OfllUOF
taNTD
3
A TEXT-BOOK
of (Jd5?
PHYS/IOLOGY
For
STUDENTS AND rflACTITIONERS OF MEDICINE
By
russeLl burton-opitz
S|M., M. D., Ph.D.
Associate Professor of Physiology, Columbia University; Professorial
Lecturer in Ppiology in Teachers College and the
Extension )epartment of Columbia University
ILLUSTRATED
PHILADELPHIA AND LONDON
W. B. §|VUNDERS COMPANY
1920
Copyright, 1920 by W. B. Sauners Company
PRINTED IN AMERICA
PRESS OF
SAUNDERS COMPANY
PHIt.ADEl.PH lA
PREFACE
In this book is embodied in large part the subject matter of a
series of lectures which it has been my privilege to deliver annually
to the students of the College of Physicians and Surgeons of Columbia
University. Fully realizing that the medical student is pressed for time
and is imbibed with a definite desire to apply his physiological knowl-
edge in a practical way at the bedside, it has been my endeavor to
invade the field of Comparative Physiology no farther than is abso-
lutely necessary to form a thorough basis for the physiological problems
which are of special iniportance to medical men. For this reason,
I have usually allowed the different discussions to be preceded by brief
remarks of a more general character, hoping thereby to retain a happy
medium between Special Physiology and Comparative Physiology.
The same principle I have followed with regard to Physics and
Chemistry. While the medical student of the present day has been
required to pass a certain number of courses in these subjects prelimi-
nary to the study of medicine, I realize that time stimulates forget-
fulness, and that he may not have been in a particularly favorable
position during his years at College to grasp the practical bearing of
many of the topics then dealt with. For this reason, I have thought it
advantageous to him, as well as to myself as a teacher, briefly to review
those physical and chemical principles which are more directly related
to the subject matter of Physiology. The same course I have followed
pertaining to Histology.
Together with Anatomy, and often with an unmistakable attitude
of charity. Physiology has been regarded as one of the foundation
stones of modern medicine. It seems to me, however, that this mile-
stone has been passed some time ago, and that the sole hope of modern
medicine is Physiology, or in a larger sense, the experimental sciences.
Since it may, therefore, be contended that ''Medicine is Physiology,"
the student should make a conscientious effort to become thoroughly
acquainted with this subject. It is by no means an easy task that Hes
before him, but having fulfilled this duty, the reward is large, because
no other science is quite so interesting as Physiology, and no other
combines theory and practice so happily. I venture to hope that this
book will help him in this attempt, in spite of its doubtlessly many short-
comings, for which I beg his generous indulgence.
Inasmuch as the subject of Physiology is altogether too large to
be dealt with in detail within the space of an ordinary text-book,
brevity and the elimination of everything that may be considered of
5
6 PREFACE
minor importance, are essential. The material gained in the course
of this process of elimination, merits no further abridgment and the
student should acquire a thorough working knowledge of it. In re-
cent years our physiological literature has been enriched by a number
of very admirable text-books upon physiological chemistry, such as
those of Hammarsten, Mathews, Mcleod, Bayliss, Oppenheimer, Lusk,
Rubner, and Gautier. I am deeply sensible of my obligations to these
authors for the material I have gathered from their writings. But,
since this field has been so minutely covered by them, I have not
attempted in the present book to give anything further than a general
story of these events. The student should be in possession of at least
one of these treatises as a means of gathering his chemical knowledge
from a more thorough and detailed source than I could possibly present.
It has been my endeavor to remain as much as possible on the mechani-
cal or physical side of Physiology without, however, completely elimi-
nating its chemical aspect. It is certainly my ardent desire to keep
Biological Chemistry within the fold of Physiology in a relationship
most beneficial to both sciences.
Being convinced that diagrams and simple sketches are of inesti-
mable value to the student, I have inserted in the present book a large
number of them. Some of these may lay claim to a certain originahty,
while others are mere modifications of earlier sketches of a similar
kind. For the latter I am indebted to the authors and publishers of
Quain^s Anatomy, Herrick's ''Elements of Neurology," Schafer's ''Es-
sentials of Histology," Starling's ''Human Physiology," and Howell's
"Text-book of Physiology." I am also very glad to acknowledge my
obligation to the publishers of Verworn's "Allgemeine Physiologie,"
Winterstein's "Handbuch der vergleichenden Physiologie," Nagel's
"Handbuch der Physiologie," Luciani's ''Fisiologia Humana,'* and
Oppenheimer's "Handbuch der Biochemie." The chemical subject
matter of this book has been kept in close conformity to this
standard work, while the introductory remarks pertaining to the
structural and functional aspects of the cell, have been closely allied
to the well-known treatises of Wilson and Verworn.
R. Burton-Opitz.
Columbia University,
New York City,
January^ 1920
COiNTENTS
PART I
THE PHYSIOLOGY OF MUSCLE AND NERVE
SECTION I
GENERAL PHYSIOLOGY
CHAPTER 1
Page
Living Substance 17
CHAPTER II
General Phenomena of Life 29
SECTION II
THE PHYSIOLOGY OF MUSCLE AND NERVE
CHAPTER III
Motion 36
CHAPTER IV
The Graphic Registration of Muscular Contraction. Methods of
Stimulation of Muscle and Nerve 53
CHAPTER V
Peculiarities of Muscle Tissue 65
CHAPTER VI
The Character of the Contraction of Muscle ............ 70
CHAPTER VII
The Factors Varying the Character of the Contraction 76
CHAPTER VIII
The Character of the Contraction of Smooth Muscle 83
CHAPTER IX
The Chemistry of Muscle 85
CHAPTER X
The Production of Energy in Muscle 93
7
8 CONTENTS
SECTION III
THE PHYSIOLOGY OF NERVE
CHAPTER XI
Page
The Neuron and Its Gonducti ng Paths 108
CHAPTER XII
The Phenomena of Conduction in Nerve 124
CHAPTER XIII
The Reaction of Normal and Abnormal Nerve and Muscle to the Con-
stant and Interrupted Electrical Currents 142
PART II
THE BLOOD AND LYMPH. IMMUNITY
SECTION IV
THE BLOOD
CHAPTER XIV
General Characteristics of the Blood 157
CHAPTER XV
The Chemical Composition of the Blood 168
CHAPTER XVI
The Red Blood Corpuscles • 172
CHAPTER XVII
The White Blood Corpuscles • 199
CHAPTER XVIII
The Blood Platelets 207
CHAPTER XIX
The Coagulation of the Blood 211
CHAPTER XX
The Total Quantity and Distribution of the Blood — ^Loss of Blood . , 226
CONTENTS 9
SECTION V
THE LYMPH
CHAPTER XXI
Page
Properties and Formation of Lymph . 233
SECTION VI
RESISTANCE AND IMMUNITY
CHAPTER XXII
The Blood and Lymph as Protective Mechanisms : . . 245
PART III
THE CIRCULATION OF THE BLOOD
SECTION VII
THE MECHANICS OF THE HEART
CHAPTER XXIII
A Comparative Study of the Circulatory System 253
CHAPTER XXIV
The Arrangement of the Musculature of the Heart , . 263
CHAPTER XXV
The Cardiac Cycle (Revolutio Cordis) 272
CHAPTER XXVI
The Phenomena Noted During Each Cardiac Cycle 280
SECTION VIII
THE NERVOUS REGULATION OF THE HEART
CHAPTER XXVII
Cardiac Inhibition and Acceleration 309
SECTION IX
FUNCTIONAL PECULIARITIES OF THE CARDIAC MUSCLE
TISSUE
CHAPTER XXVIII
The Origin of the Heart Beat 331
10 CONTENTS
CHAPTER XXIX
Page
The Physiological F^roperties of Cardiac Muscle . 338
SECTION X
THE MECHANICS OF THE CIRCULATION—
HEMODYNAMICS
CHAPTER XXX
Physical Consideration 347
CHAPTER XXXI
Blood Pressure 354
CHAPTER XXXII
The Pulsatory Variations in Blood Pressure 377
CHAPTER XXXIII
The Blood Flow 394
SECTION XI
THE NERVOUS REGULATION OF THE BLOOD-VESSELS
CHAPTER XXXIV
The Innervation of the Blood-vessels of Different Organs 411
CHAPTER XXXV
The Circulation Through Special Organs 427
PART IV
RESPIRATION, VOICE AND SPEECH
SECTION XII
RESPIRATION
CHAPTER XXXVI
The Structure and Function of the Elementary Lung 445
CHAPTER XXXVIl
The Mechanics of the Respiratory Movements . ^ . . 454
CHAPTER XXXVIII
The Frequency and Character op the Respiratory Movements . . 472
CONTENTS 11
CHAPTER XXXIX
Page
The Chemistry of Respiration 486
CHAPTER XL
The Seat and Nature op the Oxidations 508
CHAPTER XLI
The Respiratory Interchange under Different Conditions 514
CHAPTER XLII
The Nervous Regulation of Respiration 528
SECTION XIII
VOICE AND SPEECH
CHAPTER XLIII
The General Arrangement of the Phonating Organs 540
CHAPTER XLIV
Pronation 549
PART V
THE CENTRAL NERVOUS SYSTEM
SECTION XIV
THE FUNCTIONAL SIGNIFICANCE OF THE NERVOUS
SYSTEM
CHAPTER XLV
The Structural Arrangement of the Nervous System 557
CHAPTER XLVI
The Functional Arrangement of the Nervous System 565
CHAPTER XL VII
The Functional Unit of the Nervous System 574
CHAPTER XL VIII
Reflex Action. . . . * 583
12 CONTENTS
SECTION XV
THE FUNCTIONS OF THE SPINAL CORD
* CHAPTER XLIX
Page
The Spinal Cord as a Reflex Center — Its Power of Automaticity. . 594
CHAPTER L
The Spinal Cord as a Conducting Path. Its Trophic Function. . . . 603
SECTION XVI
THE AUTONOMIC NERVOUS SYSTEM
CHAPTER LI
The Sympathetic and Parasympathetic Systems 627
SECTION XVII
THE MEDULLA OBLONGATA AND THE CRANIAL
NERVES
CHAPTER LII
The Function of the Medulla Oblongata 640
CHAPTER LIII
The Cranial Nerves 642
SECTION XVIII
THE CEREBRUM
CHAPTER LIV
The General Function of the Cerebrum 657
CHAPTER LV
Cerebral Localization 671
CHAPTER LVI
Cerebral Localization (Continued) 681
SECTION XIX
THE CEREBELLUM. THE PROTECTIVE MECHANISM OF
THE NERVOUS SYSTEM
CHAPTER LVII
The Cerebellum 706
CONTENTS 13
CHAPTER LVIIl
Page
The Protective Mechanisms of the Nervous System 716
PART VI
THE SENSE-ORGANS
SECTION XX
SPECIAL SOMATIC AND VISCERAL RECEPTORS
CHAPTER LIX
Classification of the Sense-organs 727
CHAPTER LX
The Senses of Pressure or Touch, Pain, and Temperature 734
CHAPTER LXI
The Senses of Smell, Taste, Hunger and Thirst 743
SECTION XXI
THE SENSE OF HEARING
CHAPTER LXll
The Cause and Character of the Sound Waves 756
CHAPTER LXIIl
The External and Middle Portions of the Ear 763
CHAPTER LXIV
The Internal Ear or Labyrinth 771
SECTION XXII
THE SENSE OF EQUILIBRIUM
CHAPTER LXV
The Sense of Position. Static Sense 781
CHAPTER LXVI
The Sense of Movement — Dynamic Sense 785
14 CONTENTS
SECTION XXIII
THE SENSE OF SIGHT
CHAPTER LXVII
Page
Physiological Optics 794
CHAPTER LXVIII
The Globe of the Eye and Its Protective Appendages 803
CHAPTER LXIX
The Cornea, Iris and Aqueous Humor 809
CHAPTER LXX
The Ciliary Body and Lens 819
CHAPTER LXXI
The Retina 831
CHAPTER LXXII
The Formation of the Image upon the Retina 846
CHAPTER LXXIII
Abnormalities in the Refraction of the Eye 853
J^ CHAPTER LXXIV
Binocular Vision 869
CHAPTER LXXV
Color Vision 879
PART VII
SECRETION
SECTION XXIV
THE EXTERNAL SECRETIONS
CHAPTER LXX VI
The Group of the Cutaneous Secretions 891
CHAPTER LXXVIl
The Lymphatic and Mucous Secretions 903
CONTENTS 15
CHAPTER LXXVIII
Page
The Digestive Secretions 908
CHAPTER LXXIX
The Digestive Secretions {Continued) 918
CHAPTER LXXX
The Digestive Secretions {Continued) 938
SECTION XXV
THE INTERNAL SECRETIONS
CHAPTER LXXXI
The Thyroid and Parathyroid Bodies. The Thymus, Liver, and Pan-
creas 951
CHAPTER LXXXII
The Adrenal Bodies, Hypophysis, Pineal Gland, Testes and Ovaries. . 967
PART VIII
METABOLISM
SECTION XXVI
DIGESTION
CHAPTER LXXXIII
The Chemistry of Digestion . 985
CHAPTER LXXXIV
The Mechanics of Digestion 998
SECTION XXVII
ABSORPTION
CHAPTER LXXXV
The Absorption of the Reduced Foodstuffs from the Alimentary
Canal 1022
CHAPTER LXXXVI
The History of the Different Foodstuffs in the Body 1037
16 CONTENTS
CHAPTER LXXXVII
Page
The Metabolic Requirements of the Body , . . . . 1052
CHAPTER LXXXVIII
The Nutritive Value of Food 1058
SECTION XXVIII
EXCRETION
CHAPTER LXXXIX
The Secretion of Urine 1064
CHAPTER XC
The Expulsion of the Urine. Micturition 1075
CHAPTER XCI
The Composition of the Urine 1080
SECTION XXIX
ANIMAL HEAT
CHAPTER XCII
The Production and Dissipation of Heat . 1089
PART IX
REPRODUCTION
SECTION XXX
THE REPRODUCTIVE ORGANS
CHAPTER XCIII
Growth, Regeneration and Reproduction 1109
CHAPTER XCIV
The Male and Female Reproductive Organs 1122
CHAPTER XCV
The Development of the Embryo 1135
Index , , . . . 1147
PART I
THE PHYSIOLOGY OF MUSCLE AND NERVE
SECTION I
GENERAL PHYSIOLOGY
CHAPTER I
LIVING SUBSTANCE
Definition and Scope of Physiology. — The science of physiology
deals with the processes occurring in living matter. It is the study of
the dynamics of life and as such should be extended to the entire
realm of living entities, to animals as well as to plants, and to simple
as well as to complex organisms. Physiology, however, deals solely
with the functional aspect of living substance, its structural char-
acteristics being taken care of by the sciences of morphology, anatomy
and histology. But inasmuch as an analysis of the function of a part
cannot well be attempted without a thorough understanding of its
structure, it must be clear that the best results can only be obtained if
these sciences are brought into the closest possible relationship. A
study of the function of the eye is scarcely feasible without having
obtained first of all a clear conception of the general arrangement and
structural details of the tissues entering into its formation. This is
also true of the ear, the heart, the brain and all other organs of our
body. Physiology, therefore, presents itself as an important unit
of the science of biology, which takes cognizance of all things possessing
life, as follows:
Origin and Development; Embryology.
^ Histology of Plants
Biology
Structure .
Function
General; Morphology
Anatomy
Special Phytomy
Zootomy
General Physiology
[ Histology of Animals
Special Physiology
Lower Vertebrates
Mammals
Man
17
18 . GENERAL PHYSIOLOGY
The analysis of the phenomena of Ufe also necessitates as a pre-
requisite an adequate knowledge of physics and chemistry. Without
these sciences physiological progress would indeed be slow or even
impossible. This fact accounts in a way for the almost exclusive
position which anatomy has enjoyed until comparatively recent
years. As the acquisition of gross structural data is not at all depend-
ent upon the development of the supplementary sciences, anatomy
has been able to advance practically without restrictions of any kind.
At the close of the nineteenth century it had thus acquired an almost
dominating position. On the functional side, scarcely any progress
was made until the beginning of the sixteenth century, when Paracel-
sus (1493-1541) attacked the doctrines of Galinus (131-200) and
developed a physiological system of his own. Greatly aided by the
anatomical discoveries of Vesalius, Eustachius, Faloppio and Serveto,
it was left to Harvey (1578-1657) to unravel the secrets of the circu-
lation of the blood. This discovery put an end to speculative physi-
ology and initiated experimental physiological methods. Harvey,
moreover, propounded a doctrine which was destined to exert a pro-
found influence upon the development of modern physiology, namely,
his doctrine ^'de generatione animalium." In recent years this work
has dominated our views regarding the origin of animal life and has led
to the dictum of "omne vivum ex ovo.*'
The seventeenth century is a memorable one for physiology,
because it produced a Copernicus, a Galileo, a Descartes, a Boyle
and a Newton, thus furthering our knowledge of physics. Of scarcely
lesser importance, however, is the construction of the compound
microscope which made the histological discoveries of Leeuwenhoek
(1632-1723), Malpighi (1628-1694) and Swammerdam (1637-1685)
possible. Then followed Albrecht v. Haller (1708-1777) who not
only greatly promoted the experimental side of physiology but also
combined the data then known into a homogeneous whole and thus
gave an independent existence to our Science. At about this time
were made the far reaching chemical discoveries of Priestley (1773-
1804), Lavoisier (1743-1794) and Girtannei (1760-1800).
The period from 1800 to about 1860 is commonly regarded as
the renaissance period of physiology. It is dominated by such men
as Johannes v. Miiller (1801-1858) and Johannes Purkinje and, on
the chemical side, by Wohler (1800-1882)^ and v. Liebig (1803-1873).
Physiology at once began to profit by the discoveries in chemistry,
because they found immediate application in the investigations of
problems connected with respiration, digestion and secretion. From
this time on physiology shows two tendencies, namely a physical
and a chemical. Very fortunately, however, this division has re-
^ Mention is usually made of Wohler, because he succeeded in 1828 in producing
urea synthetically. In reality, however, this synthesis was preceded by several
others, namely, by that of alcohol (Hennel), that of acetic acid (Dobereiner,
1822) and that of oxalic acid (Scheele, 1776).
LIVING SUBSTANCE 19
mained largely theoretical until more recently, although it is quite
true that an expert knowledge of more than one of these fundamental
sciences can scarcely be demanded of any physiologist. This new
tendency soon forced physiologists to confine their constructive work
either to physical or to chemical physiology. The former group of
investigators includes such men as E. H. Weber (1795-1878), Volk-
mann (1801-1877), Ludwig (1816-1895), Helmholtz (1821-1894), Du
Bois-Reymond (1818-1896), Marey (1830-1904), Bernard (1813-1878);
and the latter, such men as Voit (1831-1908), Pfiuger (1829-1910),
Kossel (1853), Zuntz (1847), and Hofmeister (1808-1878).
Physiology, therefore, belongs essentially to the nineteenth cen-
tury. It is a comparatively new science, but is unfolding itself
very rapidly, so that it now forms the chief basis of modern medicine.
This is the age of the experimental sciences and very rightly so,because
in them lies our greatest hope of benefiting mankind. As Verworn
expresses it, the struggle for existence forces man to master the forces
of nature and to eradicate all those which tend to enfeeble him.
Physiology constitutes a means which is used chiefly to combat the
latter. Its ultimate object, therefore, is the welfare of mankind.
In order to attain this end, it cannot confine itself to man and the
higher animals, but must include living matter wherever found,
even that forming the most primitive organisms and plants. For
this reason, physiology does not always present a wholly practical
aspect, but follows at times a purely scientific course of inquiry.
The results of the latter, however, are not to be undervalued, because
as man is not accessible to physiological methods, excepting in a few
special instances, we are constantly forced to base our conclusions
upon the fundamental processes displayed by the lower forms of life.
That a direct comparison of this kind is permissible in most cases,
has been fully demonstrated experimentally.
Animate and Inanimate Material. — Since physiology purposes to
analyze the phenomena of life, it becomes necessary to familiarize our-
selves with the fundamental characteristics of living substance. The
layman most generally places the greatest stress upon the production
of mechanical energy, such as is evinced by those apparently spon-
taneous movements which are made use of by living entities in chang-
ing their position in space. As a last means of differentiation between
animate and inanimate bodies he employs those activities which are
associated with respiration and the action of the heart. A more far-
reaching differentiation, however, may be attempted upon the basis
of morphological, genetic, physical and chemical peculiarities.^ Thus,
it has been said that inorganic bodies possess definite geometric pro-
portions, and that they contain no organs and exhibit the simplest
possible organization. A brief survey, however, will show that these
characteristics are also presented by living substance, because organ-
1 Verworn, AUgemeine Physiologie, Jena, 1909; and Irritability, Yale Univ.
Press, 1913.
20 GENERAL PHYSIOLOGY
isms with mathematical contours are very numerous (radiolaria) and
many of them do not exhibit a differentiation of their protoplasm nor
a division of function (amoeba). Upon the genetic basis, it is usually
stated that organisms can only originate from organisms. But if we
adhere to that theory regarding the origin of life which assumes that
the first cell arose in consequence of a combination of inorganic sub-
stances at a time when conditions upon this earth permitted this union
to take place, ^ this difference cannot be said to be of fundamental
importance. It is conceivable that living matter appeared as a result
of the evaporation of water containing the common salts. In the
course of this concentration cyanides and other similar organic com-
pounds were formed in consequence of vigorous electrical disturbances.
These elementary organic globules eventually gave rise to cells and
by descendance to all the organisms inhabiting this earth. ^ It is a
well-known fact that inorganic substances are constantly made use of
by plants in their production of organic material and lastly, it must
be taken into account that not all organisms give rise to their like.
For example, the workers of the bees and ants are sexually retrogressive
and do not possess the power of reproduction.
The statement has also been made that living substance possesses
the properties of irritability and contractility, while inorganic material
does not. But if we observe an ordinary reaction between substances
occurring in a test tube, we cannot fail to recognize that even inorganic
matter is receptive and gives rise to motion. This is especially true
of those substances which cause reactions of an explosive kind, such as
nitroglycerin. The energy liberated by this body when stimulated,
can scarcely be duplicated, and hence, with the exception of the fact
that inorganic material presents an irritability and contractility of a
type somewhat different from that shown by living substance, this
ba^sis does not furnish an actual means of differentiation.
If living substance is studied from the standpoint of chemistry, it
is found that it contains certain organic bodies the complexity of
which is not equalled in the inorganic world. Indeed, one of these
groups, the proteids, forms a constant constituent of protoplasm, while
no substance can be found in the inorganic world, which at all ap-
proaches the complexity of the proteid molecule. It is true, however,
that even this difference must disappear as soon as a way has been
found to produce these bodies artificially. There is one peculiarity,
however, which is decisive and that is the specific metabolic function
of living matter. Not only is it capable of altering its composition
constantly, but also of giving off certain waste products which are
subsequently replaced by new material. Life, therefore, is character-
ized by nothing more than a specific metabolism of certain substances
and especially of the proteins. In a very general way, however, it is
permissible to state that hving substance is distinguished from life-
1 Preger : Die Hypothesen iiber den Ursprung des Lebens, Berlin, 1880.
2 E. Hackel : Gen. Morph. der Organismen, Berlin, 1866.
LIVING SUBSTANCE 21
less material, whether inorganic or organic, by its properties of irritabil-
ity, conductivity, contractility, metabolism and reproduction.
The Structural Basis of Life. — While living substance appears in
many forms, it always presents itself as an entity which is capable of
leading an independent existence. It is living organic material and
as such is generally arranged in the form of cells. In a general way, it
may be said that this term is applied to the smallest particles of living
substance still capable of existing independently of others. Hence,
the cell represents the simplest type of individuality of living substance
and constitutes a unit in structure as well as in function.
It is true, however, that our conception of a cell is not at all concise,
because cells may exhibit very different characteristics. To begin
with, the term ''cell" was employed by botanists to describe those
structural units which make up the stem and the leaves of plants.
