal of, effect of, 714
Cerebral cortex. See Cortex.

hemispheres, bilateral symmetry of the, 723
blood-supply to the, 723
functions in the, localization of, 704, 705

of the two, relative, 699
nervous pathways within the, 696
removal of the, 705-715
Cerebri n, 1001
Cerumen, 198
Charcot's crystals, 884, 885
Chemical tonus, 133, 134
Chemicals and drugs. See Drugs.
Chemistry of digestion and nutrition, 213-304
of muscle and nerve, 144-151
of the body, 943-1021
Chemotaxis or chemotropism, 904
Chest, opened, efi'ects on the heart and vessels
of the. 407
observation of heart and vessels in the, 405
unopened, probable changes in the heart's
position and form in the, 408. See
Thorax.
Chief-cells, changes during secretion in, 182,
183
of the gastric glands of the stomach, function
of, 178, 179
Chinolin, 1012
Chloral hydrate, 980
Chloride, calcium, 967
sodiun), 965
potassium, 963
Chlorides of the urine, quantity of, 280
Chlorine, 951

in the body, 9.52
Chlorocruorin, 1018
Chloroform, 977

Chocolate, physiological effect of, 297
Cliolesterilin.'lOKi
Cholcsterin, 264. 1016
elimi'.iation of. 264, 265
formation and distribution of, 264
Cholin, 986
Chondro-mucoid, 1019

Cin»rion, the. 911,912
Ciiromatin, 22, 28, 8b9, 892
Ciiromo-proteids. 1018
Chromosomes. 22, 28, 884, 889

numbir of, in fertilized ovum, 908
(.nironogra]))!, the, 100
Chyme, 237, 318
" CJirculating proteid," 285
Circulation (blood), cerebral. 495

circuit of, time retinircd to complete the, 371
coronary, blood-supply and heart-beat, 477

volume of, 476
course of the, 368
defined, .368

discovery of the, 362, '.UiH
effects of obstruction of the air-passages on
the, .")59
of the respiration of rarefied and compressed

air on, .")9
of the resi)iratory movements on the, 5.55
influence of, on heat-dissipation, 595

on heat-production, 590
influences of intrathoracic and intrapulmon-

ary pressure ui)on the, 517
in the central nervous system, conditions con-
trolling the, 734, 735
mechanics of the. .371
placental, 912, 913
proofs that the heart unaided can maintain

the, .•i9()
rapidity of the, 371
I'etinal, 768
Climacteric, the. 898, 927
changes of. pathological, physical, and psychi-
cal, 927
Climate, effect of, on sexual maturity, 927
influence of. on body-temperature, 578
on heat-dissipation. .593
on heat-production. .591
Clothing, influence of, on heat-dissipation, .593
Clotting. See Codiiulotiou.
CO2, effect of respiration of, 547. .548

elimination of, during muscular work. 299
during sleep, 300

from variations in temperature, 300. 301
excretion of, from the skin, 282
exhaled through the skin, quantity of, .530
tension of. .524
CO^-dyspncea, cause of, 550, .551
Coagulation, blood, 352

conditions necessary for, Schmidt's classi-
fication, 355
intravascular, 358, .359
means of hastening or retarding, 359
— by action of albuminose solutions, 360
— by action of neutral salts, 360
— by action of oxalate solutions, 360
— by cooling, 3.59
— by use of leech extracts, 360
mechanism of, 3.52
necessity of calcium salts to, 296
physiological value of, 35.3
process of normal, 356
relation of calcium salts to, 355
theories of, 3.53

— Hannnarsten's theory, 354
— Lilienfeld's theory, .3.56
— Pekel baring's theory, 355
— relation of .salts to, 3.55
— Schmidt's older theory, 354
— Schmidt's recent theory, 354
time of clotting, .3.5.3
lymph, 3(i3

milk, rcnnin process of, 2.34
muscle, in rigor, 146, 147
Coats, muscular, of the bladder, 328
of the stomach, 315

INDEX.

1029

Coats of till- iiriters, 327
Coflik'ii, aiialiiiiiv of tlic, {loncral, R19
nu'iiibranoiis, ,sl7, J^l!', f^~l
osseous stnu'tiirc of, Hl(»
Cotfeo, pliysiolofjtical fll'i-ct of, *2!)7
Cold and warm points, cntanoous, 841

application of, to the bodv, reactions produced

by, (iO;5
efl'ect of, on nuiscle-protoplasni, 147
on muscular contraction, 127
on the development of rigor, 145
OoUaccn, 288, 1020
Colloid, 101!)

of the thyroids, formation of, 207
Color contrast, retinal, 792
sensation, 778, 779

theory of, llering's, 782
Mrs. Franklin's, 783
Yonng-Hehnholtz, 781, 782
vision, cerebral centre for, 785
Color-blindness, 784

practical importance of determining, 785
test for, Holmgren method, 785
Color-mixture, spectral, 779
Color-reactions of proteids, 1016
Color-sensations, 778, 779
Color-theories, 781
Colorimetry, 584

Colors, binocular, combination of, 803
"complementary," defined, 780
luminosity of different, 78(>
mixture of, physiological, 780, 781
Colostrum, 204

corpuscles, origin of, 203
"Combustion equivalent," 303
Commutator, mercury, Pohl, 51
Conceptions, multiple, 920

periods of the largest number of, 899, n.
Concha, the, 807
Concord, musical, perfect, 831
Condiments and flavors, influence of, on diges-
tion, 298
Conduction, influences which alter the rate and
strength of the process, 92-96
of muscles and nerves in both directions, 86
influences which alter the rate and

strength of the process, 92
isolated, 83

nature of the process, 97
protoplasmic continuity essential to, 82
rate of, 88
Conductivity, 21, 3.5, 81-98
Consciousness, 28, 29 •

existence of, in animal life, 29
phenomena of the central nervous system in-
volving, 606
Consonants, classification of, 876, 877

phonatiou of, 876, 877
Contiuuity,'protoplasmic, of muscles and nerves,

82
Contractility, 20, 32, 98-134

power of, in simple living organisms, 34, 35
Contraction, anodic, 50, 63, 68, 69
cardiac, 441-450
idiomuscular, 42, 93
isometric, 108
isotonic, 108
kathodic, 50, 63, 68, 69
law of, Pfliiger's, 60

muscular, alterations in the form of the myo-
gram, from mechanical conditions,
108
amount of irritation process developed, esti-
mated from the amount of the, 63
as effected by heat, 66
duration of, differences in, 106
effect of cold on, 127

Contraction, muscular, effect of drugs and chem-
icals on, 128
of temperature on, 127, 128
of veratria on, 128

of body-weigiit on the form of the myo-
gram, 108
influences affecting the activity and charac-
ter of the, 106
latent p(-riod of, 101, 113, 114
law of, 53, (iO

liberation of energy by, 129-132
method of recording, 49
inyoj^rain of, simi)le, 101
nature of, in rigor, 146
normal and rigor mortis, differences in

forms of, 146
of rigor, changes resulting from, 148
of the bladder, mechanism of, 329

sjiinal centre of reflex, 330
of the intestines, 309
of the oesophagus, 312-314
of the stomach during digestion, 316, 317
of the ureters, 309, 327
of the viscera, mode of, 310
rate of, in difl'erent muscles, 107
theories of chemical changes and alterations
of form in, 104
of muscle-tissue, variation in rate of, 308
of striped muscle, rapidity of, 308
spasmodic, of the abdominal muscles, the prin-
cipal factor in vomiting, 325
ventricular, force of the, 399
vermicular, defined, 310
"Contraction-ring," 917

Contraction-wave, " antiperistaltic," of the stom-
ach, 317
cardiac, 443

peristaltic, intestinal, 321
Contractions, fibrillary, cardiac, from closure of
coronary arteries, 473, 475
from closure of coronary veins, 476
recovery from, 475
muscular, 98-134, 737

effect of fatigue on. 111, 112, 126

of increase of strength of electric cur-
rent, 54, ,55
of making and breaking the direct elec-
tric current, 50
of support on the height of, 119, 120
of tension on the activity of, 131, 132
of the strength of electric irritation on,
53, 54
fatigue from, 77

of voluntary, 126
functions of, 32, 33
post-mortem, 144-147
recording of, method, 98, 99
separate, effect of excitation upon the form

of, 113, 114
simple, studied by the graphic method, 98
"staircase." 72, 110

starting-points of excitation in the irrita-
tion process of making and breaking
electric currents, 50-53
of the bladder, influence of the force of, upon

the urinary stream, 328
of the spleen, 272
physiological, normal, 124
rhythms of, daily, 738
uterine, 917-920

duration and nature of, 918-920
ventricular, 369
"Contracture" (muscle), 115, 116
Contrast, auditory, 831, 832

color, retinal, 792
Copulation, 902
act of ejaculation in, 902, 903

1030

INDEX.

Copulation, sexual exciteiuent of, coiiUKirative,

902
Cord, spinal, hemist'ction of, degeneration of
nerve-fibres after, !)()!)
efleet of. (iTl tiT."!, (iTii
nerve-impulses iu tiie, allereut pathways of,

(>7o
plates of the, dorsiil and ventral, (i45
segmentation of the, (ilT)
Corpora Araritii of semilunar valves, 404
Corpuseles, l>l((oil-, averajje life of, 343
eomposition of, .■}47-34!)
isotonie relations of, 334, 3;?5
number of, variations in. eonditions affect-
ing the, 344
red, 333

behavior of. 373

blood-si)eed measured bj' the speed of the,

375
eolor of. 333
composition of, 333
destruction of. by ingestion, 343
evidences of friction of, 373
form of the, 330
formation of, by the erythroblastic cells

of red marrow, 343, 344
function of, 333
ha-moglobin of, condition of the, 333

nature and amount of, 335
movement of. observation of, 372
number of. 333. 344
orii^in and fate of. 343
reproduction of the, 343
specific gravity of, 333
varieties of, 331
colostrum, 203, 204
salivary, 161, 221
touch-, H.36
Corpus luteum, 893

Cortex (cerebral), afferent impulses of the, com-
posite character of, 700
y)ath\vays through gray matter of the, 702
variations iu association of, 701
area of the, 729

areas of the, centres and, separateness of. 091
latent, 702

localization of, 082, 683
result of stimulation upon, 683
mapi»ing of the, 684, 689
.sensory and motor. 683-687, 693

determination of, 696
size of the, 090
subdivisions of, 690
as.sociation-fibres of. 697
centre for color-vision in the, 785
fibres of the, increase in the, 729
impulses leaving the, course of. 695
metabolism of the, iu old age. 743
movements from the, control of. 094, 695
relation of cell-bodies in the. 729, 730
visual area of the, subdivision of, 712
Corti, cells of, 822
organ of, 821
rods of, 821-823, 825
Coughing. .562

diagnostic imimrtance of, 563
Covvper's glands, 887
secretion of. 885
"Crazy bone." the. 65
Oeatin. 278, 993
Creatinin. 278, 994
Cresol. formula. 280

Cretinism, sporadic, feeding of thyroids in, ef-
fect of, 737
Criminals, brain-weight of, 722
Crving. .5^)2
Crypts of Lieberkuhn, 184, 246

Crystals, Charcot's, 884, 885

Inemctglobin, 337, 3;i8
Cumre experiment on the independent irrita-
bility of muscle, 41
Cyanamide, 9f^5
Cyanate, ammonium, 985
Cyanide, meth.vl, 985

potassium, 9b.5
Cyste'in, 990
Cystin, 990
Cytology, 30
Cytoplasm, 20, 81

difiercntiation of, from protoplasm of the cell-
nucleus, 22

f?-FKUCTOsp:. 1005
(/-galactose. 1006
rf-glucose, 1005
" Dangerous region," 389
Daniell cell, the, 43
Deafness, cause of. 090

Death from extirpation of the thyroids, 208
symptoms [)receding, 208

from removal of sujjrarenal cajisules. 40

of living protoplasm, molecular alteration, 23

of the tissues. 92ft

rise of bodv-temperature after, cau.satiou, 604

somatic, 929, 930
Death-processes, effect of, on conduction, 92
Decidufp, the, 909-912
Decomposition, bacterial, intestinal, 248
Decussation of nerve-fibres, 647, 680, 681, 768
Defecation, 324

involuntary factor in, 324

mechanism of. 324. 325

voluntary factor in, 324, 325
Degeneration, nerve-, Wallerian. 033

of nerve-fibres, of the central system, 634
secondary. 687

of non-medullated nerve-fibres. 633

of nucleated portion of nerve-fibres, 6.35
Deglutition, 310

kronecker-Meltzer theory of. 313

nervous c(mtrol of, 314

oesophageal, number and time elap,siug be-
tween. 3i:5. 314

sound, 312, 313

stages of, 310. 311
Demilunes (cells), 100
Dendrons, neuric. 007
Depth-perception. 801
Deutero-proteoses. 230
Deutoplasm, S8.s. ,Hb9
Dextrose, 21h. 1005
Diabetes mellitus, 200, 207, 293

sugar in the urine in, 268
Dialysis defined, 251
Diaphragm, movements of the, respiratory, 506

.structure of the, 50(), .507
Dia.stase, 218
Diastole, auricular. .370. .396

ventricular, .'!?!>, 390, 405
Diet, accessory articles of, 296, 298

composition of healthy, 305

effect of. <m resi)iratory quotient. .545

influence ot'. on body-temperature, 578
on heat-i>ro<luction. .591
Dietetics, object of. 304
I Diets, effect of various, on gastric secretion. 181
1 Digestion, action of steapsin in. physiological
value of. 245
of nnoriranized and organized ferments on,
' 219

albuminoid. 2ss

bile in. i)hysiological importance of, 26.5, 266
' carbohydnite. 292
1 di-Siicciia rides of, 247

INDEX.

1031

Digestion, effect of coudimcnts aud (liivors upou,

of stimulants upon, •JH7
foruiiition of l>ile during, 189
gastric, "J^o-J.iT

proteoses of, lOlrt
influence of, on boily-teuipenilure, 578
on lieat-produclion, 591
on the viiluine of gases respired, 539
intestinal, -J-l-i-'JlS
action of the intestinal juice upon, 247
secretions acting in, 2;W
normal, tiow of gastric secretion during, cause
of, 181
physiolofiical value of saliva on, 224
object of tin? processes of, in the alimentary

canal, 213
of fats, 235, 2S9
pepsin-hydrochloric acid, 229, 240

product of, 255
peptic, 240

action of bile on, 266
end-products of, 229, 230
in the stomach, 228
steps in, 230
study of artificial, 229
physiology of, 217
products of, routes of absorption of the,

250
proteid, 285

end-products of, 255, 350, 1021
proteolytic, Kiihne's theory of, 231, n.

Xeumeister's schema, 243, n.
salivary, 220, 221

stonmch, movements of the, during, 316
of carbohydrates, 235
of fats, 235

processes of, schema of, 242
products of, 240, 255
the. not essential in, 237
tryptic, 240
Digestion aud nutrition, chemistry of, 213-304
Dioptric system, 74<}-748
Dioxide, carbon, 961

silicon, 963
Dioxyacetone, 1001
Disaccharides, the, 247, 1006
Discord, 831

Diseases, infectious, transmission of, 935, 936
Distance-perception, retinal, 799
D^ess, adaptation of, to climate, factoi-s in, 593
Drowning, death from, causation, 553
Drugs, action of, upon the salivary glands and
their secretions. 170
application of, to the eye, effects of, 771

upon the mechanism of eye-accommoda-
tion, 757
effect of, upon body-temperature, 580
upon heat-dissipation, .596
upon heat-i)roduction, 592
upon intestinal movements, 323
upon the sweat-glands, 200
Drugs aud chemicals, effect of, on conduction,
94
upon muscular contraction, 128
upon the irritabilitv of nerve and muscle,
67
Drum-skin (ear), 809

Du Bois-Eeymond law of electric nerve irrita-
tion, 47
Duct of Bartholin. 158
of Wirsung, 172
of the gastric gland, 179
Ducts, gland-. See Gland-ducts.
lymphatic, 362, 437
of Rivinus. 158
of the testis, 886

Ducts of the mammse, 201

pancreatic, 172
See Secretion.
Dumbness, 871
Dyslysin, 987
Dyspna-a, cardiac, 555

CO'i, cause of, 550, 551

delined, .548

forms and eaussition of, 550, 552

hemorrhagic, 555

Ear, analysis of composite tones by the, 828
anatomy and histology of, 807-824
of external, 807
— external auditory meatus, 807
— the concha, H(t7
— the pinna or auricle, 807
of internal, 815-824
of middle, 810-815

— auditory ossicles, 810
— Eustachian tube, 814
— muscles of the middle ear, 814
— tym])anic membrane, 809
— tympanum, 808
different parts of the, functions of, 832
fatigue of the, to sound, 831
imperfections of the, to sound-perception, 832
judgment of direction and distance by the, 833
muscles of the middle, 814
perception of time-intervals by the, 832
sensitiveness of the, to difference in musical
pitch, 829
Elasticity, muscle-, 104-106
Elastin, 1020
Electric circuiting, 45
current as an irritant, conditions determining
the efficiency of the, 43-64
effect of, 43-60
constant, effect of. on conduction, 94

effect of the, on the irritability and con-
ductivity of muscle and nerve, 61
direct, stimulating effect of making and
breaking the, on muscle and nerve, .50
effect of opening and closing the, on normal
human nerve, 63
of rate of alternations of, Tessla's experi-
ments, .58
upon muscles, 68
upon nerves. 69

upon the irritability of nerve and muscle,
67
irritating effect of, on mu.scle and nerve, 43
— angle of application. .58
— density of current, 56
— direction of flow. 60
— duration of application, .56
— rate at which the intensity changes, 46
— strength of current. 54
Gralvani and Volta's experiments, 43
relation of the method of application of.

to the, .59
relative efficacy of the different methods
of application upon the power of, 59
strength of, altering the, methods of, 55, 56
Electric currents, effect of, upon normal human
nerves, 62
induced, irritating effect of, on muscle and

nerve. 48
practical application of alterations produced

by, on conduction, 95
reaction of muscles and nerves to, 57
key, Du Bois-Reymond, 45
Electrode, the, 44 '
Electrometer, capillary, 136
Electrotonus, 69

Elements (chemic). metallic, of the body :
— ammonium, 967

1032

INDEX.

Elements, metallic:
— calcium, OfJT
— iron, !t71
— mafjncsiiim, 970
— potassium, 9G3
— sodium, JXi.^j
— strontium, 970
non-metallic :

— bromine, 9.53
— carbon, fXiO
— chlorine, 951 .
— fluorine, 9.53
— hydrogen, 943
— iodine, 9.53
— nitrojien, 9.54
— oxygen, 944
— phosi)liorus, 957
— silicon, 9(52
— sulphur, 949
Embryo, development of the, 911
growth of the cells, tissues, and organs of, 924
length and weight of tlio human, at ditfercnt

ages, 924
nutrition of the, 913

sex of the, factors determining the, 921-923
Emnlsification, 245
Emulsin, 21S, 985
Emulsion, 1002
Encephalon defined, 717
growth of body and, relation between, 727
in old age, changes in the. 743
nomenclature of, according to weight, 718
section of the, functional disturbances follow-
ing, 713
specific gravity of, 716
the "stem " of the, 717, 719
weight of the. 717
at different ages, 726
in sane ])ersons, table, 718
weights 01 different portions of, 721
Encephalon and spinal cord, weight of, 716.

See also Brain.
End-bulbs of sensory nerve-fibres, 835
End-organs, nerve, importance of, in cutaneous
sensation, 839
transmission of excitation by, to muscles
and nerves, 85, 86
Endosmosis, 251
" Endosmotic equivalent," 251
End-plates, motor, 41
Enemata, absorption of, 255
Energy, bodv-, influence of inorganic salts on,
294
muscular, electrical, amount developed, 135
liberation of, 129
— mechanical, 130
— thermal, 132
source of, 215, 298, 299, 302
nerve, .specific. 842
potential, liberation of, 302-304

direct and indirect conversion of, into
heat, .582
Enzyme, 176, 944
fat-splitting, pancreatic, 244
glycolytic, 293

zymogen and, of pancreatic secretion, 176
Enzymes, 217
action of the, incompleteness of, 219.

theories of the manner of, 219
classification of. 218
— amylolytic. 218
— coagulating, 218
—fat-splitting. 218
— glucoside-si)littiug, 218
— inverting, 218
— proteolytic, 218
— urea-splitting, 218

Enzymes, "diastatic," 218
of gastric juice, 226
of intestinal secretion, 247, 248
of the secretion of the gastric mucous mem-
brane, 179
pancreatic, 2.39
reaction of, 218

— effect of temperature, 219

— incompleteness of action, 219

— relation of the amount of enzyme to

the effect it produces, 219
—solubility, 219
Eosinophiles. .345
Epiglottis, the, 861, 862

movements of the, in swallowing, 311
Equilibrium, body-, maintenance of, 8.59, 960.

See Body-eqnUihrium.
Ervthrodextrin, 223, 1007
Ether, ethyl, 980

Ether molecules, rate of vibrations of, 777
waves, retinal changes jjroduced by, 777
synonymous terms used, 777, 778
Ethers, mixed, preparation of, 980
Ethyl alcohol, 978
compounds, 978
ether, 980
hydroxide, 978
Ethylamine, 985
Eudiometer, the, 529
Eupnoea defined, .548

Eustachian tube, structure and function, 814
Excitation, cardiac, electrical variation in, 454,
4.55
propagation of the, 454
in muscle, rate of transmission and direction
of, 66
of contraction-wave, 88
of muscle and nerve, conditions which deter-
mine the eflTect of, 42
muscular. See Muscle.
nerve, rate of, 122
respiratory, due to products of muscular

activity given to the blood, .552
vagus, inhibitory power of, on the heart, 453-
457
Excitation-wave, cardiac, 443-446
Excitations, muscular, effect of double, 118, 119
voluntary, more effective than electrical,
126
Excretion, formula of, 260
Excretion of COi by the skin, amount, 282
Excretions defined, 154

of the skin, 281
Exercise, effect of, 80, 81
muscular, effect of preliminary movements
on, 112
heat-production from, amount of energy of,

132, 1.33
promoting endurance and strength of mus-
cles, 80
Exosmosis, 251
Expiration, mechanism of, .506

muscular movements of, 514, 515
Extracts, adrenal, phvsiological action of the,
210
testicular, phvsiological action of, 211
thyroid, therapeutic value of, 208, 209, 901
Eye aberration, 760, 761
accommodation, 752
"astigmatic," 755

axial, 757, 7.58 __ _^

changes produced by the act of, 7.55, 757
theories of the mechanism tif, 7.55. 756
diminished ]iower of, with age, 7(>0
for distant olyects. 752-758
for near objects, 752-758
focal, 752-757

TXDEX.

1033

Eyt', ac'coiiiinoddtion, nicchanism of, 758
iiilhuMico of drujjs upon the, T")?

jHipillary, 7.")7, ITiS

range of, in uiyopicand liypernietropiceyes,
7(jl)
normal, 7">8

to various amounts of lifilit, 771, 772
astifjimatic, 7ti3, 7tJ5

blood-vessels of, methods of observing, 767
centre of rotation of the, 744
constants, methods of determining, 749
curvature of refracting surfaces of the, meth-
ods of determining, 750
defined, 744

dioptric apparatus of the, 746-748, 760
"far-point" of the, 758, 760
hypermetropic, 75!l, 760
images of the, intraocular, 765
iris of the, 768. See Iris.
movements of the, mechanical, 744
muscse volitantes of the, 766
muscles of the, 745, 746
myopic, 759
"near-point," 758, 760
nodal point of the, jwsition of, 751
perception of time intervals by the, 832
positions of the, axial, 745
presbyopic, 760
"reduced," 750
refracting media of the, 748
retina of the. See Retina, also Vision.