In a similar way it was found later on that the organs and tissues
of the higher animals are not composed of homogeneous masses of
living substance, but of a multitude of very small particles which are
separated from one another by partitions. In both instances the cell
was finally observed to be a definite unit of the entire mass, consisting
of a membrane investing a semi-solid globule of protoplasm and a dark
body, or nucleus.
It soon became evident that this conception is not absolutely cor-
rect, because the studies of Schultze^ upon the structure of the rhizo-
pods proved that there are organisms in existence which are not sur-
rounded by a cell membrane, but appear merely as naked masses of
living substance possessing the same characteristics as the viscous
contents of the plant cell, or protoplasm. In accordance with this
discovery, it has since been held that the essential unit of the cell is
the protoplasm, i.e., the cell consists merely of a globule of protoplasm
which may or may not be invested by a membrane. Our original
idea regarding its structure has also been modified in so far as the
nucleus is no longer regarded as an essential constituent. This con-
ception necessitated a different interpretation of the discovery of
Brown^ than that ordinarily given to it. It will be remembered that
this investigator noted that protoplasm embraces a granule possessing
the power of refracting light. This fact was greatly amplified later
on by Schleiden^ and Schwann* who found this granule so universally
present that they considered it as a constant constituent of the cell.
Hackel,^ however, proved subsequently that many rhizopods do not
contain a nucleus. In more recent years this condition has also been
shown to prevail in bacteria and fungi. It seems best, however, not
to emphasize this point too strongly, because while many cells do not
^ Archiv fur Anat. und Physiol., 1861.
2 Transact, of the Linnean Soc, London, 1833.
3 Miiller's Archiv, 1833.
^ Mikr. Unters. iiber die Struktur und den Wachstum der Tiere and Pflanzen,
1839.
^Biolog. Studien, Leipzig, 1870.
22 GENERAL PHYSIOLOGY
display a clearly recognizable nucleus, they nevertheless contain nu-
-clear material which, in accordance with Biitschli,^ appears in many
cases merely as dust-Hke fragments scattered through the cytoplasm.
At best, therefore, a cell can only be defined as a globule of protoplasm
containing a certain amount of nuclear material.
The term protoplasm (protos, first; plasma, form) is usually em-
ployed as a synonym for living substance. Huxley, for example,
speaks of it as the physical basis of life, just as the cell has been desig-
nated by Briicke^ as the elementay functional unit. It should be
emphasized, however, that protoplasm is not a single substance, but
is composed of several. It is a definite chemical compound which, in
accordance with the histologists, possesses certain staining powers and,
in accordance with the physiologists, exhibits a certain behavior to-
ward the conditions under which it is made to live. In the second
place, it must be remembered that protoplasm differs somewhat in its
chemical composition and physical arrangement. Thus, the proto-
plasm composing the muscle cell is not at all identical with that form-
ing the cells of the liver or kidney or other organs. We know this to
be true, because the reactions of these diverse types of protoplasm are
not absolutely the same, but vary in accordance with their function.
And besides, even a single cellular unit most commonly contains more
than one kind of protoplasm, namely, the fundamental substance plus
certain adjuncts which to all appearances give rise to a division of
labor. Thus, it is conceivable that in single protoplasmic entities,
such as are presented by ameba, stentor and other unicellular organ-
isms, a certain portion of the substance is set aside to serve the pur-
pose of digestion, another that of excretion and still another that of
locomotion.
The Structure of the Cell. — It is evident, therefore, that living
matter appears in the form of cells and that these cells may be either
single free-living organisms or may be combined into colonies to form
the tissues and organs of the more complex animals and plants. In
either case, whether forming a unicellular entity or united with others
into a multicellular organism, the cell presents certain morphological
and functional characteristics. Its form differs greatly, and while the
large majority of cells retain their shape throughout their life, a cer-
tain number of them, such as the ameba, change it constantly. It
may be taken for granted, however, that their fundamental shape is
round, or nearly so, and that almost any polyhedral form may be im-
parted to them by grouping them into tissues and organs. Moreover,
while some of them may attain an unusual length, others are equip-
ped with appendages in the form of pseudopodia, flagella and cilia.
Their size, on the other hand, differs only within relatively narrow
limits. By far the greatest number of them remain below the range
of ordinary vision and very few attain dimensions that may be
^ tJber den Bander Bakterien und verw. Organismen, Leipzig, 1890.
* Sitzungsber. der Wiener Akad. der Wissensch., xliv, 1861.
LIVING SUBSTANCE 23
expressed in millimeters. The latter are commonly observed to possess
ameboid motion. Consequently, the formation of a bulky organism
is possible only by the union of a multitude of relatively independent
cellular elements.
As has been stated above, the term protoplasm was employed origi-
nally in a morphological sense to designate the entire mass of living
substance inside the cell wall with the exception of the nucleus. At
the present time, however, we know that this conception is not quite
correct, because the contents of the cell are really a morphological and
chemical mixture. To begin with, it may be stated that a cell con-
sists of two parts, namely of cytoplasm and of nuclear material.
The cytoplasm appears as a clear homogeneous, viscous *' ground-
substance" in which are embedded varying numbers of formed ele-
ments.^ At times, therefore, the watery ground substance is clearly
in evidence, while at other times it is hidden by granular material.
The formed elements of the cytoplasm embrace bodies which are abso-
lutely essential to the life of the cell as well as bodies which must be
regarded as accidental admixtures. Among the former are granules
representing all stages of metabolism, namely, food material ready
for assimilation and the products of the cellular processes ready for ex-
cretion. Some of the latter may first be transported to distant parts
of the body to be used in connection with some other function. A very
important constituent of the cytoplasm of the green plants is the
so-called chloroplastic material which appears as small round or tape-
shaped bodies containing an intense green pigment. It is the func-
tion of this material to assimilate the carbon dioxid so that under the
energy of the rays of the sun an assimilation of starch and an evolu-
tion of oxygen may be had. A similar substance is the leukoplastic
material of certain plant cells which serves to build up starch from
sugars. At times the cytoplasm also contains globules of fluids, the
so-called vacuoles, which may be either quiescent or exhibit rhythmic
contractions. Among the accidental admixtures may be mentioned
the indigestible remnants of the food, such as pieces of the shells,
skeletons or capsules of the organisms which have been ingested. In
fact, the cytoplasm may also give lodgment to living organisms and
especially to certain parasites.
Under the low power of the microscope the ground-substance of the
cytoplasm presents a perfectly homogeneous hyaline appearance;
indeed, such objects as the pseudopodia of the ameba and rhizo-
pods do not display a differentiation even when observed under high
powers. In most cases, however, some kind of structure may then
be made out. Thus, Remak^ has shown (1844) that ganglion cells
possess a fibrillar interior, while Frommann and Heitzmann have
proved (1867) that the fundamental structure of protoplasm is spongy.
1 M. Heidenhain, Plasma und Zelle, Jena, 1911.
2 Archiv ftir Anat. und Physiol., 1844.
24
GENERAL PHYSIOLOGY
Butschli,^ in fact, believes that it possesses a honeycomb or froth-like
structure. These somewhat divergent views may be classified under
the following heads :
(a) The granula theory, proposed by Altman,^ holds that the
granules contained in protoplasm are the essential constituent and that
the fluid medium is not living substance at all.
(6) The fibrillar theory assumes that the protoplasm consists of a
network or clusters of fibrils containing in its meshes a certain amount
of fluid material. The fibrillar reticulum or sponge work is designated
by Schafer as the spongioplasm and the
more fluid and structureless portion as the
hyaloplasm.
(c) The alveolar theory, advocated by
Btitschli, contendg that the ground-substance
of the cytoplasm stores its material as
globules which gradually increase in size
and become separated from one another
by alveolar partitions. Microscopic for-
mations of this kind may be produced artifi-
cially by mixing oil with potassium or cane
sugar. On bringing a droplet of this oil in
contact with water, molecules of the latter
pass inward and spHt the oil droplet into
innumerable smaller ones until a very deU-
cate froth is produced. The diffusion cur-
rents resulting in this mixture, are at times
so intense that movements similar to ame-
boid motion may be observed.
The nucleus of the cell appears as a rule
as an oval or round body, situated near the center of the cytoplasm
and sharply differentiated from it by what is known as a nuclear
membrane. Many cells, however, contain nuclei which are long
drawn out or constricted so as to form band-like or bead-like chains
of nuclear material, while in others the nuclear material is scattered
through the cytoplasm in the form of dust-like particles. Consider-
able variations are also noted with regard to the relative volume of
the nucleus and cytoplasm, the latter forming at times merely a narrow
frame around a large centrally placed nucleus.
The nucleus consists of an enveloping membrane, a network of
fibers, the nuclear matrix and nucleoh. It is beUeved that the spongio-
plasm of the cytoplasm is extended into the nucleoplasm, but on a
larger scale, i.e., the threads are coarser and can therefore be more
easily seen. The interstices of this network are filled with nuclear
sap or matrix. At the different points of crossing, of the filaments, the
^ Untersuchungen iiber die mikrosk. Schaume und das Protoplasma, Leipzig,
1892.
2 Die Elementarorg. und ihre Beziehungen zu den Zellen, Leipzig, 1890.
Fig. 1. — The Structure of
Protoplasm.
An epidermal cell of the earth-
worm. (After Biltschli.)
LIVING SUBSTANCE
25
chromatin, of which they are composed, appears in the form of gran-
ules. Some of these are especially conspicuous and are then called
pseudonucleoli. Other masses of chromatin, the true nucleoli, are
sometimes found embedded in the nuclear sap. If the cell is stained
with such dyes as hematoxylin or safranin, the nucleus is made to
stand out prominently against the light protoplasmic ground-sub-
stance. The nucleus, however, does not absorb the pigment very
evenly, because the chromoplasmic network and nucleoli possess a
much greater affinity for it than the matrix. Herein really lies the
reason for saying that the cell is composed of chromatic and achromatic
substances; the former combine with many dyes with great ease
while the latter do not.
Attraction-sphere enclosing two centrosomes
Plastids lying in the
cytoplasm
Nacleus
Vacuole
Passive bodies (meta-
plasm or paraplasm)
suspended in the cy-
toplasmic meshwork
Fig. 2. — Diagram of a Cell. (Wilson.)
The Chemistry of the Cell. — The chemical analysis of protoplasm
as practised at the present time, necessitates its destruction as a
functional entity. For this reason, its composition can only be
deduced from that of dead organic material. KosseP divides its con-
stituents into primary and secondary, the latter being present only
in some types of cells. As an example of this kind might be mentioned
the glycogen of the cells of the liver. As primary constituents are
to be regarded lecithin, cholesterin (lipoids), proteids (nucleopro-
teids), inorganic salts and water.
As lipoids must be classified all those bodies which may be extracted with ether
or similar solvents.^ Whether the lecithin which belongs to the class of the
phosphatides, is actually a primary constituent of the cells is still doubtful. It is
1 Archiv fiir Anat. und Physiol., 1891.
^ Overton, Studien iiber die Narkose, Jena, 1901.
26 GENERAL PHYSIOLOGY
found in large amounts in sperm-cells, the eggs of fishes, nervous tissue, and the
yolk of eggs, and in small amounts in striated and cardiac muscle cells. Cere-
brosides, i.e., bodies, containing nitrogen but no phosphorus, are contained in
spermatozoa and leukocytes. Fatty acid and neutral fat, i.e., substances contain-
ing neither nitrogen nor phosphorus, are very common constituents of cells; the
nucleus, however, is said to be free from fat. Cholesterin, one of the substances
belonging to this group, is a primary constituent, but nothing definite regarding
its origin and condition is known. The lipoids facilitate the solubility of those
substances which are otherwise scarcely soluble in water. They also play a part
in hemolysis and absorption.
The proteins are the most constant and important constituent of the cell.^
They occur in the cytoplasm as well as in the nucleus and belong chiefly to the class
of the proteids. The nucleoproteids of the nucleus are to be sharply differentiated
from the proteins of the cytoplasm, because it has not been definitely settled as
yet whether these bodies are absolutely identical. " Nuclein " was first isolated by
Miescher^ from the nuclei of the pus-corpuscles. Somewhat later KosseP demon-
strated that the essential constituents of this body are the purin and pyrimidin sub-
stances and not the phosphorus. That this is true may be gathered from the
fact that the yolk of the unfertilized egg of birds contains no purin, while the
developing eggs yield large amounts of this substance. Somewhat later Altmann*
succeeded in abstracting nucleic acid from different proteids. This constituent
of the nucleoproteids seems to be present in rather constant quantities, while the
albuminous material appears to fluctuate considerably. It is usually combined
with a basic albuminous substance, forming such bodies as protamin or histon.
The isolation of these components of the nucleoproteid is easily effected in most
Carbohydrates are not found as free primary constituents of the cell, but are
contained in the nucleic acid portion of the nucleoproteids, in glycoproteids and
cerebrosides. In the cells of the liver glycogen in held as a reserve foodstuff.
Among the inorganic substances masked iron has been shown to exist in chro-
matin.^ Less convincing results have been obtained pertaining to phosphorus.
Protoplasm, however, contains many of the commonest salts, namely, sodium,
potassium, magnesium, calcium, iron (sulphates, chlorids, phosphates and carbon-
ates), and at times also iodin, manganese, copper, zinc, barium and silicon. The
proportion of these elements, however, differs in different cells; in fact, those named
last should be regarded merely as accidental admixtures, because they are present
only under special conditions. It should also be emphasized that these inorganic
substances may occur either independently or in combination with the organic
material; moreover, they should not be considered as passive constituents, because
they play an important part in the production of all vital phenomena.
Water constitutes about three-fourths of living substance, the remaining portion
of it being composed of inorganic and organic material. In some instances, in fact,
as much as 94 per cent, of it consists of water and the common salts. For this
reason, it must be evident that the specific gravity of protoplasm must show con-
siderable variations, although it may be said that its average value is about 1.025.
This value, for example, holds true absolutely in the case of paramecia which
Jensen® subjected to different known concentrations of potassium carbonate
solutions. It is conceivable, however, that certain cells, and especially those
containing calcareous admixtures, exceed this value, while others, possessing
prominent vacuoles, may fall below unity and be buoyant.
1 Kanitz, in Oppenheimer's Handb. der Biochemie, ii, 1910, 213.
2 Histochem. und physiol. Arbeiten, ii, 3, Leipzig, 1900.
3 Zeitschr. fiir physik. Chemie, x, 1866, 248.
* Archiv fur Anat. und Physiol., 1889, 524.
6 A. B. Maccallum, Ergebnisse der Physiol., vii, 1908, 552.
^Pfliiger's Archiv, liv, 1893, 537; also: Lillie, Journ. of Morphol., xii, 1896.
LIVING SUBSTANCE
27
The Functional Relation of the Cytoplasm and Nucleus. — The
importance of the nucleus to the cell may be shown by depriving
certain parts of it of its nuclear material. Thus, Hofer/ divided
ameba in such a manner that the nucleus came to lie in each case en-
tirely in one of the fragments. This particular fragment regenerated
very quickly into a complete cell showing a perfectly normal behavior,
while the non-nucleated portions lost their power of movement and
ingestion of food in the course of a few days and disintegrated. This
disintegration, however, could be prevented if at least a small frag-
ment of the nucleus was apportioned to these parts.
i^^l?*
yf
^-^.-^
tm.
Fig. 3. — The Functional Relation of the Cytoplasm and Nucleus.
A. An ameba divided into a nucleated and non-nucleated portion. B. The same
portion after an interval of eight days. (After Hofer.)
Quite similarly, it was found that denucleated rhizopods and
radiolaria are able to move and to ingest nutritive particles, but that
the digestion of the latter is rarely completed. Furthermore, Verworn^
has shown that polystomella which possesses the power of secreting
calcareous material, loses this function soon after its nucleus has
been removed. Plant cells behave in a similar way. Thus, Klebs^
has proved that isolated fragments of plant protoplasm are quite
unable to form a cellulose membrane, while the nucleated fragments
retain this faculty. In addition, it might be mentioned that the
nucleus is situated as a rule in that area of the cell in which the most
active growth is taking place. This tendency is well displayed in the
root-hairs of plants, in which the nuclei are retained at their very tips
during the development of these appendages and are then made to
^ Jen. Zeitschr. fiir Naturw., 1889.
2 pfliiger's Archiv, 11, 1891, 1.
3 Biol. Zentralbl., 1887.
28
GENERAL PHYSIOLOGY
retreat into the deeper layers. This is also true of the nuclei of many
secretory glands, such as the silk glands of different lepidoptera.
The nucleus, therefore, must be regarded not only as a necessary
constituent of the cell, but as its most important constructive ele-
ment. To be sure, many cells, such as the erythrocytes of the mam-
malian blood, are capable of leading an independent existence even
without a nucleus, but this example can scarcely be used as a proof
against the preceding statement, because these cells are nucleated
when formed and do not possess the power of regeneration. Even the
bacteria form only an apparent exception, because their nuclear
material is either widely disseminated through the cell in the form of
dust-like granules or is already arranged as spores. Obviously,
FiQ. 4. — Regeneration of Stentor Roeselii.
A. Stentor divided into two nucleated portions; B and C newly formed organisms.
{YeTWorn.')
therefore, the chemical and structural development of the cell depends
upon the nucleus. To some extent, however, it is also true that a
nucleus devoid of cytoplasm, cannot exist as an independent entity.
To be sure, in many cells the protoplasmic envelope is extremely
narrow and in many it does not seem to be present at all. But, the
spermatozoa, to which reference is now had, are not capable of trans-
formation nor of multiplication, their sole purpose being to unite
with the ova. Verworn, moreover, has shown that the isolated nucleus
of the large radiolaria does not long survive its removal from the cell.
These functional differences between the cytoplasm and the nucleus
are associated with definite chemical differences. This may be
inferred from the important changes which the nucleus undergoes
(
GENERAL PHENOMENA OF LIFE 29
during the division of the cell by the process of karyokinesis as well
as from its pecuUar staining reactions. Thus, we find that the growth
and activity of the cell is accompanied by definite variations in the
size and appearance of the chromatin elements. In the egg of the
shark they are small at first and stain deeply, while later on they
lose their staining qualities and increase in mass. At maturity, the
chromosomes again become smaller and finally break up into fine
granular bodies possessing an intense affinity for nuclear dyes. Re-
garding the chemical differences between the nucleus and the cytoplasm,
little is known. The proteins of living substance are conjugated in
their nature, because the simple proteins are here combined with
other complex bodies. They present, however, certain distinct
differences in that those of the nucleus form the class of the nucleo-
proteids, while those of the cytoplasm are largely compounds of protein
and lecithin. The former are characterized by their content in
phosphorus and by their decomposition products of nuclein and pro-
tein. Nuclein which seems to be the chief constituent of the nuclei
of cells, may be broken down into nucleic acid and protamine, the latter
presenting the characteristics of a protein substance.
CHAPTER II
GENERAL PHENOMENA OF LIFE
Growth and Metabolism. — ^Life may be investigated in different
ways. To begin with, the inquiry may be directed along chemical
lines, to discover not only the material entering into the composition
of Hving matter, but also the changes which this material undergoes
in the course of the vital processes. Special emphasis should in this
case be placed upon its metabolism, i.e., upon the changes presented
by it during its periods of assimilation and dissimilation. In the
second place, life may be investigated by physical means, at which
time the question regarding the energetics of protoplasm must be
most carefully considered. Living matter has been found to produce
energy in the form of mechanical energy, heat, light and electricity.
In the third place, it is possible to study either its gross or minute
structure, i.e., to pay special attention to the form in which it exists,
but naturally, life does not present itself exclusively in any one of these
ways, but as a homogeneous whole. These methods, therefore, are
Employed merely for the purpose of analyzing this process from differ-
ent standpoints. One amplifies the other.
Living substance is always in activity. It grows; it secretes; it
moves from place to place and naturally, all these processes require work
and the production of energy which is derived from the union of its dif-
30 GENERAL PHYSIOLOGY
f erent constituents with oxygen. Obviously, this constant Uberation of
energy in its various forms, must be compensated for, i.e., Uving sub-
stance must either generate it or obtain it from some outside source.
The law of the conservation of energy, however, teaches us that energy
is not created but is merely transformed from one kind into another
and hence, living matter must derive it from somewhere, namely, from
the medium in which it lives. Various substances are here at hand
which contain stored or potential energy. When assimilated by liv-
ing matter, either through its respiratory or digestive channel, these
chemical bodies are converted into kinetic energy.
The metabolism of a cell consists in a continuous decomposition
and new formation of its protoplasmic material. The former process
is designated as dissimilation or catabolism, and the latter as assimila-
tion or anabolism. It is true, however, that the metabolism is uniform
only in principle, because practically every type of cell has its own
peculiar work to perform and hence, a number of special varieties of
metabolism are obtained. Expressed in another way, it may be said
that the fundamental interchange of material between the cell and its
surroundings is modified in many cases to suit particular purposes.
Thus, a certain group of cells may be destined to give rise to a digestive
secretion, while another furnishes chiefly contractile reactions, and so
on. This specificity, however, is not so clearly marked in free-living
unicellular organisms as it is in the more complex animals and plants,
because the function of the former is not so diversified.
The catabolic processes occurring in a cell necessitate a constant
acquisition of new material to replenish that which has been lost.
It is true, however, that the manner in which this assimilation is ac-
complished, differs somewhat in different animals and plants. An
especially tedious process is in existence in the green plants, because
their protoplasm is built up from the simplest possible compounds,
such as carbon dioxid, water and various inorganic salts. The animal
cell, on the other hand, is constituted differently so that it can also
make use of the more complex foods held in the form of organic com-
binations. It must be evident, however, that the former can no longer
be regarded as synthetic and the latter as decomposition organisms,
because the metabolism of both types of cells is dependent upon proc-
esses of dissociation and synthesis. It is true, however, that the life
of the animals depends upon that of the plants, because only the latter
are capable of producing carbohydrates, fats and proteids from inor-
ganic material. These are the essentials of animal life. Animals,
therefore, are the parasites of the plants. There is, however, one ex-
ception to this rule, because those plants which contain no chlorophyl,
such as the fungi, must make use of organic substances in order to
obtain their requirement in carbon. The fungi, however, are capable
of forming nitrogen from the inorganic constitutents of the soil, while
animals must derive their supply of nitrogen exclusively from proteids
and derivative compounds. As far as their metabolism is concerned,
GENERAL PHENOMENA OF LIFE 31
the fungi and allied plants form, therefore, an intermediate group
between the green plants and the animals, i.e., between those entities
of living substance which assimilate the carbon from carbon dioxid
under the influence of the rays of the sun and those which derive their
energetics from foodstuffs.
Assimilation implies that the organisms must ingest nutritive
material which, after its digestion, is absorbed and utilized. The
manner in which this ingestion is accomplished differs materially with
the general form and behavior of the organisms. In the case of free-
living and naked unicellular masses, the acquisition of the nutritive
substances takes place apparently at any point of the surface by the
process of engolfing, while in the more specialized organisms, it occurs
in a particular place, namely at the gullet. The reduction or digestion
of the food is then effected by means of enzymes contained in secre-
tions which hydrolyze it and render it dialyzable and assimilable.
But while many cells possess the power of digesting the foodstuffs
themselves, many do not. The latter, therefore, require already
prepared food. In the higher forms this preparation is effected by
special groups of cells forming the digestive organs. Foi* this reason,
we speak of intracellular and extracellular digestion.
The phenomena of dissimilation are ushered in by the decomposi-
tion of the protoplasm, in consequence of which the various forms of
energy are then liberated. It is necessary, however, to form the ma-
terial lost anew, otherwise the catabolism might progress beyond a
certain limit and endanger the life of the cell. Clearly, oxygen is a
necessary factor in this reduction, at least in most organisms, but it
has not been definitely settled as yet whether it forms a true anabolic
product of the cell in the shape of '' intramolecular" oxygen, or whether
it is present in the surrounding medium in its molecular form to be
made use of as such whenever required. As a result of this oxida-
tion, the cell gives rise to a number of products which are of no further
use to it and are later on gotten rid of by the process of excretion.