Face, respiratory movements of the, 516
Fallopian tube, the, 894

entrance of the spermatozoa into the, mode

of, 903
reception of the ovum by the, mechanism

of, 894
structure and function of, 894
Fat in the body, 1002
formation of, 290
subcutaneous, influence of, on heat-dissipation,
593
Fatigue, eflFect of, on muscular contraction, 111,
112, 127
loss of conductivity of muscle by, 95
muscular, 76

decline of functional activity from, 79
eflect of nutriment on, 78
from functional activity, 77
recuperation from, time required for, 78
of nerves, 79, 80, 97

of voluntary muscular contractions, 126
of the ear to sound, 831
of the nervous sj'stem, 737 ,

of the retina, 790
Fatigue-prodticts of the blood, 78
Fats of the body, 215
absorption of, 2.57

from the stomach, 253
action of gastric juice on, 235

of steapsin in the decomposition of, 244
combustion equivalent of, 303
emulsification of, 245

energy of, potential, determination of, 303
nutritive value of, 215, 289
Feces, color of, 359, 260
composition of, qualitative, 259, 260
— cholesterin, 260
— excretiu, 260
— indigestible material, 259
— inorganic salts, 260
— micro-organisms, 260
— mucus, and epithelial cells, 260
— pigments, 260

— products of bacterial decomposition, 260
— undigested material, 259

Feces, composition of, quantitative, 259
odor of, derivation of the, ;i60
weight of, 259
Ferments, digestive, 217
Ferratin, 972
Ferrosulphide, 972

Fertilization (impregnation), process of, 904-906
Fetal membranes, 911
Fetus, ])osition of, at end of pregnancy, 917

respiratory centre in the, condition of, 572
Fever, body-temperature in, .580
Fevers, influence of, on heat-dissipation, 597

on heat-production, 592
Fibres, muscle-, form and arrangement of, 32
secretory, eflect of stimulation on the, 163, 164
proofs of definite, 163
stimulation of, eflect of, on the nature of

secretion, 163, 164
to the sweat-glands, 199
Fibrin defined, 352
ferment, 3.54, 355, 357
solubility of, 148
" Fibrin-globulin," 354
Fibrinogen, 351

amount of, in the blood, 352
coagulation-temperature of, 351
composition of, 351
occurrence and origin of, 351, 352
reactions of, 351
value of, physiological, 352
"Fibroplastin," 354
"Fictitious meal," experimental, 180
Fission, 878, 879

Fistulse, pancreatic, methods of making, 238
Fluoride, calcium, 967
Fluorine, 953

circulation of, in the body, 9.54
Food, absorption of food-stuffs in articles of, ex-
tent of, 306
calcium salts in the, importance of, 296
circuit taken by and the effect upon the, in

the digestive process, 318
deglutition of, normal process of, 311, 312
digestion of. See Difiestion.
influence of, on heat-production, .591
passage of, along the intestines, time required,

254
potential energy of, 302
proteid, necessity of, to the body, 214, 286
value of inorganic salts as constituents of, 294
variations in character of human, 213
Food-consumption, effect of muscular work upon,

298
Foods, animal and vegetable, analyses of, 216
composition of, 213-219
energy -yielding, 302
"nitrogenous," 214
Food-stuff, amount of energy in a, determina-
tion of, 302
capacity of, for digestion and absorption, .305
heat given off by any one, amount of, 303
Food-stuffs, absorption of, in articles of food, ex-
tent of, 305, 306
albuminoid, nutritive value of, 288
average amount of, required by an adult male,

305
carbohydrates of, nutritive value of, 292
classification of, 213-217
— albuminoids, 215
— carbohydrates, 215
—fats, 215
— proteids, 214
— water and salts, 213, 214
defined, 213

energv-vielding, constituents of, 582
fats of, nutritive value of, 289, 290
nutritive value of, 285-294

1034

INDEX.

Food .stulls, nutritive value of, methods of de-
tonuiiiiii};, 'Ir^^l
plastic or respinitory. defiiu'd, 2S6
potential ciierKV of, liberatiou of, 302
})rotcid, nutritive value of, 285

Korniose, 977

Fovea? centrales, 804

" Fraunliof'er lines," 33tt

Fruit-sugar, 1005

Furfurol, 264

Gall-bi.aubkk, motor nerve-fibres of tlie, 188
Galvani, ex])criment of, on the irritating efl'ect

of the electric current, 43
Galvanometer, the, 136
Galvanotonus, 64, 123
Gamogeuesis, 879
Ganglion-cells, intracardiac, 440
sympathetic, position of, Langley's method of
determining the, 501
Gas, cyanogen, 985

intestinal, composition of, 260
Gases in the lungs, blood, and tissues, 517
of saliva, amount of, 162
respiration of, various, eflects of, 548
respired (O, CO2), conditions afl'ectiug the vol-
ume of, 536
— age, sex, and constitution, 538
— atmospheric pressure, 542
— body-weight and l)<)dy-surface, 537, 538
— comjtosition of insjjired air, 543
— diurnal variations, 539
— food and digestion, 539
— muscular activity, 541
— nervous sys'tem, 542
— rate and depth of respiratory move-
ments, 538
— species, 537
—sunlight, 539
— temperature, 540
Gastric juic(% acid of, 226

action of, digestive, beginning of the, 225
on carbohydrates and fats, 235
on the albuminoids, 235
analvsis of, 226
artificial, 229
chlorides of, reaction in decomposition of

the, 228
color, reaction, and order of, 226
free acid of, 22(), 227
free mineral acids of, color tests for, 227
non-digestion of the stomach by the, 236
non-jmtrefaction of, 226
normal, methods of obtaining, 225
origin of the HCl of, 227
properties and composition of, 226
specific gravity of, 226. See also Secretion.
Gelatin a typical albuminoid, 215

nutritive value of, 288, 289
Gelatoses, 235

Generative organs. See Orgmis.
Germ-cells of the female. See Ova.
of the male. See Spermatozoa.
-plasm, 9.36, 937
Gestation, duration of, 916
Gland, adrenal, 210

mammary, epithelial cells of resting, 202

influence of the uterus on the, 204
pancreatic, histological changes in, during
activity, 174
histological characters of, 172
parotid, cerebral fibres of the, course of, 159
histological structure of, 160
nerve-fibres of the, 159
position of the, 158
pituitary, 211
prostate, 886

Gland, salivary, electrical changes in, during
activity of, 172
secretory, defined. 152
sublingual, histological structure of, 160

])osition of, 15K
submaxillary, histological structure of, 160

position of, 158
tubular, comi)ound, 153
and racemose, 153
Gland-cells, connection between the secretory
nerve-fibres and, 161
fundic, of the stomach, histological character-
istics of, 178
of the gastric mucous membrane, histological

characteristics of, 17^
participation of, in the formation of secre-
tions, 155
pyloric, histological characteristics, 178
Gland-ducts, cutaneous, 197

pancreatic, 238
Gland-secretion, 153, 154

of organic material, conditions determining
the, 164. 1()5
Glands, albuminous, 156

histological changes in, during activity, 167
cutaneous, secretory, 197
gastric, histological changes in the, during

secretion, 182'
influence of the, on the growth of the nervous

system, 737
intestinal, secretion of the, 246
mammary, 201-205

histological changes during secretion, 202
histology of the, 201
mucous, 1.56

changes in, during activity, 167, 169
of Brunner, 184
of C'owper, 885, 887
of Lieberkiihn, 184
of Littre, 886

of the gastric mucous membrane, 178
of the kidney, 189-195
of the liver, secretory, 184-189
of the stomach, secretory, 172, 178-182
salivary, 1.58-172

action of drugs u]ion the, 170

changes in, electrical, during activity, 172

histological, during activity, 167
nerve-fibres of the, 159
number of, 158
secretions of, character of, 160, 220

method. of obtaining, 162
structure of, 160
sebaceous, characteristics of, 197

distribution of, 281
secretory, albuminous, examples of, 157
classification of, 153, 156, 157
mucous, exampk\s of, 157
of the intestines, 181

secretions of the, chemical difl'erences in,
157
seminal, 885
stomach, changes in, during secretion, 182

characteristics of, 178
sublingual, uerve-libres of the, 160
subniaxillarv, nerve-fibres of, 160
sweat-, 198-200
testicular, 211

thyroid, secretions of, 207, 209, 210
Glauber's salt, 9()6
Globulins, .33.5, 1018
Globulose defined, 230, 11.
(Glomerulus, histology of, 190
Glutamin, 1000
Glutoses, 235
Glycerin, 1000
aldehyde, 1001

INDEX.

1035

GlvcLiin, relation of, to glycoKeu-lonuaiion,

2tJSt
Cxlycerose, lUOl
Glvcocoll, J»yl
Glycogen, -'(itJ, UIO.'). 10()8

conversion (»1", to dextrose, how eftected, 209

derived from earboliydrates, functions of, 2G9
from proteid foods, functions of, 270

end -prod nets of, 2()(j

formula, 2t)(>

function of. 209. 270

in animal and vegetable bodies, extent of dis-
tribution of, 270

in the human body, 270

in the liver, 20."), 2(i7-270

in the muscles and other tissues, value of, 270

muscle, conditions atlecting the suyiply in, 270

origin of, 2(>7

reaction of, 26(5
Glycogen-consumptiou in muscular work, 300

in starvation, 301
Glycogen-formation defined, 269
Glycogenic theory, 269
Glycolysis, 293
Glyco-pioteids. 1019
Glycoses, the, 1004

Glycosuria from removal of pancreas, 206, 207
Goitre, treatment of, with thyroid extracts, 209
Graatian follicles, b92
Grammeter, 584

Granules, cell, of the gastric glands, 183
of the pancreatic glands, 172
of the parotid. 167-169

zymogen, 169, 183
Grape-sugar, 1005

Growth-changes of the body, influence of thy-
roid gland on, 737
of the brain, 724-732
Guanidin, 993

glvcolvl methyl, 994
Guanin,'996

H^MATix, 335, 342, 1014
Hsematogeu, 295
Hismatoidin, 342, 1015
Hajmatopoiesis, 343
Haematoporphyriu, 312. 1015
Haemerythriu. 1018
Hsemin* 342, 1014

medico-legal value of. 342
Haemochroiuogeu, 335, 342, 1014

molecular formula of, 336
Haemoglobin, 335, 1014
carbon -monoxide, 336

absorption spectrum of, 342
composition of, .3;i5 ,

compounds of, derivative, 342

— bile-, and urinary pigments, 343
— hsematin, .'i42
— hsematoidin, .342
— hffimatoporphyrin, 342
— hsemin, 342
— hffimoehromogen, 342
— histohsematins, 342
— methsemoglobin, 342
with oxygen and other gases, 366
condition of the, in red blood-corpuscles, 333
crystallization of, 337
decomposition-products of, 335
distribution of, 33.5
molecule of, formula, 335

presence of iron in the, 337
nature and amount of, in red blood-corpuscles,

335
"reduced," 336
absorption spectrum of, 340, 341
Hair-cells of Corti, 822, 824, 825

Hand, contractions of, fatigue from muscular, 77

Harmony, 831

" Harveian circulation," 368

Hawking, .5(>2

IICI, origin of, in the gastric juice. 227

Head, Vii-so-motor nerves of the, 496

Hearing, sense of, 807-i"^33

cortical centres for the, 696,697
special n<-rve of, 679
Heart, beating. See Heart-beat.
method of exjiosing the, 405
position and form of, changes in, 404
blood-pas.sages in the frog's, 471
changes in form and size of, during ventric-
ular systole and diastole, 406
conduction in the, means of. 85
contractions of the, in heat-production, 400,
597
without fatigue, 77
contraction-wave of the, 443
cords of tlie, tendinous, and their uses, 401
excitation-wave of the, 443-446
impulse or apex-beat of the, 409
innervation of the, 440-470
irritability of the, diminished by vagus exci-
tation, 455
lymphatics of the, 477
mammalian, constituents of blood of, 482

nutrition of the, 482
muscle-fibres of the, 84, 85
nerves of the, 450
centres of, 467-470
inhibitory, 452
sensory, 463, 466
vaso-motor, 497
ventricular, 163
nutrition of the, 471-482
pulse-volume of the, 397, .398
pumping mechanism of the, 370
the " pause " or " repose " of the, 414
vagus influence on the, nature of, 457
stimulation on the. effect of, 4.53-457
— action on bulbus arteriosus, 455
— arrest in systole, 456
— changes in the auricle, 455
— changes in the ventricle, 453
— comparative inhibitory power, 456
— diminished irritability of the heart,

455
— effects of varying the stimulus, 4.55
— nature of vagus influence on the heart,

457
— septal nerves in the frog, 456
valves of the, mechanism of, 400-404
ventricle of, average pulse-volume of the

human, 398
voluntary control of the, defined, 469.
.See also Auricles, Ventricles.
Heart and arteries, general changes in the, 404
and vessels, observation of changes of the, in
the open chest, 405
— changes in the beating auricles, 407
— changes in the great arteries, 407
— clianges in the great veins, 407
— changes of position in the beating ven-
tricles, 406
— changes of size and form in the beating
ventricles, 40.5
Heart-beat, alterations in the, by vagus excita-
tion. 4.52-458
changes in the, from closure of the coronary

arteries, 473
conditions influencing the, 413
effect of carbon dioxide on the. 481

of stimulation of augmentor nerves, 460
following cessation of respiration, 553
influence of oxygen on the, 481

1036

IXDEX.

Heart-beat, influence of sex and age on the, 412,
413
inhibition of the, .vagus, 453^.">7
maintenance of the, artificial, Martin's ex-
periment, 75
"negative impulse" of the, 409
of pregnancy, 91G
phenomena of the, 396
refractory period and compensating pause of

the, 447
rhythmic, cause of, 440
solutions maintaining the, 477, 479, 480,481
precautions to be observed in testing, 479
stopping of the, a gradual process, 929
theory of muscular, 442
nerve-, of, 441
Heart-beat and blood-supi)ly, relation of, in the
coronary circulation, 477
and bodv-temperature, relationship between,
579
Heart-beats, frequency of, 412.
Heart-muscle, failure of tetanus in, 122

function and contraction of, 107
Heart-muscles, papillary, and their uses, 402
Heart-nerve, depressor, 4fi4

symi)athetic, 467
Heart-nerves, inhibitory centre of, 467
irradiation, 468
origin of the nerve-fibres, 468
tonus of, 468
Heart-sound, first, acoustic analysis of, 411, 412

second, cause of, 410.
Heat, animal body-, 575-604

body-, 575-580. See Temperature.
sexual, animal. 898
Heat-centres, 599, 713, 714
Heat-dissipation, channels of, 592
mechanism of, 601
physiology of, 584-597
Heat-dyspncea, causation of, 550
Heat-production after death, cause of, 604
by muscular energy, amount of, 132
mechanism of, .59<
physiology of, .597
Heat-regulation of the body. 602
Helico-proteids, 1020
Hemianopsia, 697
Hemi-peptone, 231, 241
Hemorrhage, extent of, with safe recovery, 361

regeneration of blood after, 361
Heredity. 22, 28, 931-942
Hetero-jiroteose, 2.30
Heteroxanthin, 996
Hexoses. 1004

Hibernation, absorption and elimination of
gases during, 542, 546
effect on heat-production of, 592
Hiccough, .563
Histoha-matins, 342, 1018

Histon. action of, in prevention of blood-coagu-
lation, 356
Homothemious animals, 575
Horopter, 804
Hunger, sense of, 845
Hydrate, chloral, 980
Hydration, 947
Hydrazones, 977
Hydrobilirubin. 1015

of the feces, 260, 263
Hvdroearbons or parafiins, saturated, 975
Hydrogen. 943. 944
peioxide of, 919

preparation and properties of, 943, 944
sulphuretted, 950
Hydrolysis, 94K

of enzymes defined, 219
Hydroquinone, 1011

Hydroxide, ethyl, 978
Hypermetropia, 7.59
Hyjierpnua defined, .548
Hypoxanthin, 278, 995

Illusions op touch, 840

oi>tical, 794-803
Images, after-, retinal, 791

intraocular, 765
Imbibition, 948
Imidosarcin, 995
Imido-xanthin, 996
Impulse or apex-beat of the heart, 409
Incus, the, 810, 811
Indol, 260, 280, lOlS

P-methyl. 1013
Induction apparatus, 48, 54
Inheritance, facts of, 931

of acquired characters, 934

of disease, 9.35

of latent characters, 932, 933

theories of, 936
Inhibition, cardiac, seat of the power of, 4.52
vagus, 4.52-457

of reflex action of central system, 667

respiratory, 567, 570, 571
Innervation, dermal, 673

of the blood-vessels, 482-501

of the heart, 440-470

of the jaw-muscles, 310

of the lungs, 573
Inosit, 1014

Insane, brain-weight of the, 722
Inspiration, mechanism of, 506

muscles of. .506, 513
Inspiration and expiration, relative periods o^

variations in, .532
Intensit.v of light, 778, 785
Intestine, large, absorption in the, 254
digestion in the, 248
gas of the, composition of, 260

muscl(!-tissue of the, contraction -wave of, 309

secretion of the, 246

small, absorption in the, 253
Intestines, decomposition in the, bacterial, 248

glands of the. secretory, 184

movements of the, 320

— jiendular movements, 322
— I.eristalsis, 320-322
conditions influencing the, 323

nerves of the, extrinsic, 322
vaso-motor, 498
Iodine, 9.53
Iris, the, 768

movements of the, muscular, < il

muscles of the, 769
Iron, 971

compounds of, detection of, 972

in animal and vegetable foods, absorption and
excretion of, 295

in hsemoglobin, presence of, 337

in the body, 972

in the production of liaMuoglobin, 26.3, 295
" Iron-free " ha-matin, .342
Irradiation, retinal, 794
Irritability, 38-81

alterations of electrotonic, 71

induced by anelcctrotonic and katelectro-
tonic changes, 71

anodic, 6f<, 69. 70, 72

degree of. method of ascertaining, 38

dependent ujion oxygen-supply, 73, 74

duration of, as aflected by temperature, 66

efl'ect of enforced rest on, 81
of exercise on, 80

of fretjnencv of application of stimulus ou,
72

INDEX.

lO'M

Irritability, effect on, from separation of nerves
from the ffiitral mrvoiis system, 75
efficacy ot" tlic hlood to preserve, 74, 75
influence of tlie lilood on, 73
kathodic, ti«, m, 70, 72
loss of, by separation of muscles, 76

by separation of nerves, 75, 7t>
of muscle, defined, :{.">

curare experinunt, 41
independent, 40
of muscles and nerves, conditions which deter-
mine, (>4
effect of heat and cold on, 66
of nerves, '^S-A

— chemical irritation, 40
— electriial irritation, 40
— mechanical irritation, 40
— thermal irritation, 40
curare, experiment for determining, 40, 41
influence of constant , electric currents on
the, G9
result of change in the chemical constitution

of muscles and nerves, 67, 68
vital, definition of, 18
Irritability and conductivity of nerve-fibres, 624

and contractility of ova, 37, 38
Irritant, electric current as a muscle and nerve,

43-60. See Electric current.
Irritants, classes of, 38
effect of, study rf the, 39
efficiency of, on muscles and nerves, 43
influence of, upon the irritability of muscle
and nerve, 6.5
— effect of chemicals and drugs, 67
— effect of electric current upon the mus-
cles, 68
— effect of electric current upon nerves, 69
— effect of temperature, 66
— effect of the frequent application of the

stimulus on irritability, 72
— mechanical agencies, 65
relative value of different, 38
Irritation, direct, of muscle-protoplasm, proofs
of, 42
nerve, by electric current, Du Bois-Reymond's
law, 47
frequency of stimuli and effect of, 65
of nerve and muscle, result of, conditions
determining, 42
"Isodynamic equivalent," 304
Isomaltose, 1007
Iso-nitril, an, defined, 985

Jauxdice, causation of, 189

Jaw movements, muscles concerned in the, 310

Joint-movements, classes of, 856

— ball-and-socket joint, 857

— hinge joints, 856

— saddle joint, 857

— sliding joints, 856
Joints, union of bones by, 855

Kaeyokinesis defined, 19, 20
Katabolism defined, 20

of animal protoplasm, 20
Katelectrotonus, 69
Kathode defined, 44

phvsical and phvsiological defined, 62 '
Kera'tin, 1020
Ketone, dimethvl, 982
Kidney, 189, 273

Kidneys, blood-flow through the, 195
action of dinretics on the, 195
regulation of, by the vaso-motor nerves,
196, 197

glands of the, secretory, 189-195

nerves of the, vaso-motor, 498

Knee-kick, muscular reaction involved, 649-
652
reinforced nerve-impulses of, 665-686
Kymograph, the, 381

Labor, nature of, 919, 920

stages of, 917-919. See also Parturition.
Labor-pains. 918
Labyrinth, the, 815
meml)ranons, 815
fluids of, .517

transmission of vibrations through the, 820
osseous, structure of, 815, 816
Lactates in human urine. 278
Lacteals, absorption of fat by the, 258
Lactose, 202, 1006

relations of, to glycogen-formation, 268
Laiiguuge defined, 874
Lanolin, 198

Larynx, appearance of the, laryngoscopic, 869
cartilages of the, 865
movements of the, 516
muscles of the, 865-868
nerve-supply of the, 868
self-examination of, method of, 869
stricture of, 861-869
ventricular bands of, 862, 863
Latent cliaracters, inherited human, 932
heat, iMrt
period defined, 101

differentiation of electrical and mechanical,

102
in retinal sensation, 789
of muscular contraction, 113, 114
Laughing, 562
Lecithin, 265, 1001
Lens, achromatic, discoverv of the principle of

the, 762
Leucin, 242, 983

Leucocytes, blood-, action of, 346, 374
classification of, 345, 346
— lymphocytes, 345
— mononuclear, 346
— polymorphous or poly nucleated, 346
emigration of, 346, 376
functions of, C '5, 346
movements of, 35

amoeboid, 346
origin of, .347
physiology of, 345
" Leuconuclein," 356
Levulose, 218, 1005

Life, phenomena of, hypotheses of, 25, 26
Light, "dispersion" of, 778
intensity of, 778, 785
modifications r^', 779
— color, 77j
— color-blindness, 784
— color-mixture, 779
— color-theories, 781
— intensity, 785
— luminosity of colors, 786
— saturation, 788
retinal, changes produced by, 776
saturation of, 7 . .O, 7C8
sensation of, retinal, 777, 778
Limbs, nerves of the, vaso-motor, 501
Lipochromes, 1015
Liquor amnii, function of, 911

quantity and composition of, 911
Liver, blood-flow in the, relation of the secretion
of bile to the, 187
existence of secretory nerves to the, 188
extirpation of, effect of, on urea formation, 276,

277
functions of the, 260
glands of the, secretory, 184-189

1038

INDEX.

Liver, glycogen in tlio, conditions affecting the
.sujiply of. 270
function of, "Jfiii
occurrence and origin of, "JOO, 267

nerves of the, vaso-iuotor, 49H

relations of tlie, to the circulation, 276

secretions of the, IK"), 'JO.j

structure of the, histological, 184

urea in the. formation of, 271

urea-forming power of the, 271, 272
Liver and sjileen, physiology of, 260-272
Liver-cells. t)lood-sui)ply of, sources of, 187

chemical changes hy the, 184

formation of urea by the, 271, 272, 275

glvcogen of the, 267

pllvsiologv of the, 260. 261

relations of the, to the ducts, 184, 185

secretions formed by the, 205, 206
Locomotion, body-, 860

of the spermatozoa, 883, 903

mechanisms of, 8.")5-861
Loop of Ilenle, 189. 190, 192
Lumen of the secretory cells, 161
Lung-pressure, .')04, .^05, 514, 516
Lung-ventilation, artificial, laboratory method

of, 7m.\, 554, 561
Lungs, action of the continuous pull of the, on
the blood-fiow, 387

air in the, admixture and jjurification of, 522
amount of, in adult human. 517

alveoli of the. number and size of, 504

blood-tluw through the, 395

cai>illaries of the, 504

elasticity of the, 504

expansion of, in the new-born. .504, 573

fetal, atelectatic condition of, 504
in utero, 573

gases in the, alterations in the, 517

inflation of the, artificial, 554

iunervation of the, .573

nerves of the, vaso-motor. 466

O and CO2 absorbed and eliminated by the,
quantity of. 519
diffusion in the. forces concerned in, 520

structure of the. .504
Lunuhe of the semilunar valves, 403
Lutein, 1015
Lymi>h, .36.3-367

aspiration of, thoracic, 439

composition of, 363

formation of, filtration-and-diffusion theory
of, 362-367

movement of, 362, 363, 4.37-439

occurrence of, .362

origin of the, 4.3H
Lymph-flow, influence of body-movements upon

the, 4.39
Lymph-hearts, absence of, in man. 438
Lymph-pressure, differences of, 4:J8
Lymph-valves, body-movements and the, 439
Lymphatic system, 437
Lymphocvtes, 345
Lvsatin, 994
Lvsatinin, 277, 994
Lysin, 994

Magnesium, 970

carbonates. 971

phf>sphates. 971
Malleus, the, 810, 811
Maltose. 218, 247. 1007
Mammalia, removal of cerebral hemispheres of,

effect of, 710
Mammary glands. See Glandn.
Man, reproductive power of, waning period, 927
Manometer, differential, 422, 423

elastic, 418, 419

Manometer, mercurial, 379, 380

Manometers, Uales', 378

Marsh-gas, 976

Mas.sage. effect of, on muscular fatigue, 79

Mastication, 310

normal salivary flow during, the result of re-
flex action, 171

taste-perception developed b3', 852
Maturation of the ovum. 889. 891

of the spermatozoon. Ks4. 892
Meats as a source of proteid-supply, 305
Meconium, biliary salts in, 987
Medullary sheath, 36. 151
Medullation in central nervous .system, 616

of nerve-fibres. 614, 615
significance of, 729
Melanins. 1015
Menopause, the, 898, 927
Menstruation. 895

amount of blood discharged, 896

appearance of, time of. 927

c(»nditions aflecting. 897

duration and onset. 896-898

physiology of. comparative, 898

process oC 895, 896

theory of, 898, 899
Mercaptan. methvl. 9/<
Metabolism, bcKly-. 20, 282. .302
conditions influencing. 298
— effect of muscular work, 298
— effect of starvation, 301
— efl'ect of variations in tem])erature, 300
— metabolism during sleep, .300
total, determination of, 282-284

in the ence]dialon in old age, 743

in the nerve-cells in old age, 742

of carbon, 962

of cell-body, 626

of sulphur, 951
Methffimoglobin, 342, 1014
Methane. 975, 976
Methyl aldehyde, 977

compounds. 976

cyanide, 985

mercaptan, 977

seleuide, 978

telluridc. 978
Methylamine, 984
" Micellfe." 25

Microcei)halics. the brain of, 711, 720
Micturition, .327

control of the process of, 329

mechanism of normal. 32H

— movements of the bladder, 328
— movements of the ureters, 327
— nervous mechanism of the bladder, 330

normal, a reflex act, .329, 330
" ilicturition-centre." .329
Milk. conipositi(m of, 201

secretion of normal, 204
Milk-coagulation, rennin process, 234
Milk-<lucts of the mamniiP, 201
Milk-fat. constituents and formation of, 201, 203
Milk-formation, changes in the cells of alveoli

of mammary gland during, 202
Milk-plasma, constituents of. 201, 202
Milk-sjilts. secretion of, epithelial. 202
Milk-sugar or lacto.se, 202, 247, 1006
Mitosis. 20
Molecule, protoid. size of, 1021

protoplasmic, instability of, 23, 24
^Monoxide, carbon, fKiO
Morula. fHl9

Mouth, temperature of the. 577
Mucin. 261

bile. 265

formation and function of, 221

INDEX.

1039

Mucin of >fol'li'l-f<'ll'<. formation of, 157, 15ti

of saliva, amount of, I(j-J
Mucins. lOlil

Mucous glands. See Glands.
membrane, gastric, composition of the secre-
tion of, 179
glands of the, structure, 178
irritation of, ti ininrature-sensation not

discriminated by, 842
irritation of, touch-sensation not induced

by, 840
olfactory, 850
Murexid, 998
Muscpe. volitantes, 766
Musearin, 986

action of, on the lieart, 442
Muscle, "after-loaded," 108

altered condition of, after contraction, 109
change in, iu rigor mortis, 144
conijiosition of, '.i'Z
conduction in both directions in, 86
conductivity of, loss and recovery of, 83
contraction of. See Contmction.
contraction-wave of, length of, methods of
determining, 90
rate of transmission of, 88-90
death of, chemical change in, 144
digastric, function of, 310
dying, circumscribed contraction of, 42
etlect of mechanical stimulus on, 93
elasticity of, 104

changes in the. conditions influencing, 105
excitation of, effect of rate, on height and
form of contraction, 109
— continuous contractions caused by con-
tinuous excitation, 123
— effect of frequent excitation on the
height of separate muscular contrac-
tions, 109
— eflect of frequent excitation to produce

tetanus, 114
— effect of frequent excitations upon the

form of separate contractions, 113
— effect of exceedingly rapid excitations,

122
— effect of gradually increasing the rate

of excitation, 121
— eflect of, upon the form of separate con-
tractions, 113, 114
— explanation of the great height of

tetanic contractions, 118
— number of excitations required to tetan-

ize, 121
— relative intensity of tetanus and single

contractions, 122
— summary of the efl'ects of rapid excita-
tion that produce tetanus, 121
excitations, double, effect of, 118, 119
extensibility and elasticity of, 104-106

a protection against injury, 106
gases of, 150

glycogenetic function of, 270
importance of the blood-supply to the, 75

of the circulation to the, 73
injured, "diminution effect" upon, 141

tetanized, changes of electric potential in,
140
intestinal, of the fly, structure of, 84
irritability of, independent, 40-42
curare experiment, 41
conditions which determine the effect of, 42
"loaded," 108

masseter, function of the, 310
omohyoid and pectoralis, of turtle, contraction

and function of, 107
phenomena, electric, theories of, 1.38
pterygoid, external, function of, 310

Muscle, pterygoid, internal, function, 310
reaction of human, to electric currents, a

means of diagnosis, 58
rest of, neces.sjiry to restoration of normal

condition, 109
stapediu.s, 814

stretching of, effect of, on irritability, G6
striated, conductivity of, 82

optical pr<jperties of, during rest and action,

102
contraction of, rapidity of, 308
temporal, functifjii of, 310
tensor-lynipani, Ml4

tetanized, amount of shortening. in, 122
Muscle and nerve, chemistry of, 144-151

conditions which determine the efficiency of

irritants on, 43
effect of constant electric current on the

irritability and conductivity of, 61
electrical phenomena in, i:j4-143
excitation of. conditions which determine

the eflect of, 42
influences favoring the maintenance of the
normal physiological condition of, 73
irritability of, influence of irritants upon

the, 65
irritant, electric i^urrent as an, effect of,

43-60
irritating effect of induced electric currents,
48
of the electric current, 43
result of, conditions determining the, 42
physiology of, general, 32
reflex movements of, 41
stimulating effects of making and breaking
the direct electric current, 50
Muscle -contraction, influences affecting the
activity and character of the, 106
latent period' of, 101, 113, 114. See Contrac-
tion.
Muscle-contractions, graphic method of study,

98-101
Muscle-fibre, structure of, histological, 103
Muscle-fibres, condtiction in, rate of, 92
Muscle-injury, electrical current of, 138
Muscle-plasma, 146, 147

Muscle-protoplasm, direct irritation of, proofs of,
42
irritability of, 35, 40-42
Muscle-serum, constituents of, 148-150
Muscle-sounds, 124
iluscle-spindles, 845

Muscle-tissue of the bladder, histology of, 328
of the intestines, contraction -wave of, 309
of the ureter, contraction-wave of, 309
plain, of the alimentary canal, 307
contraction of, 308, 310
" tone " of, defined, 309
smooth, conductivity of, 82
structure of, 32, 33
Muscle-tonus, 133

Muscles, abdominal, contraction of the, spas-
modic, influence of, in vomiting, 325
functions of, 515
action of the, in standing, 859 _

upon the bones, method of, 857
capacity of the, for work or exercise, 77
chemical changes in, 73
classes of, 33
concerned in the act of vomiting, 326

in the movements of the jaw, 310
condition of, following removal of the cere-
bellum, 714
conduction in, 84

rate of, 88-90
contraction in different, rate of, with their
function, 107

1040

INDEX.

Musclrs, ort'iitin «>f, 279
ett'ect of electric current upon, 68
endurance of, cU-lined, 80
enforced rest of, etlect of, 81
expinitory, cliief, 525

actioUfi of, 515
eye, 745, 74G

nerve-supply of the, 746
fatigue of, etlect of, 7li
glycotieu in, value of, 270
inspiratory and expiratory, chief, 506, 513
intercostal, actions of, exemplitied, 510-512

functions of, 510, 512, 513, 515
intestinal, histology of, 320
intrinsic laryngeal, actions and origin of,

8()6-8(!8
involuntary, delined, 33
jaw, innervation of, mode of, 310
laryngeal, intrinsic, 86t>-868

— aryteno-epiglottidian, 867, 868
— arytenoid, 867
— crico-arytenoid, lateral, 866
— crico-arytenoid, posterior, 866, 867
— crico-thyroid, 866
— thyro-arytenoid, 868
levator, functions of the, 510, 513

ani, function of, 515
movements of the rib, controlling the, 509
myosin of, 1018
nerves of the, vaso-motor, 501
non-striated, 33
of inspiration, contraction of, action on the

blood-flow of, 387
of the iris, 769
of the larynx, 865-868
of the middle ear, 814
of the vagina, 900
oxidization jjroccsses of, 73, 74
quadrati luniborum, function of, 507, 513
reaction of. to electric current, 57
rectiil, physiology of, 324
recuperative power of, 77-79
relations between separate contractions and

tetanus of, 123
scaleni, function of, 509, 513
serrati postici, functions of, 510-513
skeletal, 84
and the venous valves, action on the blood-
flow of, 387
relation of, to heat-production, 597
striated or striped, 33

apj)earance of, after contraction, 104
contractions of, diflerences in duration of.

106
excitation of, rate of, 122
function of, 98

properties of, optical, during rest and action,
102
structure of, 102-104
ten.sion of. sense-perception of the, 844
thoracic, 512, 513

triangulares sterni, function of, 515
uterine, 895

use and disuse of, efiect of, 80
voluntary, defined, 3.3
Muscles and nerves, changes in. influenced by
the eflects of batterj* currents, 69
conduction of, protoplasmic continuity
essential to, 82
in both directions, 86
influences which alter the rate and

strength of the process, 92
isolated, 83
rate of, 88
efiect of influences which result from func-
tional activity of, 76
— ett'ect of enforced rest, 81

Muscles and nerves :

— eflect of use and disuse, 80
— fatigue of muscles, 76
— fatigue of nerves, 79
irritabilitv of, conditions which determine
the, 64
etfect of heat and cold on the, 66
transmission of excitation to, by end-organs,
H5
Muscular activity, dyspncua of, 552

eflict of, on tiie resi)iratory quotient, 546
influence of, on body-temperature, 578
influence of, on heat-dissiiiation, 595
on the volume of gases respired, .541
mechanisms, s])ecial ])liysiology of, 85.5-877
Musical note, highest, number of impulses pro-
ducing the, 778
Mydriatics, 771
Myogram, the, 50, 101

of simple muscle-contraction, 101
Myogniph, 50, 51, 99

double, experiments with the, 52
Myopia, 759
Myosin, 147, 148
Myotics. 771
Myrosin, 218

Myxoedema, treatment of, with thyroid extracts,
208, 209

Nativk albumins, 349
" Negative variation current," 140
Nerve, auditory, 679, 818
chorda tympani, course of the, 159, 160
conductivity of, effect of .stretching on, 93
depressor, effects of stimulation of the, 464
dying, eflect of mechanical stimulation on, 93
end-organs of, importance of. 839
glosso-pharyngeal, excitation of the, eflect on

respiratory movements of, 570
irritation of, chemical, 40

conditions determining the eflect of, 42
electrical, 40
mechanical, 40
temperatural, 47
thermal, 40
layngeal, superior, excitation of the, eflect of^

on respiratory movements, 570
of Jacobson, 159
olfactory, 682
optic, 679

relations of afferent fibres in the, 680
pressure upon a. irritating eflect of. 47
reaction of a, eflect of making and breaking

induction shocks on the, 49
relation of the strength of a current to the

irritating eflect upon a. test of. 54
sen.sory, excitation of, efl'ect of mechanical, 65
separation of a. break in conductivity by, 82
stretching a. effect of. on irritability, 65
sympathetic, effect of stimulation of the, 467
ulnar, effect of jiressurc on the. 93

excifcition of the, eflect of ice-water on the,66
vagus, of the dog, morphology of, 450
Nerve and mn.scle protoplasm, resemblance of,

30, 37
Nerve-cell, anatomical characteristics of, 607
bodies, sizes and shai>es of, 607, 608

volume relations of, 608
body, im])ulses on the, effect of, 622
metabolism of. 6C<»
points of the. at which the nerve-impulse

can be aroused, 624
shape of, sigTiificance of, 622
structure of, 608
chemical changes in, 626
defined, 607
fatigue of, influence of, 628

INDEX.

1041

Nerve-cell, maturing of the, 611

nutritiuii of thi', iufluciices acting on the,

62U «:«»
physiology of the, (iOT-fi.'JJt
single, nerve-iMipiilso, vvitliin a, 618
spinal-cord, volume of, (!11
stimuli neeessary to elicit a response in a,

nuinlter of, 62.")
tropiiic iulliieiices on the, 627
Nerve-cells, ehanges in, due to age, 617
classes of, defined, 641
cytoplasm of, ciuinges in the, 617
disuse of, elfeet of, upon reflex action of

nerve-lihres, iii'A^
efferent, sympathetic relations of the, 654
forms of, (>07

groups of, in central nervous system, 639
growtii of, 610

impulses of, rate of discharge of, 623
in central nervous system, number of, 731
increase in the mass of, 731

in the number of, in central nervous sys-
tem, 727, 728
location of, 3()
medulJation of, 614
metal>olism in, in old age, 742
peculiarilics of, 6(t8
size and function of, (ilO

in ditfcreiit animals, 609
types of, 612, 613
unipolar, 441
vaso-motor, 4H8, 489
Nerve-elements, classification of, 641

degeneration and regeneration of, 633
enlargement in tlie, average, 731
functional, increase in the number of, in
central system, 727
Nerve-fibre, axis-cylinder, conductivity of, 82
branches, growth of, 613
chemical reaction of, 151
composition of, 150, 151
defined, 607

degeneration and regeneration of, 52, 82
injured, absorption-process following, 82, 83

recovery, functional, 83
irritability and conductivity of, 624
Nerve-fibres, afferent or centripetal, 36
of spinal cord, 645
arrangement of, 36
association, cortical, 697
auditory, of the cochlea, 821

terminations of, 815-818
cardiac inhibitory, origin of, 468
cerebral, of the salivary glands, 1.59, 160

varieties of, 729
cholesterin of, 264
classes of, 36

— medullated, 36
— non-mednllatud, 36
constrictor, of the pupils, 769, 770
cortical, increase in the, 729
decussation of, 647, 680, 681, 768
degeneration of, after hemisection of cord,
669
in the central system, 6.34
of non-medulla'ted, 633
of nucleated portion of, 635
secondary, of cortical, 687
dependence of, on the blood-supply, 74
diameters of the neurons of, 613
dilator, of the pupils, 769, 770
dorsal root, number of, 673
efferent or centrifugal, ,36
extrinsic, intestinal, .322, 323

of the stomach muscles, 316, 319, 320
function of, 36
"germinal," 688

Nerve-fibres, glyco-secretory, 188

growth of the medullary sheath of, 615

lecithin of, 265

meduilation of, <)14, til."), 729

motor, of the gall-bladder, 188

of liver-ci^lls, existence of, 185

of salivary glands, l.">9

of sweat-glands, 199

of the bladder, 330

of tlu! eye-muscles, 746

of the jiarotid, 159

of the skin, 281, 835

of the sphincter ani, 324

of the spleen, 272, 273

of the stomach, 316

olfactory, 8.50

optic, insensibility of, to light, 774

number of, 770
pressor and dejjressor, 494
regeneration of, .58, 82, 6.36
relation of medullary sheath and axis-cyl-
inder of, to the central system, (il6
to the p(5ri)theral nervous system, 615
secretory, action of, upon the formation of
bile, 188
connection between the gland-cells and

the, l6l
in the pancreas, ])roof of, 173, 174
normal function of the, in the sympa-
thetic, 171
of the kidney, 191
termination of, 161
theory of, 1<)5, 166
varieties of, l.")5
sensory, ending of, in the .skin, 835

of the tongue, 8.52
stimulation and changes in temperature on,

effect of, 614, 615
structure of, 36
trophic, theory of, 16.5, 166
thermogenic, 598
vaso-constrictor of the kidneys, action of,

196, 197
vaso-dilator of the kidneys, action of, 196,

197
vaso-motor of the lungs, 574
Nerve-impulse, afferent, of the cortex composite
character of, 700
defined, 40, 611
direction of the, 619
extension of the, conditions surrounding

the, 619
pathways of the, double, 621
points in the cell-body at which the, can be

aroused, 624
rate of, 618, 738, 7.39

theories of the passage of the, in the cen-
tral system, 644
within a single nerve-cell, 618
Nerve-impulses, arrangement of, in the central
system, 621
course of the, on leaving the cortex, 695
effect of, on the cell-body, 622
efferent, reaction of, 660
olfactorv, pathwav of, 682'
pathways of the, (318, 647-657, 668, 682
sensory, pathways of, 668
Nerve-injury, electrical current of, 139
Nerve-muscle preparation, 49
Nerve-roots, afferent, 644, 645
Nerve-supply of the larynx, 868
Nerve-theory of heart-beat, 441
Nerve-tissnes, specific gravity of, 7.32
Nerve-tracts in the central system, 668
Nerve-trunks, direct irritation of, excites no
sensations of temperature and touch,
841, 842

1042

INDEX.

Nene-tniiiks, conduction in, 83
Nerves, action of the, on the pancreatic secre-
tion, 173
auditory, of the cochlea, ftJl
aufimentor, course of, in various animals, 459

stiniuhition of, ettects of, 4(30
branchiii}; of, 84
cardiac, 430

— au^nientor nerves, 458
— centrifugal nerves, 462
— centriin'tal nerves, 463
— inhibitory nerves, 452
centres of the, 467-47U
— augnientor centre, 469
— inhibitory centre, 467
— intra-ventricular centre, 470
— peripheral reflex centres, 470
division of the, 451
inhibitory, 452
chemical chaufjes in, by conduction, 96
chemistry of, 150
concerned in the reflex action of deglutition,

314
conduction in both directions in, 86

experimental methods of determining, 87
rate of, 90

— in motor nerves, 91
— in sensory nerves, 92
conductivity of, efl'ect of pressure upon, 93

effect of temperature on the, 93
cutaneous, excitation of the, effect on the

respiratory movements of, 571
effect of electric current upon, 69
on normal humaTi, 62
of sudden alterations in the intensity of
stimuli, 4(), 47
electro-motive force of, 139
extrinsic, of the intestines, 322

to the stomach muscles, 319
fatigue of, l)y conduction, 79, 97
influence of the, ou the gastric secretion, 180
inhibitory, defined, 36
and augmentor. Pawlow's classification, 462
effect of simultaneous stimulation of, 461
intracardiac, 440

effects of stimulation of the, 463
irritability of, 38-40

testing anelectrotonic and katelectrotonic
alterations of, 69, 70
irritation of, by electrical current, Du Bois-

Reymond's law, 47
liberation of heat in, by conduction, 96
motor, conduction in human, 91, 92
defined, 36

of the bile-vessels, 188
of common sensation, 843
of special sense, effect of stimulation of the,

467
of the eye, 769-772
of the spleen, 499
olfactory, excitation of the, effect of, on the

respiratory movements, 571
pancreatic, 172

phrenic, result of section of, 571
pueumogastric, 573
functions of, 568-570
pulnumary branches of, 573, 574
reaction of, to currents of gradually increas-
ing strength, 64
respiratory, afferent, 568

efferent, 571
sciatic and sensory, excitation of the, effect

of, on respiration, 571
secretory, 36. 162-164

action of drugs upon the, 170
existence of, to the liver, 188
of the pancreas, 173

Nerves, sensory, defined, 36
of the muscles, 844, 845
stimulation of the, effect of, 466
septal, effect of vagus excitation on tlie, of a

frog, 456
splanchnic, excitation of the, effect of, on the

respiration, 571
sweat-, 19!»

sympathetic, pulmonary, 574
temperature, 840-842
thermogenic, 598
trigeminal, excitation of the, effect on the

respiration of, 591
" trophic." defined, 36
vagus, stimulation of the, effects of, 463
vaso-dilator, early demonstration of, 484
vaso-motor, defined, 36

differences between the constrictors and

dilators of the, 487
early exi)erimental demonstrations of, 482-

486
observation of, methods of, 486
origin and course of, 488
reflex excitation of, 492
topography of, 494
— of the back, 501
—of tlie bladder, 500
— of the brain, 494

— of the external generative organs, 499
—of the head, 496
—of the heart, 497

— of the internal generative organs, 500
— of the intestines, 498
—of the kidnevs, 498
—of the limbs, 501
—of the liver, 498
— of the lungs, 496
— of the muscles, 501
— of the portal system, 501 '

— of the spleen, 499
—of the tail. 501
ventricular, 463
distribution of, 440
Nerves and muscles of cold-blooded animals,
effect of irritants l)est studied l).y, 39
Nervous system, alterations in the, due to preg-
nancy, 916
central, 605-743

activities of the, summary of, 656

anatomy of the, physiological, 644

architecture of, general, 639

asymmetry of, 723

cells in the, number of, 731

circulation in the, 734-737

conditions of the, during sleep, 740

conditions of the, favoring sleep, 739

connections between cells in the, 643

constituents of the, 716

development in different parts of the,

relative, 642
development of the, defective, 734
effect of fatigue on the, 737
effect of loss of .sleep on the, 742
effect of removal of cerebral hemispheres,

705-715
effect of starvation on the, 737
influence of tlie. on gastric secretion, 180
growth and organization, 606
growtii of, influence of glands on the, 737
medullation in, 616
nerve-elements of the, cla.ssification of,

641
nerve-elements of the, increa.se in num-
ber of functional. 727
nerve-fibres in the, degeneration of, 634,

669, 670
nerve-impulses of tlie, arrangement of,621

TNDEX.

i()4;i

NtTVOussvstL'iii, mrvi'-iniiuilsfs of tlu', diffusion
'of, (MS, (;r)-2, (i.j:{
nerve-iinimlsis i»l' tlie, evideucc of con-
tinuous outfjoing of, 6.55
uerve-impulses of tlit-, theories of the

passage of till', (>44
ncrve-traots in tht-, (ids
nerves of the, specific afferent, 673
— auditory, 67!>
— olfacfory, 682
— optic, <)7y

— special nerves of pain, 674
old age of the, 742, 743
organization of, 642, 734
organization and nutrition of the, 732-739
pathways of the, 64s. 670, 67.5
phenomena of the, involving conscious-
ness, 60(i
physiology of the, comparative, 703-705
pn'ncsscs in the, time taken in, 738
reaction of the efferent impulses, 660
reactions of, from fractures of the spinal

cord, 660
reactions of, during sleep, 740, 741
reactions of the spinal cord, segmental, 6.58
reflex action of, 6.57-667
relations between body-weight and, 719
stimulation of the. conditions of, 647
strength of stimulus and strength of re-
sponses of. 64S
subdivisions of, 60.5
symmetry of, bilateral, 645, 723
unity of "the, 60.5, 639
sweat-centres in, 200
volume of the, 731
changes in the, dependent upon age, 715
control of the mammary secretion by the,

203
disturbances of the, influence of, on body-
temperature, 580
influence of the, on functional activity, 81

on heat-dissipation, 596
physiology of the, as a whole, 715
sympathetic, nerve-impulses in the

sion of, 6.54
weight of the, interpretations of, 717
Neuridin, 986
Neurilemma, 36, 150
Neurin, 986

Neuroblast, the, 610, 611
Neuroblasts, polarization of, 611
Neuro-keratin, 151, 1020

Neuron, axis-cylinder of the, constitution of, 614
defined, 607

form of the, as a means of classification, 611
structure of the, 607
volume of the, 609
Neurons, medullation of, 614-616

size of. in different animals, 609
Neutrophiles, 345

New-born, body-temperature of, .577
expansion of the lungs in, 504, 573
respiratory movements of, 573
Nicotin, action of, upon the salivary glands and

their secretions, ITT)
Nipple, origin of the, 201
Nitril defined, 985
Nitrogen, 954
compounds of the alcohol radicals with, 984

with oxygen, 9.56
effect of respiration of. .548
equilibrium, defined, 284
in the body, 956
tension of, .525
Nitrogenous material, determination of amount

destroyed in the body, 282
" Nceud vital," 564

diffu-

Noises, 832

Non-nitrogenous material, determination ot

amount destroyed in the body, 283
Nose, tracts of tlie, 849
Notes, musical, quality of, 827, 828
Nuclein, 1019
Nucleo-albuniins, 1019
Nucleo-histon, 347, .356, 1019, 1020
Nucleo-proteids, 1019
Nucleus, cell-, protoplasm of the, differentiation

from cytoplasm of, 22
Nutriment, effect of, on muscular fatigue,^ 78
Nutrition, body-, bile not essential for, 261
defined. 18, 19, 213

of the embryo, 913

of the placental process of, 914, 915

of the heart, 461-482

Odors, detection of, by sensations of smell, 8.50,

851
skin, racial and individual, 851
(l^sophagus, deglutition in the, 312
Oil, emulsions of, artificial, 245
Old age. See Age.
Olefines, amines of the, 986
Oncometer, Roy's, 196
Ophthalmometer, the, 7.50, 765
Ophthalmoscope, the, 772
" Optogram," 776
Organ of Corti. See Corti.
Organization. See Central Nervous System.
Organs, reproductive, female, 887-901
male, 882-887

mechanical and pathological changes in the
female, due to pregnancy, 915, 916
respiratory. .503
secretory, internal, 205-211
sexual, classification of, 882
' vocal, 107, 870-877
Ornithin. 994
Osazones, 1004
Osmometer, 251
Osmosis, 2.50-252
Ossicles, auditory, 810
function of, 813
ligaments of the, 811
Otoliths or otoconia, 819, 849
Ova, irritability and contractility of, 37, 38
movements of, amoeboid, 37, 38
primitive, number of, in the ovaries, 892
Ovaries, primitive ova in, number of, 892

structure of the, 892
Ovary, the, 892
Overtones, musical, 827

inharmonic, 830
Ovulation, 892-894
Ovum, the, 888

action of the spermatozoa in entering the, 904
chemistry of the, 889

chromosomes of, power of hereditary transmis-
sion due to the, 22, 28
fertilization of, 904-906
growth of the, uterine, 911
human and fowl's, compared, 888, 913
discovery of, 888
form and size of, 888
structure of, 888, 889
impregnation of, movements during the, 37, 38
maturation of the, 889-891
nucleolus of the, 889
nucleus of the, 888
nutrition of the, mode of, 37
protoplasm of, 37

reception of the, by the Fallopian tube, 894
segmentation of the, 907, 908
Oxidation, body-, Hoppe-Seyler's theory of, 949
Traube's theory of causation, 946

1044

INDEX.