These waste materials are of many kinds. Chief among them are those
arising from carbon and hydrogen, namely carbon dioxid and water.
A number of them are derived from the proteids, for example, urea,
uric acid, hippuric acid, creatin, etc., which are either suspended or
dissolved in water. Their complete reduction frequently requires
special agents which are brought to bear upon them through the media
of the excretions.
The purpose of metabolism is to keep the cells in a physiological
condition, as evinced by the amount of energy liberated by them.
The cell, therefore, is the seat of life. It receives certain substances
and with them a definite amount of potential energy which is then
transformed into kinetic energy in its various forms. Thus, cells are
destined to produce work, either directly or indirectly. The green
plants, for example, may be regarded very largely as potential factors,
because their energy must first be produced in the presence of sunlight.
32 GENERAL PHYSIOLOGY
To begin with, the substances consumed by them, possess no potential
energy, but light, in connection with their content in chlorophyl, gives
rise to a splitting of the molecules of the carbon dioxid and water so
that the resulting atoms of carbon, hydrogen and oxygen are at liberty
to enter other chemical combinations. In this way, a number of com-
plex substances are produced, representing a large store of potential
energy, which is made use of later on by the animal cell. It is true,
however, that this assimilation and synthesis is associated with dis-
similation, in the course of which the plant gives rise to waste products
and generates certain forms of energy, such as motion, heat, light, and
osmotic power. It is quite apparent, however, that in the case of the
plants the kinetic energy is rather subordinate to the potential — a rela-
tionship which is reversed in the animal.
The. energetics of a cell present themselves in various forms which,
as we have just seen, may be grouped as resting or potential energy
and as moving or kinetic energy. Among the former we have chemical,
osmotic, cohesion and gravitation forces, and among the latter mechan-
ical power, heat, light and electricity. But naturally, this classi-
fication is not fixed, because some of these energies may present them-
selves in either form. The chemical energy, for example, remains
potential only as long as the atoms retain their position toward one
another and becomes kinetic as soon as they rearrange themselves in
accordance with their specific affinities. Thus, the animal receives
potential chemical energy in the shape of complex organic substances
and as oxygen. The regrouping of the former under the influence
of oxygen eventually gives rise to carbon dioxid, water and simpler
nitrogenous bodies as well as to a large amount of actual energy.
Metabolism, therefore, is intended to keep the organism in energy-
equilibrium. The chemical intake and outgo are balanced in such
a way that the cells can continue to furnish the energy required of
them. The metabolic equilibrium and the dynamical equilibrium
must in the long run pursue a parallel course.
Living substance presents itself in many characteristic forms, the
study of which has always been apportioned to morphology. It is
true, however, that a hard and fast line between the structural and
functional aspect of living matter cannot be drawn, because the former
changes constantly under the influence of different physiological
conditions. An organism is always in activity and conditions within
it are never at a standstill, although in many cases these processes
may be either very slow or too minute to be immediately apparent.
Thus, the metabolic changes are balanced in such a way that the
losses suffered in consequence of dissimilation are always made up,
allowing the cell to increase its substance and to grow. Growth is
the simplest manifestation of organic progress. In the second place,
living substance in any form is capable of reproducing its like so that
its continuance is assured as long as conditions favorable for its exist-
ence prevail. If the environment changes, living substance possesses
GENERAL PHENOMENA OF LIFE 33
the power of adapting itself to the new conditions, provided, of course,
that the change to which it is subjected, is not extreme. Hence, our
conception of Ufe is Hmited to such phenomena as metaboHsm, growth
and evolution, reproduction, irritabihty and contractiUty, inclusive
of motion.
General Conditions of Life. — The reason for the great diversity in
the form of living matter must be sought in the conditions under which
it is made to exist. Any change in the latter varies its metabolism,
shape and energetics, but naturally, it would lead us altogether too
far to study the different aspects of life in detail. In general, however,
it may be stated that living matter presents certain internal as well as
external characteristics. Among the former might be mentioned its
structure, composition and physical properties, the study of which
would necessitate an analysis of the cell and its component elements.
Among the latter are to be noted the different conditions under which
the cell is made to live, inclusive of the character of the medium, the
temperature, the atmospheric pressure, osmotic pressure, moisture,
and store of nutritive material.
As long as these conditions remain the same, life is said to be spon-
taneous. This term, however, is not a very good one, because life
is never actually unconditioned. Thus, an organism leading appa-
rently a perfectly spontaneous existence, is constantly under the in-
fluence of internal and external conditions. Its spontaneity, therefore,
is only apparent, owing to the fact that the influences acting upon it
are normal in their character and remain constant in their intensity.
On the other hand, if the latter suddenly assume a different quality or
become augmented by new conditions, the spontaneity immediately
gives way to phenomena of stimulation. Hence a stimulation must
result whenever the conditions of life are suddenly and markedly al-
tered. In view of the fact that the latter are very numerous and
relatively inconstant, the possibility of stimulation is always present,
provided the protoplasm retains its receptive power.
Upon this basis, a stimulus may be defined as any extraordinary
change in the conditions to which an organism may be subjected.
While the number of stimuli is practically unlimited, it is possible to
arrange them qualitatively in the following manner:
(a) Mechanical stimuli, inclusive of such influences as touch, pressure, stroking,
pulling, the effects of gravitation, cohesion and adhesion, etc.
(6) Chemical stimuli, produced by various normal and abnormal substances.
Among the former may be included the nutritive substances ordinarily required by
living matter, and among the latter, practically any chemical agent with which it is
accidentally brought into contact.
(c) Osmotic stimuli, consisting in changes in the osmotic pressure of the sur-
rounding medium. As these alterations are commonly associated with chemical
reactions, they are frequently included among the former.
{d) Thermal stimuli, produced by variations in the temperature of the niedium.
(e) Photic or radiating stimuli, caused by changes in the intensity and quality
of the light. Under this heading may also be placed the peculiar rays discovered
3
34 GENERAL PHYSIOLOGY
in more recent years by Hertz and Rontgen, and those emitted by uranium and
radium.
(/) Electrical stimuli, produced by the exposure of the organism to the electri-
cal current. Magnetic stimuli are no longer recognized, because it seems that
living substance cannot be influenced by magnets.
Besides the quality of the stimulus, we must also take into account
its ''strength, " this term being employed at this time in a quantitative
way to characterize the sum total of its intensity, duration and fre-
quency. Every organism is constantly under the influence of stimuli
of all sorts which, as long as they retain a normal intensity, give rise
to normal reactions. The conditions prevailing at this time, may
be said to be optimum in their character. Living substance reacts
toward these in the best possible manner. But, stimuli may also be-
come excessive, and force the living substance to react maximally. It
is only natural to assume that a continued maximal activity must finally
produce injurious effects. Lastly, stimuli may possess so slight an
intensity that they fail absolutely in producing an effect. Minimal
stimuli, and especially subminimal stimuli, must eventually prove as
dangerous to life as maximal ones.
STlli 7?!'
Trt STR
T
A b K
Fig. 5. — Intensity of Stimulation.
L, life; D, death; SMi, subminimal; Mi, minimal; 0, optimum; M, maximal; SM,
supramaximal stimuli; T, threshold.
It appears, therefore, that Hfe is possible only between these
two extremes and that death must result whenever this realm is
exceeded in either direction. To begin with, therefore, living matter
may be subjected to the subminimal stimuli toward which it does
not react at all, at least not visibly. Eventually, however, a strength
of stimulus will be reached toward which it reacts just barely. At
the point where these minimal reactions just begin to appear lies
the threshold of stimulation. If the strength of the stimulus is now
increased still further, a point will be reached at which the reactions
become maximal and finally, a point at which they show a supra-
maximal character.
It should be emphasized, however, that the preceding outline can-
not be applied rigidly in all cases, because living substance exhibits
certain differences in its behavior which are dependent upon differ-
ences in its chemical and physical constitution. Thus, optimum
conditions are not always found midway between the minimal and
maximal extremes, and neither does a certain kind of maximal stimulus
invariably cause fatigue or death. It is a matter of common observa-
tion that the energy contained in a stimulus is always very much
smaller than the subsequent production of kinetic energy. To some
extent living substance also possesses the power of adapting itself
GENERAL PHENOMENA OF LIFE 35
to stimuli. Thus, while a certain stimulus may at first produce a
maximal reaction, it often loses its stimulating qualities altogether
in the course of time. This state of adaptation should be sharply-
differentiated from a somewhat similar one which is known as the
refractory state. It has been previously emphasized that every
activity of protoplasm incurs a certain destruction of material which
must first be overcome by assimilation before another reaction can
take place. Thus, if the dissimilation has been severe, or if the as-
similation has been hindered in some way, the living substance sud-
denly finds itself unable to receive stimuli, or to develop them into a
reaction. This period during which living matter remains, so to speak,
impermeable to stimuli, is known as the refractory period.
The property of protoplasm to receive stimuli and to undergo in
consequence of them characteristic chemical and physical changes, is
known as irritability. Most generally, however, these alterations are
not confined to the seat of the excitation but are propagated to other
parts of its mass. This transmission of the waves of irritabihty is
dependent upon its property of conductivity. In the multicellular
forms, conduction between widely separated parts is greatly facilitated
by the interposition of nervous tissue which is peculiarly suited for
this function. The impulses leave these conducting paths eventually
to be transferred to the constituents of the motor organ. The recep-
tion of an impulse by the cell is usually followed by the shifting of its
constituents which in turn leads to a change in its form and position.
This behavior of living matter is dependent upon its property of
contractility.
SECTION II
PHYSIOLOGY OF MUSCLE AND NERVE
CHAPTER III
MOTION
Different Types of Motion. — The phenomenon of contractility
consists in a shifting about of the constituents of the cell. It may
be perfectly local or more far reaching, leading finally to changes in
the shape and position of the organism as a whole. In this way, this
liberation of energy gives rise to motion and locomotion, phenomena
which the layman regards as the most certain proofs of life. The
character of these movements is very manifold and is in keeping
with the general structure and arrangement of the motor organs pro-
ducing them. In general, it may be said that motion may be accom-
phshed either passively or actively, in consequence of the following
processes:^
Motion <
A. Passive
. B. Active
Swelling of the cell wall
Changes in the cell-turgor
Changes in the specific gravity-
Secretion
Growth f ameboid
Contraction and expansion \ ciliary
I muscular
A passive motion results whenever the power to move is not inherent in the
object. Thus, if we observe the circulation of the blood under the microscope, the
erythrocytes are seen to traverse the vascular channels with a certain speed, but
this movement is imparted to them by an outside force residentin the musculature
of the heart. We may also study the streaming of the protoplasm in such organ-
isms as the rhizopods. We note here the slow progression of the granules to and
from the cells, but they themselves are quite inactive and move solely in conse-
quence of the flow of the medium in which they are contained. In this connection,
mention should also be made of the so-called Brownian molecular motion which is
displayed by many plant cells, and lower organisms. A very favorable object
for observation is the unicellular green alga, called closterium (Fig. 6, I) which
contains in each end of its crescent-shaped body a vacuole filled with fluid and fine
granules (K). If the latter are observed under the high power of a microscope,
they are seen to be engaged in an incessant trembling motion. The same pheno-
^ Verworn's Allg. Physiol., Jena, 1909, and Winterstein's Handb. der allg.
Physiol., Jena, 1912.
36
MOTION
37
menon may be studied in the so-called salivary corpuscles (Fig. 6, II) which are
dead leukocytes that have entered the saliva and have absorbed much water. The
delicate molecular movement is displayed in this case by the fine granules situated
in the immediate vicinity of the nucleus. Brown, who discovered this phenome-
non in the cells of plants (1827), attributed it to the vibration of the molecules
themselves and regarded it therefore as
active. Wiener and Exner, however,
have proved that it is passive, and that it
represents an instability similar to that
exhibited by the molecules of any liquid.
The latter are never at a standstill, but
always change their position and con-
stantly move toward and away from one
another.
Movements by swelling of the cell -walls
are produced whenever the constituents
of a dry, expansible body are brought into
a moist medium so that they can attract
molecules of water. The latter are stored
in between them and force them apart
until the body as a whole increases
markedly in volume. As an example of
this type of motion might be mentioned
the so-called resurrection-plants found in
desert regions. These plants may remain
in a perfectly dried up condition for several years, their leaves being folded to-
gether like the fingers of a closed hand. When brought into a moist environ-
ment, they immediately unfold and assume definite shape.
Movements by changes in the cell-turgor are observed chiefly in plants. In-
side the walls of the different cells is found a delicate protoplasmic sac, formed by
the so-called primordial utricle. The latter is filled with a liquid, the cell-sap, the
U
Fig. 6. — Brownian Motion.
Closterium; with vacuole. II. Sali-
vary corpuscle. (Verworn.)
Fig. 7. — Sensitive Plant (Mimosa pudica). (Verworn after Detmer.)
A. Resting position. B. Stimulated.
concentration of which is varied by the addition of certain chemical substances
which are formed in the course of the vital activities of these cells. As a result
of the osmotic influx of water, the pressure in the primordial sac is increased. If
the concentration of the medium is increased, water is abstracted from- the cell.
Variations in the pressure of the cell-sap may also be brought about by the con-
traction of the primordial utricle. Of greatest importance at this time, is the
38
PHYSIOLOGY or MUSCLE AND NERVE
fact that the tension or turgor existing in the sap-sac is brought to bear upon the
elastic wall of the cell with the result that the size of the latter is either increased
or diminished. In many plants these changes in the turgescence occur very sud-
denly and either spontaneously or in consequence of a stimulus of some kind. As
an example of this type of motion might be mentioned the folding up and drooping
of the leaflets of the sensitive plants (mimosa pudica), when touched or when ex-
posed to low intensities of light. Sunlight, on the other hand, causes them to
unfold and to erect their stems and leaflets. A similar phenomenon is exhibited
by the insect-catching flowers of the carnivorous plants.
Movements by changes in the specific gravity may be observed in certain
radiolaria. Ordinarily these organisms are heavier than water and creep along
the bottom of stagnant pools. They are capable, however, of rising to the surface
by generating small bubbles of carbon dioxid which are deposited among their
protoplasmic streamers. At the surface this gas
is quickly discharged. In consequence of the in-
crease in their specific gravity then resulting they
again sink to the bottom.
Movements by secretion result in algae and
oscillariae and are produced by the projection from
their bodies of a sticky liquid which adheres to
the surface of the receptacle. As a result of this
secretion the body of the organism is slowly forced
forward in a definite direction.
Movements by growth are very general and
occur whenever a cell increases its mass. But as
the ordinary processes of assimilation are slow,
the detection of this movement often necessitates
a comparison of conditions at different periods of
the life of the organism. Many seedlings display
a more perceptible growth. Moreover, many
seeds and fruits require only the slightest touch
to make them burst and to discharge their con-
tents. In these cases the mechanical energy de-
veloped by growth has been stored, and has placed
the capsular investment under a high degree of
tension.
The alternate contraction and expansion of a
mass of protoplasm means that it assumes a
rounded shape during the former phase and a
flat outline during the latter. Its surface, there-
fore, undergoes constant changes, but naturally,
only those organisms can display this phenomenon
in a plastic manner which possess a liquid consistency. We have previously seen
that this characteristic is universal among living substance, but whether an organ-
ism as a whole is motile, depends, of course, upon the character of its framework
which may or may not be sufficiently yielding to permit the contraction of its
protoplasm. Three types of structures are evidently well adapted for this pur-
pose, namely, (a) small masses of living substance which are not surrounded by a
distinct cell wall, (6) hair-like protoplasmic processes with which many cells are
beset, and (c) the muscle cell as it appears in striated, non-striated and cardiac
tissue.
Ameboid Movement. — When placed upon a slide under the micro-
scope, an ameba-cell appears as a gray droplet embracing a nucleus
and contracting vacuole. Its central portion, consisting of endoplasm,
contains as a rule a number of granules, while its peripheral zone, or
exoplasm, is more or less hyaline. When kept under optimum condi-
Fig. 8. — Diatomae
Showing Protrusion of Mu
cous Material. (Verworn.)
MOTION
39
tions, this droplet of living substance sends out lobate processes into
the surrounding medium which are constantly increased in size and
length. These feelers, or pseudopodia, may be sent out in all direc-
tions, or may be restricted to one particular locaUty. In the latter
case, the entire mass of the cell may eventually be transferred into
one of these projections, occasioning in this way a slow onward streaming
of the protoplasm and its admixtures. This centrifugal movement,
however, may be changed at any moment into a centripetal one by
stimulation. The cell then assumes a nearly spherical outline, repre-
senting the state of contraction.
This type of movement is not confined to the ameba, but is also
exhibited by the rhizopods, the egg cells of certain animals, pigment
and giant cells and the leukocytes of the. blood; In the leukocytes it
Fig. 9. — An Ameba, Showing Different Stages of Movement. (Verworn.)
serves the primary purpose of engulfing nutritive particles, so that
these may be digested and assimilated by the living substance. It
is also made use of in ridding the body of toxic materials of all sorts,
this process having been designated by Metchnikoff as phago-
cytosis. In the plant cells in which this protoplasmic streaming is very
general, it serves the additional purpose of disseminating the food
substances.
Ciliary Movement.' — Cilia are cellular appendages possessing the
shape of slender, tapering hairs. Their length varies greatly in dif-y^
ferent animals. In the trachea of man, for example, they measure
0.003-0.005 mm. in length and 0.0003 mm. in thickness. Their num-
ber also varies. Some of the infusoria, such as Paramecium, are beset
with several thousands of them, while an ordinary lining cell of the
digestive or respiratory passage may possess only several hundreds of
^ Engelmann, in Hermann's Handb. der Physiol., 1879, i, 380; Putter, Ergebn.
der Physiol., i, 1903, and Verworn, Allg. Physiol., Jena, 1910.
40
PHYSIOLOGY OF MUSCLE AND NERVE
them. While their number is generally proportional to the size of the
cell, it may also happen that a single cell is equipped with only one
or several cilia. When especially long and thick, they are known
as flagellae. In the protozoa, these cihated cells usually extend over
the entire surface, while in the metazoa they occupy more restricted
regions of the body. They are found, for example, (a) upon the ova
and embryos of many invertebrates, fish, and amphibia, (6) upon the
epidermis and in the digestive tract of the coelenterates, worms, echino-
derms, and molluscs, (c) in the respiratory passage of molluscs,
amphibia, fish, birds and mammals, and (d) in the urogenital tract
of vertebrates. In man, they are in evidence upon the mucous mem-
brane of the nose, lacrimal duct and sac, Eustachian tube and tym-
panic cavity, upper portion of the pharynx, larynx with the exception
Fig. 10. — Ciliated Cells.
A, from a liver duct of the garden
snail; B, from mucosa of frog. (After
M. Haidenhain.)
Fig. 11. — Movement of
A Single Ilium.
A, Progressive in direction of arrow;
B, Regressive. {After Verworn.)
of the vocal cords, trachea and bronchi, uterus. Fallopian tube, vagina,
central canal of the spinal cord and the cerebral ventricles. During
embryonal life ciliated epithelium is also present in the mouth, esoph-
agus and stomach
The phenomenon of ciliary motion is brought about by a peculiar
to and fro movement of these projections.^ Being firmly anchored in
the outer portions of the cells, they swing like pendula along parallel
planes and thus avoid striking one another. In many cases, however,
the planes in which they move are not straight, but curved, similating
circles, ovals, or even the course of a whip-lash. The latter is espe-
cially true of the flagellae with which, for example, sperm cells are beset.
Moreover, if our attention is directed to a single row of ciHa, it is
noted that this movement is progressive in character, beginning with
their position of rest. The latter may be determined most easily
by rendering them inactive by means of a narcotizing agent. At this
^ Erhart, Studien iiber Flimmerzellen, Archiv fiir Zellforschung, xxxi, 1910.
MOTION 41
time, the different cilia do not project vertically outward, but are
more or less bent. When contracting the cilium curves strongly toward
its vertical position, its convex border being at first strongly inclined
in this direction. Having reached its extreme position on the other,^
side of the vertical line, it returns to the position of rest by the process
of relaxation. The former movement is, of course, more rapid than
the latter and constitutes the effective stroke of the cilium. It is
accomplished by the contraction of the ciliary substance situated on
the side toward which the stroke is being directed, the opposite side
meanwhile being put on the stretch. The contraction having been
completed, the cilium is forced into its original position in consequence
of the elastic recoil of the stretched side.
If a cell is beset with only one of these hair-like projections, an
interference with its motions is not likely to occur, but as there usu-
ally are a number of cilia situated upon a single cell, the question may
be asked how they can avoid beating against one another. Their
strokes are of course very rapid, so that the eye is scarcely able to
follow them. We thus obtain merely the impression of a general
motion which, however, it is possible to render more conspicuous by
adding some granular material to the medium in which they are
contained. The individual granules will then be forcibly thrown in
the direction of the effective stroke of the cilia. The character of
their beat may be studied more advantageously in preparations which
have been under observation for some time, because the movements ,
of dying cilia gradually become less rapid until eventually a number of
them may be found which beat only at intervals. Their movements y
may also be considerably retarded by moistening them with a few drops /
of ice-cold saline solution. Under ordinary conditions the cilia of the^
frog's pharynx beat at the rate of 12 times in a second. Their con- \^^
tractions, however, do not take place simultaneously but successively,
those in the front row of each field becoming active first, those in the
second next, and so on, until the last one has been involved. In
this way, it is brought about that the cilia of each field present all the
different stages of contraction and relaxation and give the impression
of regular waves passing over them.
The regular sequence of these waves of contraction is not effected
with the aid of nervous structures, but is dependent upon a proto-
plasmic continuity between the different cells. Naturally, this V
action arises in consequence of extraneous stimuli, but the impulses
themselves are generated in the ciHum, or rather, in the cell to which
it is attached. That this is so, may be gathered from the fact that the
ciHum ceases to beat, if K-oken off at its base, but continues to act if
left in contact witli at leas . a small fragment of the cell in the vicinity
of its root. Ihe con traction of the cilia takes place with rhythmic
regularity; moreover, ainceit occurs without the intervention of the
nervous system, it may bt said to be automatic in its character.
The function ^^f rbo < Dii; is entirely mechanical, in that they impart
42 PHYSIOLOGY OF MUSCLE AND NERVE
motion to the organism as a whole or cause bodies to move with
which they are brought into contact. Thus, the ciha Uning the upper
digestive tract of the frog, beat in the direction of the stomach so
that those small particles which are beyond the reach of the process
of deglutition, are nevertheless projected into this organ. In the
respiratory passage, their effective stroke is directed toward the mouth
with the result that the air-passages are constantly cleared of dust
and mucous globules. In the female genital tract they beat in the
direction of the external orifice, and thus exert a stimulating action
upon the spermatozoa, forcing them to progress directly against the
ciliary stream. In those protozoa in which the entire external surface,
or parts thereof, are beset with cilia, they impart a motion to the
entire organism in a direction opposite to that of their effective stroke.
They act in this case in the manner of the lateral fins of the fish. As
far as the work performed by the cilia is concerned, little can be said.
Jensen^ states that the cilia of a Paramecium possessing a length of
about 0.25 mm., are able to raise a weight of 0.00158 mgr., or about
nine times the actual weight of one of these cells.
Muscular Movement. — In the higher forms, all motions, as well as
the movements occurring inside the body, are carried on with the help of
specialized cells forming the so-called muscle tissue. These elements
appear first of all in the infusoria, such as stentor and vorticella. If
one or the other of these organisms is observed under the microscope,
its protoplasm will be seen to be permeated by a number of long
extended fibrillse, the so-called myoids. In stentor, these fibrillse
are arranged singly below the surface of the trumpet-shaped body,
while in vorticella they are cemented together to form a thick stalk
upon which the bell-shaped upper portion of this organism is situated.