Oxick'. iiitrif, 95(1

uitroiis, !)")()
Oxvl'eii/.ol, KtlO
Oxyrholiii. Of^U
Oxytri'ii, !>ll
jibsorptioii-ciiinK'itios of tissues for, 530

-coi'lliciiiit of blood lor, 523
conipouiuls, 5)56, 958
ottict of nspiration of, 548
iiiflueiu'c of, on the heart-beat, 481
of uuisclo, 150

preparation and properties of, 945
reduction defined, 946
Oxygen and CO2, ditfusion of, in the luugs,
forces concerned in, 520
interchange of, between the alveoli and the
blood, 522, 525
between the blood and tissues, 527
jtroportion of, in the blood, 519

in room-ventilation, 547
([uantity of, absorbed and eliminated, 518
tension of, 523

volumes of, respired, 53fi
Oxygen, CO2, and N, absorption-coefficients of
water for, 522
and other gases, compounds of haemoglobin
with, 33(5
Oxygeu-dysimcea, cause of, 550, 551
()xyhtemoglol)iii, 336

absorption spectrum of, 339, 340
Oxyphiles, 345
Ozone, 946, 947

Pacinian bodies, 836
Pain, 842, 843

special nerves of, 674
Pains, "sympathetic" or transferred, 844
Pancreas, 172-17f>

anatomical relations of the, 172
changes during activity in the, 174
characters of the, 172
consumption of sugar by the, 293
removal of the, result of the, 206
secretion of the. See Secretion.
Pancreatic diabetes, 293
juice, action of, in the emulsification of fats,
24()
artificial, 240
composition of, 238, 239
enzymes of, 238-244
— amylopsin, 243
— steapsin, 244
— trypsin, 239
flow of, during digestion, rapidity of, 176
obtaining the, methods of, 238
Papilla; of the tongue, 851, K52

sensitiveness of, to stimuli, 854
Paraffins or hydrocarbons, saturated, 975
Paraglobulin, 350

amount of, in the blood, 351
coagulation-temperature of, .351
composition and reaction of, 350, 351
function of, 351
occurrence and origin of, 351
Paralvsis agitaiis, 73, 743
Paraiiuclein, 1019
Parapcptone, 230
Parathyroids, 207
Paraxanthin, !J'J6

Parotid, appearance of, after stimulation, 168
in a fresh state, 16H
in a resting condition, 167
changes in, following stimulation, 167
nerve-fibres of the, 159
position of, 15H
structure of, 160
Parturition, contractions in, uterine, 919, 920

Parturition, date of, estimating the, 916

mechanism of, 917-919
pate de foie gras, 1002
Pause, resi)iratorv, 50(;, 532
P-cresol, 1011
Penis, the, H,>7

erection of, mechanism of, 902, 903
Pen tame thy lene-diamine, 986
Pentyl compounds, 983
Pepsin, action of, 235
on proteids, 219

nature and properties of, 228

preparations of, Briicke's method, 229
commercial and laboratory, 228
Pepsin and trypsin, ditt'erences in action of, 241
Peptones, 232, 1018

absorption of, from the stomach, 253

diftusibilitv of, 233

formation of, 230-232

])roperties and reactions of, 232
Peptones and proteoses, analysis of, 233

conversion of, into serum-albumin, 350
Peristalsis defined, 310

intestinal, 320-322

of the oesophagus in deglutition, 312

of the stomach during digestion, 317

of the ureters, causation, 327
Peroxide, phosjihorus, 958
Perspiration, 198, 281
" Pettenkofer's test," 988
Phagocytes, 346

Phagocytosis theory of Metschnikoff, 346
Phakoscope, the, 754
Pharynx, deglutition in the, 311

respiratorv movements of the, 516
Phenol, 280," 1010

Millon's reagent, 1011
Phenyl-hydroxide, 1010
Phonation, 874
Phosphate, ferric, 972

sodium-ammonium, 967
Phosphates, calcium, 967

excreted, derivation of, 959

magnesium, 971

of urine, 280

potassium, 903

sodium, 966
Phospheues, 751 , 777
Phosphorus, 957

compounds of, with oxygen, 958

detection of, 958

in the body, 959
Phosphorus-i)oisouing, 957
Physiology defined, 17

divisions of, 17

special, ditlerentiation of, from gt'ueral, 29, 30

study of, experimental methods used and pre-
liminary knowledge required in, 30,31
Pia and fluid, weight of, 716
Pigments, bile. See BUe-piiimcntn.

urinary, i-elationship of hivmoglobin to, 343
Pilocarpine, action of, upon the salivary glands

and their secretions, 170
Pince myograiihique and recording tambour, 89
Pinna or auricle, 807
Pitch, musical, 825, 826
Pituitary body, internal secretions of, 211
Placenta, the," 912

relationship of the, to euibrvonic nutrition,
914, 915
Plant-cell assimilation, 18
Plant-cells, conductivity in, 84
Plants and animals, structural dissimilarity of,
17, 18

enzymes of, 218
Plasma (blood-), coagulation of, 147, 148

composition of, 347-349

INDEX.

1045

Plasma, "inert laver " of, in small blood- vessels,
374
proteids of, .'Mit

pure, method of obtaining, 360
rogeneiation of, after hemorrhage, 361
"salted," :jr)7, 360
structure ami color of, 331
I'Kiuroncctidic, clironiotoblasts of, 35
l'ncuMH>»rapli of .Mai'cy, r>31
I'oikilotliermous aninials, 575
I'oisoninfj, pliosi)lu)rus, !)57
Polymerization, 23
I'olvpno'a, causation of, 550
Tolyspcrmy, !»()!»

Portal system, vaso-motor nerves of the, 501
Post-mortem rise of body-temperature, 145, 604
Potassium, i)(i3
carbonates, !)(i4
chloride, !»(>3
cyanide, 9H5
in the body, f)64
phosphates, 9()3
sulphocyaiiidc, 221, 222
thiocyauide, !/\S(i
Pregnancy, influence of, on the mammary
glands, 204, 915
multiple, 920, 921

physiological eflects upon the mother of, 915
position of fetus at end of, 917
sign of, urinary coat as a, 968
Presbyopia, 7()0
Pressure, blood-, and speed, compared, 393

arterial and venous, method of studying,

377
capillarj-, causation, 385
symptoms of bleeding in relation to, 383
the mean arterial, capillary, and venous,

382
venous, causation, 386
intrapulmonary, 505, 516
intrathoraci , 505, 516
sense of. See Touch.
upon a nerve, irritating effect of, 47
Pressure-curve, ventricular, and the auricular
systole, 422
and the valve-play, 422
ventricular, general chai'acters of, 419
Pressure-points, cutaneous, 839
Pressure-sense, tympanic membrane as an organ

of, 826
Propeptone, 230
Prostate, secretion of the, 885
Protagon, 1001
of nerve, 151
Proteid, composition of, 1016
digestion, products of, 1021
loss of, during starvation, 302
molecule, size of, 1021
oxidization of, power of tissue in, 286
putrefaction, products of, 1021
supply, value of meats as, 305
synthesis, experiments, 1021
Proteids, 214, 1016
absorption of, intestinal and stomach, 252-254
action, of pepsin-hydrochloric acid on, 229
bacterial, upon the, products of, 249
of pepsin on, products of digestion in, 219
animal-food, digestibility of, 217
blood-, 346

of lymph, 363
chromo-, 1018
coagulated, 1018
combined, 1018
digestion of, 214, 1021
effect of, on glycogen-formation in the liver,

268
glyco-, 1019

Proteids, importance of nutritive, to the body,
211,285
luxus consumption of, 288
of milk, 201

of muscle, fractional heat-coagulation to de-
termine the, 148, 149
nucleo , 1019
of tiie l)lood-plasma, 349
— fii)riiiogen, 3.50
— paraglobulin, 350
— serum albumin, 349
phos])ho-glyco-, 1020
potential energy of, 303
production of fiits by the, 290, 291

of glycogen from, 2()8
properties of, dependent upon the presence of

inorganic salts, 294
putrefaction of, bacterial, 249
reaction of, general, 1016
remarks on the, general, 1021
vegetable, digestibility of, 217
Proteose defined, 230, n.
Proteoses, 230, lOlH
Protoplasm, animal, katabolism of, 20
synthetic properties of, 18
cell, continuity of, 84, 85
conductivity of, 35
contractu itv of, 32-35
defined, 17,^943

dying, chemical changes in, 9.30
irritability of, 35
irritating effect of irritants upon different

forms of, 39
living and dead, differentiation, 18
death of, molecular change in, 23
divisions of, 17
instability of, 23, 24

specialization of function of, in highly
organized animals, 21, 22
muscle, 35, 40-42
necessity of pi-oteids for the formation and

preservation of, 214
nerve and muscle, resemblance of, 36, 37
plant, nutrition of, 215
primitive, immortality of, 930
properties of, fundamental, 21
structure of, molecular, 23-25
vegetable, synthetic properties of, 18
Proto-proteose, 230
Pseudo-mucoid, 1019
Ptyalin, 218, 222, 1008
action of, 222

conditions influencing the, 224
— conditions of the starch, 224
— effect of reaction, 224
— temperature, 224
of acids on, 224
specific, in saliva, 162
Puberty, 926
changes at, anatomical and physiological, 927

voice, 871, 872
period of, in the female and male, 927
Pulsation, cardiac. See Heart-heat.
Pulse, arterial, 385, 431

celerity of stroke of, 432
dicrotic wave of, 435
extinction of the, 386
frequency and regularity of, 432
investigation of the, by the finger, 432
nature and importance of, 431
size of the, 433
tension of, 433
transmission of, 4.32
"bounding." defined, 433
compressible and incompressible, 433
"dicrotic," 435
digital examination of, in diagnosis, 432

1046

INDEX.

Pulse, effects of resjii ration ou the, 559

resj)iratory, in the veins near the diest, 388
varieties of, \'.V.\
venous, Ut?
Pulse-rate, intlueneo of variations in body-tem-
l)erature on the, 57!>
relation of frequency of respirations and
the, 534
Pulse-trace, arterial, 434

Pulse-volume, average, of the human ventriclej
3!),S
defined, 3S)7
force exerted upon the ventricles, during

each systt)le, 3f»!)
measuring the, methods of. 397, 398
of the heart, variation in, 397
Pulse-wave, dicrotic, 435

transmission of, rate of, 432
Pupil, changes in size of, method of observing,
7()8
contraction and dilatation of, 769-771
effects of drugs ujion the, 771
reflex action of, to light, 7(59-772
Purkiiije's i)henomenou, 787, 788
Putrefaction. 945
liroteid, intestinal, 248, 249
products of, 1021
Putre.scin, 986
"Pyramid of light," 810
Pyridin, 1012
Pyrocatechin, 1011

Race, influence of, upon body-growth, 926
Races, brain-weight of different, 722

skin odors of, 851
Radiation, coetlicient of, 596
Reaction, biuret, of urea, 992

of a nerve, effect of making and breaking in-
duction shocks on the, 49

of blood, 332

of efferent nerve-impulses, 660

of muscle in rigor, cause of, 964

of muscles and nerves to electric currents, 57

of nerve-tibre, chemical, 151

of saliva, 221, 224

of sweat, 199, 281

of the efferent impulses of central system, 660

of urine, 273, 274, 280

produced by application of cold to the body,
603
Reactions of enzymes, 218, 219

of intestinal secretion, 247

of nervous system, involuntary, 651-667
voluntary, 667-682

proteid, 1016
Rectum, absorption by the, 2.55

mu.scles of the, function of, 324
Rectum and colon, nerve-supply of, 323
Reflex action of light upon the jiupil, 769-772
of deglutition, nerves concerned in the, 314
of muscle and nerve, 41
of normal salivary flow during mastication,

171
of the central nervous system, 657-667

contractions of uterus during labor, 919, 920

excitation of vaso-motor nerves. 492

movements of muscle and nerve. 41

of spinal cord, in lower vertebrates, 703-705
Reflex and voluntary actions, difference between,

667
Regeneration of blood after hemorrhage, 361

of nerve-fibres. .58, 82, 636

pathological. 933

physiological. 933
Relief, perception of. 800
Rennin, 218. 23.3, 234

extracts, method of obtaining, 234

Reniiin-zymogen, 2.34
Rei)rodu("tiou, 877-942
asexual, 878
bv conjugation, 879
defined, IH. 20
desire and power of, jjcriods in animals of the,

898, 899
double function of, 28
organs of, female, 882, 887-901

male, 882-887
periods of, seasonal, 899
process of. 901-923
sexual, 879
theories of, 880, 881
Resemblances, congenitiil, hereditary, 932

variations in, 938
Resonators, 829
Respiration, .503-.574

appearance of the larynx in, 869
artificial, 553

laboratory method of, .553, 554, 561
average rate in man, 533
centre of, cxi)iratory, 565
insi)irat<irv. 565
ill the fitiis. condition of, 572
location of the. .563
rhythmic activity of, .566
discharges from the, causation, 567
centres, .56.3-567
subsidiary, 565
"Cheyne-Stokes," .532
cutaneous, 530

quantity of QO-i exhaled, .530
influence of. internal or tissue-, 530
on licat-dissi])ati(>ii. 595
on heat-production. 590
movements r)f. .503-516

centre of the, location of, 563, 564
effects of the gaseous composition of the blood
(m the, 548
on blood-pressure, 555
on the circulation, 555
on the pulse, 5.5.5
frequency of, 533

increase in dejith of, in C'( )2-dyspn(Ea, 551
influence of rate and depth of the volume

of gases exjiii'ed on, .538
instrumental recording of, 531
nervous mechanism of, 563
of the new-born. .573

relative periods in, variations in the, 532
rhythm of. .5;',]

jjcriodical alterations in, .532, 533
sequence of, rhythmic, causation, .566
special, 561

— coughing, 562
— crying, 562
—gargling, 563
—hawking. 562
— hiccough. .563
— laughing, 562
— sneezing. 5(52
— snoring. 563
— sobbing, 562
— yawning, .562
object of, 517, 530
of various gases, effect of, 548
organs of, .503
rate of. 518
conditions affecting the, 533, 534
—age, 53.3

— atmospheric pressure, .5.34
— composition of inspired air, 534
— diurnal changes. 5.33
— emotions and will-power, .534
— posture, 533
— respiratory centres and nerves. 5.34

INDEX.

1047

Respiration, rate of, coiulitious affecting the :
— season, 534
— species, fiUIJ
— temperature, 5:51
types of, 5()()
Kespinitor, Ileriiiji's, 557
Kespiratory (luotient, 51S, 544
conditions afl'ectiug the, 545
— age, 546

— conii)osition of the inspired air, 547
—diet, 545

— diurnal variation, 546
—muscular activity, 546
— species, 545
— temperature, 546
sounds, 517
tract, function of, 849
Rest, muscular, eflect of enforced, 81

electrical currents of, 137-139
Resuscitation from drowning, 553
Retina, the, 773
activity of the, oscillatory, 790
after-images of the, 791
"blind spot" in the, 774
blood-circulation in the, 768
blood-vessels of the, 767
changes produced in the, by light, 776
color contrast of the, 792, 793
sensations upon the, 778-788
distance-perception of the, 799
fatigue of, 790
irradiation of, 794
projection of inverted images on, 751

of a shadow on, 751
rods nnd cones of, function of, 773, 787

structure of, 775
sensation of the, persistence of, 791

of light on the, 777, 778
space-percei)tion of the, 793, 796
structure of the, 773, 775
stimulation of, phenomena of, 788-791
— after-effects, 791
—fatigue, 790
— latent period, 789
— rise to maximum of sensation, 789
visual purple of the, 776, 784, 1015
Retinal image, size of, 750
Reversion, hereditary, 932, 933
Rheocord, the, 56
Rheometer, the, 391
Rheonome, 46

Rheoscope, physiological, 140
Rheostat, the, 55
Rhythm of respiration, 531-533
of muscular contractions, 738
Ribs, axes of rotation of, obliquity of, 508
eversiou of the, 508
movements of the, respiratory, 508
of the intercostal spaces, 509
Rigor caloris, 66
"cataleptic," 145
mortis, 144

appearance and duration, 145, 146
disappearance of, 147
heat-production during development of,
influence of nerve-impulses upon, 656
reaction of muscle in, cause of, 964
Rima glottidis or glottis, 863

respiratoria, 863
Ritter-Valli law of irritability, 75
"Rivalry of the fields of vision," 803
Rods and cones. See Corti and Retina.
Running, mechanism of, 861

Saccharose, 1006
Saliva, action of ptyalin on the, 222
conditions influencing, 224

Saliva, anmunt of, secreted, 221
analysis of, 162, 221
appearance and specific gravity, 161
glands forming tiie, 159
origin of tlu-, 220
physiological value of, 224
properties and composition of mixed, 221
reaction of, normal, 221, 224
salts of, inorganic, 221
specific gravity of, 161, 221
Salivary glands. See (Hands.
Salt, use of, by herbivora and carnivora, 295
Salt-solution, physiological, 362
Salts, biliary, 9H7

calcium, excretion of, by the body, 296

importance of, in food, 296
inorganic, nutritive value of, 294

reactions of, 294
iron, importance of, to body-metabolism, 295
Saponification, 1000
Saprin, 986
Sarcin, 995
Sarcolemma, .32, 103
Sarcoplasm, conductivity of, 82
Sarcosin, 982

Saturation of light, 779, 788
Schneiderian membrane, 849
Sebum, composition of, 198
Secretion, 152-211
biliary, activity of, formative, 186, 187
digestive function of, 265
normal mechanism of, 189
physiology of, 261
quantity of, 186, 187

variations in ejection from the liver, 186,
187
centre, salivary, 171

changes in the gastric glands during, 182
cutaneous, 197-204

digestive, exemption of tissues from, 237
double, of the liver, 184
effect of stimulation of secretory fibres on,

163, 164
from stimulation of secretory fibres, nature

of, 163, 164
gastric, cause of, during normal digestion, 181
effect of chemical stimulus on the, 182

of various diets on, 181
influence of the central system on, 180
quantity of, variation in, 181, 182
rapidity of the, during digestion, 176, 177
gland, of organic material, conditions deter-
mining, 164, 165
internal, of reproductive glands, 901
intestinal, action of, digestive, 246-248
color and reaction of, 247
composition of, 247
method of obtaining, 246
quantity of, 184, 246, 247
mammary, composition of, 201
conditions controlling the, 203
control of the, by the nervous system, 203
influence of artificial nerve-stimulation on,
204
604 normal, 204

of seminal vesicles, 885
of small intestine, 246

of the gastric juice, normal mechanism of, 181
of the gastric mucous membrane, acidity of,
226
digestive action of, 225
methods of obtaining, 225
properties and composition, 179, 226
of the liver, composition of, 185
of the sweat-glands, physiological value, 281
of the testis, 211
pancreatic, 206, 238

1048

INDEX.

Secretion, pancreatic, action of nerves on, 173
aniylolytic, 24:{, 244
analysis of, 173, 239
characters ol" the, 238
enzyme and zymogen of, 176
enzymes of, 173
normal mechanism of, 17(5
properties of, 238
putrefaction of, 239
rellex excitation of, by stimuli, 177
specific gravity of, 239
jiyloric, composition of, 179
relation of the strength of stimulation to the

cou>])(isition of. 1(!4
salivary, antiparalytic oraulilytic, 171
composition of. Hil
normal n)echanism of, 171
paralytic. 170
sebaceous, 197. 2H2
composition of, 282
of the skin, 198

of un)pygal glands of birds, function of, 198
physiological value of, 282
uriiuvry, amount of, 191

conditions inlhieiwiiig the, 197
nitrogenous elements of the, of birds, 192
of water and siilts, 193, 194
theoretical considerations, 191-195
Secretion and absorption, i)henonieua, 27
Secretions, animal, pro])erties of, 27
therapeutic value of, 210
formation of, 154
gland, composition of, 153, 154
internal, 2(tri-211

—adrenal bodies, 210
—liver, 205
■ — pancreas, 20G
— pituitary body, 211
—testis, 211
— thyroid, 207
organs of, 152
of the gastric mucous membrane, 226-228
of the liver, 205 >

of the male acces.sorv sexual organs, 885
of the thyroids, 207-210, 901
salivary, action of drugs on the, 170
method of obtaining, 1()2
Segmentation of the ovum, 907, 90S
Selenide, methyl, 978
Semen, the, 884

amount ejected, 884
composition of, chemical, 804
derivation of. 884

ejaculation of, in copulation, 902, 903
Semicircular canals, function of, 846, 848

structure of, 816
Seminal vesicles, 885, 886
Senescence, 928

Sensation, auditory, theory of, 824
color, phenomena of, 779
co-ordinated movements of, 83, 84
muscular, b34, 844
of light, retinal, 777

qualitative modifications, 778
retinal, latent ])eriod in, 789
of white, 787
persistence of, 791
rise to maximum of, 789
touch. See Toueh-sensation.
Sen.sations, common, 843

c\itaneous and muscular, 694, 8.34-846

of consciousness of surrounding objects, 826,

834
painful, localization of, 842
temperature, of the skin, 840-842
Sense of equilibrium, 846
of hearing, 807-833

Sense of pain, 842

of posture, 843

of .smell, 849

of taste, 851

of temperature, 840

of touch, 836-840

of vision, 696, 697, 744-806
Sense-organs. Sec Eiid-or(ians or End-bulbs.

functional independence of, 845
Senses, special, 744-854
Sensibilitj', cutaneous, 674
Serum. Sec Blood-nerum.

muscle, 148-150
Serum-albumin, 349, 3.50
Sex, characters of, i)rimary and secondary, 881

determination of, Hofacker-.Sadler law, 922

influence of, on heat-dissi])ation, 592

of the embryo, determination of, 821-923

origin of, 880
Sexes, body-growth in both, relative rapidity of, •
926

stature and weight of both, after birth, 925
Sight. Sec Vision.
Silica, 963
Silicon, 962

dioxide, 963
"Sinuses" of Valsalva, 403
Skatol, 260, 280, 1013
" Skiascopy," 765
Skin, cold and warm points of, 841

excretions of the, 281, 282

functions of the, 281

greasing the, ettect of, 593

nerve-fibres in the, 281. H.'i")

pressure-i)oints of the. 839 •

pressure-sensibility of the, discriminating
diflerences of, tests, 836, 837

respiration of. See liespirafion.

secretions of, 197-204
• sensations of the, cla.ssification of, 834

sense-perception of the, diflerences in, 841

sensitiveness of the, to temperature, 840

"tactile areas" of the, 8:J8, 839

temperature of the, of various points of the
body, 576

temperaturc-seuse of, 840

touch-sensation of the, 8.36
Skin-tenderness, topographical association of,

with visceral diseases, 844
Sleep, 739-742

body-metiibolism during, 300

body-temperature during, 578

cause of, 740

conditions favoring, 7.39, 740

loss of, 742
Smegma prjeputii, 198
Smell, sense of, 696, 849-851
Sneezing, .562
Snoring, .56.3
Sobbing, .562
Sodium, 965-967

carbonates, 966

chloride, 965

phosi>hates. 966

sulphate, 96(>
Sodium-ammonium jihosphate. 967
Solutions, carbon-monoxide haemoglobin, prepa-
rati(jn of, 342

maintaining the heart-beat, 4//-481

oxyha-moglobin, conversion of. into haemo-
globin solutions, 341
" Somacules," 25

Sound, relation l)etween physical and physi-
ological, 825-8.34. See Tone.
Sound-perception, functions of difl'erent parts
of the ear to. relative, Ki2
judgment of direction and distance by, 833

INDEX.

1049

Soiiud-sensatiou, vibration-rate necessary to pro-
duce, fcf-J(>
Sound-wavi's. production of, 825
Sounds, audible, liuiit.s of, 826
heart-, -110

praitiial ai)plication of observation of, 410
musieal, analysis of, 829
respiratory, 517
Spaee-perce|>tion, illusions of, 79(3-799
Specilic heat of the body, itl8
Species, elfect of, on resj)iratory (juotient, 545
intluenee of, on heat-dissipation, 592
on heat-])ro(luetion, 590
on the respiratory rate, 5.'J3
on the voliinie of gases resi)ired, 537
Spectroscojje, the, '.V.\A, 339
Spectrum, absorption of bile, 262
of blood, 338

of carbon-monoxide hajmoglobiu, 342
of Invmatin, 312
of methienioglobiu, 342
of oxyhiemoglol)in, 339, 340
of reduced ha-moglobin, 340,- 341
colors, number of, 778
defined, 338

intensity of the, distribution of the, 786
Speech, 861-877

impairment of, cause of, 698
Speech and hearing centres, relations of, 871
" Speech-centre," Broca's, 698
Spermatocyte, 884
Spermatozoa, the, 882

action of the, in entering the ovum, 904
contractility of, 35
di.scovery of, 882, 936
duration of life of the, 903, 904
locomotion of the, 883, 903
maturation of, 884

passage of the, time required in, 903
presence of, in the testes of the aged, 885
production of, average, 883
structure of human, 882, 883
Spermatozoon and ovum, place of union, 903
Spermine, 211, 884
Sphincter ani pylorici, 315
of the cardiac oriiice, 312
pyloric, 315, 319
urethras, 328
vesicffi internus, 328
Sphincters, rectal, function of, 324
" Sphygmogram," the, 434-436
Sphygniograph, the, 434
Sphygmomanometer, the, 433
Spinal cord, nerve-libres in the, ending of, 85
reactions of portions of the, 704
weight of the, 723
and of the brain, 715-724
Spirometer, the, 535
Spleen, composition of, chemical, 273
extirpation of, result of, 272
functions of the, 272, 273
movements of the, 272
nerves of the, vaso-motor, 499
theory of reproduction of blood-corpuscles,
343
" Staircase contractions," 72, 110
Standing, muscular action in, 846, 859
Stapedius (muscle), 814
Stapes, the, 810, 812
Starch, 1007
action of amylolopsin on, 243, 244
animal, 1008

conversion of, 223. 224, 257
digestion of, intestinal, 247
Starvation, effect of, on body-metabolism, 301

on the nervous system, 737
Stature, decrease of, in old age, 929

Stature and weight of both sexes at birtb, 925
Steapsin, 244

action of, influence of temperature on, 245

reaction of, 244

value of, in digesti<jn and absorption of fats,
245
Stenson's duct, 1.58
Stereoscope, the, 801
Sternum, respiratory movements of, 509
Stimulants, action of, upon the pancreatic secre-
tion, 177

as articles of diet, 297
Stimulation, electrical, of the cut vagus, results
of, 568, 569

muscle, effect of artificial, compared with
normal, 126

nerve, relation of tlie composition of the secre-
tion to the strength of, 164

of secretory nerve-fibres, effect of, 163, 164

retinal, 788, 791

vagus, effect of, on the heart, 453-457
Stimuli, number of, necessary to elicit a response
in a nerve-cell, 625

rapidly-repeated, eflect of, on muscle and
nerve, 72, 73

reaction to. See Reflex action.
Stokes' reagent, 341, u.
Stomach, absorption in, 252, 2.53

bacteria of the, 248

coats of the, 315

contents, ejection of the, 318, 319, 325, 326

digestion in the, i)ei)tic, 228-232

functions of the, 237

glands of the, secretory, 178-182

movements of the, 315, 316

muscles of the, 315, 319

not essential in digestion, 237

physiology of the, 237

secretions of, acidity of, 226-228

self-digestion of, exemption from, 236
Striae gravidarum, 915
Stromuhr, the, 391
Strontium, 970
Strychnin, influence of, on the dififusibility of

nerve impulse, 652
Succus entericus, 184, 286
Suffocation. See Asphyxia.
Sugar of the body, 292, 293
Sugars, absorption of, 253, 257
Sulphate, calcium, 967

sodium, 966
Sulphates of urine, conjugated, 279

quantity of, 280
Sulphide, ferro-, 972
Sulphur, 949

detection of, 950

metabolism of, 951
Suprarenal capsules, 210
Sutures, union of bone by, 855
Swallowing, act of, nervous control of, 314

mechanism of, 311-313, 866

stages of, 310, 311
Sweat, 198-200, 281

color and odor of, 281

composition of, 198, 199, 281

elimination of urea in, 275

influence of, on heat-dissipation, 595

reaction of, 199, 281

specifi(?gravity of, 199, 281
Sweat-centres, in central system, 200
Sweat-glands, action of nerve-fibres on, 199

• distribution of the, 281
effect of drugs on the, 200
effect of temperature on the, 200
histology of, 198
number of human, 198
secretion of the, 198-200

1050

INDEX.

Sweat-nerves, lt)i)

Sweatiii);, inol'iise, cause of, 200

Sympathetic jiaius, 844

vibratiou, ^29
Symphyses, 85")
Syiulesiuoses, 855
Synovial fluid, 855
Synthesis, 962

proteiil, experiments, 1021
Syntoniu, 2;50

Syphilis, transmission of, 936
Svstole. arrest of, from vafjus stimulus, 456
"auricular, 370, 396, 422, 427

ventricular, 370, 396, 399, 415
Systole anil diastole, auricular, relative duration
of the, and of the pause, 416
time relations of the, 428

Taste, sense of, 851

cortical centre for the, 696
Taste-buds, structure of, 851
Taste- perceptions modified by sight and smell,

852
Taste-sensation, contrasts of, 854
destruction of, 854
intensified bv mastication and swallowing,

852
primary, 853
sensitiveness of, 853
Taurin, 951, 986
Tea, physiological eflect of, 297
Teeth, tartar on the, 968
Telluride, methyl, 978
Temperature, body, 575-604
alniormal, 580
conditions afl'ecting, 577
conduction of, from part to part, 576
constant, defined, 581
diminished, defined, 58
dissipation of, 584-588, 592
eflfect of, on respiratory quotient, 546
evolution of, 581. 582
expenditure and income of, 581-584
increased, defined, 581
influence of, on heat-dissipation, 594

on the volume of gases respired, 540
mechanism of, 597, 601
of animals, methods of taking the, 575
of different regions of the body, 576
of the new-born, 577
origin of, 302

post-mortem rise of, 145, 604
production of, 302, 584, 588, 589
regulation of, 580
rise and fall of, 576, 577
specific, 948
effect of on conduction, 93
on muscular contraction, 127
on elasticity of muscle, 105
on the development of rigor, 145
on the irritability of muscle and nerve, 65
on the reaction of enzymes, 219
external, changes in, effect on irritability and
conductivity of nerve-fibres, 614, 615
effect of, on the respiratory quotient, 546

on the sweat-glands, 200
influence of, on heat-dissipation, 594
on heat-production, 591
on the volume of gases respired, 540, 541
upon the respirations, 566
upon the respiratory rate, 534
reactions produced by, 603
sense-perceptions of, 840-842
variations in, on body-metabolism, 300
on the oxidation of non-proteid material
in the body, 300
of blood of the brain, 736

Temperature of ex])ired air, 518
Temperature-sense of the skin, 674, 840-842
Tension, muscular, effect on the extent and

course of contraction of, 108
Tessla, experiment of, on the effect of rapid

alternations of electric currents, 58
Testes, embryonic, structure of, 885
Testicular extracts, effect of injections of, on

the neuro-muscular system, 901
Testis, the, 885, 886

internal secretion of, 211
Tetanus. 65, 73

closing, Wundt's, 52, 68, 123

complete, conditions necessary to effect, 122

continuous, causation, 123

duration of contracture of, 122

effect of double excitation on, 118-120

of frequent excitations to produce, 114, 116
effect of gradually increasing the rate of ex-
citation, 121
effect of rai)id excitations to produce, 117, 118,

122
explanation of the great height of contrac-
tions in, 118-120
height and strength due to intensity of stimu-
lus, 123
incomplete, effect of frequent stimuli to pro-
duce, 115
and contracture, development of, by indi-
rect stimulation, 117
intensity of, relative, and single contractions,

122
method of exciting, by breaking induction-
shocks, 121
number of excitations required to produce, 121
opening, Rittcr's, 52, 68, 123
production of, factors in the, 121
secondary, 140

summary of the effects of rapid excitation, 121
" Tetanus muscles," 122
Tetramethvlene-diamine, 986
Thein, 996"
Theobromin, 996
Theophyllin. 996

Thermo-accelerator centres, 599-601
Thermogenesis, .597
Thermolysis, .597, 601 .
Thermoi)ile, the, 133
Thermo]iolvpnflca, 550
Thermotaxis, .597, 602-604
Thiocyanide, potassium, 986
Thirst, sense of, 845
"Thiry-Vvlla fistula," 246, 321
Thorax, .505

inspiratory changes in form of the, .506
muscles of the, 512
Tlu-onihin, 218, .355
Thrombosin, .356
Thrombus (blood), 3.58
Thyreo-antitoxin, 210

Thvroid extracts, therapeutic value of, 208. 209,
901
glands, influence on growth-changes of the

body of, 737
secretions of the, internal, 207-210
Thyroidalbumin, 210
Thyroidectomy, results following, 208
Thyroids, 207," 208

function of the, 208,209
Thyro-iodin, 209, 953
"Tidal air" (respiration), 534
Tissue differentiation, 22, 23
Tissue- proteid, 285
Tissue-respiration, .530
Tissues, absorption-capacities of, for O, 530
death of the, 929
effect of depriving, of blood, 73

INDEX.

1051

Tissues, embryonic, growth of, 924
glycogen in the, value of, 270
influence of activity of, on body-temperature,

57H
musck'. ^va Muscle.
nerve-, si)ecilic gravity of, 732
temperature of dillerent, variations in, 577
thermogenic, r)!)7
Tissues and tlie bh)()d, interchange of O and CO2
hetween the, 527
and fluids of the body, importance of the in-
organic salts to the, 294
and organs, efl'ect of starvation upon, 301
Tone, musical, diflerential, 831
fundamental, 815, 827
sensation of, production of, 825
"Tone" of muscle-tissue, 309
Tones, musical, 832

combinational, 831, 832
complex, 827

composite, analysis of, by the ear, 828
concordant and discordant, 831
factors (letcrniining, s;;!
production of l)eats in, 830
Tongue, nerves of the, sensory, 852
papilla^ of the, 851, 852

sensitivi'uess of, to stimuli, 854
tastc-iicrcciition ))v the, points of, 854
"Touogi-aphs," 419*
Touch, illusions of, 840
pressure sensibility to, 836, 837
sense of, 83(5-840
Touch-corpuscles, 836

Touch-sensation and stimulus, relations of, 836
importance of the nerve end-organ in, 839
localization of, 838, 839
Tracts, pyramidal, size of, 695
Transfusion, l)lood, danger attending, 362
Transmissii)n, hereditary, 22, 28, 931-942
Traube-Hering waves, 492
Tremors, muscle, 124
Trichlormethane, 977
Trimethvlamine, 985
Trioses, 'lOOl
Trypsin, 231, 239-241

extracts, methods of preparing, 240
Trypsinogen, 176, 240
Tryptophan, 1015

Tubules, uriniferous, histologj' of, 189, 190
Tympanic membrane, 809

as an organ of pressure-sense, 826
function of, 815

perforation or extirpation of, efi"ect of, 815
vibrations of, 815, 820
Tvmpanum, the, 808
Tyrosin, 242, 1011

Units, calorimetric, 584

Urates, deposition of, in the kidneys, by ligation

of ureters, 192
Urea, 274, 991

biuret reaction of, 992

combustion-equivalent of, 303

derivation of, 205, 206, 274-276

elimination from urine of, 192
in sweat, 275
process and rate of, 195

formation of, in the liver, 271, 272, 275

in milk, 202, 275

in sweat, 199, 281

in the body, 992

in the urine, 274

preparation and properties, 991, 992

quantity of, eliminated, 274
Ureter, muscle-tissue of the, contractioii-wave

of, 309
Ureters, movements of, 327

Urethra, the, 886
Urination. See Micturition.
Urine, accunuilation of, in the bladder, 328
amount s«'creted, 191, 274
color of the, 191, 273
constituents of. 191, 274-280
— conjugated suliihatcs, 279
— creatinin, 278
— hippuric acid, 279
— urea, 274
— uric acid, 277
— water and salts, 280
— xanthin bodies, 277
creatinin in, 278, 279

elimination of nrea and related bodies of, 192
fermentation of the, ammoniacal, 956
hippuric acid of, 279
injecting the, into the bladder, mechanism of,

327
lactates in human, presence of, 278
phosphatic coating of, as a sign of pregnancy,

968
reaction of, 273, 274. 280
salts of, inorganic, 280
secretion of, 191-193
specific gravity of, 191, 273
sulphur in, form eliminated, 279
urea in the, 274
uric acid in, 272, 273, 277, 278
Urobilin, 1015
Uterus, the, 895
changes in the, during menstruation, 896, 897

iu early gestation, 909, 910
enti'ancc of spermatozoa into, mode of, 903

V'agina, the, 900
Vagus, the, 463

stimulation of the, results of, 568
Valve, auriculo-veutricular, 400
Valve-play, cardiac, method of recording, 423-

425
Valves, heart-, mechanism of, 400-404

semilunar, mechanism of, 402-404
" Valvulte couniventes," 254
Vas deferens, the, 886
Vaseline, 975

Vaso-constrictor centre, bulbar, 489-492
Vaso-motor centre, bulbar, 489

centres, relation of cerebrum to, 490-493
cerebral, 495
spinal, 490
reflexes, 492

spinal, discovery of, 490
Vein, wounded, entrance of air into a, danger

of, 389
Veins, blood-flow in, subsidiary forces assisting
the, 387
blood-pressure in, causation, 386
blood-speed in the, 393
coronary, closure of the, results of, 476
great, changes in the, iu the open chest, 407

contraction of the, rhythmic, 407
valves of the. See Valves.
Ventilation, principles of, 547
Ventricle, changes in the, from vagus excita-
tion, 453
— force of the contraction, 453
— periodicity of contraction, 453
• — the diastolic pressure, 454
— the output and input, 454
— the ventricular tonus, 454
— the volume of blood, 454
closure of the, two periods of complete, 425
the auricle a mechanism for the quick-charg-
ing of, 428
Ventricles, changes in size of, during the heart-
beat, 404, 405

1052

INDEX.

Ventricles, beatiuR, changes in size and foi-m of,
in the open chest, 405
of position in the open chest, 406
contracting, force of, 398, 399
of .Morgagni, .S(i3
pressure within the, 416-418

negative, 425
suction within the, 387, 426. See also Heart.
Ventricular hands of larynx, 862, 863
cycle, perioils of the, 425
relations in time of the, 413
Vernix caseosa, 198
Vestibule, auditory, 816

Vertebrates, comparative physiology of the cen-
tral nervous system in, 703-705
Viscera, abdominal, cardiac cflfect of stimulating
the, 4C7
muscular contraction of the, 310
Villi, chorionic, 912

intestinal, 254, 258
Vision, binocular and monocular, compared, 801
defective, 097, 759, 760, 763
physiology of, 744

caution in the study of, 806
points of, corresponding, 803
pseudoscopic, 802
sense of, 696, 697, 744-806
stereoscopic, 801-803
" Vital force " of life. 25, 26
Vocal cords, false and true, 862. 863
in voice-production, 870-8/ /
structure of, 863, 864
Vocal organs, muscles of, reaction and contrac-
tion of, 107
Voice, the, 870-877

— changing the pitch, 872
— speech, 874
— vocal machinery, 870
— vowel and consonantal sounds, 874-877
— whispering, 875
changes in the. at puberty, 871, 872, 927
characters of the :
— loudness, 870
—pitch, 870
— quality, 870
eflFect of castration on the, 871, 872
pitch of the, 872
range of the, 872, 873
registers of the, 872-874

Voice, speaking and singing, distinguished, 874

Voice and speech, 861-877

Voice-i)roduction, 861, 870

Voices, classification of, 873

Voltaic pile, invention of, 43

Vomiting, nervous mechanism of, 325, 32()

centre, lociition of .i, .'12()
Von Frey's experiment of artificially preserving

the irritability of muscle, 74
Vorticella, .34. 35
Vowel sounds, difference in quality of, 829

mechanism of i)roduction of, 874-876
Vowels, phonation of, 874-876
Vulva, the, and its parts, 900

Walking, mechanism of, 860, 861
Water, 947

deprivation of, effect of continued, on the

body, 294
distilled, preparation of, 947
drinking-, 948
elimination from the body of, channels of,

280, 293
in the brain, percentage of, 716
Water and salts, absorption of, 258
from the stomach, 253
intestinal, 254, 259
in secretions, theories of the formation of,

1.5.5, 1.56
necessity of, to the body, 214
of food-stuffs, 213, 214
of urine, 193, 280
value of, nutritive, 293, 294
Waves, sound-, jiroduction of, 825
Wharton's duct. 1.58
Whispering, 876
Whistling register, 873
Womb, the, 895

Women, sexual period in, of reproductive power,
927

Xanthin, 277, 278, 996
dimethyl, 996
monoraethyl, 996
trimethyl,'99()

Zymogen, 176
cell-granules, 169, 183

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London Lancet.

AN AMERICAN TEXT=BOOK OF THE THEORY AND PRACTICE
OF MEDICINE.

By 12 Distinguished American Practitioners. Edited by William
Pepper, M.D., LL.D., Professor of the Theory and Practice of Medi-
cine and of Clinical Medicine in the University of Pennsylvania. Two
handsome imperial octavo volumes of about 1000 pages each. Illus-
trated. Prices per volume : Cloth, $5.00 net ; Sheep or Half Morocco,
$6.00 net. Sold by Subscription.

" I am quite sure it will commend itself both to practitioners and students of medicine,
and become one of our most popular text-books." — Alfred Loomis, M.D., LL.D., Pro-
fessor of Pathology and Practice of Medicine, University of the City of New York.

" V.'e reviewed the first volume of this work, and said : ' It is undoubtedly one of the
best text-books on the practice of medicine which we possess.' A consideration of the
second and last volume leads us to modify that verdict and to say that the completed work
is in our opinion the best of its kind it has ever been our fortune to see." — A^ew York Medical
Journal.

Illustrated Catalogue of the ** American Text-Books*' sent free upon application*

Medical Publications of W. B. Saunders,

AN AMERICAN YEAR-BOOK OF MEDICINE AND SURGERY.

A Yearly Digest of Scientific Progress and Authoritative Opinion in all
branches of Medicine and Surgery, drawn from journals, monographs,
and text-books of the leading American and Foreign authors and
investigators. Collected and arranged, with critical editorial com-
ments, by eminent American specialists and teachers, under the general
editorial charge of Geor(;e M. Gould, M.D. One handsome imperial
octavo volume of about 1200 pages. Uniform in style, size, and
general make-up with the "American Text-Book" Series. Cloth,
$6.50 net; Half Morocco, $7.50 net. So/d by Subscription.

" It is difficult to know which to admire most — the research and industry of the distin-
guished band of experts whom Dr. Gould has enlisted in the service of the Year-Book, or the
wealth and abundance of the contributions to every department of science that have been
deemed worthy of analysis. . . . It is much more than a mere compilation of abstracts,
for, as each section is entrusted to experienced and able contributors, the reader has the
advantage of certain critical commentaries and expositions . . . proceeding from writers
fully qualified to perform these tasks. ... It is emphatically a book which should find
a place in ever)- medical library, and is in several respects more useful than the famous
'Jahrbiicher' of Geiinany." — London Lancet.

THE AMERICAN POCKET MEDICAL DICTIONARY.

[See Borland' s Pocket Dictionary, page 10.]

ANDERS' PRACTICE OF MEDICINE. Second Edition.

A Text-Book of the Practice of Medicine. By James M. Anders,
M.D., Ph.D., LL.D., Professor of the Practice of Medicine and of
Clinical Medicine, Medico-Chirurgical College, Philadelphia. In one
handsome octavo volume of 1287 pages, fully illustrated. Cloth,
$5.50 net; Sheep or Half Morocco, $6.50 net.

" It is an excellent book, — concise, comprehensive, thorough, and up to date. It is a
credit to you ; but, more than that, it is a credit to the profession of Philadelphia— to us."
James C. Wilson, Professor of the Practice of Medicine and Clinical Medicine, Jefferson
Medical College, Philadelphia.

ASHTON'S OBSTETRICS. Fourth Edition, Revised.

Essentials of Obstetrics. By W. Easterly Ashton, M.D., Pro-
fessor of Gynecology in the Medico-Chirurgical College, Philadelphia.
Crown octavo, 252 pages; 75 illustrations. Cloth, $1.00; interleaved
for notes, $1.25.

[See Saunders' Question- Cotnpends, page 21.]
" Embodies the whole subject in a nut-.shell. We cordially recommend it to our read
ers." — Chicago Medical Times.

BALL'S BACTERIOLOGY. Third Edition, Revised.

Essentials of Bacteriology ; a Concise and Systematic Introduction
to the Study of Micro-organisms. By M. V. Ball, M.D., Bacteriol-
ogist to St. Agnes' Hospital, Philadelphia, etc. Crown octavo, 218
pages; 82 illustrations, some in colors, and 5 plates. Cloth, ,^i.oo;
interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]
«« The student or practitioner can readilv obtain a knowledge of the subject from a perusal

of this book. The illustrations are clear and satisfactory."— il/<?a'jVa/ Record, New York.

Medical Publications of W. B. Saunders.

BASTIN'S BOTANY.

Laboratory Exercises in Botany. By Edson S. Bastin, M.A.,
late IMofessor of Materia Medica and Botany, Philadelphia College of
Pharmacy. Octavo volinne of 536 pages, with 87 plates. Cloth, ^2.50.

"It is unquestionably the best textbook on the subject that has yet appeared. The
work is eminently a practical one. We regard the issuance of this book as an important
event in the history of pharmaceutical teaching in this country, and predict for it an unquali-
fied success." Alumni Report to the Philadelphia College of Pharmacy.

"There is no work like it in the pharmaceutical or botajiical literature of this country,
and we predict for it a wide circulation." — American Journal of Pharmacy.

BECK'S SURGICAL ASEPSIS.

A Manual of Surgical Asepsis. By Carl Beck, M.D., Surgeon to
St. Mark's Hospital and the New York German Poliklinik, etc. 306
pages; 65 text-illustrations, and 12 full-page plates. Cloth, $1.25 net.

" An excellent 'exposition of the ' very latest' in the treatment of wounds as practised
by leading German and American surgeons." — Birmingham (Eng.) Medical Review.

"This little volume can be recommended to any who are desirous of learning the details
of asepsis in surgery, for it will serve as a trustworthy guide." — London Lancet.

BOISLINIERE'S OBSTETRIC ACCIDENTS, EMERGENCIES, AND
OPERATIONS.
Obstetric Accidents, Emergencies, and Operations. By L. Ch.

BoisLiNiERE, M.D., late Emeritus Professor of Obstetrics, St. Louis
Medical College. 381 pages, handsomely illustrated. Cloth, $2.00 net.

" It is clearly and concisely written, and is evidently the work of a teacher and practi-
tioner of large experience." — British Medical Journal.

" A manual so useful to the student or the general practitioner has not been brought to
our notice in a long time. The field embraced in the title is covered in a terse, interesting
way." — Yale Medical Journal.

BROCKWAY'S MEDICAL PHYSICS. Second Edition, Revised.
Essentials of Medical Physics. By Fred J. Brockway, M.D.,
Assistant Demonstrator of Anatomy in the College of Physicians and
Surgeons, New York. Crown octavo, 330 pages ; 155 fine illustrations.
Cloth, 51.00 net ; interleaved for notes, ^1.25 net.

[See Saunders' Question- Compends, page 21.]

" The student who is well versed in these pages will certainly prove qualified to com
prehend with ease and pleasure the great majority of questions involving physical principles
likely to be met with in his medical studies." — American Practitioner and News.

<'We know of no manual that affords the medical student a better or more concise
exposition of physics, and the book may be commended as a most satisfactory presentation
of those essentials that are requisite in a course in medicine." — Nezv York Medical Jourttal.

" It contains all that one need know on the subject, is well written, and is copiously
illustrated." — Medical Record, New York.

BURR ON NERVOUS DISEASES.

A Manual of Nervous Diseases. By Charles W. Burr, M.D.,

Clinical Professor of Nervous Diseases, Medico-Chirurgical College,
Philadelphia; Pathologist to the Orthopedic Hospital and Infirmary
for Nervous Diseases; Visiting Physician to St. Joseph's Hospital, etc.
Jn Preparation.

8 Medical Publications of W. B. Saunders.

BUTLER'S MATERIA MEDICA, THERAPEUTICS, AND PHAR-
MACOLOGY. Second Edition, Revised.
A Text-Book of Materia Medica, Therapeutics, and Pharma-
cology. By Georcje ¥. ikriLER, Ph.G., M.D., Professor of Materia
Medica and of Clinical Medicine in the College of Physicians and
Surgeons, Chicago ; Professor of Materia Medica and Therapeutics,
Northwestern University, Woman's Medical School, etc. Octavo, 860
pages, illustrated. Cloth, $4.00 net ; Sheep, $5.00 net.

*' Taken as a whole, the book may fairly be considered as one of the most satisfactory
of any single-volume works on materia medica in the market." — Journal of the Avierican
Medical Association.

CERNA ON THE NEWER REMEDIES. Second Edition, Revised.
Notes on the Newer Remedies, their Therapeutic Applications
and Modes of Administration. By David Cekna, M.D., Ph.D.,
formerly Demonstrator of and Lecturer on Experimental Therapeutics
in the University of Pennsylvania; Demonstrator of Physiology in the
Medical Department of the University of Texas. Rewritten and
greatly enlarged. Post-octavo, 253 pages. Cloth, ;^ 1.25.

" The appearance of this new edition of Dr. Cerna's very valuable work shows that it
is properly appreciated. The book ought to be in the possession of every practising physi-
cian."— Netu York Medical Journal.

CHAPIN ON INSANITY.

A Compendium of Insanity. By John B. Chapin, M.D., LL.D.,
Physician-in-Chief, Pennsylvania Hospital for the Insane ; late Physi-
cian-Superintendent of the Willard State Hospital, New York ; Hon-
orary Member of the Medico-Psychological Society of Great Britain,
of the Society of Mental Medicine of Belgium. lamo, 234 pages,
illustrated. Cloth, $1.25 net.

" The practical parts of Dr. Chapin's book are what constitute its distinctive merit. We
desire especially to call attention to the fact that on the subject of therapeutics of insanity
the work is exceedingly valualjle. It is not a made book, hut a genuine condensed thesis,
which has all the value of ripe opinion and all the charm of a vigorous and natural style." —
Philadelphia Medical Journal.

CHAPMAN'S MEDICAL JURISPRUDENCE AND TOXICOLOGY.
Second Edition, Revised.
Medical Jurisprudence and Toxicology. By Henry C. Chapman,
M.D., Professor of Institutes of Medicine and Medical Jurisprudence
in the Jefferson Medical College of Philadelphia. 254 pages, with 55
illustrations and 3 full-page plates in colors. Cloth, $1.50 net.

"The best book of its class for the undergraduate that we know of." — A^ew York
Medical Times.