When in a condition of rest, their long bodies extend far out into the
medium. Upon stimulation their head portions are swiftly retracted
toward the surface to which they are attached. This change in
their shape and position is made possible by the contraction of these
elementary muscle cells.
Broadly speaking, these contractile fibrillse reappear in the higher
animals in the shape of the smooth or non-striated muscle cells. Be-
sides, a second type of cell is found here which possesses a much greater
complexity of structure and forms the chief constituent of striated mus-
cle. The first enter very largely into the formation of what might be
termed the visceral musculature v^hich. performs work in the interior
of the body, while the latter constitute the skeletal musculature which
is concerned with the regulation of the position of the animal in space.
The striated is under the direct control of the will, while the non-striated
is not, and has to do solely with the vegetative processes of Hfe. Be-
sides these, the animal body also contains a third type of contractile
tissue, namely the cardiac muscle, but the function of this one is
1 Pfliiger's Archiv, liv, 1893, 537.
MOTION
43
more specific, because it develops the pressure which is required to
drive the blood through the circulatory channels.
The principle of action, however, is the same in all three cases,
because every muscular movement consists of two phases, namely, a
period of contraction and a period of relaxation. During the former
stage the individual cells or fibers shorten and thicken, while during
the latter they assume their original long and thin shape. Obviously,
if each constituent undergoes these changes, the muscle as a whole
must present very similar alterations. Its contraction is characterized
by a decrease in its length in favor of its breadth, and its relaxation,
by a decrease in its breadth in favor of its length. During the first
period, therefore, its outhne is more spherical.
Fig. 12. — Stentor Cceruleus, Show-
ing Myoids.
A, position of rest; J?, contracted state
upon stimulation.
Fig. 13. — Vorticella.
A, resting position; B,
contracted upon stimu-
lation.
The Structure of Muscle Tissue.^ — The chief element of muscle
tissue is the muscle cell which, in the case of the striated type, is gen-
erally designated as a fiber. The latter term seems the more appro-
priate, because they may attain a length of 30 to 40 mm. or, as some
authors claim, of 100 to 150 mm. Their thickness varies between 0.1
to 0.01 mm., differing not only in different muscles, but also in the
same muscle. Their thickness, in particular, may be much increased
by exercise and also during certain pathological conditions, such as
hypertrophy and dystrophia muscularis. If we confine ourselves to the
striated type, constituting the mass of the skeletal musculature, we
find that each muscle is invested by a connective-tissue sheath (peri-
mysium) which then extends into its interior (epimysium) and forms
small compartments in which the individual muscle fibers are con-
1 Kollicker's Gewebelehre, Leipzig, 1889, and Schafer, Essentials of Histology,
London, 1916.
44
PHYSIOLOGY OF MUSCLE AND NERVE
tained. This connective-tissue reticulum serves as the highway for
the local blood-vessels and nerves. If one of these fibers is examined
in cross-section, it appears as a rounded area possessing a rather dark
granular center and a lighter non-differentiated outer zone, or sarco-
plasm. In longitudinal section, these fibers are
cylindrical in shape and rounded at their ends,
where they are joined with neighboring ones by
means of connective tissue. They do not branch
as a rule, but those of the tongue and skin divide
into finer filaments which are finally inserted in the
mucous membrane.
Each fiber consists of a thin, hyaline sheath, or sarco-
lemma which fulfills the purpose of a cell membrane, and
should not be confounded with the more external connec-
tive-tissue envelope. These saccules are filled with soft
contractile protoplasm arranged in alternate discs of dark
and light substance. The former which is doubly refract-
ing, or anisotropic, forms the so-called transverse discs, and
the latter which is singly refracting, or isotropic, the so-
called lateral discs. In the middle of the clear band is seen
a very delicate dark line which has been regarded by Krause
as a dividing membrane to mark off definite segments,
called sarcomeres. In accordance with the preceding termi-
nology, these lines may be referred to as the intermediate
discs. Each fiber is provided with a number of nuclei which,
in mammals and birds, are situated directly below the sarco-
lemma and are embedded in a mass of sarcoplasm. Owing
largely to the transverse bands which recur in numbers of
close to 10,000 for each 1 cm. of distance, these muscle fibers
present a distinct striated appearance.^
These fibers also display a delicate longitudinal stria-
tion, for the reason that each fiber is really made up of a
number of extremely fine contractile filaments which are
arranged parallel to one another. They are known as the
primitive fibrillce or sarcostyles. These fibrillae are closely
packed together in sarcoplasm which unites them in turn
with the fibrillae of neighboring fibers. Hence, each striated
muscle fiber consists of fibrillae, sarcoplasm and sarcolemma.
A large number of fibers (2000) are bound together into
muscle-bundles which are separated from one another by
the epimysium, and many bundles into a muscle which is
enveloped externally by the perimysium. This arrange-
ment may be brought out most clearly in a muscle which
is copiously supplied with sarcoplasm, by hardening it in
alcohol. Naturally, each fibrilla presents alternate discs of
dark and light substance, the different fibrillae of the fibers
being arranged in such a way that their cross-bands come
to lie in practically the same horizontal plane. In this con-
nection it should be remembered that some of the higher vertebrates are in
possession of two types of striated muscle tissue which is either rich or poor in sarco-
plasm. In fact, certain animals, such as the rabbit and different fish, possess certain,
muscles which are composed of only one type of fibers and thus present either a dark
or a light appearance. The former are commonly designated as red (semitendi-
^ Gutherz, Archiv fiir mikr. Anat., Ixxv, 1910.
Fig. 14. — Mus-
cular Fibers of the
Adductor Magnus
OF A Dog.
M, muscular fiber ;
n, nuclei; s, sarco-
lemma; ee, spaces left
by the retraction of
the muscular sub-
stance from the in-
terior of the sarco-
lemma. (Ranvier.)
MOTION
45
nosus) and the latter as pale muscles (adductor magnus). It is readily conceiv-
able that this peculiarity in the chemical nature of the dififerent muscles must
. Fig. 15. — Muscle Fiber of Mammal Highly Magnified, Showing Its Tbansvebse
AND Lateral Discs, (a, from Schdfer; b, from Sharpey.)
lead to differences in the strength and speed of their contraction. Thus, it is
found that the dark muscles are best
adapted for the lifting of heavy loads, while
the pale muscles excel rather by their
greater rapidity of contraction. The latter,
however, are more easily fatigued.
The more primitive smooth muscle tissue''-
consists of spindle-shaped cells possessing
either a cylindrical or a slightly flattened
outline. Their length varies between 45
and 225ai and their thickness between 4 and
7/i. During pregnancy, the cells of the
uterus frequently attain a length of 0.5 mm.
Inasmuch as these cells are also composed
of a number of fibrillse, they exhibit a deli-
cate longitudinal striation. Their nucleus
occupies a central position and possesses a
long-oval shape which, however, becomes
more rounded during the contracted condi-
tion of the cell. In its immediate vicinity,
as well as in the tapering ends of the cell, is
found a considerable amount of undifferen-
tiated protoplasm or sarcoplasm. While
the striated muscle cells are generally bound
together to form compact, rounded masses,
the smooth muscle cells are usually em-
bedded in a heavy substratum of connec-
tive tissue, and the tendency is to spread them out in the form of membranes
1 McGill, Am. Jour, of Anatomy, ix, 1909.
Fig. 16. — Sensory Nerve Termi-
nations IN Arborizations Around
THE Ends of Muscle-Fibers. (Cec-
cherelli.)
46
PHYSIOLOGY OF MUSCLE AND NERVE
Cardiac muscle tissue occupies a special position, because embryologically as
well as histologically it appears in the form of modified contractile fibers. This
is especially evident in the lower vertebrates in which these cells possess a spindle-
shape, a marked cross-striation, and a long-oval nucleus. In mammals, the cardiac
muscle cell appears as a short cylinder which is usually united with a neighbor-
ing one by an oblique process to form a muscular plexus. ^ Functionally it is of
interest to remember that these prolongations bring the cells of adjoining rows or
•/'■;.'
f'
1\
Fig. 18.
Muscles of a Wasp, Prepared by Rollett's
B
Fig. 17.
Fig. 17. — Fibrils of the Wing
Method. Highly Magnified.
A, a contracted fibril; B, a stretched fibril with its sarcous elements separated at the
line of Hensen; C, an uncontracted fibril showing the porous structure of the sarcous
elements. (Schdfer.)
Fig. 18. — Smooth Muscle Cells, Teased Apart and
Nuclei Surrounded by Undifferentiated Protoplasm.
Showing Long Oval
areas into closer relation. The oval nucleus occupies a position in the axial portion
of the cell which also contains much undifferentiated protoplasm, or sarcoplasm.
The other parts of the cell exhibit a very delicate cross-striation.
The Action of Striated Muscle in Locomotion. — As far as the
mechanical properties of the resting muscle are concerned, we have
previously seen that it is a very yielding tissue and possesses a soft
consistency so that its shape may be varied with ease. The contracted
muscle, on the other hand, is firm to the touch and exhibits a more
rounded outline, because its length is diminished in favor of its breadth.
1 Zimmermann, tJber den Bau der Herzmuskulatur, Archiv f ur mikr. Anat.,
Ixxv, 1910.
MOTION
47
Thus, as most striated muscles are affixed to the skeleton in such a way
that one of their ends is stationary and the other freely movable, their
contraction invariably results in a closer approximation of their points
of insertion and attachment. In this way, movements are produced
which, if the bones are employed as levers, give rise to locomotion.
A lever is a rigid bar, one part of which is relatively fixed and the other freely
movable. It possesses a point of support, or fulcrum, a point of resistance, or weight,
and a point to which the force, or power is applied. In accordance with the relative
positions of these points, we recognize three different systems of levers, namely :
( 1 ) The fulcrum is placed between the power and the weight. When this lever is
moved, the weight and the power describe arcs the concavities of which are turned
toward one another.
Fig. 19 a. — Cabdiac
Muscle.
Fig. 19B. — Single Cardiac
Cells. Magn. 1000.
(2) The fulcrum is at one end and the weight between it and the power. The
arcs described by the weight and the power are concentric, but the weight moves
less.
(3) The fulcrum is at one end and the power between it and the weight. The
arcs are concentric, but the weight moves a greater distance than the power.
As an example of a lever of the first order might be mentioned the movement of
the skull upon the spinal column. The articulation between the axis and occipital
bone serves in this case as the fulcrum, the face as the weight and the posterior
muscles as the power. As an example of a lever of the second order may serve the
foot when employed to raise the body upon the toes. The fulcrum is formed in
this case by the toes resting upon the ground, the weight by the body resting upon
the ankle-joint and the power by the gastrocnemius and soleus muscles. As an
example of a lever of the third order might be mentioned the arm wheji it executes
the movement of flexion. In this case, the fulcrum is formed by the elbow-joint,
the weight by the hand and the power by the biceps muscle, the tendon of which
is inserted in front of the elbow-joint. These three systems may also be illustrated
by giving to the foot the three different positions indicated in Fig. 21.
48
PHYSIOLOGY OF MUSCLE AND NERVE
Theories of Muscular Contraction. — The contracting striated
muscle also presents certain microscopic changes which have been em-
ployed in the formulation of several theories regarding the manner
in which the contraction is brought about. To begin with, it should
w
r
^
I ^
W
F
w
Fig.
20. — Different Systems of Levers.
F, fulcrum; P, power; W, weight.
be remembered that the different elements composing a muscle, do not
contract simultaneously, but successively, those nearest the seat of the
stimulation being activated first. Consequently, the contraction
progresses over the muscle in the form of a wave which is directed
toward the part farthest removed from the point stimulated. The
Fig. 21. — Different Positions Given to the Foot in Illustration of the Three
Systems of Levers.
details of this wave of contraction may be studied under the micro-
scope in fresh preparations of muscle from the legs or wings of insects.
Moreover, if a muscle is dropped into alcohol or osmic acid, a series
of waves are evoked in its component fibers which are then fixed as
nodular or fusiform swellings.
MOTION
49
It is commonly believed that the primary source of the energy of
muscle is to be found in the interaction of several of its chemical con-
stituents. The potential energy here stored is transformed into kinetic
energy of the mechanical variety in accordance with the law of the
conservation of energy. Thus, the resting muscle represents an un-
stable system which may readily be transformed by the mere appli-
cation of a stimulus. The question now arises, how is it possible that
this explosive process leads to a shortening of the individual muscle
fibers as well as of the muscle as a
whole? Several explanations are
at hand, although the best of them
cannot be said to be absolutely
satisfactory.
Weber ^ has claimed that the
contraction of muscle results in con-
sequence of the sudden alteration of
its elastic power, this change being
brought about by a chemical trans-
formation following in the wake of
the stimulus. These internal
chemical forces tend to cause varia-
tions in the elastic equilibrium of
the muscle, leading to a change in
its form. In accordance with the
view of Mayer (1845), muscle tissue
may be compared to a steam engine
which transforms the heat generated
by it into mechanical energy. En-
gelmann^ assumed later on that the
heat evolved results in a transfer of
molecules of water and a change in
the form of the muscle as a whole.
Fig. 22, — Artificial Muscle.
The artificial muscle is represented
by the catgut string, m. This is sur-
rounded by a coil of platinum wire, w,
through which an electrical current may
be sent. The catgut is attached to a
lever, h, its fulcrum is at c. The cat-
gut is immersed in a beaker of water
at 50° to 55° C, and "stimulated" by
the sudden increase in temperature
caused by the passage of a current
through the coil. {Howell, after Engel-
mann.)
This assumption has given rise to the
t30-called thermodynamic theory of mus-
cular contraction which is based upon
the observation that the contracting
fiber suffers an inversion of its elements,
le., the dark discs become more fluid and
lighter in color, while the light discs become more compact and darker. But as
the width of the contracting portion of the fiber becomes greater, both bands must
be pushed out laterally and must therefore decrease in height. Engelmann then
assumed that the contraction of the fiber is caused by a rapid transfer of water
from the isotropic into the anisotropic substance under the influence of the chemical
energy set free in the form of heat. This imbibition with molecules of water tends
to impart a more oval or spherical shape to the individual contractile elements.
Later on, as the heat is dissipated, the water again returns into the light substance
and causes the fiber to relax. Engelmann has imitated this process of swelling
1 Muskelphysik., 1846.
2 pfliiger's Archiv, xi, 1875, 432 and xxv, 1881, 538.
50 PHYSIOLOGY OF MUSCLE AND NERVE
and shortening with the help of a violin string which he first passed through a coil
of platinum wire and then attached under some tension to a writing lever. If this
string was immersed in water and then subjected to heat by passing an electrical
current through the wire, it shortened very considerably. The subsequent dis-
continuance of the current permitted the string to regain its original length. The
curves recorded in this manner are very similar to those obtained with muscle
preparations under ordinary conditions of experimentation.
Ranvier^ agrees with Engelmann in so far as he believes that the anisotropic
substance is the only contractile part of the fiber. He holds, however, that the
anisotropic discs lose water on contraction which is transferred to the interfibrillar
substance. Schafer^ adheres to Engelmann 's hypothesis and states further that
the anisotropic substance is permeated by minute channels which run parallel to
the axis of the fiber and serve to accommodate isotropic material. In consequence
of the filling of these canaliculi the individual segments or prisms of the anisotropic
substance are forced farther apart, causing a widening of the fiber on contraction.
Absorption is also the principle of the hypothesis of McDougalL^ It is be-
lieved that the sarcostyles or fibrillae of striated muscle are constructed in such a
way that their distention immediately produces a reduction in their length. This
distention is assumed to take place as a result of an influx of the sarcoplasmic fluid
which surrounds them. Meigg* has applied this conception to smooth muscle and
claims that its contraction is dependent upon the passage of fluid from the cell
into the interstitial spaces.
A hypothesis has also been formed by Miiller^ which attributes muscular
contraction to an electrical attraction and repulsion of doubly refracting crystal-
loids. In consequence of a production of heat, these bodies change their poten-
tial, relaxation resulting when the polarity subsides owing to the equalization of
the temperature. It is a well-known fact that muscular contraction, as well as
any other activity of protoplasm, is associated with electrical variations, but these
changes have been proved to be quite independent of contractility.^ All these
hypotheses are very indefinite. Based upon the work of Berthold^ a hypothesis
has been formulated by Verworn^ which holds that the chemical changes in muscle
result in alterations in the surface tension of the isotropic and anisotropic discs.
In consequence of these variations, the histological constituents of muscle change
their power of cohesion and adhesion and hence, their shape and position. Jenson'
has put forward the so-called coagulation-hypothesis which bases the contraction of
muscle upon changes in the aggregate condition of the sarcoplasm. In accordance
with this view, its relaxation is not regarded as a passive phenomenon, but is said
to occur in consequence of processes the reverse of the former.
It is to be noted especially that the contraction of muscle re-
quires merely an internal readjustment of its constituents and does
not involve changes in its volume which could only be had by a
transfer of material from and to other tissues. This fact may be
proved by placing a muscle in a glass receptacle fiilled with boiled
saline solution, and equipped with a capillary tube in which the water
1 Logons d'anat. gen. sur le syst. muse, Paris, 1880.
2 Proc. Royal Society, xlix, 1891.
3 Journ. of Anat. and Physiol., xxi, 1897, 410; and xxii, 1898, 187.
* Am. Journ. of Physiol., xxii, 1908, 476; also Hiirthle, Pfluger's Archiv, cxxvi,
1909, 1.
^ Theorie der Muskelkontraktion, Leipzig, 1891.
* Helmholtz (1855) and Biedermann, Elektrophysiol., Jena, 1895.
^ Studien iiber die Protoplasma Mechanik, Leipzig, 1886.
* Allg. Physiologic, Jena, 1910; and Saleotti, Zeitschr. fiir Allg. Physiol.,
vi, 1906.
9 Pfluger's Archiv, cxxxvii, 1901, 367.
MOTION
51
forms a meniscus. If the muscle is now made to contract, it will be
seen that the meniscus does not move.
The Excitation of Muscle. — We have seen that all movements
which are to be carried out with precision, are effected by means of
striated muscle. In nearly all cases this tissue is under the control
of the central nervous system and especially of the cerebrum which
gives rise to volition. Non-striated muscle, on the other hand, is not
absolutely dependent upon central nervous structures, but is regulated
by peripheral or local centers. For this reason, it is able to show a
marked degree of spontaneity and is, therefore, not wholly under the
guidance of the will. It is true, however, that its independency is
not absolute, because its connection with the
cerebrospinal system is necessary to bring it into
functional relation with other parts of the body.
The different muscles are connected with the
central nervous system by means of nerves which
conduct impulses either toward them or away
from them. Hence, muscle tissue must be in
possession of two types of end-organs, namely
one for the reception of the stimuli and one for
the production of the motor reaction. The sen-
sory end-organ or muscle-spindle , is composed of
a group of delicate fibers which are invested by
a thick covering of perimysium. Around these
the nerve terminals are arranged in the form of
spirals or rings. The motor end-organ, or motor
plate, consists of a bulbular enlargement of the
axis cylinder which is pressed flat against the Show That Contract-
T . ^ ,1 1 r«i T, ING Muscle Does Not
sarcolemm^ of the muscle fiber. It
Fig. 23.— Schema to
appears as change Its Volume.
a rounded granular mass, the substance of which
contains numerous nuclei.
M, meniscus of sa-
lt is invested solely ^^^^ solution; ,S, elec-
trodes ^'^ '^ — 1----1-
1 1 r* i_ • J* J.1 J.' 'J.^ troues through which
by neurolemma which is directly continuous with ^^^^^^ j^ receptacle is
the sarcolemma. The medullary sheath dis- stimulated,
appears at some distance from the motor plate,
namely, at the point where the nerve fiber begins to divide to form this
ramification of axis cylinders. Most generally, a single muscle fiber
contains only one of these motor plates, but if it is very long, it usually
embraces two or several of these endings. The different nerve fibrils
arising from these plates, unite into larger ones so that their number
is much reduced when leaving the muscle. That this is a very econom-
ical arrangement may be gathered from the fact that inasmuch as a
muscle, such as the oculomotorius, contains about 15,000 muscle fibers,
about 180 million nerve fibers would be required for 30,000 grams of
muscle substance. Stilling, however, has found only about 30,000
fibers in the anterior roots of the spinal cord. In smooth muscle, the
individual nerve fibers terminate in complicated networks which are
52
PHYSIOLOGY OF MUSCLE AND NERVE
beset with ganglion cells. From these plexuses delicate fibrils then
pass to the different muscle cells.
Under ordinary conditions, a muscle contracts only in response
to impulses generated in the central nervous system and conveyed
to it through its nerve. Under experimental conditions, however,
these impulses may be generated anywhere along the course of the
nerve, and most easily by electrical or mechanical
stimuli. The natural excitatory agents are usually
designated as adequate stimuli and the uncommon
ones, as inadequate stimuli. It is also possible to
produce a contraction of a muscle by stimulating
it directly. In the latter case the stimulation is
said to be direct, while the activation of the muscle
through its nerve constitutes the method of indirect
stimulation.
Independent Irritability of Muscle. — If a muscle
is stimulated directly, it may be contended that it
reacts in consequence of the excitation of its ner-
vous constituents and not on account of the exci-
tation of its myoplasmic elements. Obviously, it
is quite impossible under ordinary conditions to
differentiate between these two factors, unless one
of them can be rendered temporarily useless. An
experiment^ enabling us to exclude the nervous
elements may be performed as follows: Having
isolated the sciatic nerve of a frog in the region
of the thigh, a ligature is tightly drawn around
all the other tissues of this part. The blood
A, dorsaTiymph ^^PP^y having thus been cut off from this extremity,
sac into which curare a few drops of curare^ are injected into the dorsal
is injected; L, liga- lymph-sac. About 20 to 30 minutes later, the op-
ture upon left thigh. .: ... - - ^ , ^ i ^^ •
The stimulation of posite sciatic nerve IS isolated, and a small opening
the sciatic nerve at 1 made in the skin over each gastrocnemius muscle.
ineffTctfre'rt^2! ^^ ^^^^ ^^ ^^^ ^^^^^® ^^^ ^^^en effect, the
Both gastrocnemius Stimulation of the sciatic nerve fails to evoke a
muscles, when stimu- contraction of the gastrocnemius on the side which
Ln*d 4, ^vra^fontrac^ ^as not been ligated (at 2), but produces a reaction
tion. on the side of the ligature (at 1). If the gastroc-
nemii muscles are now stimulated directly (at 3
and 4), it will be found that both are responsive. By applying a
galvanometer to the sciatic nerve of the leg which has not been
ligated, it may readily be proved that this nerve has retained its
functional power, because every stimulus gives rise to a deflection of
1 Archiv fiir path. Anat., 1856, or Claude Bernard, Comp. rend., 1856, 825.
2 Curare, wurare or urare is a poison used by South American Indians upon
arrows and other weapons. It is prepared from the roots of the wurare plant,
B. concoction being formed with other ingredients to hide the real active principle.
Fig. 24.— Inde-
pendent Irritabil-
ity OF Muscle.
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION 53
the needle of this instrument. The above results clearly show that
the curare has destroyed the connection between the nerve and the
muscle substance. In other words, this agent has paralyzed the
motor plate, so that the centrifugal impulses can no longer reach
their destination. On the side on which the curare has been prevented
from producing its characteristic effect by the ligature, the impulses
pursue as before a perfectly straight course into the muscle. The latter
fact may also be demonstrated by stimulating the central end of the
sciatic nerve on the curarized side. The impulses here generated now
travel in a centripetal direction into the cord, whence they attain the
opposite gastrocnemius muscle by the sciatic nerve of the non-cura-
rized side. Clearly, therefore, the normal muscle may also be stimu-
lated reflexly.
The chief conclusion to be derived from this experiment, is this:
Inasmuch as the nervous elements in the muscle have been rendered
functionally useless by the curare without destroying the susceptibility
of the muscle substance to direct stimulation, it must necessarily
follow that the myoplasm is independently irritable. In other words,
normal myoplasm is capable of receiving stimuli and of reacting even
without the aid of nervous tissue. This conclusion may be substan-
tiated by other facts. Thus it has been observed that the hearts of
embryos possess rhythmical activity long before any nerve tissue can
be recognized within them. Moreover, if the motor nerve of a
muscle is cut, it undergoes degenerative changes and finally becomes
functionally useless. At this time, however, it is still receptive to direct
stimulation. Ktihne, moreover, has observed that the sartorius
muscle of the frog reacts even if stimulated at its very end, in spite
of the fact that its ends are devoid of nerve fibers. In addition, Schiff
has shown that dying muscle reacts toward mechanical impacts by
a local contraction, i.e., the fibers near the seat of the irritation are
drawn together into a nodular swelling.
CHAPTER IV
THE GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION
METHODS OF STIMULATION OF MUSCLE AND NERVE
A. Muscle-nerve Preparation. — While no serious objection can
be raised against the use of almost any muscle, our knowledge regard-
ing the behavior of this tissue has been gathered chiefly from prepara-
tions of the gastrocnemius and sartorius muscles of the frog, owing to
the relative ease with which they may be isolated and rendered ac-
cessible to the recording apparatus. It is also true that the muscles
of cold-blooded animals retain their irritability after their removal from
54 PHYSIOLOGY OF MUSCLE AND NERVE
the body for a much longer time than those of warm-blooded animals.
It is a simple matter to reflect the skin from the leg of a pithed frog
and to isolate the gastrocnemius muscle by cutting through the tendo
Achillis and the fascia uniting it with the neighboring tibia. This bone
is then cut through directly below the knee-joint. Above the latter
is found the sciatic nerve which may be traced along the» posterior
aspect of the thigh into the pelvis where its three roots are seen to arise
from the posterior end of the spinal cord. It should be divided at this
point and carefully separated all the way down to the muscle with
Tib. ant. long.
Tendo Achillis
FiQ. 25. — Muscles of Hind Leg of Frog. (Ecker.)
which it must of course be left in contact. The fibers of the gastroc-
nemius muscle are short and are arranged obliquely into a compact
mass of tissue. For this reason, the actual shortening of this muscle is
really quite inconsiderable in comparison with its power of contraction.
In the sartorius muscle, on the other hand, the fibers are long and are
placed more parallel to one another. This is also true of the gracilis
and semimembranosus muscles. Preparations of the latter give high
contractions, but the weight which they are able to lift is relatively
small.
Methods of Registration. Myography. — Soon after the experi-
ments of E. Weber (1846), pertaining to the elasticity of muscle,
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION 55
Helmholtz (1850-1852), devised a recording apparatus which he desig-
nated as a myograph. This instrument has subsequently been modi-
fied by Pfliiger, Fick and Du Bois-Reymond. It would lead us
altogether too far to give even a tolerably accurate description of these
and other graphic appliances, and hence, it may suffice to say that the
registration of the contraction of muscle necessitates first of all a
means of holding the muscle, secondly, an outfit for recording its
movements, and thirdly, a surface upon which this record may be
made. One end of the freshly excised muscle is fastened in a station-
ary clamp, while the other is connected by means of a string with a
writing lever placed horizontally underneath it. This leyer should be
-. ■ -c a
,l! '■ ,'l
/ K "
' 1 WL^ Mr— =1
...J... u 11
1 [
^
^1
i w
■'1
1' „)i/l
1 ^
9t
''f 1 1
Fig. 26. — A Method Used to Register Muscular Contraction.
St, stand for holding of clamp C and writing lever. WL, the muscle M is attached to
the lever by means of a small hook and string. The lever is counterpoised by weight W.
The stimulation is effected through the electrodes, S. The speed of the kymograph K
may be varied by fan F.
properly counterpoised by weights or tension springs so as not to
extend while it rests. Moreover, the muscle should be surrounded by
a small bell jar so as to be able to keep it under proper conditions of
moisture and temperature. The recording surface generally employed
to-day, consists of a sheet of glazed paper which is attached to the
cylindrical drum of a kymograph and is then evenly covered with soot
by rotating it in a broad gas flame. The drum carrying the blackened
paper, is moved by clockwork at different speeds, the velocity of its
movement being indicated in seconds by a chronograph which is ad-
justed underneath the muscle lever. If the rotation is rapid, an ordi-
nary tuning fork may be permitted to register its vibrations below the
myogram.
56
PHYSIOLOGY OF MUSCLE AND NERVE
Isotonic and Isometric Myograms. — If a muscle is made to contract
after it has been attached to the writing lever, it must suffer an initial
stretching and this stretching must be the greater, the heavier the
load against which it acts. A certain part of its energy, therefore, must
be lost without being able to produce a visible effect. To counteract
this distention, it is customary to after-load the muscle with a slight
weight which is neither increased nor diminished during the contrac-
tion, or to hold the writing lever in a horizontal position by means of
a support or a tension spring. While thus subjected, to the least pos-
sible tension, it is not hindered in changing its length and in generating
Fig, 27.— Different Ways of Counterpoising the Writing Lever.
A, B and C, isotonic arrangements; D, isometric arrangement; S, spring.
visible mechanical energy. A myogram obtained under this condition
is characterized as isotonic. As far as the adjustment of the muscle
and weight is concerned, the latter may be affixed (a) directly
beneath the point of attachment of the muscle (method of loading),
(6) precisely in the same place with this modification, however, that
the lever is held in a horizontal position by a counterpoising load
or other appKance (method of after-loading), and (c) to the axis of
the lever by means of a pulley. The latter arrangement gives the
most perfect isotonicity.
If the muscle is attached near the fulcrum of the writing lever,
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION
57
while at the same time the long arm of the latter is prevented from
moving upwards by a counter force, such as a spring (Fig. 27D),
the shortening of the muscle will be insignificant in comparison with
the tension to which it is subjected. A curve of this kind, displaying
almost no change in the length of the muscle and practically no me-
chanical energy, is characterized as isometric. In this way, a relatively
much larger proportion of the total energy liberated is transferred into
heat. While the muscles ordinarily used by us in the production
of work, are not arranged in a strictly isometric manner, our con-
tractions most generally possess an isometric
character for the reason that they are ex-
ecuted against resistances.
Electrical Stimulation. Battery. Poten-
tial. Strength of Current. Resistance. — A
muscle-nerve preparation may of course be
subjected to the different kinds of stimuli
mentioned previously, namely, mechanical,
such as may be produced by pricking or
pinching; chemical, such as result from con-
tact with sodium chlorid and other agents;
thermal, such as may be caused by a heated
wire, and electrical. Any one of these influ-
ences may be brought to bear upon the
muscle directly or through the intervention
of its nerve. Under ordinary conditions of
experimentation preference is given to the
electrical method of stimulation, because it
is by far the most convenient, and although
the electricity may be produced by a mag-
net or by friction, the common practice is
to derive it from a Voltaic cell.
II "S
l-i
^
^
=
r? C«
M
Ca
-^
;;;J';"
~~
■:'*•■
>^
"~_--
Fig. 28. — Diagram of
Daniell Cell.
Cu, copper plate (+); Z,
zinc plate (— ). The direc-
tion of the current is indicated
by the arrows.
The place of the generator may be taken by a
Daniell, Grove or Leclanche cell. The first consists
of a glass jar filled with a concentrated solution of
sulphate of copper in which is immersed a round sheet of copper. Inside the latter
is a porous earthen cup filled with dilute sulphuric acid in which is contained a rod of
zinc. If the outside poles of this cell are now connected by wires, the current leaves
at the copper and enters at the zinc. The former pole, therefore, is the positive
pole or anode, and the latter, the negative pole or cathode. Inside the cell, of
course, conditions are reversed, because in order to complete the circuit the current
must flow from the zinc to the copper. The former, therefore, must be positive
and the latter negative. A cell of this kind generates a constant electromotive
force of about 1.07 volts, but possesses the disadvantage of giving oiT fumes and
acids and requires to be renewed from time to time. These difficulties are not
present in the so-called dry cell which is usually a modified type of the Leclanche
cell. The latter consists of a glass jar filled with a saturated solution of ammonium
chlorid and containing a plate of amalgamated zinc. The inner area of this cell
is occupied by a porous cup, containing pieces of carbon and dioxid of manganese.
The plate of carbon projecting from this mixture forms the positive pole, while the
negative pole is represented by the zinc. The electromotive power of this cell
58 PHYSIOLOGY OF MUSCLE AND NERVE
is 1.5 volts. The ordinary type of dry cell consists of a zinc jacket lined with
plaster of Paris and saturated with ammonium chlorid. Its inner space is taken
up by a carbon plate surrounded by black oxid of manganese.
While the nature of electricity has not been recognized as yet, we know that ^n
electrical current passes over a system of wires in the same manner as water flows from
a high to a low level. It leaves the generator at its place of high electrical potential
and reenters it at its place of low potential. The point of exit forms the positive
pole or anode (ana = up) and the point of entrance, the negative pole, or cathode
(cata = down). The difference in the potential between these two points is
designated as the electromotive force. It is easy to understand that this difference
can only be kept up if there is a constant supply of current. As the zinc is being
dissolved, the chemical energy liberated thereby tends to maintain a constant
electrical pressure at the two poles. The cell, therefore, represents a reservoir of
electricity which remains filled as long as there is sufficient material present to
generate chemical energy. If, however, the material is used up, the difference in
potential can no longer be maintained and an equalization must finally result
which causes the current to cease. In this regard electricity behaves like water,
because the flow of the latter from a reservoir continues only as long as the outgo
is balanced by an adequate ingo.
While traversing a system of wires the electrical current loses a certain amount
of its initial energy, owing to the resistance which it must overcome. Hence, the
strength of the current or the rate of flow of electricity between two different points
of a conductor is dependent not only upon the electromotive force but also upon
the resistance resident in the conducting path. Obviously, if the poles of a cell are
connected by means of a short and thick wire, the resistance to be overcome will be
less than if joined by a long and thin wire. In the former case, therefore, the flow
of electricity will be greater than in the latter, provided, of course, that the electro-
motive force remains unaltered. It must also be evident that the strength of a
current through a certain length and thickness of wire must be directly proportional
to the electromotive force. In addition to this external resistance which the elec-
trical current encounters in its passage through a conductor from copper to zinc,
it must also overcome the internal resistance, resident in the constituents of the cell
between the zinc and copper. Provided that the conducting power of the liquid
remains the same, the resistance must decrease with the size of the plates and
increase with the distance between them.
Measurement of Electrical Quantities. — In accordance with the
metric system, a unit of current is designated as an ampere, a unit
of electromotive force as a volt, and a unit of resistance as an ohm.
An ohm equals the resistance of a column of mercury 1 mm. in cross-
section and 1063 mm. in length at 0° C. The electromotive force or the
electrical pressure, so to speak, of a Daniell cell is about one volt.
If this power is permitted to act through a resistance of one ohm,
a current of approximately one ampere is obtained. In the case of the
Daniell cell, however, the amperage is really somewhat smaller, because
even if the outside wire p>ossesses a resistance of only one ohm, the total
resistance to be overcome by the current is actually greater, owing to
the fact that it is also opposed by the internal resistance of the cell.
The relationship existing between these different factors has been
determined experimentally by G. S. Ohm (1827), in accordance with
the following formula :
^ X X ^1 electrom. force volts ^.
Current strength = ^p- t^ftt or amperes = -r — * Smce
'^ Int. res. + Ext. res. ^ ohms
these factors are very closely related, it is possible to determine any
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION 59
one of them, provided the values of the other two are known. Thus:
volts = amperes X ohms
amperes = volts -i- ohms
ohms = volts -^ amperes
Polarization. — The two metals of a battery, copper and zinc,
are surrounded by electrolytes, the tendency of which is to pass
toward the opposite pole. Thus, the positive ions, Cu and H, progress
toward the cathode, while the negative OH and SO4 pass toward the
anode which, inside the cell, is the zinc. The copper plate then be-
comes covered with bubbles of hydrogen which finally place so high a
resistance in the path of the current that
it is neutralized and ceases to flow. This
action which is called polarization, finally
leads to the production of secondary
currents, the direction of which is oppo-
site to that of the primary one. It may
also happen that some of the sulphate
of zinc is attacked by the hydrogen and
is deposited upon the copper plate in the
form of a film of constantly increasing
thickness. This action must necessarily
lead to a reduction of the electromotive
force and finally to a cessation of the pri-
mary current. In the Daniell cell, the
occurrence of polarization is prevented
by the copper sulphate and in the
Leclanche cell by the dioxid of man-
ganese.
Under ordinary conditions the electrical cur-
rent is passed through living substance by means
of two copper wires which may be equipped
with small platelets of platinum. In order
to lessen the resistance, these points of contact
should be covered with cotton moistened with
saline solution. If applied for a considerable length of time, these metal elec-
trodes become covered with the products of the electrolysis resulting in the course
of the passage of the electrical current through this moist conductor, formed by
the muscle and nerve tissue. Thus, if a current is conducted through water, a
film of bubbles of oxygen eventually accumulates upon the platinum of the
positive pole, while the negative pole becomes covered with hydrogen. Presently,
the latter assumes a positive change and gives rise to a current which passes in a
direction opposite to that of the original current. The final outcome of this is a
neutralization of the primary difference in potential. This polarization of the
electrodes may be avoided by using so-called non-polarizable electrodes. Those
devised by Du-Boid-Raymond consist of zinc terminals immersed in a solution
of zinc sulphate. A very simple form may be made by taking two pieces of
curved glass tubing, measuring 4 mm. in diameter and about 6 cm. in length.
The lower end of each tube is filled with modelling clay or kaolin moistened with
normal saline solution. The remaining space in each tube is filled with a satu-
29. non-polarizable
Electrodes.
M, muscle or nerve; C, cotton
or camel's hair brush; S, solution
of zinc sulphate; Z, amalgamated
zinc.
60
PHYSIOLOGY OF MUSCLE AND NERVE
rated solution of sulphate of zinc into which is placed a short rod of amalga-
mated zinc carrying the end of the copper wire. At their points of contact with
the muscle or nerve a small tuft of cotton should be placed which has been
thoroughly moistened with saline solution. These electrodes must be carefully
washed after each experiment and must always be kept in saline solution for several
hours before they are used in order to render the clay completely permeable.
Polarization is impossible in this case, because at the junction of the cathodal metal-
lic zinc with the liquid conductor ZnS04, the cation Zn deposits itself upon the zinc
electrode and does not act upon the water to liberate hydrogen gas. In quite the
same way, the anode is kept free, because there the sulphion SO4 does not attack
the water but the zinc, forming ZnS04.
The Making and Breaking of the Current. — The electrodes are
always permitted to remain in contact with the muscle-nerve prep-
aration, while the making and breaking of the current is accomplished
Fig. 30.
-The Making and Breaking of the Current by Means of a DuBois-
Reymond Key (K).
by the closing and opening of a key or switch, interposed between the
positive pole of the battery and the positive electrode. The DuBois-
Reymond key consists of two bars of brass connected by a rocking
plate. If arranged as is shown in figure 30 A, the current is made to
pass through the muscle by closing this bridge, while its opening
breaks the circuit. If arranged as is represented in figure SOB, the
bridge remains down to begin with. The current then flows from the
anode to the cathode of the battery through the key and does not
reach the muscle at all, because the resistance offered by the tissue
between the points of contact of the electrodes, is very much greater
than that resident in the brass bridge. Conversely, if the key is
raised, the current must seek its level by way of the longer course
through the muscle, while its closure again permits the current to
seek the battery by following the path of least resistance through the
brass bridge. By the latter procedure the current is short-circuited.
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION
61
In many cases it matters little which way this friction key is ad-
justed. Under certain conditions, however, it is desirable to stimulate
while the current is already under way and in closest proximity to the
muscle (B) rather than that it must first expend a certain amount
of its initial energy in passing all the way from the battery to the
preparation (A). Furthermore, if adjustment B is employed, the
muscle does not remain in direct connection with the battery, while
in A it remains in contact with the positive pole as long as the key
is kept open. This arrangement may at times give rise to unipolar
stimulation. Many other forms of keys have been devised. A
Fig. 31. — Pohl Commutator.
By moving the bridge B in the manner here indicated the current may be reversed
at the preparation ikf. The cross-bar of the bridge is insulated.
very convenient one has been described by Morse. The current is
made by pressing upon a lever which is again forced upward by a
spring as soon as it is no longer pressed upon. In the mercury key,
contact is made by dipping the pointed end of the bridge into a
small porcelain cup filled with mercury.
Commutators or pole-changers, such as have been devised by Pohl, are some-
times inserted in the circuit in order to be able to divert the current alternately
into two sets of electrodes and also to reverse its direction. A very useful type of
pole changer consists of a round block of wood containing six depressions filled
with mercury. The wires from the battery are connected with the two central
<;ups situated upon the opposite sides of the block. These cups contain the sup-
ports of a double rocking bridge which may be adjusted in such a way that the
•current is diverted into the wires leading off from either pair of outside cups, or is
jeversed by directing it across the central connections (Fig. 31).
02 PHYSIOLOGY OF MUSCLE AND NERVE
Different Types of Current. — If the two poles of a Voltaic battery-
are connected with one another by wires and a simple key, the current
begins to flow as soon as the bridge is closed and ceases to flow as soon
as it is opened. Moreover, provided that the electromotive force
and the resistance remain the same, the current must retain a definite
strength or volume from its make to its break. A current of this kind
is characterized as a constant or galvanic current. It must be kept in
mind, however, that the flow of an electrical current is not identical
with that of water through a pipe, but consists merely of a transfer of
energy in the form of electricity. The nature of this force is not
known.
In 1831, Faraday wound two coils of insulated wire around a ring
of iron, the ends of which he connected with a galvanometer. On
passing a galvanic current through the iron, he found that the needle
of the galvanometer was deflected first on the make and again on the
break of this current. This deflection was only of momentary dura-
tion, but clearly proved that the primary current also produced a
current in the second closed circuit of wires. Peculiarly enough, the
secondary current appeared only at the very moment when the bat-
tery current was made and broken. He obtained very similar results
with coils placed next to one another on wooden cylinders and also
with the aid of a magnet surrounded by a coil of wire. A current
which is produced in a closed secondary circuit whenever the current
flowing through a neighboring primary circuit is made or broken, is
called an induced current. Inasmuch as this induction may be re-
peated either at longer intervals or in very rapid succession, we recog-
nize single as well as quickly repeated induction shocks. The former
represent widely separated make and break shocks, while the latter
are made to follow one another in such rapid succession that they give
rise to an almost constant flow of stimuli. The latter constitute the
so-called ^'tetanic" current.
The Induction Coil. — The induction apparatus devised by DuBois-
Reymond, consists of a spiral of about 130 coils of insulated copper
wire of medium thickness, the ends of which are connected through a
key with the two elements of a battery. These connections form the
primary circuit. The core inside the primary coil is filled with a
bundle of straight pieces of thin iron wire coated with shellac. A sec-
ond spiral containing about 6000 coils of insulated copper wire of a
thickness of 0.1 mm., is placed around the primary coil in such a way
that it may be pushed completely over it or farther away from it.
The two ends of this secondary coil are continued onward to the elec-
trodes. These connections form the secondary circuit.
At the very moment when the primary current is made, a current is also set up
for a brief period of time in the secondary circuit. It should be emphasized, how-
ever, that this secondary current is merely induced, and is therefore absolutely in-
dependent of the primary current. This fact may be made more evident by plac-
ing the secondary coil at some distance from the primary so that there is an empty
GRAPHIC REGISTRATION OF MUSCULAR CONTRACTION
63
space between them. A similar induction is developed when the primary current
is broken. During the interim, however, there is no induction in spite of the fact
that the current in the primary coil continues without interruption.
If the direction of the induced current is now determined by means of a gal-
vanometer, it is found that the making induction shock is opposed to the primary
current, while the breaking induction shock possesses the same direction as the
primary current. It should also be emphasized that the make induction develops
more slowly than the break induction. This difference is due to the fact that the
Fig. 32. — The Inductorium (DuBois-Reymond).
A, primary coil; B, secondary coil; P', binding posts for wires from battery; j/'
binding posts for wires leading to stimulating electrodes. {Howell.)
entering primary current must first of all overcome the self-induction of the primary
coil before it can produce its characteristic effect in the secondary coil. While it
passes from segment to segment of the primary wire, an induced current is momen-
tarily set up in the more distant stretch of wire which pursues a direction opposite
to it and tends therefore to lessen its strength. Until this resistance has been over-
come, it cannot possibly exert its full energy upon the secondary circuit. On ibhe
break, however, this hindrance is not present, so that the induction in the secondary
coil can reach its maximum with much greater rapidity. For this reason, the break
Fig. 33. — The Inductorium.
I, primary circuit and coil; 11, secondary coil and circuit; K, key; J, automatic
interrupter; N, nerve.
shock always stimulates living substance more intensely than the make shock.
The constant current, on the other hand, stimulates more on the make, i.e., at
the time when it first enters the living substance with its initial amplitude.
The strength of the induction shocks depends first of all upon the strength of
the primary current and therefore also upon the strength of the battery. In the
second place, it is proportional to the distance between the two coils, i.e., it be-
comes the weaker, the farther the secondary coil is removed from the primary.
Thus, we generally estimate the strength of an induction shock by determining the
64
PHYSIOLOGY OF MUSCLE AND NERVE
distance of the coils in centimeters in conjunction with the strength of the cells in
volts. 1 It need scarcely be mentioned that the induction may also be diminished
by placing the secondary coil at an oblique angle to the primary. When at right
angles to one another, the secondary current fails to develop.
The primary current may be made and broken at different intervals, an induc-
tion resulting each time. When interrupted very rapidly, the inductions in the
secondary circuit follow one another in such quick succession that they are fre-
quently designated as a faradic or tetanic current. In order to avoid in the latter
case the opening and closing of the key with the hand, an interrupter has been
provided which automatically makes and breaks the primary current. The one
devised by Neef consists of a vibrating steel rod ( V) and a magnet (E) . The curre nt
Fig. 34. — The Automatic Interrupter of the Inductorium (Neef's).
A, entrance of current from battery into post B and vibrator V as far as D. In
accordance with the position of the vibrating plate, the current now flows either back to
the battery C through post F or into the primary coil PC through D. In the latter
case, the current first traverses magnet E before it can reach the battery by way of
post F.
from the battery (A) is led into the pillar B as far as the platinum contact (D)
upon the vibrator. If the latter is in contact with the end of the wire of the pri-
mary coil {PC) at Df the current traverses this spiral and returns to pillar F and
the battery (CO by way of a double spiral (E) . But as the current passes through
spirals E, their iron cores are magnetized and attract the iron plate H of the
vibrator, thus breaking the contact of the vibrator at D. The current then
flows directly into F and back to the battery (C) by way of contact K. When
the primary current is broken in this way, the spirals {E) are again demagnetized.
The iron plate {H) being released, the vibrating rod moves upward and again makes
contact at D. At the very moment when the primary current is thus made and
broken, an induced current is developed in the secondary coil which, however, is
not shown in figure 34.
1 Martin, Am. Jour, of Physiol., xxviii, 1911, 49.
PECULIARITIES OP^ MUSCLE TISSUE
65
CHAPTER V
PECULIARITIES OF MUSCLE TISSUE
Extensibility and Elasticity of Muscle. — If a rubber band is suc-
cessively loaded with a number of small weights, it suffers an extension
each time. The height of these extensions remains the same through-
out this test and is proportional to the load applied. If the weights
are then removed one by one, the rubber band again shortens and
eventually assumes its original length. If a muscle, such as the
gastrocnemius, is successively extended by a limited number of weights
of 10 grams each, it is found that the extensions are greatest directly
after the application of the weight and then gradually decrease^
/
Fig. 35. — Extensibility and Elasticity.
A, rubber band and B, gastrocnemius muscle of frog successively loaded with 10
gram weights. The second curve shows a decreasing extension for equal increments,
hence, the line joining the end of the ordinates is curved.