CHURCH AND PETERSON'S NERVOUS AND MENTAL DISEASES.
Nervous and Mental Diseases. By Archii.ai.u Church, M. D.,
Professor of Mental Diseases and Medical Jurisprudence in the North-
western University Medical School, Chicago; and Frederick Peter-
son, M. D., Clinical Professor of Mental Diseases, Woman's Medical
College, N. Y.; Chief of Clinic, Nervous Dept., College of Physi-
cians and Surgeons, N. Y. Handsome octavo volume of 843 pages,
profusely illustrated. Cloth, ;;^5.oo net; Half Morocco, 56.00 net.

Medical Publications of W. B. Saunders.

CLARKSON'S HISTOLOGY.

A Text-Book of Histology, Descriptive and Practical. By

Arthur Clakkson, M.B., CM. Edin., formerly Demonstrator of
Physiology in the Owen's College, Manchester; late Demonstrator of
Physiology in Yorkshire College, Leeds. Large octavo, 554 pages;
22 engravings in the text, and 174 beautifully colored original illustra-
tions. Cloth, strongly bound, $6.00 net.

" The work must be considered a valuable addition to the list of available textbooks,
and is to be highly recommended." — Ne7v York Medical Journal.

'« Tliis is one of the best works for students we have ever noticed. We predict that the
book will attain a well-deserved poinilarity amongom 'iiwA&nXs:'— Chicago Medical Recorder.

CLIMATOLOGY.

Transactions of the Eighth Annual Meeting of the American
Climatological Association, held in Washington, September 22-25,
1 89 1. Forming a handsome octavo volume of 276 pages, uniform with
remainder of series. (A limited quantity only.) Cloth, $1.50.

COHEN AND ESHNER'S DIAGNOSIS.

Essentials of Diagnosis. By Solomon Solis-Cohen, M.D., Pro-
fessor of Clinical Medicine and Applied Therapeutics in the Philadel-
phia Polyclinic ; and Augustus A. Eshner, M.D., Professor of Clinical
Medicine in the Philadelphia Polyclinic. Post-octavo, 382 pages; 55
illustrations. Cloth, ^1.50 net.

[See Saunders' Question- Compends, page 21.]

"We can heartily commend the book to all those who contemplate purchasing a 'com-
pend ' It is modern and complete, and will give more satisfaction than many other works
which are perhaps too prolix as well as behind the \\m^%:'— Medical Review, St. Louis.

CORWiN'S PHYSICAL DIAGNOSIS.

Essentials of Physical Diagnosis of the Thorax. By Arthur
M. CoRWiN, A.M., M.D., Demonstrator of Physical Diagnosis in Rush
Medical College, Chicago ; Attending Physician to Central Free Dis-
pensary, Department of Rhinology, Laryngology, and Diseases of the
Chest, Chicago. 200 pages, illustrated. Cloth, flexible covers, ^i. 25 net.

"It is excellent. The student who shall use it as his guide to the careful study of
physical exploration upon normal and abnormal subjects can scarcely fail to acquire a good
working knowledge of the subject." — Philadelphia Polyclinic.

"A most excellent little work. It brightens the memory of the differential diagnostic
signs, and it arranges orderly and in sequence the various objective phenomena to logical
solution of a careful diagnosis."— >2/r«a/ of Nervous and Mental Diseases.

CRAGIN'S GYN/ECOLOGY. Fourth Edition, Revised.

Essentials of Gynaecology. By Edwin B. Cr.^gin, M. D., Lecturer
in Obstetrics, College of Physicians and Surgeons, New York. Crown
octavo, 200 pages; 62 illustrations. Cloth, $1.00 ; interleaved for notes,

^ 1 . 2 ^ .

[See Sajmders' Question- Canpends, page 21.]
« A handy volume, and a distinct improvement on students' compends in general. No
author who was not himself a practical gynecologist could have consulted the student's needs
so thoroughly as Dr. Cragin has d.ont."— Medical Record, New York.

10 Medical Publications of W. B. Saunders.

CROOKSHANK'S BACTERIOLOGY. Fourth Edition, Revised.

A Text-Book of Bacteriology. By Edgar M. Crookshank, M.B.,
Professor of Comparative I'athology and Bacteriology, King's College^
London. Octavo volume of 700 pages, with 273 engravings and 22
original colored plates. Cloth, $6.50 net; Half Morocco, 57.50 net.

" To the student who wishes to obtain a good resume of what has been done in bacteri-
ology, or wlio wishes an accurate account of the various methods of research, the book may
be recommended with confidence that he will find there what he requires." — London Lancet.

DaCOSTA'S surgery. Second Ed., Revised and Greatly Enlarged.
Modern Surgery, General and Operative. By John Chalmers
DaCosta, M.D., Clinical Professor of Surgery, Jefferson Medical
College, Philadelphia; Surgeon to the Philadelphia Hospital, etc.
Handsome octavo volume of 900 pages, profusely illustrated. Cloth,
;^4.oo net; Half Morocco, 55.00 net.

"We know of no small work on surgery in the English language which so well fulfils-
the requirements of the modern student." — ALeJico-Chiruigical Journal, Bristol, England.

DE SCHWEINITZ ON DISEASES OF THE EYE. Third Edition,
Revised,
Diseases of the Eye. A Handbook of Ophthalmic Practice.

By G. E. DE ScHWEiNiTZ, M.D., Professor of Ophthalmology in the
Jefferson Medical College, Philadelphia, etc. Handsome royal octavo
volume of 696 pages, with 256 fine illustrations and 2 chromo-litho-
graphic plates. Cloth, 54.00 net; Sheep or Half Morocco, 55- 00 net.

" A clearly written, comprehensive manual. One which we can commend to students
as a reliable text-book, written with an evident knowledge of the wants of those entering
upon the study of this special branch of medical science." — British Medical JournaL

" A work that will meet the requirements not only of the specialist, but of the general
practitioner in a rare degree. I am satisfied that unusual success awaits it." — William
Pepper, M.D., Professor of the Theory and Practice of jMedicine and Clinical Medicine,
University of Pennsylvania.

DORLAND'S DICTIONARY.

The American Pocket Medical Dictionary. Containing the Pro-
nunciation and Derivation of over 26,000 words and phrases, and a large
number of useful tables. Edited by W. A. Newman Dorland, M. D.,
Assistant Demonstrator of Obstetrics, LIniversity of Pennsylvania ; Fel-
low of the American Academy of Medicine. 518 pages; handsomely
bound in full leather, limp, with gilt edges. Price, 51.25 net.

DORLAND'S OBSTETRICS.

A Manual of Obstetrics. By W. A. Newman Dorland, M.D.,
Assistant Demonstrator of Obstetrics, University of Pennsylvania;
Instructor in Gynecology in the Philadelphia Polyclinic. 760 pages;
163 illustrations in the text, and 6 full-page plates. Cloth, $2.50 net.

"By far the best book on this subject that has ever come to our notice." — American
Medical Review.

" It has rarely been our duty to review a book which has given us more pleasure in its
perusal and more satisfaction in its criticism. It is a veritable encyclopedia of knowledge,
a gold mine of practical, concise thoughts." — American Medico-Surgical Bulletin.

Medical Publications of W. B. Saunders. 11

FROTHINGHAM'S GUIDE FOR THE BACTERIOLOGIST.

Laboratory Guide for the Bacteriologist. By Langdon Froth-
in(;ham, M.D.V., Assistant in Bacteriology and Veterinary Science,
Sheffield Scientific School, Yale University. Illustrated. Cloth, 75 cts.

" It is a convenient and useful little work, and will more than repay the outlay neces-
sary for its ]HUchase in the saving of time which would otherwise be consumed in looking
up the various points of technique so clearly and concisely laid down in its pages." — Ameri-
can Medico- Surgical BuUelin.

GARRIGUES' DISEASES OF WOMEN. Second Edition, Revised.
Diseases of Women. By Henry J. Garrigues, A.M., M.D., Pro-
fessor of Gynecology in the New York School of Clinical Medicine ;
Gynecologist to St. Mark's Hospital and to the German Dispensary,
New York City, etc. Handsome octavo volume of 728 pages, illus-
trated by 335 engravings and colored plates. Cloth, $4.00 net;
Sheep or Half Morocco, ^5.00 net.

" One of the best text-books for students and practitioners which has been published in
the English language ; it is condensed, clear, and comprehensive. The profound learning
and great clinical experience of the distinguished author find expression in this book in a
most attractive and instructive form. Young practitioners to whom experienced consultants
may not be available will find in this book invaluable counsel and help." — Thad. A.
Reamv, M.D., LL.D., Professor of Clinical Gymecology, Medical College of Ohio.

GLEASON'S DISEASES OF THE EAR. Second Edition, Revised.
Essentials of Diseases of the Ear. By E. B. Gleason, S.B.,
M.D., Clinical Professor of Otology, Medico-Chirurgical College,
Philadelphia ; Surgeon-in-Charge of the Nose, Throat, and Ear Depart-
ment of the Northern Dispensary, Philadelphia. 208 pages, with
114 illustrations. Cloth, ^i.oo ; interleaved for notes, $1.25.
[See Saunders' Question- Compends, page 21.]

" It is just the book to put into the hands of a student, and cannot fail to give him a
useful introduction to ear-affections ; while the style of question and answer which is adopted
throughout the book is, we believe, the best method of impressing facts permanently on the
mind. " — Liverpool Medico- Chiru7gical Journal.

GOULD AND PVLE'S CURIOSITIES OF MEDICINE.

Anomalies and Curiosities of Medicine. By George M. Gould,
M.D., and Walter L. Pyle, M.D. An encyclopedic collection of
rare and extraordinary cases and of the most striking instances of
abnormality in all branches of Medicine and Surgery, derived from an
exhaustive research of medical literature from its origin to the "present
day, abstracted, classified, annotated, and indexed. Handsome im-
perial octavo volume of 968 pages, with 295 engravings in the text,
and 12 full-page plates. Cloth, $6.00 net; Half Morocco, $7.00 net.
Sold by Subscription.

" One of the most valuable contributions ever made to medical literature. It is, so far
as we know, absolutely unique, and every page is as fascinating as a novel. Not alone for
the medical profession has this volume value : it will serve as a book of reference for all who
are interested in general scientific, sociologic, or medico-legal topics." — Brooklyn Medical
Journal.

"This is certainly a most remarkable and interesting volume. It stands alone among
medical literature, an anomaly on anomalies, in that there is nothing like it elsewhere in
medical literature. It is a book full of revelations from its first to its last page, and cannot
but interest and sometimes almost horrify its readers." — Atnerican Medico- Surgical Bulletin.

12 Medical Publications of W. B. Saunders.

QRAFSTROM'S MECHANO-THERAPY.

A Text-Book of Mechano-Therapy (Massage and Medical Gym-
nastics). I'.y AxKi, V. CiRAi'STKOM, H. Sc, M. D., late Lieutenant in
the Royal Swedish Army ; late House Physician City Hos])ital, Ijlack-
well's Island, New York. i2nio, 139 pages, illustrated, ("loth, ;f!i.oonet.

GRIFFITH ON THE BABY. Second Edition, Revised.

The Care of the Baby. By J. P. Ckozer Griffith, M.D., Clini-
cal Professor of Diseases of Children, University of Pennsylvania;
Physician to the Children's Hospital, Philadelphia, etc. i2mo, 404
pages, with 67 illustrations in the text, and 5 plates. Cloth, $1.50.

" Tlie best book for the use of the young mother with which we are acquainted. . . .
There are very few general practitioners who could not read the book through with advan-
tage."— Archives of Pediatrics.

"The whole book is characterized by rare good sense, and is evidently written liy a
master liand. It can be read with benefit not only by mothers but by medical students and
by any practitioners who have not had large opportunities for observing children." — Ameri-
can Journal of Obstetrics.

GRIFFITH'S WEIGHT CHART.

Infant's Weight Chart. Designed by J. P. Crozer Griffith, M.D.,
Clinical Professor of Diseases of Children in the University of Penn-
sylvania, etc. 25 charts in each pad. Per pad, 50 cents net.

A convenient blank for keeping a record of the child's weight during the first two years
of life. Printed on each chart is a curve representing the average weight of a healthy infant,
so that any deviation from the normal can readily be detected.

GROSS, SAMUEL D., AUTOBIOGRAPHY OF.

Autobiography of Samuel D. Gross, M.D., Emeritus Professor of
Surgery in the Jefferson Medical College, Philadelphia, with Remi-
niscences of His Times and Contemporaries. Edited by his Sons,
Samuel W. Gross, M.D., LL.D., late Professor of Principles of Sur-
gery and of Clinical Surgery in the Jefferson Medical College, and
A. Haller Gross, A.M., of the Philadelphia Bar. Preceded by a
Memoir of Dr. Gross, by the late Austin Flint, M.D., LL.D. In
two handsome volumes, each containing over 400 pages, demy octavo,
extra cloth, gilt tops, with fine Frontispiece engraved on steel. Price
per volume, $2.50 net.

" Dr. Gross was perhaps the most eminent exponent of medical science tiiat America
has yet produced. His Autobiography, related as it is with a fulness and completeness
seldom to be found in such works, is an interesting and valuable book. He conmients on
many things, especially, of course, on medical men and medical practice, in a very interest-
ing way." — IJie Spectator, London, England.

HAMPTON'S NURSING. Second Edition, Revised and Enlarged.
Nursing: Its Principles and Practice. By Isabel Adams Hami-
TON, Ciraduate of the New York Training School for Nurses attached
to Bellevue Hospital ; late Superintendent of Nurses and I'rincipal of
the Training School for Nurses, Johns Hopkins Hospital, Baltimore,
Md. 12 mo, 512 pages, illustrated. Cloth, $2.00 net.

" Seldom have we perused a book upon the subject that has given us so much pleasure
as the one before us. We would strongly urge upon the members of our own profession the
need of a book like this, for it will enable each of us to become a training school in him-
self."— Ontario Medical Journal.

Medical Publications of W. B. Saunders. 13

HARE'S PHYSIOLOGY. Fourth Edition, Revised.

Essentials of Physiology. ]}y H. A. Hakk, M.I)., Professor of
'Ihcrapcutics and Materia Mcdica in the Jefferson Medical College of
Phihulclphia. Crown octavo, 230 pages. Cloth, $1.00 net; inter-
leaved for notes, $1.25 net.

[See Saunders' Question- Compends, page 21.]

" The best condensation of physiological knowledge we have yet seen." — Medical
Record, New York.

HART'S DIET IN SICKNESS AND IN HEALTH.

Diet in Sickness and in Health. By Mrs. Ernest Hart, formerly
Student of the Faculty of Medicine of Paris and of the London School
of Medicine for Women ; with an Introduction by Sir Hknrv
Thompson, F.R.C.S., M.D., London. 220 pages. Cloth, $1.50.

" We recommend it cordially to the attention of all practitioners ; both to them and to
their patients it may be of the greatest service." — New York Medical Journal.

HAYNES' ANATOMY.

A Manual of Anatomy. By Irving S. Havnes, M.D., Adjunct
Professor of Anatomy and Demonstrator of Anatomy, Medical Depart-
ment of the New York University, etc. 680 pages, illustrated with 42
diagrams in the text, and 134 full-page half-tone illustrations from
original photographs of the author's dissections. Cloth, $2.50 net.

" This book is the work of a practical instructor — one who knows by experience the
requirements of the average student, and is able to meet these requirements in a very satisr-
factory way. The book is one that can be commended." — Medical Record, New York.

HEISLER'S EMBRYOLOGY.

A Text=Book of Embryology. By John C. Heisler, M.D., Pro-
fessor of Anatomy in the Medico-Chirurgical College, Philadelphia.
hi Preparation.

HIRST'S OBSTETRICS.

A Text=Book of Obstetrics. By Barton Cooke Hirst, M.D.,
Professor of Obstetrics in the University of Pennsylvania. Handsome
octavo volume of 848 pages, with 618 illustrations, and a number of
colored plates. Cloth, $5.00 net; Sheep or Half Morocco, $6.00 net.

This work represents the very latest teaching in the practice of obstetrics by a man of
extended experience and recognized authority. The book emphasizes especially, as a work
on obstetrics should, the practical side of the subject, and to this end presents an unusually
large collection of illustrations, the majority of them original.

HYDE AND MONTGOMERY ON SYPHILIS AND THE VENEREAL
DISEASES.
Syphilis and the Venereal Diseases. By James Nevins Hyde,
M.D., Professor of Skin and Venereal Diseases, and Frank H. Mont-
gomery, M.D., Lecturer on Dermatology and Genito-L'rinary Diseases
in Rush Medical College, Chicago, 111. 618 pages, profusely illustrated.
Cloth, $2.50 net.

" We can commend this manual to the student as a help to him in his study of venereal
diseases. ' ' — Liverpool Medico- Chirurgical Journal.

"The best student's manual which has appeared on the subject." — St. Louis Medical
and Surgical Journal.

14 Medical Publications of W. B. Saunders.

JACKSON AND QLEASON'S DISEASES OF THE EYE, NOSE, AND
THROAT. Second Edition, Revised.
Essentials of Refraction and Diseases of the Eye. By Edward
Jackson, A.M., M.D., Professor of Diseases of the Eye in the Phila-
delphia Polyclinic and College for Graduates in Medicine; and —
Essentials of Diseases of the Nose and Throat. By E. Bald-
win Gleason, M.D., Surgeon-in-Charge of the Nose, Throat, and
Ear Department of the Northern Dispensary of Philadelphia. Two
volumes in one. Crown octavo, 290 pages; 124 illustrations. Cloth,
$1.00; interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]

" Of great value to the beginner in these branches. The authors are both capable men,
and know what a student most needs." — Medical Record, New York.

KEATINQ'S DICTIONARY. Second Edition, Revised.

A New Pronouncing Dictionary of Medicine, with Phonetic
Pronunciation, Accentuation, Etymology, etc. Bv John M.
Keating, M.D., LL.D., Fellow of the College of Physicians of Phila-
delphia ; Vice-President of the American Psediatric Society ; Editor
"Cyclopaedia of the Diseases of Children," etc.; and Henry
Hamilton, Author of '-'A New Translation of Virgil's ^neid into
English Rhyme," etc.; with the collaboration of J. Chalmers Da-
Costa, M.D., and Frederick A. Packard, M.D. With an Appendix
containing Tables of Bacilli, Micrococci, Leucomaines, Ptomaines;
Drugs and Materials used in Antiseptic Surgery ; Poisons and their
Antidotes ; Weights and Measures ; Thermometric Scales ; New
Official and Unofficial Drugs, etc. One volume of over 800 pages.
Prices, with Denison's Patent Ready-Reference Index: Cloth, $5.00
net; Sheep or Half Morocco, $6.00 net; Half Russia, $6.50 net.
Without Patent Index: Cloth, $4.00 net; Sheep or Half Morocco,
$5.00 net.

" I am much pleased witli Keathig's Dictionary, and shall take pleasure in recommend'
ing it to my classes." — Henry M. Lyman, M.D., Professor of the Principles and Practict
of Medicine, Rush Medical College, Chicago, III.

" I am convinced that it will be a very valuable adjunct to my study-table, convenient
in size and sufficiently full for ordinary use." — C. A. Lindslev, M.D., Professor of the
Theory and Practice of Medicine, Medical Dept. Yale University.

KEATINQ'S LIFE INSURANCE.

How to Examine for Life Insurance. By John M. Keating,
M.D., Fellow of the College of Physicians of Philadelphia; Vice-
President of the American Pediatric Society ; Ex-President of the
Association of Life Insurance Medical Directors. Royal octavo, 2H
pages ; with two large half-tone illustrations, and a plate prepared by
Dr. McClellan from special dissections ; also, numerous other illustra-
tions. Cloth, $2.00 net.

" This is by far the raost useful book which has yet appeared on insurance examination,
a subject of growing interest and importance. Not the least valuable portion of the volume
is Part II, which consists of instructions issued to their examining physicians by twenty-four
representative companies of this country. If for these alone, the book should be at the right
hand of every physician interested m this special branch of medical science." — The Medical
News.

Medical Piihlicntions of W, B. Saunders. 15

KEEN ON THE SURGERY OF TYPHOID FEVER.

The Surgical Complications and Sequels of Typhoid Fever.

By Wm. W. Kkkn, M.D., LI-.D., I'rofcssor of the I'rinciplcs of Sur-
gery and of Clinical Surgery, Jefferson Medical College, Phila(ie]i)liia ;
Corresponding Member of the Societe de Chirurgie, Paris; Honorary
Member of the Soci6t6 Beige de Chirurgie, etc. (Jctavo volume of
386 pages, illustrated. Cloth, 113.00 net.

" This is probably the first and only work in the Knglish language that gives the reader
a clear view of what typlioid fever really is, and what it does and can do to the human
organism. This book should be in the possession of every medical man in America." —
Atiurican MeiiiiO-Sur;^ic(il Hullitin.

KEEN'S OPERATION BLANK. Second Edition, Revised Form.
An Operation Blank, with Lists of Instruments, etc. Required
in Various Operations, rrejjared by W. W. Kken, M.D., LL.D.,
Professor of the Principles of Surgery in Jefferson Medical College,
Philadelphia. Price per pad, containing blanks for fifty operations,
50 cents net.

KYLE ON THE NOSE AND THROAT.

Diseases of the Nose and Throat. By D. Braden Kyle, M.D.,
Clinical Professor of Laryngology and Rhinology, Jefferson Medical
College, Philadelphia; Consulting Laryngologist, Rhinologist, and
Otologist, St. Agnes' Hospital ; Bacteriologist to the Philadelphia
Orthopedic Hospital. /// Preparation.

LAINE'S TEMPERATURE CHART.

Temperature Chart. Prepared by D. T. Laine, M.D. Size 8 x 13^
inches. A conveniently arranged Chart for recording Temperature,
with columns for daily amounts of Urinary and Fecal Excretions,
Food, Remarks, etc. On the back of each chart is given in full the
method of Brand in the treatment of Typhoid Fever. Price, per pad
of 25 charts, 50 cents net.

" To the busy practitioner this chart will be found of great value in fever cases, and
especially for cases of typhoid." — Indian Lancet, Calcutta.

LOCKWOOD'S PRACTICE OF MEDICINE.

A Manual of the Practice of Medicine. By George Roe Lock-
wood, M.D., Professor of Practice in the Woman's Medical College
of the New York Infirmary, etc. 935 pages, with 75 illustrations in
the text, and 22 full-page plates. Cloth, $2.50 net.

•' Gives in a most concise manner the points essential to treatment usually enumerated
in the most elaborate works." — Massachusetts Medical Journal.

LONG'S SYLLABUS OF GYNECOLOGY.

A Syllabus of Gynecology, arranged in Conformity with «' An
American Text=Book of Gynecology." By J. W. Long, M.D.,
Professor of Diseases of Women and Children, Medical College of
Virginia, etc. Cloth, interleaved, $1.00 net.

" The book is certainly an admirable ristimt of what every gynecological student and
practitioner should know, and will prove of value not only to those who have the ' American
Text-Book of Gynecology,' but to others as well." — Brooklyn Medical Journal.

16 Medical Publications of W. B. Saunders.

MACDONALD'S SURGICAL DIAGNOSIS \ND TREATMENT.

Surgical Diagnosis and Treatment. By J. W. Macdonald, M.D.
Edin., F.R.C.S., Edin., Professor of the Practice of Surgery and of
Clinical Surgery in Hamline University; Visiting Surgeon to St.
Barnabas' Hospital, Minneapolis, etc. Handsome octavo volume of
800 pages, profusely illustrated. Cloth, $5.00 net; Half Morocco,
$6.00 net.

" A thorough and complete work on surgical diagnosis and treatment, free from pad-
ding, full of valuable material, and in accord with the surgical teaching of the day." — 7'ke
Medical Ne-vs, Nrw York.

"The work is brimful of just the kind of practical information that is useful alike to
students and practitioners. It is a pleasure to commend the book because of its intrinsic
value to the medical practitioner." — Cincinnati Lancet- Clinic.

MALLORY AND WRIGHT'S PATHOLOGICAL TECHNIQUE.

Pathological Technique. A Practical Manual for Laboratory Work
in Pathology, Bacteriology, and Morbid Anatomy, with chapters on
Post-Mortem Technique and the Performance of Autopsies. By Frank
B. Mallory, A.M., M.D., Assistant Professor of Pathology, Harvard
University Medical School, Boston; and James H. Wright, A.M.,
M.D., Instructor in Pathology, Harvard University Medical School,
Boston. Octavo volume of 396 pages, handsomely illustrated. Cloth,
$2.50 net.

" I have been looking forward to the publication of this book, and I am glad to say that
I find it to be a most useful laboratory and post-mortem guide, full of practical information,
and well up to date." — William II. Welch, Professor of Pathology, Johns Hopkins Uni-
versity, Baltimore, Md.

MARTIN'S MINOR SURGERY, BANDAGING, AND VENEREAL
DISEASES. Second Edition, Revised.
Essentials of Minor Surgery, Bandaging, and Venereal
Diseases. By Edward Martin, A.M., M.D., Clinical Professor of
Genito- Urinary Diseases, University of Pennsylvania, etc. Crown
octavo, 166 pages, with 78 illustrations. Cloth, $1.00 ; interleaved for
notes, $1.25.

[See Satinders' Question- Compends, page 21.]

"A very practical and systematic study of the subjects, and shows the author's famil-
iarity with the needs of students." — Therapeutic Gazette.

MARTIN'S SURGERY. Sixth Edition, Revised.