(Fig. 35B). But naturally, each weight must be permitted to act
for a moderate length of time, because the muscle substance is viscous
and yields only slowly to the strain. If the weights are now removed
one by one, the muscle again shortens, but does not attain its former
length. Its detension, therefore, is imperfect and hence, the excised
muscle must be regarded as being incompletely elastic. Its behavior
is similar to that of other organic bodies.^ While in its normal posi-
tion in the body, its elastic power is of course absolute, so long as it is
not acted upon by excessive weights.
If the weights are added continuously, the elastic power of the
muscle is eventually overcome. Beginning at this point, its extension
occurs with great rapidity until it tears. In the case of the sartorius
muscle, this breaking point lies at 500 grams and in the case of the
gastrocnemius at about 750 grams. From these figures it may
readily be gathered that the strain which such small masses of muscle
^ Dreser, Archiv fiir Exp. Path. u. Pharm., xxvii, 1890, 51.
2 Brodie, Jour, of Anat. and Physiol., xxix, 1895, 367; and Haycroft, Jour, of
Physiol., xxxi, 1904, 392.
5
66 PHYSIOLOGY OF MUSCLE AND NERVE
tissue are capable of withstanding, is astonishingly great. To begin
with, therefore, the successive application of these weights gives rise
to a curve, the concavity of which is turned toward the abscissa,
while eventually, when the elasticity of the muscle has been overcome,
it is turned downward. Dead muscle is less extensible than living
muscle, whereas contracted or fatigued muscles are more extensible.
The elastic power of muscle tissue serves as a protection against
injury by sudden counter forces. Especially in the case of the striated
type, it minimizes the possibility of damage to the bones and tendons.
Furthermore, this elastic tension prevents the muscles from relaxing
completely so that they are always held in a condition of ''setting"
which enables them to react more promptly as well as more smoothly.
It serves, therefore, to conserve the energy which is required to produce
a contraction. In many cases, the skeletal muscles are arranged
antagonistically to one another, so that the contraction of one set places
the others under a certain elastic tension. This is especially true of the
flexors and extensors of the arms. Elastic forces also play a most
important part in the production of the pressure which is required to
drive the blood through the circulatory system. In this particular
instance, however, this function is assigned to the elastic tissue of the
blood-vessels rather than to the smooth muscle cells. Cardiac muscle
exhibits its elastic power most clearly at the beginning of ventricular
systole, i.e., directly after the ventricular wall has been fully distended
by the forcible emptying of the auricles.
Tonicity of Muscle. — A normal muscle, when resting, is not re-
tained in a condition of complete relaxation, but is held in a state of the
slightest possible contraction. The factor which is chiefly responsible
for this tonic setting of a muscle is the elastic tension of its constituents.
Thus we find that the division of one sciatic nerve causes the cor-
responding leg to hang down much lower than that of the opposite side,
because its muscles have now entered a state of complete relaxation.
It should be noted, however, that the tension of the muscles does not
constitute the condition of tonus, but is merely one of the prerequisites
thereof. Tonus in reality is the result of a continuous influx of im-
pulses from the central nervous system.
In further analysis of this phenomenon it will be found that
ganglion cells and their efferent adjuncts retain their function only
if allowed to remain in contact with those sense organs which keep
them in activity by means of their centripetal impulses. If these
impulses are prevented from reaching the center, the corresponding
effector becomes inactive and loses its tonus. So it is with muscle.
It cannot be said, therefore, that the cells of the spinal cord are auto-
matically concerned with the production of tonus, because their
activity, and hence also the tonus of the muscles innervated by them,
disappears very promptly after the dorsal roots of the spinal nerves
have been divided. It will be remembered that these paths serve as
highways for a large number of afferent impulses. Their destruction,
PECULIARITIES OF MUSCLE TISSUE 67
therefore, must give rise to a loss of stimulation and tonus. Afferent
impulses may come from the skin and subcutaneous tissue as well as
from the muscles themselves; in fact, they may also arise in higher
centers. Concerning those arising in the muscles themselves, it may
be stated at this time that the division of the afferent path of a muscle,
or groups of muscles, is generally followed by a considerable loss of
their tonus. It seems, therefore, that the so-called muscle-sense has
much to do with this phenomenon. The pressure exerted by the con-
tracting fibers upon the muscle-spindles, sets up certain afferent im-
pulses which are eventually relayet . he effector, and keep the latter
in a condition of functional alertnes^s. In last analysis, therefore, the
tonus of muscle must be regarded as a reflex phenomenon.
The Trophic State of Muscle. — The anatomical and functional
integrity of a muscle can only be retained if it is subjected to frequently
repeated stimulations. In case the latter cease at any time, say, in
consequence of the severance of the path by means of which the mus-
cle is connected with the central nervous system, it undergoes retro-
gressive changes and finally loses its functional usefulness entirely.
This atrophic state is ushered in by a diminution in its irritability,
lasting a number of days. Subsequent to this period its irritability
again increases and remains high for several weeks until it is abolished
altogether. During the second* phase the muscle is prone to exhibit
irregular contractions which remain confined to certain groups of its
fibers and impart a peculiar fibrillary motion to its substance as a
whole. Peculiarly enough, this degeneration may be arrested at any
time by reuniting the ends of the cut nerve. The muscle then grad-
ually recovers and regains its normal trophic condition in the course
of time. During the interim the muscle may in a measure be pre-
vented from losing its function altogether by stimulating it artifically
through the integument.
It must be evident, therefore, that the metabolism of a muscle is
absolutely dependent upon its connection with the central nervous
system. For this reason, it is commonly held that the ganglion cells
exert a trophic influence upon the muscle, which, however, is brought to
bear upon it through its ordinary motor nerve and not through special
trophic fibers. Hence, any motor nerve may be said to possess trophic
qualities, because it keeps the muscle in activity, thereby favoring its
metabolic processes. The blood supply is, of course, of some impor-
tance, because a copious flushing out of the muscle retards the process
of degeneration, while a scanty blood supply greatly favors the occur-
rence of these changes. This fact is demonstrated in a convincing
manner by Stenson's experiment. If the abdominal aorta of a rabbit
is Ugated, the muscles of the posterior extremity soon lose their irri-
tability, owing to the decrease in the supply of oxygen and other
nutritive material. Upon releasing the compression their func-
tion reappears very quickly. The same results may be obtained
by perfusing them with venous blood or by retarding the flow
68
PHYSIOLOGY OF MUSCLE AND NERVE
until the venous blood has acquired considerable anounts of carbon
dioxid.
The Wave of Contraction. — A long muscle generally receives its
nerve fibers from a place about midway between its two ends, while
a short and compact muscle usually receives them at its upper pole.
It is of course essential that its constituent fibers contract at about the
same time, otherwise the best mechanical results cannot be obtained.
For this reason, the nerve terminals are commonly distributed in such
a way that the impulses reach the individual fibers at about the same
time and produce, therefore, a contraction which, to all appearances,
occurs practically simultaneously throughout the muscle.
It can easily be shown, however, that the contraction of striated
muscle starts at the point stimulated and progresses from here to its
Fig. 36. — The Wave of Contraction.
M, sartorius muscle of frog, A and B, two levers placed horizontally upon muscle ;
S, stimulating electrodes; T, time; K, kymograph. When stimulated at S, lever A is
raised first.
more distant segments. Thus, if the sartorius muscle of a frog, or one
of the long muscles of the neck of a turtle, is placed flat upon a board
with two writing levers resting horizontally upon its two ends, a stimu-
lus applied to one of its ends first of all produces a rise of that lever
which lies nearest the seat of the stimulation (Fig. 36). No special
record of the time need be taken, because the interval between the
contractions of the two poles of the muscle is quite apparent even
without this. It is advisable, however, to curarize the muscle before-
hand so that the wave of excitation cannot be spread by means of the
intra-muscular nerve fibers. From this fact it may be deduced that
the contraction travels over muscle in the form of a wave possessing a
definite velocity. If the distance between the two levers is compared
with the difference in the time between the two contractions, the speed
with which this wave is propagated, can easily be determined. Ac-
PECULIARITIES OF MUSCLE TISSUE 69
cording to Rollett and Engelmann, it amounts to 3-5 m. per second
in cold-blooded animals, and to 6 m. per second in warm-blooded
animals. For human muscle the value of 10-13 m. in a second has
been given. The removal of the muscle from the body, cooling or
fatiguing it, and other factors, tend to diminish the speed of this wave.
It is independent of the strength of the stimulus.
Very characteristic progressive contractions of muscle are also
exhibited by the stomach, intestine and ureter, but naturally, we are
dealing in these cases with smooth muscle which gives the so-called
peristaltic wave. This form of contraction is produced by the inter-
action of the circular and longitudinal fibers, and although regulated
by a nervous mechanism in most cases, this regulation is not absolutely
essential, as may be gathered from the observation that the upper por-
tion of the ureter contracts with perfect precision although it contains
no nervous elements. The same may be said regarding excised seg-
ments of arteries. The contraction of the heart is also described as
wave-like, the auricles contracting first and the ventricles last, and
both in a direction from base to apex. Even excised pieces of cardiac
muscle exhibit this wave-like manner of contraction, as may be shown
by converting the ventricle of a frog into a zigzag strip by several trans-
verse incisions and stimulating this preparation either at its base or
at its apex. The contraction will then be seen to progress from the
area stimulated to the opposite end of the strip.
The Muscle Sound. — If a stethoscope is applied over a contracting
muscle, such as the biceps, a low rumbling sound is heard, ^ corres-
ponding to a frequency of 30-40 vibrations to the second. A sound
is also produced by the contracting masseter muscle which may be
rendered audible by placing the side of the face flat against a receiving
body or by shutting the ears with the index fingers.^ Helmholtz^ has
called attention to the fact that this sound corresponds in reality to
the resonance sound of the external ear. By determining its pitch with
the help of different vibrating reeds held in contact with the con-
tracting muscle, he came to the conclusion that it is chiefly constituted
by the first overtone of a sound possessing a frequency of vibration
of 18-20 in a second. Two very characteristic sounds are also pro-
duced by the contracting ventricle of the heart, of which the first is
almost entirely muscular. Even excised pieces of ventricle emit a
sound.
1 Discovered by Wollaston and Erman 90 years ago.
2 Stern, Pfliiger's Archiv, Ixxxii, 1900, 34.
3 Wissensch. AbhandL, ii, 928.
70 PHYSIOLOGY OF MUSCLE AND NERVE
CHAPTER VI
THE CHARACTER OF THE CONTRACTION OF MUSCLE
The Simple Twitch. — In accordance with the frequency and char-
acter of the stimulus, striated muscle reacts by giving either a simple
twitch-like contraction or a prolonged contraction, known as tetanus.
The former is obtained whenever the muscle or its motor nerve is
excited with a single stimulus, whether it be mechanical, electrical,
thermal or chemical. A graphic record of it may be made by con-
necting the muscle with a writing lever in the manner described
previously. If the kymograph is permitted to remain stationary, the
contracting muscle registers merely a straight line approaching the
Fig. 37. — A Muscle Twitch.
M, make shock recorded by magnetic signal connected with primary circuit. Time
ill Hoo sec. ; L, latent period ; C, period of contraction ; R, period of relaxation.
vertical, whereas a revolving kymograph will tend to separate the up
and down strokes more and more as its speed is increased. The result
is a wave-hke curve, possessing a certain height and length. A tuning
fork, carrying a marker upon one of its prongs, is usually permitted to
register its vibrations below the writing lever of the muscle. More-
over, if the electrical method of stimulation is employed, the moment
at which the shock is thrown into the muscle or its nerve, may be
registered by means of an electro-magnetic signal which is inserted in
the primary circuit and is permitted to write in the same ordinate as
the other levers.
If a muscle-curve of this kind is studied in detail, it is seen to con-
sist of two principal phases, namely a period of contraction and a period
of relaxation. During the former the muscle shortens until it has
attained its state of maximal contraction, while during the latter it
relaxes until it has again reached its natural length and form. If a
comparison is now made between this curve and the record of the signal
THE CHARACTER OF THE CONTRACTION OF MUSCLE 71
and that of the tuning-fork, it will be found that the muscle does not
begin to contract precisely when the shock is passed into it, but a
moment thereafter. This period, intervening between the application
of the stimulus and the reaction, is designated as the latent period.
Hence, a muscle curve really presents three phases, namely a latent
period, a period of contraction and a period of relaxation. No visible
mechanical energy is liberated during the first, because it is occupied
solely by various changes anteceding the actual contraction.
If the indirect method of stimulation is employed, it may be
thought that a large part of the latent period is consumed in the pas-
sage of the nerve impulse to the muscle. This contention, however,
cannot be considered of much value, because the shifting of the elec-
trodes to a place very close to the muscle does not materially shorten
this interval, nor does their removal to a more distant point give rise
to an appreciable lengthening. It must be evident, therefore, that the
conduction of the impulse over the nerve consumes only the briefest
possible time and that by far the greatest part of the latent period is
consumed in initiating those changes which finally bring the mech-
anism of contraction into play.
As far as the time relationship between these periods is concerned,
it should be stated first of all that the duration of a simple contraction
of muscle is subject to certain variations which depend upon the char-
acter of the muscle tissue and its condition at the time of experimen-
tation.^ A perfectly fresh gastrocnemius muscle of the frog completes
its contraction in about 0.1 sec, of which 0.01 sec. is taken up by
the latent period, 0.04 sec. by the contraction and 0.05 sec. by the
relaxation.
Summation and Fusion of Contractions. — If a second shock is
sent into the muscle very shortly after the beginning of its relaxation
following the first stimulus, a second contraction will be obtained which
is higher than the first. This phenomenon is known as summation of
contractions. In quite the same manner, a third contraction may be
added to the second and a fourth to the third, and so on, until the
relaxations intervening between them become very incomplete and
the individual contractions are fused into an incomplete tetanus. If
the individual stimuli are now permitted to succeed one another so
rapidly that- the relaxations cease to be discernible and the curve as a
whole pursues a straight course, the muscle records what is commonly
described as a tetanus.
It should be remembered, however, that the interval between the
succeeding shocks cannot be shortened indefinitely, because a point
will eventually be reached when the second stimulus loses its effect-
tiveness. This fact implies that a certain period must always be
allowed to intervene between the different stimulations, otherwise the
muscle will be in no condition to receive the succeeding stimulus. In
^Schultz, Archiv fur Anat. und Physiol., 1897, 22; also see: C. C. Stewart,
Am. Jour, of Physiol., iv, 1901, 202.
72 PHYSIOLOGY OF MUSCLE AND NERVE
other words, the destruction of the myoplasmic material must first be
made good by anabolic changes before the muscle can again respond.
This period during which the muscle remains inexcitable to a second
stimulus, is known as the refractory period. Its duration is only about
0.0015 sec. Thus, a muscle is in a position to react to stimuli only if
Fig. 38. — Summation of Contractions.
M and B, make and break shocks indicated by an electro-magnetic signal. Time
in Moo sec. As the break contraction occurs during the period of relaxation of the
make contraction, it is added to the first.
they recur with a lesser frequency than one in every 0.0015 sec. If their
rate is increased beyond this limit, not every stimulus will be capable
of producing a reaction. As will be shown later, the refractory period
is of especial functional significance in the case of cardiac muscle.
Fig. 39. — Fusion and Tetanus.
S, summation; F, fusion; T, tetanus. Time in seconds. The individual make and
break shocks are repeated so quickly that a continuous contraction is obtained.
Tetanus. — A tetanic contraction of muscle exhibits a greater
height and length than the simple twitch. It must be evident from the
preceding discussion that a tetanus is really composed of a multi-
tude of single contractions which have been fused into a continuous-
curve by permitting the stimuli to enter the muscle at very brief in-
THE CHARACTER OF THE CONTRACTION OF MUSCLE 73
tervals. Hence, the height of a tetanic contraction must always ex-
ceed that of a twitch and its summit must be attained more quickly,
provided, of course, that the same strength of stimulus is employed in
both cases. Having reached its maximal degree of shortening, the
muscle remains in the contracted condition until the stimuli are made
to cease. It need not surprise us, however, to find that the continued
activity of the muscle leads to a destruction of material which eventu-
ally causes it to become fatigued. This phenomenon is indicated
in the curve by a gradual decline of the lever which becomes the greater,
the longer the duration of the stimulation. Eventually, therefore, the
muscle must return into the position of complete relaxation in spite
of the continuance of the stimulation. Under ordinary conditions,
however, the stimuli are sent into a muscle only for a relatively short
period of time, but naturally, even the briefest tetanus is longer than
a simple twitch.
Fig. 40. — Tetanic Contraction.
Recorded by means of Neef s automatic interrupter. Time in seconds. The de-
cline of the curve is an indication of fatigue.
Whether or no a muscle will become greatly fatigued depends, of
course, upon its condition at the time of experimentation and upon
the strength and duration of the stimulation. Thus, an already
somewhat fatigued muscle requires a much smaller number of stimuli
to be tetanized than one just freshly prepared. The same is true
of a cooled muscle as against one which is kept at the temperature
of the room. It is evident, therefore, that the number of stimuli
which are necessary to tetanize a muscle completely, differ very widely.
Ordinarily a frog's gastrocnemius necessitates about 20-30 in a second,
and smooth muscle one in every 5-7 seconds.
Voluntary Contractions. — Inasmuch as our skeletal muscles con-
tract normally in consequence of an influx of stimuli from the cerebral
cortex, their reactions may be of almost any length, until they are
finally cut short by fatigue. We have seen that a frog's gastrocnemius
completes its contraction in about 0.1 second. Contractions of such
brevity are not given by mammalian muscles, because even such seem-
ingly instantaneous movements as the closure of the eyelids or the
trilling motion of the fingers, cannot be executed in a shorter time
74 PHYSIOLOGY OF MUSCLE AND NERVE
than 0.5-1.0 second. In accordance with this result, it is generally
beUeved that our voluntary contractions bear a close resemblance
to the tetanus of excised muscle. This would imply that even our
briefest muscular movements are the result of a series of stimuH sent
into the muscle at regular intervals during the continuance of its con-
traction. From this it may be inferred in turn that even the shortest
contractions of our muscles are composed of a number of simple
twitches. This inference is strengthened by the observation that a
contracting muscle emits a sound which possesses a vibration frequency
of 30-40 in a second. This discontinuity of the contractions of our
skeletal muscles is indicated further by the curve recorded by our fin-
gers when held in voluntary tetanus. When registered upon a slowly
revolving drum, this curve invariably exhibits irregular oscillations,
such as occur in the course of general spasms of the musculature
resulting from irritations of the central ganglion cells. Quite similarly
it has been shown by Piper ^ that if a string-galvanometer is applied
to the flexor muscles of the forearm, the stimulation of the median
nerve elicits a typical diphasic deflection of the needle. It was also
found that the voluntary contraction of these muscles gives rise to
about 40 or 50 of these diphasic variations in the course of a second.
Other muscles gave similar results. By connecting this instrument
with the phrenic nerve, Dittler has proved that the diaphragm may
be contracted by a discharge of impulses possessing a frequency of
50 to 70 in a second.
These results indicate very clearly that a muscle does not contract
in consequence of the influx of a single stimulus, but in consequence of
a series of stimuli. It must be evident, therefore, that the motor cells
innervating a muscle always discharge a series of impulses which give
rise to a serial evolution of muscular energy. Their discontinuance
then permits the relaxation to set in. The analogy between a volun-
tary contraction and one produced in excised muscle by artificial
stimuli, is therefore a very close one. These statements may also be
appHed to the tonus of muscle, with this modification, however, that
the stimuli upon which the tonic condition of muscle tissue depends,
are of subminimal intensity. These rhythmic discharges by the cen-
tral ganglion cells give rise to a discontinuous evolution of energy
which just suffices to keep the mus.cle in a semi-active condition, ready
to respond to any supraminimal stimuli that may impinge upon its
neuromuscular junction.
Contracture. — The term contracture signifies that the relaxation
of the previously contracted muscle is unduly prolonged, or, as may
also be said, that its contraction is maintained for an abnormally
long time. This condition is frequently encountered during fatigue,
or when a fresh muscle is cooled or is subjected to excessive stimulation.
It may also be produced in a chemical way by the administration of
small doses of veratrin or barium, and, in a lesser degree, also by
1 Pfluger's Archiv, cxix, 1907, 301, and Archiv fiir Physiol., 1914, 345.
THE CHARACTER OF THE CONTRACTION OF MUSCLE 75
strontium and calcium. It is frequently associated with lesions of the
central nervous system, such as give rise to hemiplegia. It may also
appear as a functional disorder in somnambulism and hysteria; in
fact, if these conditions have persisted for sometime, it may happen
that entire groups of muscles remain permanently in an exaggerated
tonic or contractured state. Unless degenerated, muscles of this kind
may still be made to give either short twitches or tetani. This fact
tends to show that an ordinary contracture is different from a tetanus.
It represents rnerely a tonic setting or contraction of the muscle in
consequence of an intrinsic or extrinsic excitation and may be classi-
fied either as functional or organic, in accordance with its cause and
duration.
Explanations of this phenomenon have been submitted by Fick,
Grlitzner and von Frey. More recently Botazzi^ has stated that a
contracture represents merely an exaggerated condition of tonus
Mrscc
Fig. 41. — Contra ctube of Muscle.
A, contracture; B, tonic contracture; C, clonic contracture.
which serves as an ''internal support" to the muscle. It is a well
known fact that tonus varies negatively as well as positively. Hence,
if a muscle is stimulated while maintaining its shortened condition, the
resulting contraction rises above the level of the contracture, but the
quick shortening observed at this time is independent of the slow
persistent shortening causing the contracture. It is believed by
Botazzi that the former is made possible by the activity of the aniso-
tropic substance, and the latter by that of the isotropic substance.
Under certain conditions, and especially during irritations of the
central nervous system, these prolonged tonic contractions frequently
assume a rhythmic character. They are then designated as clonic
contractions. A brief clonus of certain muscles is often obtained
in neurasthenia and hysteria. A very typical one may be produced
in certain cases of organic disease of the spiaal cord by suddenly
flexing the foot upon the leg. This abrupt stretching of the calf
muscles causes them to contract rhythmically for some time, thus
giving rise to the so-called ankle-clonus.
^ Jour, of Physiol., xxi, 1897, 1.
76 PHYSIOLOGY OF MUSCLE AND NERVE
CHAPTER VII
THE FACTORS VARYING THE CHARACTER OF THE
CONTRACTION
The Strength of the Stimulus. — In general it may be stated that
the height of the contraction is proportional to the strength of the
stimulus. A very convenient way of illustrating this rule is to permit
a muscle to record its contractions upon a stationary drum while being
stimulated with single make or break induction shocks. By varying
the distance between the secondary and primary coils of the induc-
torium the strength of these stimuli may be accurately graded. If
this experiment is begun with the coils far apart, no contractions are
obtained at first, although it may be surmised that the different
stimuli then give rise to certain chemico-physical alterations in the
(f if ,( ^1
B
I i 3 t S- 6 7 8 9 to II 12. JJ I^^AAAAAAAAAAAAAAAAAy\^^
Fig. 45, — Effect of (Jhamgjss in Temperature on Muscular Contraction.
The temperature was raised 5° each time.
Influence of Temperature. — Warmth increases the power and
speed of reaction of this tissue, because it exerts a favorable influence
upon the chemical processes underlying muscular contraction. Hence,
a series of myograms recorded at gradually rising temperatures, usu-
ally shows a progressive increase in the height and corresponding de-
crease in the length of the different contractions.^ At 0° C, or rather,
a httle below this point, the muscles of the frog lose their irritability
entirely. Consequently, if a muscle of this kind is stimulated at a
degree or two above freezing, it gives solely a very low and prolonged
contraction. If the temperature is now raised, say, three degrees at a
time, the individual contractions decrease in length but increase in
height. Beginning at about 9° C, their height is slightly decreased,
but again increased at about 18° C. A second maximum is reached
at 30° C. Subsequent to this point they again diminish in size until
1 Gad and Hey mans, Archiv fur Physiol., 1890, 59.
FACTORS VARYING THE CHARACTER OF THE CONTRACTION 79
at about 37° C. the muscle begins to lose its irritability and to pass,
at about 40°-42° C, into the condition of heat rigor. Regarding the
cause of these variations little can be said; in fact, it has been stated
repeatedly that these fluctuations are not altogether constant. It
must be concluded, however, that muscle tissue requires a certain
optimum temperature which allows it to give reactions of maximal
amplitude. For the warm-blooded animals the most favorable tem-
perature is 37° C, and for the cold-blooded animals, the temperature
of the medium iii which they are living.
Heat rigor, or rigor caloris, is a permanent condition, correspond-
ing in a way to the coagulation of egg albumin. When entering this
state, the muscle gradually shortens and becomes firm to the touch
and opaque in its appearance. These characteristics it retains.
When placed under a greater tension than 15-20 grams per gram milli-
meter of substance, it ruptures abruptly.
Effect of Drugs and Chemicals. — Certain chemicals affect the
irritability and contractility of muscle in a very characteristic manner.
Fig. 46. — The Effect of Veratrin on Muscular Contraction.
This is especially true of veratrin. A few drops of a 1.0 per cent,
solution of its acetate, injected into the dorsal lymph sac of a frog,
generally suffice to produce its characteristic effect. The muscle may
also be immersed in a solution containing 1 part of the alkaloid to
100,000 parts of a 0.7 per cent, solution of sodium chlorid.^ By this
means a simple twitch of the gastrocnemius may be made to last
50-60 sec, instead of the normal 0.1 sec. Thus, the peculiarities
presented by a veratrinized muscle, consist in a surprisingly long period
of relaxation which usually presents two summits. It frequently hap-
pens, however, that a second stimulus sent into the muscle shortly after
it has completed one of these prolonged contractions, again results in
a very rapid twitch. If the muscle is then allowed to rest, the suc-
ceeding excitation may again produce a long drawn-out contraction.
Biedermann has stated that these peculiar effects are dependent upon
a dissociation of the red and pale fibers of the muscle. Carvalho and
Weiss, 2 however, have observed the same behavior in muscles which
are composed exclusively of either type of fibers; hence, it is quite im-
^ Bucannan, Jour, of Physiol., xxv, 1899, 137.
2 Jour, de la Physiol, et de la path, gen., 1899.
80 . PHYSIOLOGY OF MUSCLE AND NERVE
possible at this time to assign a definite cause to this reaction. Barium
salts, glycerin, and nicotin produce somewhat similar effects.^
If a muscle is placed in a 0.6 per cent, solution of sodium chlorid
or is frequently moistened with it, it retains its functional qualities
for a long time, because this fluid is practically isotonic to the myo-
plasm. A strong solution of this salt, on the other hand, causes the
muscle to twitch irregularly, either as a whole or along certain of its
strands of fibers. The muscle then exhibits a behavior very similar
to that shown by the fibrillating heart. Inasmuch as these results
are also obtained with sodium chlorid dissolved in distilled water, the
ordinary preservative fluid for muscle should be made with tap-
water which contains at least a trace of calcium. This salt neu-
tralizes the excitatory action of the sodium. More pronounced
stimulating effects may be obtained with solutions of Na2C03, or with
a solution containing 0.5 per cent. NaCl, 0.2 per cent. NaHP04 and 0.04
per cent. Na2C03 (Biedermann). When mixed in this proportion,
these salts aie capable of inducing an almost rhythmic activity of
skeletal muscle. Potassium salts act as depressants. Thus, even
normal saline solution when mixed with a few drops of potassium, will
induce fatigue within a very short time. Owing to this fact and be-
cause the ash of muscle contains a considerable amount of potassium,
it has been thought that the liberation of these salts during muscular
activity is responsible for the phenomena of fatigue.
Fatigue. — If a fresh muscle is stimulated for some time with in-
duction shocks of moderate strength, the successive contractions gradu-
ally decrease in height but increase in length. Furthermore, if a
record is made of the latent period, it will be found that its length is
steadily increased, indicating thereby a very definite diminution in the
irritability of the muscle substance. This observation may also be
made upon a muscle which is subjected to a quickly interrupted current
of long duration. The height of the contraction decreases gradually
as the current is continued. Quite similarly, it will be noted that the
repeated tetanization of a muscle gives rise to curves of slowly de-
creasing amplitude.
Inside the body, a muscle cannot be fatigued so easily, because its
waste products are constantly removed by the blood stream, while new
substances are brought to it to replace those which have been lost
during the preceding contractions. An excised muscle, on the other
hand, possesses only a small store of reserve material and has no
means of ridding itself of the fatigue substances. For this reason,
it shows these phenomena more promptly and never recovers com-
pletely from the stimulations. Its condition, however, may be ma-
terially improved by perfusing it with defibrinated blood or normal
saline solution. Contrariwise, it is possible to hasten its exhaustion
by perfusing it with a dilute solution of lactic acid, or with saline
containing a considerable amount of carbon dioxid. These two agents,
^ Motinsky and Straub, Arch, fiir exp. Path. u. Pharm., li, 1904, 310.
FACTORS VARYING THE CHARACTER OF THE CONTRACTION 81
together with monopotassium phosphate and certain toxins, are said
to be responsible for the development of fatigue in muscle. They
are spoken of collectively as the fatigue substances.
The phenomena of fatigue are also exhibited by human muscle
when subjected to excessive stimulation. We then become cognizant
of a peculiar strained f eeUng and eventually also of pain which prevents
us from continuing these efforts. It appears that these sensations are
the direct result of an irritation of the muscle-spindles and of the cor-
'ftstC
Fig. 47. — Fatigue of Muscle.
A gastrocnemius muscle of the frog stimulated successively 150 times.
1st, 50th, 100th, and 150th contractions are recorded.
The
responding receptors in the tendons and joints. Under ordinary con-
ditions the tests upon human muscles require the use of an instrument,
which is known as the ergograph. The one devised by Mosso^ consists
of a support for the arm and a weight which acts in a sliding path or
across a pulley and is connected with the tip of one of the fingers,
preferably the index finger of the right hand. A spring ergograph,
or dynamograph, has been devised by Waller. It consists of a strong
Fig. 48. — Fatigue Curves of Frog's Muscle. (Waller,)
oval steel spring which is compressed by the hand, while a pointer is
moved across a graduated scale to indicate the degree of compression
as well as the power of the group of muscles used in this act. In either
method, the displacement of the weight or of the spring may be
registered upon a kymograph by means of a writing lever, the resulting
record being known as an ergogram.
The fatigue of human muscle may be illustrated either by recording a
series of voluntary twitches or a long-continued tetanus of, say, the muse.
1 Arch. ital. de biologie, xiii, 1890; also see: Treves, ibid., xxix, xxx, and xxxi,
1898-1900, and Schenck, Pfiuger's Archiv, Ixxxii, 1902.
82
PHYSIOLOGY OF MUSCLE AND NERVE
flexor digitorum sublimis, or of the muse, abductor indicis.^ The
former type of contraction, however, must be repeated in rapid suc-
FiG. 49. — Mosso's Ergogbaph.
c, is the carriage moving to and fro on runners by means of the cord d, which passes
from the carriage to a holder attached to the last two phalanges of the middle finger
(the adjoining fingers are held in place by clamps) ; p, the writing point of the carriage,
c, which makes the record of its movements on the kymograph; w, the weight to be
lifted. (Howell)
j
i
1
i
1
i
j
1
:
li ,
11' 1
M
ill
I !
lllllllll
1
liillli
III
mm'
Fig. 50. — Normal Fatigue Curve of the Flexors of the Middle Finger of Right
Hand.
Weight 3 kilograms, contractions at intervals of two seconds. (Maggiora.)
cession, because even a load of as much as 6 kg. Hfted at intervals of
1 Storey, Am. Jour, of Physiol., viii, 1903, 356.
FACTORS VARYING THE CHARACTER OF THE CONTRACTION 83
10 seconds, may not be able to induce fatigue. It is also essential to
use maximal weights, because the effects of small weights are generally
compensated for within a very short time. The interval which should
elapse between two successive ergograms showing complete normal
fatigue, is close to 2 hours. If a muscle is made to contract before it has
fully recovered from a preceding exertion, it may be more severely
injured than if it had been forced to lift excessive loads to begin with.
Practically no two ergograms are alike, because every person presents
certain individual peculiarities which are dependent upon his physio-
logical condition. Thus, pronounced mental or bodily fatigue from
such causes as loss of sleep, anemia, lowered nutrition, etc., is prone to
produce a more rapid exhaustion of the muscle than could possibly be
obtained in a perfectly robust person. Practice and training enhance
the power of a muscle, and this end may also be attained by augment-
ing the local or general circulation by drugs, massage, baths as well as
by the ingestion of certain foods, such as sugar.
CHAPTER VIII
THE CHARACTER OF THE CONTRACTION OF SMOOTH
MUSCLE
The Tonicity of Smooth Muscle. — The organs and structures con-
taining non-striated muscle cells are innervated by the autonomic
system and are therefore not under the direct control of the will.
In fact, they are in a way independent of the cerebro-spinal system,
because their function continues even after they have been separated
from it. Herein lies the implication that they are well equipped with
intrinsic nervous elements which are capable of controlling their action
even in the absence of the higher centers. If the bladder or a segment
of the stomach or intestine is excised and suspended in a chamber
under proper conditions of moisture and tempeiature, it may easily
be observed that it retains its tonus and even executes spontaneous
contractions. The latter may be of myogenic or neurogenic origin,
although Schultz^ claims that they arise solely in consequence of exci-
tations of local nervous elements and are therefore reflex in their
character. In accordance with this statement, the ordinary condition
of tonus of non-striated muscle may be said to have both a myogenic
and neurogenic cause, "the former giving rise to the ordinary elastic
state of its substance, and the latter to periodic excitations which are
relayed to it by way of definite reflex paths. Considered in this light,
the spontaneous contractions of smooth muscle are mere variations
in the neurogenic tonus.
^Archiv fur Physiol., Suppl., 1903, 1; also see: Griitzner, Ergebnisse der
Physiol., iii, 1904, 2.
84 PHYSIOLOGY OF MUSCLE AND NERVE
The Character of the Contraction. — Even the most casual observa-
tion of the peristaltic wave of the stomach, intestine or ureter must
show that smooth muscle reacts in a very sluggish manner, but it would
be going too far to state that its irritabiUty is less than that of striated
tissue. Practically all the different types of stimuH are effective; in
fact, in the case of the iris of the eye of frogs and other animals it is
possible to produce constrictor reactions even with light. ^ Obviously,
this phenomenon cannot be explained by saying that it is due to reflex
causes, because the same results may be obtained with small pieces
of excised iris. It is also evident that smooth muscle is very suscep-
tible to mechanical and thermal stimuli, but rather insensitive to
electrical stimuli. The latter peculiarity necessitates the use of some-
what stronger induction shocks than are ordinarily required to activate
striated muscle.
Different types of smooth muscle differ in their speed of reaction,
but, broadly speaking, it may be said that their latent period is from
Fig. 51. — Contraction of Smooth Muscle (Cat's Bladder.)
L, latent period; C, period of contraction; R, period of relaxation; time in seconds.
100 to 500 times as long as that of striated muscle. But inasmuch
as the amplitude of the reaction of smooth muscle is directly propor-
tional to the strength of the stimulus, it forms no exception to the
general law and gives, therefore, an ascending series of minimal and
maximal contractions which increase with the strength of the current.
The chief peculiarity of the curve of contraction of smooth muscle
is its great length. Thus, if a preparation of the frog^s stomach, the
bladder of a cat,^ or a segment of intestine is stimulated with a current
of moderate strength, minutes usually elapse before it again regains its
normal form. In the case of striated muscle, on the other hand,
the same quality of stimulus evokes a contraction which is generally
completed in less than a second. This difference is dependent upon
the fact that the periods of contraction and relaxation of plain muscle
are greatly prolonged, so that the entire curve really acquires the char-
acteristics of a contracture of striped muscle. Inasmuch as its short-
ening is always accomplished in a much briefer time (10-15 sec.) than
its relaxation (60 sec), it is claimed by Winkler^ that the strength of
iGuth, Pfliiger's Archiv, Ixxxv, 1901, 118.
• « C. C. Stewart, Am. Jour, of Physiol., iv, 1900, 185.
» Pfliiger's Archiv, Ixxi, 1898, 386.
THE CHEMISTRY OF MUSCLE 85
the stimulus required to cause it to contract, must always be great
enough to produce a contracture-like effect. Smooth muscle may also
be made to show the phenomenon of summation by stimulating it
again very soon after it has entered upon its period of relaxation.
This summation may be repeated until its maximal degree of short-
ening has been obtained which, according to Schultz, is frequently
73 per cent, above its resting position or abscissa.
The character of the contraction of cardiac muscle will be discussed
in a later chapter dealing with the dynamic importance of the heart.
It may be stated at this time, however, that its contraction is inter-
mediate between those of striated and non-striated muscle, and is
most closely allied to the simple twitch of the former. Moreover,
cardiac muscle does not react intermittently, but possesses an auto-
matic power which makes it contract rhythmically in consequence of
the generation of certain internal stimuli.
CHAPTER IX
THE CHEMISTRY OF MUSCLE
General Composition.^ — Inasmuch as the muscle tissue of an
adult constitutes about 42 per cent, of the body weight, it forms a
very considerable part of the total mass of our body. It is also very
important functionally, because it produces nearly 50 per cent, of the
total metabolism in persons at rest, and almost 75 per cent, in
persons undergoing moderate activity. In analyzing muscle tissue,
it must be taken into account that it embraces a certain amount of
connective tissue and also blood-vessels and nerves. Its principal
element is, of course, the fiber which is composed of a contractile
albuminous substance or sarcoplasm, and an elastin-like investnient,
or sarcolemma. The former possesses a semifluid or jelly-like con-
sistency and displays a series of doubly refracting elements. The
striated and non-striated types of mammalian muscle contain from 72
to 78 per cent, of water and from 22 to 28 per cent, of solids, the latter
being composed largely of proteins.
Proteins of Muscle. — The fact that muscles become perfectly rigid after death
as well as on exposure to heat, has led to the belief that their albuminous constitu-
ents undergo a process of coagulation similar to that exhibited by the blood of the
warm-blooded animals. Thus, Kiihne^ has succeeded in isolating from them a
liquid by first freezing them and then subjecting them to a high pressure. This
so-called muscle-plasma clots almost immediately when slightly warmed. The
remaining portion of the muscle substance forms the so-called stroma. Under
ordinary conditions it suffices to divide the muscle into small pieces and to subject
^ V. Fiirth, Oppenheimer's Handb. der Biochemie, Jena, 1910.
2 Unters. iiber das Protoplasma, Leipzig, 1864.
86 PHYSIOLOGY OF MUSCLE AND NERVE
them to a pressure of from 250-300 atmospheres. About 60 per cent, of the weight
of the muscle is then obtained as plasma.
The Proteins of the Plasma. — Halliburton/ has shown that muscle-plasma
contains two coagulable proteins, namely myosin and myogen which upon coagu-
lation are transformed into myosinfibrin and myogenfibrin. But this transfer
does not seem to be a direct one, because, in the case of myogen, v. Fiirth has found
an intermediary product which he has called soluble myogenfibrin. This author
also calls attention to the fact that the coagulation of muscle-plasma is not strictly
comparable to the coagulation of blood, as has been held by Ktihne and Halli-
burton, because the clot is floccular and forms as a rule very slowly. Furthermore,
while fresh muscle-plasma is neutral or slightly alkaline in reaction, it becomes
distinctly acid after coagulation has set in. This acidity is due to the formation
of sarcolactic acid. The serum formed in the course of this process, contains the
soluble constituents of muscle.
The Proteins of the Stroma. — The residue left over after the plasma has been
squeezed out, consists chiefly of connective tissue, sarcolemma and nuclei. By
preventing as much as possible the occurrence of rigor in the excised muscles, Saxl^
has found that only a small portion of their total mass consists of stroma. He also
states that the plasma proteins in skeletal muscle amount to seven-eighths of the
total protein content, while their relationship in cardiac muscle^ is as l-i '.% and
in smooth muscle as 3'^ : ^:^ . The stroma contains phosphorus which is held
in the nucleoprotein. It also embraces phospholipins in combination with the
proteins.
Lipins of Muscle. — The fat of muscle is contained chiefly in the connective
tissue between its different bundles, but a certain amount of it is also held in the
cells themselves. On analysis the former in all probability gives rise to neutral
fat, while the latter yields cholesterol and phospholipins. The proportion of these
bodies differs greatly in different types of muscle tissue. In skeletal muscle, they
may amount to as much as 30 per cent., and in cardiac muscle to as much as 60
or 70 per cent, of the total lipins.^ Cardiac tissue is characterized by a large per-
centage of cuorin which is a monoamidodiphosphatide.
Carbohydrates of Muscle.^ — The presence of glycogen in muscle tissue was
recognized soon after the discovery of this substance by Claude Bernard. It may
be present in considerable amounts, namely 1.0 per cent, in the muscles of the cat,
0.4-0.7 per cent, in those of man, and as much as 3.7 per cent, in those of the dog.
It seems to be derived from the sugar of the blood, muscle tissue possessing the
power of converting the monosaccharide dextrose by dehydration and condensa-
tion into the polysaccharide glycogen. The following formula may serve to illus-
trate this reaction :
NCCeHiaOe) - NCHzO) = (C6Hio05)N
Glycogen is stored in the muscle tissue and forms an important nutritive material.
For this reason, it must be a constant constituent of all well-nourished resting
muscles.
Inorganic Constituents. — Muscle tissue contains a number of salts such as the
chlorides, sulphates and phosphates of sodium, potassium, calcium, magnesium
and iron, but its chief characteristic is its large content in potassium and phos-
phoric acid.^ The total amount of phosphorus is 0.2 per cent., it being present
chiefly in an inorganic form. Ox muscle, for example, contains 81 per cent, of
inorganic and 19 per cent, of organic phosphorus, while heart muscle embraces
1 Jour, of Physiol., viii, 1888, 133.
2 Hofmeister's Beitrage, ix, 1906, 1.
^ Lederer and Stotte, Biochem. Zeitschr., xxxv, 1910, 108.
■* Erlandson, Zeitschr. fiir phys. Chemie, li, 1907, 71.
6 V Fiirth, Ergebn. der Physiol., Bioch., ii, 1903, 580.
• Urano, Zeitschr. fur Biol., 1, 1907, 212.
THE CHEMISTRY OF MUSCLE 87
40 per cent, of the former and 60 per cent, of the latter. By far the greatest
amount of organic phosphorus is present in the form of phosphatide.
Lactic Acid. — Most generally muscle tissue also contains a certain amount of
ethidene lactic acid or sarcolactic acid, CH3CHOHCOOH. This acid is a product
of tissue metaboHsm. It is dextrorotary, while that contained in sour milk, is in-
active to polarized light and finds its origin in bacterial fermentations. In normal
resting muscle it is difficult to detect it, because it is oxidized as rapidly as it is
formed, but its removal may be greatly interfered with by restricting the entrance
of oxygen. The amount of this acid is greatly augmented during muscular activity.
Extractives. — If muscle tissue is extracted with boiling water, a number of sub-
stances are obtained which are of especial interest, because they represent in all
probability the products of the metabolism of muscle. Chief among these are
those of nitrogenous origin, because they give rise to some of the substances ex-
creted in urine. As a rule, fresh muscle yields about 2 per cent, of its weight in
extractives of which 0.7 per cent, is of organic and 1.3 per cent, of inorganic origin.
The one present in largest amounts is creatin, C4H9N3O2, which equals 0.1 to 0.4
per cent, of the weight of the mammalian muscle. Creatinin, C4H7N3O, is present
in much smaller amounts, but constitutes 0.3 per cent, of the weight of the muscles
of fish. No definite conclusions have been reached as yet regarding the origin of
these bodies and even the statement of Liebig and Ranke, ^ that creatin is a fatigue
substance and increases with muscular activity, has not been substantiated by
the more recent and more exact quantitative determinations of these substances. ^
Carnosin,^ CgHi4N405, is a basic extractive and is said to be derived from histidin,
because on hydrolysis it yields histidin and /3-alanin. It is present in about the
same proportion as creatin. Other bodies are carnitin, novain and taurin.
The purins of muscle are relatively scanty in amount, because by far the great-
est part of the muscle cell is composed of cytoplasm. They are represented by
such bodies as uric acid (C5H4N4O3), xanthin (C5H4N4O2), hypoxanthin (C5H4N4O),
guanin (C5H5N5O), adenin (C5H5N5) and carnin (C7H8N4O3). Urea is present in
very small amounts in the muscles of mammals (0.04 to 0.08 per cent.), but in
much larger quantities in the muscles of certain fish (1 to 2 per cent.).
Pigments and Enzymes. — The red color of muscle is said to be due to a pigment
which is known as myohematin or myochrome. Inasmuch as this body presents
several of the characteristics of hemoglobin, it is commonly said to be identical
with it. Its chief function is respiratory, because it furnishes the muscle with
oxygen which it holds in loose combination.
The substances furnished to the muscles by the blood, are made available for
their metabolism b}^ hydrolysis, oxidation, reduction and synthesis. It is believed,
therefore, that muscle tissue is in possession of certain enzymes which are capable
of instigating these processes. Their function is proteolytic, lipolytic and amylo-
lytic. They also act as oxidases or peroxidases, reductases, deaminases, etc. The
products of muscular metabolism frequently exert a certain influence upon the
function of other structures. Thus, lactic acid and carbon dioxid serve as stimu-
lants to the respiratory center, while the accumulation of these and other bodies
in consequence of disturbances in their excretion, may give rise to toxic symptoms.
The Chemical Changes in Contracting Muscle. — The metabolic
alterations in the contracting muscle are characterized by a constancy
of the catabolism of the proteins and an increase in the catabolism of
the carbohydrates, together with a production of lactic acid and carbon
dioxid. This is clearly shown by the fact that muscular work does not
augment the nitrogen output of the muscle nor of the body, but is
* Tetanus, eine physiol. Studie, Leipzig, 1865.
^jGrindley and Woods, Jour. Biol. Chem., .ii, 1906, 309; Urano, Hofmeister's
Beitrage, ix, 1906, 104, and Meyers and Fine, Jour. Biol. Chem., xv, 1913, 283.
' Gulewitch and Amiradzibi, Zeitschr. phys. Chem., xxx, 1900, 565.
88 PHYSIOLOGY OF MUSCLE AND NERVE
followed by (a) a greater production of carbon dioxid and a greater con-
sumption of oxygen, (b) a formation of lactic acid, and (c) a gradual
disappearance of the glycogen. Hence, as the contraction of a muscle
is made possible by chemical alterations in the myoplasm, it must be
evident that this energy is chiefly derived from the carbohydrates.
The statement that this foodstuff is the most available source of
muscular energy, is substantiated further by the fact that muscular
exercise immediately raises the respiratory quotient.
The production of carbon dioxid by the active muscles is clearly proved by the
fact that the expired air contains a larger amount of carbon dioxid than the
inspired. Obviously, this gas is transferred from the tissues to the blood and
is subsequently gotten rid of through the respiratory channel. It has also been
shown that an excised muscle evolves a much larger quantity of carbon dioxid
when tetanized than when allowed to rest.^ This increased production of carbon
dioxid is associated with an increased intake of oxygen, but the respiratory quo-
CO
tient, —p—^' increases, because the output of carbon dioxid exceeds the absorption
O2
of oxygen. Moreover, this evolution of carbon dioxid ceases if no oxygen is al-
lowed to enter the body. In explanation of these phenomena it has been stated
that this gas does not constitute a primary product, but arises secondarily in con-
sequence of the oxidation of the products of muscular metabolism. 2 Thus, it has
been assumed that the chemical processes in muscle result first of all in a decom-
position of the complex nutritive material into intermediary substances, such as
lactic acid, which are then reduced in the presence of an adequate supply of oxygen.