Essentials of Surgery. Containing also Venereal Diseases, Surgi-
cal Landmarks, Minor and Operative Surgery, and a complete de-
scription, with illustrations, of the Handkerchief and Roller Bandages.
By Edward Martin, A.M., M.D., Clinical Professor of Genito-
urinary Diseases, University of Pennsylvania, etc. Crown octavo, 338
pages, illustrated. With an Appendix containing full directions for the
preparation of the materials used in Antiseptic Surgery, etc. Cloth,
$1.00; interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]

"Contains all necessary essentials of modem surgery in a comparatively small space.
Its style is interesting, and its illustrations are admirable." — Medical and Surgical Reporter.

Medical Publications of W. B. iSaunders. 17

McFARLAND'S PATHOGENIC BACTERIA. Second Edition, Re-
vised and Greatly Enlarged.
Text-Book upon the Pathogenic Bacteria. By Joseph McFar-
LAND, M. D., Professor of Pathology and Bacteriology in the Medico-
Chirurgical College of Philadelphia, etc. Octavo volume of 497 pages,
finely illustrated. Cloth, $2.50 net.

" Dr. McFarland lias treated the subject in a systematic manner, and has succeeded in
presenting in a concise and readable form the essentials of bacteriology up to date. Alto-
gether, the book is a satisfactory one, and I shall take pleasure in recommending it to the
students of Trinity College."— H. B. Anderson, M.D. , Professor of Pathology and Bac-
teriologv. Trinity JMedical College, Toronto.

MEIGS ON FEEDING IN INFANCY.

Feeding in Early Infancy. By Arthur V. Meigs, M.D. Bound

in limp cloth, flush edges, 25 cents net.

"This pamphlet is worth many times over its price to the physician. The author's
experiments and conclusions are original, and have been the means of doing much good." —
Medical Bulletin.

MOORE'S ORTHOPEDIC SURGERY.

A Manual of Orthopedic Surgery. By James E. Moore, M.D.,
Professor of Orthopedics and Adjunct Professor of Clinical Surgery,
University of Minnesota, College of Medicine and Surgery. Octavo
volume of 356 pages, handsomely illustrated. Cloth, $2.50 net.

" A most attractive work. The illustrations and the care with which the book is adapted
to the wants of the general practitioner and the student are worthy of great praise." — Chicago
Medical Recorder.

" A very demonstrative work, every illustration of which conveys a lesson. The work is
a most excellent and commendable one, which we can certainly endorse with pleasure." —
St. Louis Aledical and Surgical Journal.

MORRIS'S MATERIA MEDICA AND THERAPEUTICS. Fifth
Edition, Revised.
Essentials of Materia Medica, Therapeutics, and Prescription-
Writing. By Henry Morris, M.D., late Demonstrator of Thera-
peutics, Jefferson Medical College, Philadelphia; Fellow of the College
of Physicians, Philadelphia, etc. Crown octavo, 288 pages. Cloth,
$1.00; interleaved for notes, $1.25.

[See Saunders' Question- Compe?ids, page 21.]

" This work, already excellent in the old edition, has been largely improved by revii-
sion." — American Practitioner and News.

MORRIS, WOLFF, AND POWELL'S PRACTICE OF MEDICINE,
Third Edition, Revised.
Essentials of the Practice of Medicine. By Henry Morris, M.D.^
late Demonstrator of Therapeutics, Jefferson Medical College, Phila-
delphia ; with an Appendix on the Clinical and Microscopic Examina-
tion of Urine, by Lawrence Wolff, M.D. , Demonstrator of Chemistry,.
Jefferson Medical College, Philadelphia. Enlarged by some 300 essen-
tial formulae collected and arranged by William M. Powell, M.D..
Post-octavo, 488 pages. Cloth, ^2.00.

[See Saunders' Question- Compends, page 21.]

" The teaching is sound, the presentation graphic ; matter full as can be desired, and
style attractive." — American Practitioner and News.

18 Medical Publications of W, B. Saunders.

MORTEN'S NURSE'S DICTIONARY.

Nurse's Dictionary of Medical Terms and Nursing Treat-
ment. Containing Definitions of the Principal Medical and Nursing
Terms and Abbreviations ; of the Instruments, Drugs, Diseases, Acci-
dents, Treatments, Operations, Foods, Appliances, etc. encountered
in the ward or in the sick-room. By Honnor Morten, author of
" How to Become a Nurse," etc. i6mo, 140 pages. Cloth, $1.00.

" A liandy, compact little volume, containing a large amount of general information, all
of which is arranged in dictionary or encyclopedic form, thus facilitating (piick reference.
It is certainly of value to those for whose use it is published." — Chicago Clinical Kernew.

NANCREDE'S ANATOMY. Fifth Edition.

Essentials of Anatomy, including the Anatomy of the Viscera.
By Charles B. Nancrede, M.D., Professor of Surgery and of Clini-
cal Surgery in the University of Michigan, Ann Arbor. Crown octavo,
388 pages; 180 illustrations. With an Appendix containing over 60
illustrations of the osteology of the human body. Based upon Gray' s
Anatomy. Cloth, $1.00; interleaved for notes, $i.2c^.
[See Satmders' Question- Compends, page 21.]

" For self-quizzing and keeping fresh in mind the knowledge of anatomy gained at
school, it would not be easy to speak of it in terms too favorable." — American Practitioner.

NANCREDE'S ANATOMY AND DISSECTION. Fourth Edition.
Essentials of Anatomy and Manual of Practical Dissection.

By Charles B. Nancrede, M.D., Professor of Surgery and of Clinical
Surgery, University of Michigan, Ann Arbor. Post-octavo ; 500 pages,
with full-page lithographic plates in colors, and nearly 200 illustrations.
Extra Cloth (or Oilcloth for the dissection-room), ^2.00 net.

" It may in many respects be considered an epitome of Gray's popular work on general
anatomy, at the same time having some distinguishing characteristics of its own to commend
it. The plates are of more than ordinary excellence, and are of especial value to students
in their work in the dissecting room." — Journal of the American Aledical Association.

NORRIS'S SYLLABUS OF OBSTETRICS. Third Edition, Revised.
Syllabus of Obstetrical Lectures in the Medical Department
of the University of Pennsylvania. By Richard C. Norris,
A.M., M.D., Demonstrator of Obstetrics, University of Pennsylvania.
Crown octavo, 222 pages. Cloth, interleaved for notes, $2.00 net.

"This work is so far superior to others on the same subject that we take pleasure in
calling attention briefly to its excellent features. It covers the subject thoroughly, and will
prove invaluable both to the student and the practitioner." — Medical Record, New York.

PENROSE'S DISEASES OF WOMEN. Second Edition, Revised.
A Text=Book of Diseases of Women. By Charles B. Penrose,
M.D., Ph.D., Professor of Gynecology in the University of Pennsyl-
vania ; Surgeon to the Gynecean Hospital, Philadelphia. Octavo
volume of 529 pages, handsomely illustrated. Cloth, ^3.50 net.

<'I shall value very highly the copy of Penrose's 'Diseases of Women' received.
I have already recommended it to my class as THE BEST book."— Howard A. Kelly.
Professor of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Md.

" The book is to be commended without reserve, not only to the student but to the
general practitioner who wishes to have the latest and best modes of treatment explained
with absolute clearness." — Therapeutic Gazette.

Medical Publications of W. B. Saunders. 19

POWELL'S DISEASES OF CHILDREN. Second Edition.

Essentials of Diseases of Children. By William M. Powell,
M.D., Attending Physician to the Mercer House for Invalid Women
at Atlantic City, N. J. ; late Physician to the Clinic for the Diseases of
Children in the Hospital of the University of Pennsylvania. Crown
octavo, 222 pages. Cloth, j^i-oo; interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]

"Contains the gist of all the best works in the department to which it relates."—
American Practitioner and News.

PRINQLE'S SKIN DISEASES AND SYPHILITIC AFFECTIONS.
Pictorial Atlas of Skin Diseases and Syphilitic Affections
(American Edition). Translation from the French. Edited by
J. J. Pringle, M.B., F.R.C.P., Assistant Physician to the Middlesex
Hospital, London. Photo-lithochromes from the famous models in
the Museum of the Saint-Louis Hospital, Paris, with explanatory wood-
cuts and text. In 12 Parts. Price per Part, $3.00. Complete in
one volume, Half Morocco binding, $40.00 net.

** I strongly recommend this Atlas. The plates are exceedingly well executed, and
will be of great value to all studying dermatology." — Stephen Mackenzie, M.D.

"The introduction of explanatory wood-cuts in the text is a novel and most important
feature which greatly furthers the easier understanding of the excellent plates, than which
nothing, we venture to say, has been seen better in point of correctness, beauty, and general
merit." — AWc Vori Aledical Journal.

PYE'S BANDAGING.

Elementary Bandaging and Surgical Dressing. With Direc-
tions concerning the Immediate Treatment of Cases of Emergency.
For the use of Dressers and Nurses. By Walter Pye, F.R.C.S., late
Surgeon to St. Mary's Hospital, London. Small i2mo, with over 80
illustrations. Cloth, flexible covers, 75 cents net.

" The directions are clear and the illustrations are good." — London Lancet.
" The author writes well, the diagrams are clear, and the book itself is small and port-
able, although the paper and type are good." — British Medical Journal.

RAYMOND'S PHYSIOLOGY.

A Manual of Physiology. By Joseph H. Raymond, A.M., M.D.,
Professor of Physiology and Hygiene and Lecturer on Gynecology in
the Long Island College Hospital; Director of Physiology in the
Hoagland Laboratory, etc. 382 pages, with 102 illustrations in the
text, and 4 full-page colored plates. Cloth, ^1.25 net.

'• Extremely well gotten up, and the illustrations have been selected with care. The
text is fully abreast with modern physiology." — British Medical Journal.

RONTGEN RAYS.

Archives of the Rontgen Ray (Formerly Archives of Clinical
Skiagraphy). Edited by Sydney Rowland, M.A., M.R.C.S., and
W. S. Hedley, M.D., M.R.C.S. A series of collotype illustrations,
with descriptive text, illustrating the applications of the new photo-
graphy to Medicine and Surgery. Price per Part, $1.00. Now ready:
Vol. I , Parts I. to IV.; Vol. II., Parts I., II.

Saunders'
Question
compends

Arranged in Question and
Answer Form,

npHE MOST COMPLETE AND BEST
ILLUSTRATED SERIES OF

COMPENDS EVER ISSUED.

Now the Standard Authorities in Medical Literature ....

with Students and Practitioners in every City of the United States and Canada.

•<3

^ OVER ^ 65,000 COPIES SOLD. ^
THE REASON WHY,

They are the advance guard of "Student's Helps" — that DO HELP. They are the
leaders in their special line, well and authoritatively written by able men, who, as teachers in
the large colleges, know exactly what is wanted by a student preparing for his examinations.
The judgment exercised in the selection of authors is fully demonstrated by their professional
standing. Chosen from the ranks of Demonstrators, Quiz-masters, and Assistants, most of
them have become Professors and Lecturers in their respective colleges.

Each book is of convenient size (5x7 inches), containing on an average 250 pages,
profusely illustrated, and elegantly printed in clear, readable type, on fine paper.

The entire series, numbering twenty-three volumes, has been kept thoroughly revised
and enlarged when necessary, many of the books being in their fifth and sixth editions.

TO SUM UP>

Although there are numerous other Quizzes, Manuals, Aids, etc. in the market, none of
them approach the " Blue Series of Question Compends;" and the claim is made for the
following points of excellence :

1. Professional distinction and reputation of authors.

2. Conciseness, clearness, and soundness of treatment.

3. Quality of illustrations, pajier, printing, and binding.

Any of these Compends will be mailed on receipt of price (see next page for .List).

Saunders^ Question-Compend beries*

Price» Cloth, $1.00 per copy, except when otherwise noted,

"Where Ihe work of prepariiiR students' manuals is to end we cannot say, but the
Saunders Series, in our opinion, bears off the palm at present."— iV^zt/ Vork Medical Record.

1. ESSENTIALS OF PHYSIOLOGY. By H. A. Hare, M.D. Fourth edition,

revised and enlarged. ($l.oo net.)

2. ESSENTIALS OF SURGERY. By Edward Martin, M.D. Sixth edition,

revisetl, with an Appendix on Antiseptic Surgery.

3. ESSENTIALS OF ANATOMY. By Charlks B. Nancrede, M.D. Fifth

edition, with an Appendix.

4. ESSENTIALS OF MEDICAL CHEMISTRY, ORGANIC AND INORGANIC.

By Lawrence Wolfe, M.D. Fourth edition, revised, with an Appendix.

5. ESSENTIALS OF OBSTETRICS. By W. Easterly Ashton, M.D. Fourth

edition, revised and enlarged.

6. ESSENTIALS OF PATHOLOGY AND MORBID ANATOMY. By C. E.

Armand Semple, M.D.

7. ESSENTIALS OF MATERIA MEDICA, THERAPEUTICS, AND PRE-

SCRIPTION=WRITING. By Henry Morris, M.D. Fifth edition, revised.

8. 9. ESSENTIALS OF PRACTICE OF MEDICINE. By Henry Morris,

M.D. An Appendix on Urine Examination. By Lawrence Wolff, M.D.

Third edition, enlarged by some 300 Essential Formulae, selected from eminent

authorities, by Wm. "^M. Powell, M.D. (Double number, ^2.00.)
10. ESSENTIALS OF GYNECOLOGY. By Edwin B. Cragin, M.D. Fourth

edition, revised.
U. ESSENTIALS OF DISEASES OF THE SKIN. By Henry W. Stelwagon,

M.D. Third edition, revised and enlarged. ($1.00 net.)

12. ESSENTIALS OF MINOR SURGERY, BANDAGING, AND VENEREAL

DISEASES. By Edward Martin, M.D. Second ed., revised and enlarged.

13. ESSENTIALS OF LEGAL MEDICINE, TOXICOLOGY, AND HYGIENE.

By C. E. Armand Semple, M.D.
14 ESSENTIALS OF DISEASES OF THE EYE, NOSE, AND THROAT.

By Edward Jackson, M.D., and E. B. Gleason, M.D. Second ed., revised.

15. ESSENTIALS OF DISEASES OF CHILDREN. By William M. Powell,

M. D. Second edition.

16. ESSENTIALS OF EXAMINATION OF URINE. By Lawrence Wolff,

M.D. Colored " VoGEL Scale." (75 cents.)

17. ESSENTIALS OF DIAGNOSIS. By S. Solis Cohen, M.D., and A. A. Eshner,

M.D. ($1.50 net.)

18. ESSENTIALS OF PRACTICE OF PHARMACY. By Lucius E. Sayre.

Second edition, revised and enlarged.

20. ESSENTIALS OF BACTERIOLOGY. By M. V. Ball, M.D. Third edition,

revised.

21. ESSENTIALS OF NERVOUS DISEASES AND INSANITY. By John C.

Shaw, M.D. Third edition, revised.

22. ESSENTIALS OF MEDICAL PHYSICS. By Fred J. Brockway, M.D.

Second edition, revised. ($1.00 net.)

23. ESSENTIALS OF MEDICAL ELECTRICITY. By David D. Stewart, M.D.,

and Edward S. Lawrance, M.D.

24. ESSENTIALS OF DISEASES OF THE EAR. By E. B. Gleason, M.D

Second edition, revised and greatly enlarged.

PampWet containing specimen pages, etc sent free upon application.

I

1-

Saunders'

New Series
of Manuals

for Students
and
Practitioners.

■* I 'HAT there exists a need for thoroughly reliable hand-books on the leading branches
of Medicine and Surgery is a fact amply demonstrated by the favor with which
the SAUNDERS NEW SERIES OF MANUALS have been received by medical
students and practitioners and by the Medical Press. These manuals are not merely
condensations from present literature, but are ably w^ritten by w^ell-known authors
and practitioners, most of them being teachers in representative American colleges*
Each volume is concisely and authoritatively w^ritten and exhaustive in detail, without
being encumbered -with the introduction of "cases," which so largely expand the
ordinary text-book. These manuals will therefore form an admirable collection of
advanced lectures, useful alike to the medical student and the practitioner: to the
latter, too busy to search through page after page of elaborate treatises for w^hat he
wants to know^, they w^ill prove of inestimable value ; to the former they will afford
safe guides to the essential points of study.

The SAUNDERS NEW SERIES OF MANUALS are conceded to be superior
to any similar books now on the market. No other manuals afford so much infor-
mation in such a concise and available form. A liberal expenditure has enabled the
publisher to render the mechanical portion of the w^ork worthy of the high literary
standard attained by these books.

Any of these Manuals w^ill be mailed on receipt of price (see next page for List).

Saunders^ New Series of Manuals*

VOLUMES PUBLISHED.

PHYSIOLOGY. By Joski>h Howard Raymond, A.M., M.D., Professor of Physiology
and Hygiene and Lecturer on Gynecology in the Long Island College Hospital;
Director of Physiology in the Hoagland Laboratory, etc. Illustrated. Cloth, jgl.aj; net.

SURGERY, General and Operative. IJy John Chai.mkks DaCosta, M.D., Clini-
cal I'rolcssor of Surgery, Jelierson Medical College, Philadelphia; Surgeon to the
Philadelphia Hos]iilal, etc. Second edition, thoroughly revised and greatly enlarged.
Octavo, 911 pages, profusely illustrated. Cloth, M-OO net ; Half Morocco, $5.00 net.

DOSE=BOOK AND MANUAL OF PRESCRIPTION-WRITING. By E. Q.

TiioKNToN, M.I)., Demonstrator of Therapeutics, Jeffer.son Medical College, Phila-
(lel[ihia. Illustrated. Cloth, $1.25 net.

SURGICAL ASEPSIS. By Car t. Beck, M.D., Surgeon to St. Mark's Hospital and
to the New York German PoliUlinik, etc. Illustrated. Cloth, ;?1.25 net.

MEDICAL JURISPRUDENCE. By Henry C. Chapman, M.D. Professor of Insti-
tutes of Medicine and Medical Jurisprudence in the Jeffenson Medical College of Phila-
delphia. Illustrated. Cloth, #1.50 net.

SYPHILIS AND THE VENEREAL DISEASES. By James Nevins Hyde, M.D.,
Professor of Skin and Venereal Diseases, and Frank H. Montgomery, M.D.,
Lecturer on Dermatology and Genito-Urinary Diseases in Rush Medical College,
Chicago. Profusely illustrated. Cloth, ^2.50 net.

PRACTICE OF MEDICINE. By George Roe Lockwood, M.D., Professor of
Practice in the Woman's Medical College of the New York Infirmary ; Instructor in
Physical Diagnosis in the Medical Department of Columbia College, etc. Illustrated.
Cloth, ^2.50 net.

MANUAL OF ANATOMY. By Irving S. Haynes, M.D., Adjunct Professor of
Anatomy and Demonstrator of Anatomy, Medical Department of the New York
University, etc. Beautifully illustrated. Cloth, $2.50 net.

MANUAL OF OBSTETRICS. By W. A. Newman Dorland, M.D., Assistant
Demonstrator of Obstetrics, University of Pennsylvania ; Chief of Gynecological Dis-
pensary, Pennsylvania Hospital, etc. Profusely illustrated. Cloth, ^2.50 net.

DISEASES OF WOMEN. By J. Bland Sutton, F. R. C. S., Assistant Surgeon to
Middlesex Hospital and Surgeon to Chelsea Hospital, London; and Arthur E.
Giles, M. D., B. Sc. Lond., F.R.C.S. Edin., Assistant Surgeon to Chelsea Hospital,
London. Handsomely illustrated. Cloth, ^2.50 net.

VOLUMES IN PREPARATION.

NOSE AND THROAT. By D. Braden Kyle, M.D., Clinical Professor of Laryn-
gology and Rhinology, Jefferson Medical College, Philadelphia ; Consulting Laryngolo-
gist, Rhinologist, and OtologLst, St. Agnes' Hospital; Bacteriologist to the Philadel-
phia Orthopedic Hospital and Infirmary for Nervous Diseases, etc.

NERVOUS DISEASES. By Charles W. Burr, M.D., Clinical Professor of Nervous
Diseases, Medico-Chirurgical College. Philadelphia; Pathologist to the Orthopaedic
Hospital and Infirmary for Nervous Diseases; Visiting Physician to the St. Joseph
Hospital, etc.

*** There will be published in the same series, at short intervals, carefully-prepared works
on various subjects by prominent specialists.

Pamphlet containing specimen pages, etc. sent free upon application.

24 Medical Publications of W. B. Saunders.

SAUNDBY'S RENAL AND URINARY DISEASES.

Lectures on Renal and Urinary Diseases. P>y Robert Saundby,
M.D. Edin., Fellow of the Royal College of Physicians, London, and
of the Royal Medico-Chirurgical Society ; Physician to the General
Hospital ; Consulting Physician to the Eye Hospital and to the Hos-
pital for Diseases of Women; Professor of Medicine in Mason College,
Birmingham, etc. Octavo volume of 434 pages, with numerous illus-
trations and 4 colored plates. Cloth, $2.50 net.

" The volume makes a favorable impression at once. The style is clear and succinct.
We cannot find any part of the subject in which the views expressed are not carefully thought
out and fortified by evidence drawn from the most recent sources. The book may be cordially
recommended." — British IMedical Jonrnal.

5AUNDERS' MEDICAL HAND=ATLASES.

This series of books consists of authorized translations into English of
the world-famous Lehmann Medicinische liandatlanten. I<2ach

volume contains from 50 to 100 colored lithographic ])lates, besides
numerous illustrations in the te.xt. There is a full description of each
plate, and each book contains a condensed but adequate outline of the
subject to which it is devoted. For full description of this series, with
list of volumes and prices, see page 2.

"Lehmann Medicinische liandatlanten belong to that class of books that arc too good
to be appropriated by any one nation." — Journal of Eye, Ear, and T/iroat Diseases.

'• The appearance of these works marks a new era in illustrated English medical

works."' — Thr Canaiiian Practitioner.

5AUNDERS' POCKET MEDICAL FORMULARY. Fifth Edition,
Revised.

By William M. Powell, M.D., Attending Physician to the Mercer
House for Invalid Women at Atlantic City, N. J. Containing i8qo
ibrmulce selected from the best-known authorities. With an Appen-
dix containing Posological Table, Formulae and Doses for Hypo-
dermic Medication, Poisons and their Antidotes, Diameters of the
Female Pelvis and Foetal Head, Obstetrical Table, Diet List for Various
Diseases, Materials and Drugs used in Antiseptic Surgery, Treatment
of Asphyxia from Drowning, Surgical Remembrancer, Tables of
Incompatibles, Eruptive Fevers, Weights and Measures, etc. Hand-
somely bound in flexible morocco, with side index, wallet, and flap.
$1.75 net.

" This little book, that can be conveniently carried in the pocket, contains an immense
amount of material. It is very useful, and, as the name of the author of each jirescription
is given, is unusually reliable." — Medical Record, New York.

SAYRE'S PHARMACY. Second Edition, Revised.

Essentials of the Practice of Pharmacy. By Lucius E. Sayre,
M.D., Professor of Pharmacy and Materia Medica in the University of
Kansas. Crown octavo, 200 pages. Cloth, $1.00; interleaved for
notes, $1.25.

[See Saunders'' Question- Coftipends, page 21.]

" The topics are treated in a simple, practical manner, and the work forms a very useful
Student's manual." — Boston iMedical and Stiigical Journal.

Medical Publications of W. B. Saunders. 25

SEMPLE'S LEGAL MEDICINE, TOXICOLOGY, AND HYGIENE.

Essentials of Legal Medicine, Toxicology, and Hygiene. By

C. E. Armanu Skmi'Lk, B. A., M. 1}. Cantab., M. R.C.I'. Lond.,
Physician to the Northeastern Hospital for Children, Hackney, etc.
Crown octavo, 212 pages; 130 illustrations. Cloth, ;gi. 00; interleaved
for notes, Si. 25.

[See Saunders' Question- Compends, page 21.]

" No general practitioner or student can afiord to be without this valuable work. The
subjects are dealt with by a masterly hand." — Loudon Hospital Gazette.

SEMPLE'S PATHOLOGY AND MORBID ANATOMY.

Essentials of Pathology and Morbid Anatomy. By C. E.

Armand Semple, B.A., M.B. Cantab., M.R.C.P. Lond., Physician to
the Northeastern Hospital for Children, Hackney, etc. Crown octavo,
174 pages; illustrated. Cloth, $1.00; interleaved for notes, $i. 25.
[See Saunders' Question- Compends, page 21.]

" Should take its place among the standard volumes on the bookshelf of both student
and practitioner." — London Hospital Gazette.

SENN'S GENITO=URINARY TUBERCULOSIS.

Tuberculosis of the Genito-Urinary Organs, Male and Female.

By Nicholas Senn, M.D., Ph.D., LL.D., Professor of the Practice of
Surgery and of Clinical Surgery, Rush Medical College, Chicago.
Handsome octavo volume of 320 pages, illustrated. Cloth, $3.00 net.

" An important book upon an important subject, and written by a man of mature judg-
ment and wide experience. The author has given us an instructive book upon one of the
most important subjects of the day." — Clinical Reporter.

" A work which adds another to the many obligations the profession owes the talented
author." — Chicago Medical Recorder.

SENN'S SYLLABUS OF SURGERY.

A Syllabus of Lectures on the Practice of Surgery, arranged
in conformity with " An American Text=Book of Surgery." By

Nicholas Senn, M.D., Ph.D., Professor of the Practice of Surgery and
of Clinical Surgery in Rush Medical College, Chicago. Cloth, ;^2.oo.

" This syllabus will be found of service by the teacher as well as the student, the work
being superbly done. There is no praise too high for it. No surgeon should be without

it. " — Ne7v York Medical Times.

SENN'S TUMORS.

Pathology and Surgical Treatment of Tumors. By N. Senn,
M.D., Ph.D., LL.D., Professor of Surgery and of Clinical Surgery,
Rush Medical College ; Professor of Surgery, Chicago Polyclinic ;
Attending Surgeon to Presbyterian Hospital ; Surgeon-in-Chief, St.
Joseph's Hospital, Chicago. Octavo volume of 710 pages, with 515
engravings, including full-page colored plates. Cloth, $6.00 net;
Half Morocco, $7.00 net.

" The most exhaustive of any recent book in Engush on this subject. It is well illus-
trated, and will doubtless remain as the principal monograph on the subject in our language
for some years. The book is handsomely illustrated and printed, and the author has given a
notable and lasting contribution to surgery. "—_/(?«/-««/ of the American Medical Association.

26 Medical Publications of W. B. Saunders.

SHAW'S NERVOUS DISEASES AND INSANITY. Third Edition,
Revised.
Essentials of Nervous Diseases and Insanity. By John C.
Shaw, M.D., Clinical Professor of Diseases of the Mind and Nervous
System, Long Island College Hospital Medical School ; Consulting
Neurologist to St. Catherine's Hospital and to the Long Island College
Hospital. Crown octavo, 186 pages; 48 original illustrations. Cloth,
$1.00 ; interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]

"Clearly and intelligently written." — Boston Medical atiJ Surgical Journal.

"There is a mass of valuable material crowded into this small compass." — American
Medico-Surgical Bulletin.

STARR'S DIETS FOR INFANTS AND CHILDREN.

Diets for Infants and Children in Health and in Disease. By

Louis Starr, M.D. , Editor of "An American Text-Book of the
Diseases of Children." 230 blanks (pocket-book size), perforated
and neatly bound in flexible morocco. $1.25 net.

The first series of blanks are prepared for the first seven months of infant life ; each
blank indicates the ingredients, but not the quantities, of the food, the latter directions being
left for the physician. After the seventh month, modifications being less necessary, the diet
lists are printed in full. Formulas for the preparation of diluents and foods are appended.

STELW AGON'S DISEASES OF THE SKIN. Third Edition, Revised.
Essentials of Diseases of the Skin. By Henry W. Stelwagon,
M.D., Clinical Professor of Dermatology in the Jefferson Medical
College, Philadelphia; Dermatologist to the Philadelphia Hospital;
Physician to the Skin Dei)artnient of the Howard Hospital, etc.
Crown octavo, 270 pages; 86 illustrations. Cloth, $1.00 net; inter-
leaved for notes, $1.25 net.

[See Saunders' Question- Compends, page 21.]
" The best student's manual on skin diseases we have yet seen." — Times and Register.

STENGEL'S PATHOLOGY.

A Text=Book of Pathology. By Alfred Stenoei., M. D., Physician
to the Philadeli)hia Hospital ; Clinical Professor of Medicine in the
Woman's Medical College ; Physician to the Children's Hospital ;
late Pathologist to the German Hosi)ital, Philadelphia, etc. Handsome
octavo volume of 848 ])ages, with nearly 400 illustrations, many of them
in colors. Cloth, $4.00 net; Half Morocco, $5.00 net.

STEVENS' MATERIA MEDICA AND THERAPEUTICS. Second
Edition, Revised.
A Manual of Materia Medica and Therapeutics. By A. A.

Stevens, A.M., M.D., Lecturer on Terminology and Instructor in
Physical Diagnosis in the University of Pennsylvania ; Professor of
Pathology in the Woman's Medical College of Pennsylvania. Post-
octavo, 445 pages. Flexible leather, $2.25.

"The author has faithfully presented modern therapeutics in a comprehensive work,
and, while intended particularly for the use of students, it will be found a reliable guide and
sufficiently comprehensive for the physician in practice." — University Medical Magazine.

Medical Publications of W. B. Saunders. 27

STEVENS' PRACTICE OF MEDICINE. Fifth Edition, Revised.
A Manual of the Practice of Medicine. \',y A. A. Si kvkns, A.M.,
M. 1)., IxctuiLT on Icrminology and Instructor in Physical Diagnosis
in the University of Pennsylvania; J'rofessor of Pathology in the
Woman's Medical College of Pennsylvania. Speciallv intended for
students preparing for graduation and hospital examinations. Posi-
octavo, 519 pages; illustrated. Fle.xible leather, $2.00 net.
"The frequency with which new editions of this manual are demanded bespeaks its
popularity. It is an excellent condensation of the essentials of medical practice for the
student, and maybe found also an excellent reminder for the busy physician." — Buffalo
Medical Jounial. ^ ■"

STEWART'S PHYSIOLOGY. Third Edition, Revised.

A Manual of Physiology, with Practical Exercises. For
Students and Practitioners. By G. N. Stewart, M.A., M.D.,
D.Sc, lately Examiner in Physiology, University of Aberdeen, and
of the New Museums, Cambridge University ; Professor of Physiology
in the Western Reserve University, Cleveland, Ohio. Octavo volume
of 848 pages; 300 illustrations in the text, and 5 colored i>lates.
Cloth, $3.75 net.

" It will make its way by sheer force of merit, and amply deserves to do so. It is one
of the very best English text-books on the subject." — London Lancet.

"Of the many text-books of physiology published, we do not know of one that so
nearly comes up to the ideal as does Prof. Stewart's volume." — British Medical Journal.

STEWART AND LAWRANCE'S MEDICAL ELECTRICITY.

Essentials of Medical Electricity. By D. D. Stewart, M.D.,
Demonstrator of Diseases of the Nervous System and Chief of the
Neurological Clinic in the Jefferson Medical College ; and E. S.
Lawrance, M.D., Chief of the Electrical Clinic and Assistant Demon-
strator of Diseases of the Nervous System in the Jefferson Medical
College, etc. Crown octavo, 158 pages; 65 illustrations. Cloth,
;^i.oo ; interleaved for notes, $1.25.

[See Saunders' Question- Compends, page 21.]

" Throughout the whole brief space at their command the authors show a discriminating
knowledge of their subject." — Medical News.

STONEY'S NURSING. Second Edition, Revised.

Practical Points in Nursing. For Nurses in Private Practice,

By Emily A. M. Stoney, Graduate of the Training-School for Nurses,
Lawrence, Mass.; late Superintendent of the Training-School for
Nurses, Carney Hospital, South Boston, Mass. 456 pages, illustrated
with 73 engravings in the text, and 8 colored and half-tone plates.
Cloth, $1.75 net.

" There are few books intended for non-professional readers which can be so cordially
endorsed by a medical journal as can this one." — Therapeutic Gazette.

" This is a well-written, eminently practical volume, which covers the entire range of
private nursing as distinguished from hospital nursing, and instructs the nurse how best to
meet the various emergencies which may arise, and how to prepare everything ordinarily
needed in the illness of her patient." — American Journal of Obstetrics and Diseases of
Women and Children.

" It is a work that the physician can place in the hands of his private nurses with the
assurance of benefit." — Ohio Aledical Journal.

28 Medical Publications of W. B. Saunders.

STONEY'S MATERIA MEDICA FOR NURSES.

Materia Medica for Nurses. P.y Kmii.y A. M. Stoney, Graduate of
the 'rraining-School lor Nurses, Lawrence, Mass. ; late Superintendent
of the Training-School for Nurses, Carney Hospital. South Boston, Mass.
Handsome octavo volume of about 300 pages. Cloth, $1.50 net.

The present book differs from other similar works in several features, all of which are
intended to render it more practical and generally useful. The general plan of the contents
follows the lines laid down in training-schools for nurses, but the book contains much use-
ful matter not usually included in works of this character, such as Poison-emergencies,
Ready Dose-list, Weights and Measures, etc., as well as a Glossary, defining all the terms
used in Materia Medica, and describing all the latest drugs and remedies, which have been
generally neglected by other books of the kind.

SUTTON AND GILES' DISEASES OF WOMEN.

Diseases of Women. By J. Bland Sutton, F.R.C.S., Assistant
Surgeon to Middlesex Hospital, and Surgeon to Chelsea Hospital,
London; and Arthur E. Giles, M.D., B.Sc. Lond., F.R.C.S. Edin.,
Assistant Surgeon to Chelsea Hospital, London. 436 pages, hand-
somely illustrated. Cloth, $2.50 net.

"The text has been carefully prepared. Nothing essential has been omitted, and its
teachings are those recommended by the leading authorities of the day.'"— Journal of tkt
Avieiican Medical Association.

THOMAS'S DIET LISTS AND SICK=ROOM DIETARY.

Diet Lists and Sick=Room Dietary. By Jerome B. Thomas,
M.D., Visiting Physician to the Home for Friendless Women and
Children and to the Newsboys' Home ; Assistant Visiting Physician
to the Kings County Hospital. Cloth, $1.50. Send for sample sheet.

THORNTON'S DOSE=BOOK AND PRESCRIPTION=WRITING.

Dose=Book and Manual of Prescription=Writing. By E. Q.

Thornton, M.D., Demonstrator of Therapeutics, Jefferson Medical
College, Philadelphia. 334 pages, illustrated. Cloth, $1.25 net.

"Full of practical suggestions; will take its place in the front rank of works of this
sort." — Medical Record, New York.

VAN VALZAH AND NISBET'S DISEASES OF THE STOMACH.
Diseases of the Stomach. By Willl\m W. Van Valzah, M.D. ,
Professor of General Medicine and Diseases of the Digestive System
and the Blood, New Vork Polyclinic; and J. Douglas Ntsbet, M.D.,
Adjunct Professor of General Medicine and Diseases of the Digestive
System and the Blood, New Vork Polyclinic. Octavo volume of 674
pages, illustrated. Cloth, $3-50 net.

" Its chief claim lies in its clearness and general adaptability to the practical needs of
the general practitioner or student. In these relations it is probal)ly the best of the recent
special works on diseases of the stomach." — Chicago Clinical Review.

VECKI'S SEXUAL IMPOTENCE.

The Pathology and Treatment of Sexual Impotence. By Victor
G. Vecki, M.D. From the second German edition, revised and en-
larged. Demi-octavo, about 300 pages. Cloth, $2.00 net.

The subiect of impotence has seldom been treated in this country in the truly scientific
spirit that it deserves. Dr. Vecki's work has long been favorably known, and the German
book has received the highest consideration. This edition is more than a mere translation,
for, although based on the German edition, it has been entirely rewritten in English.

Medical Publications of W. B. Saunders. 29

VIERORDT'S MEDICAL DIAGNOSIS. Fourth Edition, Revised.
Medical Diagnosis. By Dr. Oswald Vierordt, Professor of Medi-
cine at the University of Heidelberg. Translated, with additions,
from the fifth enlarged German edition, with the author's permission,
by Francis H. Stuart, A. M., M. D. Handsome royal octavo volume
of 603 pages; 194 fine wood-cuts in text, many of them in colors.
Cloth, $4.00 net; Sheep or Half Morocco, $5.00 net.

" A treasury of practical information which will be found of daily use to every busy
practitioner who will consult it." — C. A. LlNDSLEY, M.D., Professor of the Theory and
Practice of Medicine, Yale University .

" Rarely is a book published with which a reviewer can find so little fault as with the
volume before us. Each particular item in the consideration of an organ or apparatus, which
is necessary to determine a diagnosis of any disease of that organ, is mentioned ; nothing
seems forgotten. The chapters on diseases of the circulatory and digestive apparatus and
nervous system are especially full and valuable. The reviewer would repeat that the book is
one of the best — probably the best — which has fallen into his hands." — University Medical
Magazine.

WARREN'S SURGICAL PATHOLOGY AND THERAPEUTICS.

Surgical Pathology and Therapeutics. By John Collins Warren,
M.D., LL.D., Professor of Surgery, Medical Department Harvard
University; Surgeon to the Massachusetts General Hospital, etc.
Handsome octavo volume of 832 pages; 136 relief and lithographic
illustrations, 33 of which are printed in colors, and all of which were
drawn by William J. Kaula from original specimens. Cloth, $6.00
net; Half Morocco, $7.00 net.

"There is the work of Dr. Warren, which I think is the most creditable book on
Surgical Pathology, and the most beautiful medical illustration of the bookmaker's art, that
has ever been issued from the American press." — Dr. Roswell Park, in the Harvard
Graduate Magazine.

" The handsomest specimen of bookmaking that has ever been issued from the American
medical press." — American Journal of the Medical Sciences.

" A most striking and very excellent feature of this book is its illustrations. Without
e.xception, from the point of accuracy and artistic merit, they are the best ever seen in a work
of this kind. Many of those representing microscopic pictures are so perfect in their coloring
and detail as almost to give the beholder the impression that he is looking down the barrel
of a microscope at a well-mounted section." — Annals of Surgery.

WOLFF ON EXAMINATION OF URINE.

Essentials of Examination of Urine. By Lawrence Wolff, M.D.,
Demonstrator of Chemistry, Jefferson Medical College, Philadelphia,
etc. Colored (Vogel) urine scale and numerous illustrations. Crown
octavo. Cloth, 75 cents.

[See Saunders' Question- Compends, page 21.]

" A very good work of its kind — very well suited to its purpose." — Times and Register.

WOLFF'S MEDICAL CHEMISTRY. Fourth Edition, Revised.
. Essentials of Medical Chemistry, Organic and Inorganic.

Containing also Questions on Medical Physics, Chemical Physiology,
Analytical Processes, Urinalysis, and Toxicology. By Lawrence
Wolff, M.D., Demonstrator of Chemistry, Jefferson Medical College,
Philadelphia, etc. Crown octavo, 218 pages. Cloth, ^i.oo; inter-
leaved for notes, ^1.25.

[See Saunders' Question- Compends, page 21.]

"The scope of this work is certainly equal to that of the best course of lectures on
Medical Chemistry." — Pharmaceutical Era.

CLASSIFIED LIST

Medical Publications

W. B. SAUNDERS,

925 Walnut Street, Philadelphia.

ANATOMY, EMBRYOLOGY,
HISTOLOGY.

Clarkson — A Text-Book of Histology, 9
Haynes — A Manual of Anatomy, . . . 13
Heisler — A Text- Book of Embryology, 13
Nancrede — Essentials of Anatomy, . . 18
Nancrede — Essentials of Anatomy and

Manual of Practical Dissection, . . . 18
Semple — Essentials of Pathology and

Morbid Anatomy 25

BACTERIOLOGY.

Ball — Essentials of Bacteriology, ... 6
Crookshank — A Text- Book of Bacteri-
ology, 10

Frothingham — Laboratory Guide, . . 11
Mallory and Wright — Pathological

Technique, 16

McFarland — Pathogenic Bacteria, . . 17

CHARTS, DIET-LISTS, ETC.

Griffith — Infant's Weight Chart, ... 12

Hart — Diet in Sickness and in Health, . 13

Keen — Operation Blank, 15

Laine — Temperature Chart, .... 15

Meigs — Feeding in Early Infancy, . . 17

Starr — Diets for Infants and Children, . 26
Thomas — Diet-Lists and Sick-Room

Dietary, 28

CHEMISTRY AND PHYSICS.

Brockway — Essentials of Medical Phys-
ics, 7

Wolff — Essentials of Medical Chemistry, 29

CHILDREN.

An American Text-Book of Diseases

of Children, . . 3

Griffith — Care of the Baby 12

Griffith — Infant's Weight Chart, ... 12

Meigs — Feeding in Early Infancy, . . 17

Powell — Essentials of Dis. of Children, 19

Starr — Diets for Infants and Children, . 26

DIAGNOSIS.

Cohen and Eshner — Essentials of Di-
agnosis 9

Corwin — Physical Diagnosis, .... 9

Macdonald — Surgical Diagnosis and
Treatment, 16

Vierordt — Medical Diagnosis, .... 29

DICTIONARIES.

Dorland — Pocket Dictionary, .... 10

Keating — Pronouncing Dictionary, . . 14

Morten — Nurse's Dictionary, .... 18

EYE, EAR, NOSE, AND THROAT.

An American Text- Book of Diseases

of the Eye, Ear, Nose, and Throat, . 3
De Schweinitz — Diseases of the Eye. . 10
Gleason — Essentials of Dis. of the Ear, il
Jackson and Gleason — Essentials of

Diseases of the Eye, Nose, and Throat, 14
Kyle — Diseases of the Nose and Throat, 15

GENITO=URINARY.

An American Text-Book of Genito-
urinary and Skin Diseases, 4

Hyde and Montgomery — Syphilis and

the Venereal Diseases, 13

Martin — Essentials of Minor Surgery.

Bandaging, and Venereal Diseases, . 16
Saundby — Renal and Urinary Diseases, 24
Senn — Genito-Urinary Tuberculosis, . 25
Vecki — Sexual Impotence, 28

GYNECOLOGY.

American Text- Book of Gynecology, 4
Cragin — Essentials of Gynecology, . . 9
Garrigues — Diseases of Women, ... 11
Long — Syllabus of Gynecology, ... 15
Penrose — Diseases of Women, . ... 18
Sutton and Giles — Diseases of Women, 28

MATERIA MEDICA, PHARMACOL-
OGY, AND THERAPEUTICS.

An American Text-Book of Applied

Therapeutics 3

Butler — Text-Book of Materia Medica,

Therapeutics and Pharmacology, . . . 8
Cerna — Notes on the Newer Remedies, 8
Griffin — Materia Med. and Therapeutics, 12
Morris — P'ssentials of Materia Medica

and Therapeutics, . . 17

Saunders' Pocket Medical Formulary, 24,
Sayre — Essentials of Pharmacy, . . 24
Stevens — Essentials of Materia Medica

and Therapeutics ... 26

Stoney — Materia Medica for Nurses, . 28
Thornton — Dose-Book and Manual of

Prescription-Writing, 28

MEDICAL JURISPRUDENCE AND
TOXICOLOGY.

An American Text-Book of Legal
Medicine and Toxicology, 4

Chapman — Medical Jurisprudence and
Toxicology, 8

Semple — Essentials of Legal Medicine,
Toxicology, and Hygiene, 25

Medical Publications of W. B. Saunders.

31

NERVOUS AND MENTAL
DISEASES, ETC.

Burr — Nervous Diseases, 7

Chapin — Compendium of Insanity, . . 8
Church and Peterson — Nervous and

Mental Diseases, 8

Shaw — Essentials of Nervous Diseases

and Insanity, 26

NURSING.

An American Text-Book of Nursing, 29

Griffith — The Care of the Baby, ... 12

Hampton — Nursing, 12

Hart — Diet in Sickness and in Health, 13

Meigs — Feeding in Early Infancy, , . 17

Morten — Nurse's Dictionary, .... 18

Stoney — Practical Points in Nursing, . 27

OBSTETRICS.

An American Text-Book of Obstetrics,
Ashton — Essentials of Obstetrics, . . .
Boisliniere — Obstetric Accidents, Emer

gencies, and Operations, ....
Dorland — Manual of Obstetrics, .
Hirst — Text-Book of Obstetrics, .
Norris — Syllabus of Obstetrics, . .

PATHOLOGY.

An American Text-Book of Pathology, 5
Mallory and Wright — Pathological

Technifjue, 16

Semple — Essentials of Pathology and

Morbid Anatomy, . . 25

Senn — Pathology and Surgical Treat-
ment of Tumors, 25

Stengel — Text- Book of Pathology, . . 26
Warren — Surgical Pathology and Thera-
peutics, 29

PHYSIOLOGY.

An American Text-Book of Physi-
ology, 5

Hare — Essentials of Physiology, . . . 13

Raymond — Manual of Physiology, . . 19

Stewart — Manual of Physiology, ... 27

PRACTICE OF MEDICINE.

An American Text-Book of the The-
ory and Practice of Medicine, .... 5

An American Year-Book of Medicine
and Surgery, 6

Anders — Text-Book of the Practice of
Medicine, ... 6

Lockwood — Manual of the Practice of
Medicine, 15

Morris — Essentials of the Practice of
Medicine, 17

Rowland and Hedley — Archives of
the Roentgen Ray, 19

Stevens — Manual of the Practice of
Medicine, 27

SKIN AND VENEREAL.

An American Text-Book of Genito-
urinary and Skin Diseases, 3

Hyde and Montgomery — .Syphilis and
the Venereal Diseases, 13

Martin — Essentials of Minor Surgery,
Bandaging, and Venereal Diseases, . 16

Pringle — Pictorial Atlas of Skin Dis-
eases and Syphilitic Affections, ... 19

Stelwagon — Essentials of Diseases of
the .Skin, 26

SURGERY.

An American Text-Book of Surgery, 5
An American Year-Book of Medicine

and Surgery 6

Beck — Manual of Surgical Asepsis, . . 7
DaCosta — Manual of Surgery, .... 10

Keen — Operation Blank, 15

Keen — The Surgical Complications and

Sequels of Typhoid Fever, 15

Macdonald — Surgical Diagnosis and

Treatment, 16

Martin — Essentials of Minor Surgery,

Bandaging, and Venereal Diseases, . 16
Martin — Essentials of .Surgery, .... 16

Moore — Orthopedic Surgery, 17

Pye — Elementary Bandaging and Surgi-
cal Dressing, 19

Rowland and Hedley— Archives of

the Roentgen Ray, 19

Senn — Genito-Urinary Tuberculosis, . 25

Senn— Syllabus of Surgery, 25

Senn — Pathology and Surgical Treat-
ment of Tumors, 25

Warren — Surgical Pathology and Ther-
apeutics, 29

URINE AND URINARY DISEASES.

Saundby — Renal and Urinary Diseases, 24
Wolff — Essentials of Examination of
Urine, 29

MISCELLANEOUS.

Bastin — Laboratory Exercises in Bot-
any, 7

Gould and Pyle — Anomalies and Curi-
osities of Medicine, ir

Grafstrom — Massage, ....... 12

Keating — Howr to Examine for Life

Insurance, , I4

Rowland arid Hedley — Archives of

the Roentgen Ray, I9

Saunders' Medical Hand-Atlases, . . 2
Saunders' New Series of Manuals, 22, 23
Saunders' Pocket Medical Formulary, . 24
Saunders' Question-Compends, . . 20, 21
Senn — Pathology and Surgical Treat-
ment of Tumors, -25

Stewart and Lawrance — Essentials of

Medical Electricity, 27

Thornton — Dose-Book and Manual of

Prescription-Writing, 28

Van Valzah and Nisbet — Diseases of
the Stomach, 28

In Preparation for Early Publication.

THE INTERNATIONAL TEXT=BOOK OF SURGERY. In two volumes.

By American and Briiish authors. Edited by J. CoLLiNS Warren, M. D., LL.D.^
Professor of Surgery, Harvard Medical School, Boston; Surgeon to the Massachusetts
General Hospital ; and A. Pearck Gould, M. S., F. R. C. S., England, Lecturer on
Practical Surgery and Teacher of Operative Surgery, Middlesex Hospital Medical
School; Surgeon to the Middlesex Hospital, I^ondon, England.

AN AMERICAN TEXT-BOOK OF PATHOLOGY.

Edited by John Guiteras, M.D., Professor of General Pathology and of Morbid
Anatomy in the University of Pennsylvania; and David Riesman, M.D., Demon-
strator of Pathological Histology in the University of Pennsylvania.

AN AMERICAN TEXT=BOOK OF LEGAL MEDICINE AND TOXICOLOGY.

Edited by Frederick Peterson, M.D., Clinical [Professor of Mental Diseases in
the Woman's Medical College, New^ York; Chief of Clinic, Nervous Department,
College of Physicians and Surgeons, New York; and Walter S. Haines, M.D.,
Professor of Chemistry, Pharmacy, and Toxicology in Rush Medical College, Chicago,
Illinois.

AN AMERICAN TEXT=BOOK OF DIAGNOSIS.

Edited by ALFRED STENGEL, M. D., Physician to the Philadelphia Hospital ; Professor
of Clinical Medicine in the Woman's Medical College; Physician to the Children's
Hospital ; late Pathologist to the German Hospital, Philadelphia, etc.

HEISLER'S EMBRYOLOGY.

A Text=Book of Embryology. By John C. Heisler, M.D., Professor ot
Anatomy in the Medico-Chirurgical College, Philadelphia.

KYLE ON THE NOSE AND THROAT.

Diseases of the Nose and Throat. By D. Braden Kyle, M. D., Clinical Pro-
fessor of Laryngology and Rhinology, Jefferson Medical College, Philadelphia; Con-
sulting Laryngologist, Rhinologist, and Otologist, St. Agnes' Hospital ; Bacteriologist
to the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases, etc.

PRYOR— PELVIC INFLAMMATIONS.

The Treatment of Pelvic Inflammations through the Vagina. By W. R.

Pryor, M. D., Professor of Gynecology in the New York Polyclinic.

WEST'S NURSING.

An American Text=Book of Nursing. By American Teachers. Edited by
RoBERiA M. West, late Superintendent of Nurses in the Hospital of the University
of Pennsylvania.

/ ^.

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