This explanation finds substantiation in the fact that frog's muscle, when sus-
pended in an atmosphere of nitrogen, soon ceases to respond to stimulation. If it
is then subjected to an analysis, it will be found to contain 0.2 per cent, of lactic
acid, but only traces of carbon dioxid. The latter, in all probability, have been
liberated in consequence of the change of the muscle medium from faintly alkaline
to acid. Conversely, if a muscle is first fatigued in an atmosphere of nitrogen,
and is then transferred into a medium of pure oxygen, it soon recovers its irritability
and may be stimulated for a long time before it again exhibits indications of
fatigue. On subsequent analysis, it will be found to contain practically the same
amount of lactic acid as resting muscle, but much larger quantities of carbon
dioxid. A contracting muscle, therefore, liberates carbon dioxid in amounts
which are almost directly proportional to the quantity of oxygen available for the
reduction of the lactic acid.
The Formation of Lactic Acid. — Resting muscle exhibits a neutral or feebly
alkaline reaction, while active muscle is distinctly acid.^ This general statement,
as we have just seen, holds true only if inconsiderable amounts of oxygen are
available, because a copious supply of this gas reduces the sarcolactic acid still
further, while a scarcity of it causes the acid to accumulate. But, since mechanical
manipulation and thermal and chemical irritations are very prone to increase the
production of this acid, it is difficult to obtain an excised muscle with a perfectly .
neutral reaction.^ In most cases it will show an acidity equalling 0.02 per cent.,
expressed as zinc lactate. This may be considerably increased (0.2 per cent.) by
causing the muscle to undergo a few contractions. Blue litmus paper will then be
reddened and brown turmeric paper turned yellow.
The production of lactic acid during muscular activity may be proved by inject-
ing a solution of acid fuchsin into the dorsal lymph sac of a frog, whence it will be
1 Hermann, Unters. iiber d. Stoffwechsel d. Muskeln., Berlin, 1867.
2 Fletcher, Jour, of Physiol., xxviii, 1902, 474.
' Proved by DuBois-Reymond, in 1859.
* Fletcher and Hopkins, Jour, of Physiol., xxxv, 1907, 247; and xliii, 1911, 12.
THE CHEMISTRY OF MUSCLE 89
absorbed and distributed to the different tissues through the circulation, but as the
different media of the body are normally neutral or faintly alkaline, no change in
color will result. If one of the posterior extremities is now tetanized by stimulating
its sciatic nerve, the muscles so activated gradually assume a reddish hue. This
change appears more quickly, if the corresponding femoral artery is ligated after
the injection of the fuchsin, because lessening the oxygen supply greatly favors
the accumulation of lactic acid.
The origin of the lactic acid in muscle has been the subject of much contro-
versical discussion. Some investigators, indeed, have sought to displace the old
view of Liebig which holds that the acidity of muscle is due to the formation of
lactic acid, by the theory that it is caused by the mono-phosphate of potassium. ^
Again, it has been assumed that the free lactic acid acts on the potassium biphos-
phate normally present in muscle and forms potassium lactate by the reduction of
the neutral into acid phosphate. It is also believed that lactic acid arises in the
course of the disintegration of glycogen, but this view seems untenable because it
has been shown that the glycogen content of muscle in death-rigor remains prac-
tically the same, in spite of the fact that its content in lactic acid is very high,
namely 0.5 per cent. In addition, it has been proved that muscles which have been
deprived of their glycogen by fasting, yield as much lactic acid as normal muscles.
Hill, 2 moreover, claims that the precursor of lactic acid is a substance which
possesses a heat value at least 70 per cent, greater than that of this acid. But
the heat liberated by dextrose, is only slightly greater (3 per cent.) than that of
lactic acid, and furthermore, an excised muscle frequently yields a quantity of acid
which is considerably above that actually to be derived from the glycogen normally
present in muscle. These results clearly demonstrate that glycogen cannot be the
mother-substance of this acid. The only alternative, therefore, is that it is a de-
rivative of the proteins. More recently, it has been asserted that muscle tissue
contains a carbohydrate-phosphoric acid group which yields lactic and phosphoric
acids in about equimolecular amounts. It is believed that the sugar of muscle is
synthetized with phosphoric acid and other constituents into the aforesaid complex
compound. On breaking down, the carbohydrate group of this body gives rise
to lactic acid. «
The Disappearance of Glycogen. — Weiss^ has shown that frog's muscle loses
from 24 to 50 per cent, of its glycogen on tetanization. This observation has been
confirmed repeatedly by other investigators so that it may now be considered as
definitely proven that this constituent of muscle diminishes during activity. A
normal resting muscle, on the other hand, increases its store in glycogen and much
more rapidly, if its motor nerve is cut to prevent contraction. In a similar way,
it may be proved that general muscular exercise reduces not only the glycogen store
of the muscles, but also that of the liver. This consumption of glycogen may be
rendered even more striking by temporarily discontinuing the intake of food.
Cardiac muscle, in particular, possesses very marked storing qualities, and retains
its glycogen even more tenaciously than skeletal muscle.'*
The liberation of heat and electrical changes concomitant with muscular con-
traction, will be discussed in a later chapter. Suffice it to say at this time that the
muscles constitute the chief heat producing tissue of our body and that their
activity is associated with clearly recognizable electrical variations.
The Chemistry of the Fatigue of Muscle. — We have previously
seen that the continued or excessive stimulation of muscle eventually
causes it to become functionally useless. It loses its irritability and
contractility so that even the strongest stimulus is no longer able to
1 Dreser, Zentralbl. fiir Physiol., i, 1887, 195.
2 Jour, of Physiol., xlvi, 1913, 28.
sgitzungsb. der Wiener Akad., Ixiv, 1871.
* Aldehoff, Zeitschr. fiir Biol., xxv, 1889, 137.
90 PHYSIOLOGY OF MUSCLE AND NERVE
activate it, and naturally, an excised muscle is more susceptible to
fatigue than a normal one, because it is quite unable to obtain new-
material and to discharge the products of its metabolism. Likewise,
it may be inferred that a normal muscle is able to regain its functional
qualities within a relatively short time, while an excised muscle is not.
This exhaustion, therefore, is referable to two causes, namely an
insufficient supply of nutrient material, inclusive of oxygen, and an
accumulation of depressing waste products. The fact that substances
of this kind are actually formed, needs no further substantiation,
because Ranke^ has shown that the irritability of a fatigued muscle
may be restored by perfusing it with an ordinary non-nutritive solu-
tion, such as sodium chlorid. In addition, this investigator has
proved that the injection of extracts of the fatigued muscles of one
frog into the circulation of another gives rise to a typical depression
in the second animal. Inasmuch as these results can also be obtained
with solutions of lactic acid and creatin, he gave to these agents
the name of '' fatigue substances," and later on included under this
term also carbon dioxid and acid potassium phosphate. (KH2PO4).
More recently Mosso^ has extended these experiments to warm-blooded
animals and has shown that the transfusion of the blood of a fatigued
dog into the circulatory channels of a second perfectly normal dog
produces in the latter most decided symptoms of fatigue.
Weichardt^ has attempted to add to the three fatigue substances
carbon dioxid, lactic acid and monopotassium phosphate, also a
certain specific muscle toxin which he calls kenotoxin. When isolated
from the other substances, this toxin, when injected into other animals,
is capable of producing the phenomena of fatigue. He also claims to
have obtained, by bacteriological methods, an antitoxin which serves
to counteract the effects of this toxin and to retain the muscle in a
reactive condition. These tests have more recently been repeated by
Lee and Aranowich,^ but no evidence has been found to substantiate
the formation of an actual muscle toxin.
It has also been shown by Lee^ that small quantities of any of the
three fatigue substances previously mentioned, cause a temporary aug-
mentation in the activity of the muscle, as is evinced by an increase
in its irritability and working power. Thus, if a muscle is succes-
sively stimulated at intervals of, say, one second and its contractions
are registered upon a slowly revolving drum, the injection of a small
amount of any one of these agents temporarily increases the height
of these contractions. In this manner the curve may be made to show
periodic augmentations. This phenomenon is known as the '* Treppe. "
In this connection it might also be mentioned that these stair case-
1 Tetanus, Leipzig, 1865.
2 Arch, de biolog. ital., xiii, 1890.
3 Miinchener med. Wochenschr., li, 1904, 12;lii, 1905, 1234; and liii, 1906, 1701.
* Proc. Exp. Soc. of Biology and Medicine, 1917.
» Am. Jour, of Physiol., xx, 1908, 170.
THE CHEMISTRY OF MUSCLE 91
like increases are frequently observed at the beginning of a series of
contractions of either striated, non-striated or cardiac muscle when
stimulated with induction shocks of constant strength. According
to Lee, this initial "Treppe" is due to a sudden increase in the
irritability of the muscle, following the early production and accumula-
tion of small quantities of the fatigue substances. It may be accepted
as proven that the seat of this excitation is the myoplasm and not the
neuroplasm, because these increases also develop in curarized muscles
and in muscles which have suffered a degeneration of their nervous
elements.
The Chemistry of Rigor Mortis. — The condition of death rigor is
characterized by a rigidity of the musculature which makes its appear-
ance very shortly after the general functions of the body have ceased.
It manifests itself by a loss of the irritability and contractility of the
myoplasm. The muscle becomes opaque, stiff, and firm to the touch
and, unless its tendency to shorten is opposed by a slight counterforce,
is prone to assume a state of very slight contraction.
Under ordinary conditions, rigor mortis affects the different muscles
in a definite sequence from above downward, beginning with those of
the jaws and neck and finally involving those of the trunk, arms and
legs. It is also noted that these muscles are affected gradually, i.e.,
fiber after fiber and not simultaneously throughout their substance.
The degree of their shortening is determined by the weight of the part
moved by them and the force opposing this tendency. Thus, the
simultaneous stiffening of the flexors and extensors finally gives rise
to a fixed position of the extremities so that the joints become im-
movable, but inasmuch as these muscles are antagonistically placed,
practically no shortening results. This fact that the muscle in rigor
retains its normal form almost completely, may be more plastically
portrayed by cutting the tendons of either the flexors or extensors of
the foot at death. It will then be found that the subsequent rigor
of the opposing muscles does not materially change the position of the
foot.
The time required for the development of rigor mortis is very
variable. Most generally it makes its appearance in from 1 to 5 hours,
but in some cases it may begin as early as 10 minutes after death. A
delay of from 20 to 24 hours is not unusual. Under certain conditions
it may develop almost instantaneously, giving rise to the so-called
cataleptic rigor. Thus, it is narrated that soldiers have been found
in rigor with the gun at their shoulders and with one eye open and the
other closed as in the act of taking aim. In all these and similar cases,
the central nervous system was found to have been seriously lacerated.
The duration of rigor mortis is also very uncertain, because it may
last anywhere from a few hours to a few days, or even a week. A
quick onset, however, usually suggests a short duration. Forced
movement of the parts frequently tends to bring on relaxation.
The factors which may be held responsible for this variation in the
92 PHYSIOLOGY OF MUSCLE AND NERVE
character of rigor mortis are several. First of all we might mention the
condition of the muscles at the time of death. Thus, it is a matter of
common observation that muscles which have been enfeebled by dis-
ease show a rapid onset and dissolution, while strong and vigorous
muscles are affected rather slowly. Cold delays and warmth hastens
its onset. The same is true of muscular fatigue and certain diseases
of the spinal cord and brain. Extensive lesions of these parts greatly
favor its development. Young individuals, and especially infants,
are affected more rapidly than adults, and red muscles more slowly than
pale muscles.
In analogy with muscular contraction it is believed that rigor
mortis is caused by a coagulation of the protein material. It is held
that the myosin and myogen are temporarily converted into their
insoluble forms, ^ myosinfibrin and myogenfibrin, this change being
associated with an increase in the acidity of the muscle. Inasmuch
as the latter is dependent upon the production of lactic acid, it has
been assumed that this acid is the actual cause of this coagulation,
or is at least very closely concerned with it. This inference is entirely
justified, because lactic acid is not copiously produced in the presence
of an abundant supply of oxygen. Rigor mortis then fails to develop.
A deficiency in oxygen, on the other hand, favors the accumulation of
lactic acid and hence, also the occurrence of this condition. In accord-
ance with this conception, the dissolution is said to be dependent upon
the reestablishment of the neutral reaction of the medium or upon
intracellular autolyses due to ferments. ^ It has been proved, however,
that bacteria are not the primary cause of the dissolution, because the
rigor also disappears when their growth is prevented.^ In analogy
with the coagulation of the blood, the attempt has also been made by
Danilewsky^ and others to bring the development of rigor mortis into
relation with the calcium content of the muscle plasma. We have prev-
iously seen that this relationship is only a general one; moreover, it
has been shown that calcium-free solutions of myogen are not exempt
from coagulation.^
In the third place, a muscle in rigor mortis gives rise to a consider-
able amount of carbon dioxid which may have its source either in an
increased general catabolism or in those oxidations which are primarily
concerned with the reduction of lactic acid. In accordance with the
experiments of Fletcher and Brown, ^ this point has been decided in
favor of the latter view, the increase in carbon dioxid being the indirect
result of the formation and oxidation of the lactic acid. Some ob-
servers also claim that the glycogen content of muscle is diminished
during rigor mortis.
1 Saxl, Hofmeister's Beitrage, ix, 1906, 1.
2 Vogel, Deutsch. Arch, fiir klin. Med., 1902, 292.
'Bierfreund, Pfliiger's Archiv, xliii, 1888, 195; and Karpa, ibid., cxii, 1906, 199.
* Zeitschr. phys. Chemie, vi, 1882, 158.
* V. Furth, Hofmeister's Beitrage, iii, 1903, 453.
* Jour, of Physiol., xlviii, 1914, 177.
THE PRODUCTION OF ENERGY IN MUSCLE 93
The Chemistry of Rigor Caloris. — It has previously been shown
that the continued appUcation of heat causes the muscle to lose its
irritability and to become functionally useless. In this condition of
rigor caloris the muscle presents an opaque appearance, a firm con-
sistency and a change in its form, approaching its state of maximal
shortening. The skeletal muscles of the frog enter this condition at 40°
or 41° C, while those of warm-blooded animals require a temperature
of about 47° C. This difference in their behavior may be ascribed to
the fact that the muscles of amphibia contain preformed soluble
myogen fibrin which coagulates at 40° C, while those of mammals con-
tain soluble myosin which coagulates at 47° to 50° C. While rigor
caloris may be said to be dependent upon a conversion of the proteins^
into their insoluble forms, a muscle entering this condition also liber-
ates carbon dioxid and heat, and acquires a larger store of lactic
acid. Fletcher claims that this carbon dioxid is preexisting and is set
free at 40° C. from carbonates and similar bodies through the inter-
vention of the lactic acid. At higher temperatures (75° C.) it is given
off by the colloids and amino-acids.
Muscles may also be thrown into a state of rigor by means of a
number of chemical substances. Water-rigor, for example, results in
consequence of their immersion in distilled water, while coagulation-
rigor is the outcome of the coagulation of their protein material
by such agents as alcohol and chloroform. ^ The same result may be
obtained with dilute acids, veratrin, caffein, quinine and different tox-
ins.^ While it is often difficult to differentiate between these different
types of rigor, heat rigor mayeasily be distinguished from death rigor,
because the former is a permanent and the latter a temporary condi-
tion. Furthermore, a muscle in rigor caloris shows a more decided
opacity, and possesses a more solid consistency than a muscle in rigor
mortis. The latter is rather unevenly turbid and its color may be
considerably lightened by a 0.2 per cent, solution of sulphuric acid.
CHAPTER X
THE PRODUCTION OF ENERGY IN MUSCLE
Forms of Energy Liberated. — ^Life manifests itself by incessant
changes and every manifestation of it necessitates the Hberation of
energy in some form or other. Work must be done and a body that
cannot yield energy, accomplishes neither changes nor work. But
since the law of the conservation of energy applies equally to all living
entities, these alterations cannot be associated with a gain or loss in
^ V. Ftirth, loc. ciL; Inagaki, Zeitschr. flir Biol, xlviii, 1907, 313, and Meiggs,
Am. Jour, of Physiol., xxiv, 1909, 178.
* Brooks, Am. Jour, of Physiol., xvii, 1906, 218.
' Heinz, Handb. der exp. Path, und Pharm., i, 1905, 576.
94 PHYSIOLOGY OF MUSCLE AND NERVE
material. It merely means that one kind of energy is transformed
into another without actually causing a change in the total amount
of the energy available in the universe. It is true, however, that the
proportion of "bound'' and ''free" energy does not remain the same;
in fact, the latter invariably diminishes and never increases. Like
all protoplasm, muscle tissue contains a store of chemical substances
from which it derives its necessary energy. When stimulated, certain
chemical processes of an explosive type are initiated in its substance
which cause its potential energy to be converted into kinetic energy.
The latter presents itself as mechanical work, heat and electricity,
light being excluded in this particular case. But naturally, the re-
lative amounts of these three forms of energy must vary considerably,
the production of heat greatly exceeding that of mechanical energy
and electricity. Individual variations are common and find their
origin in the character of the muscle tissue as well as in the conditions
under which it is made to contract. Thus we find that the muscles
of warm-blooded animals are able to do twice as much work per unit
of mass as those of cold-blooded animals and that the muscles of in-
sects are even more powerful than these. It has already been men-
tioned that red striated muscles are more powerful than pale muscles,
the greater effectiveness of the latter lying rather in their quickness of
action than in their actual strength. The liberation of energy is af-
fected unfavorably by fatigue, low temperatures, a high humidity of
the air, a poor nutritive condition of the body, and other factors. In
general, however, it may be said that about one-third of the total
amount of energy appears in the form of- mechanical energy and some-
what less than two-thirds in the form of heat.^ Fick,^ working with
excised muscles, states that under favorable conditions^ about one-
fourth of the total energy can be given off as mechanical work, pro-
vided the load used is relatively large. With smaller weights this
amount is proportionately diminished.
The Work Performed by Muscle. — For ordinary purposes it suffices
to determine the work performed by a muscle by simply multiplying
the load by the height to which it has been lifted. The product is
then expressed in terms of milligram-meters. Thus, if a muscle raises
a weight of 25 grams to a height of 10 millimeters, as determined
by the weight of the curve recorded by it upon the kymograph, it has
done 250 gram-millimeters of work. In this calculation, however,
an allowance must be made for the magnification of the writing lever
in accordance with the formula: L :H : :l:h, in which L equals the
total length of the lever, I the length of its short arm from the axis
to the attachment of the muscle, H the height of each line of contrac-
tion and h the actual height to which the load has been lifted. The
work (W) is then computed in gram-millimeters in accordance with
1 Zuntz, Pfliiger's Archiv, Ixviii, 1897, 191.
Ubid., xvi,.1878, 85.
THE PRODUCTION OF ENERGY IN MUSCLE 95
the formula : W = wh, in which w signifies the weight and h the height
to which it has been raised.
From these results it may be gathered first of all that the product
must become zero if no weight at all is attached to the muscle. When
not loaded, therefore, a muscle does practically no external work and
the chemical changes occurring during its contraction are almost
wholly converted into heat and a small amount of electricity. The
word "practically" is inserted here, because a muscle even when not
carrying a weight, must overcome its own resistance which, to be sure,
is so slight that nearly all of its energy can appear as heat. This
modification could of course be rendered superfluous by adjusting the
muscle in a horizontal manner and immersing it in oil to overcome this
friction as much as possible. In the second place, it is also evident that
the product must become zero if H equals zero, and even when the
muscle is loaded with so heavy a weight that it is quite unable to lift it.
As in the preceding case, most of the energy liberated is then turned
into heat.
Attention should also be called to the fact that a muscle which
merely contracts and relaxes, raising and lowering a weight, really
furnishes no energy to its surroundings, because it develops no kinetic
energy at this time. In order to accomplish actual work, it would be
necessary for it to produce certain changes. This end it could easily
accomplish by raising a weight to a definite height and permitting it
to fall to the surface of the earth. The potential energy stored in it
would then be converted into kinetic energy.
We have previously seen that a muscle, when properly counter-
poised and made to react successively against a steadily increasing
load, exhibits a gradual decrease in the height of its contractions.
Eventually a weight will be found which it is quite unable to lift. At
this time, therefore, the load counteracts the contractile power of the
muscle and no mechanical energy is liberated. This weight which
merely places the muscle under a maximal degree of tension and does
not permit it to change its length, has been designated by Weber as the
absolute power of the muscle. Moreover, since this power is propor-
tional to the cross-section of the muscle, we are in a position to obtain
a standard by simply determining the absolute force for one square
centimeter of muscle substance. This value, to be sure, differs in
different muscles, because such factors as the character of the myo-
plasm and the number and arrangement of the muscle fibers, give rise
to individual variations. For frog's muscle, values ranging between
0.7 and 3.0 kilograms per centimeter of cross-section have been found.
The experiments upon human muscles have been made during volun-
tary contractions and not during artificial tetanization, while the cross-
sections of the muscles employed for these tests have been determined
upon dead subjects of the same physique as the person experimented
upon. Hermann 1 gives the average absolute force of human muscle
» Pfltiger's Archiv, Ixxiii, 1898, 429.
96
PHYSIOLOGY OF MUSCLE AND NERVE
as 6.25 kilograms, a value which is considerably higher than the pre-
ceding one for frog's muscle. This calculation becomes of practical
value in testing the power of the muscles of persons suffering from
various types of nervous diseases. A so-called dynamograph is com-
monly used for these determinations. This instrument consists of a
tension-spring against which the muscles of the hand are voluntarily
contracted.
A close study of the curve represented by Fig. 43 also shows that a
muscle reacts better when a slight load is attached to it than when it is
not weighted at all. To begin with, therefore, the contractions in-
crease in height, quickly at first and then more slowly, until a certain
Fig. 52. — Diagram op Work-adder.
A, wheel which is turned by muscle M in direction of arrows. It is held in place
by brake B. Each contraction of muscle raises weight W .
maximum has been reached. 'Subsequent to this point the increasing
loads gradually diminish the contractions until the muscle is no longer
able to raise the lever above the abscissa. Hence, a muscle yields
maximal work only when made to act against a certain moderate
weight which places it under a physiological tension.
In order to determine the work performed by a muscle during a long
period of time, it becomes necessary at times to employ an ergograph
or a work-adder.* The former instrument has been described in an
earlier chapter. The latter consists of a small windlass which the
muscle (Af ) turns sUghtly in one direction with each contraction. The
weight (TF) which is suspended from the wheel (^) by a thread is
* Fick, Unters. aus dem physiol. Lab. der Zuricher Hochschule, Wien, 1869.
THE PRODUCTION OF ENERGY IN MUSCLE 97
raised a certain distance with every contraction, its descent being
guarded against by an automatic brake {B) which retains the wheel
in its newly acquired position during the subsequent resting period of
the muscle. At the end of this experiment the total work performed
by the muscle, may be computed by multiplying the weight by the
height to which it has been raised.
The Muscle as a Thermogenic Organ. — We have seen that the
largest amount of the energy liberated by the body leaves it in the
form of heat. We are also justified in concluding that this heat is
derived very largely from the activity of the musculature, because the
latter constitutes about 40 per cent, of the total weight of the body and,
after the removal of the skeleton, more than 50 per cent. The bones,
as may readily be surmised, do not possess a vivid metabolism, while
that of the muscles is greater than that of any other tissue. Thus,
it is a matter of common experience that the temperature of the body
increases very markedly during exercise, frequently to 39° or 40° C,
Fig. 53. — Arrangement of Thermoelectric Elements (A and B) and Gal-
vanometer C.
but this rise is only temporary in its nature, because the heat is again
dissipated during the subsequent period of relative muscular rest.
The production of heat may also be registered locally in the contract-
ing muscles of the thigh or arm of a mammal, the bulb of a thermom-
eter being pushed in among the muscle fibers (Gierse, 1842). More
exact values, however, may be obtained with the help of thermoelec-
tric elements, but naturally, the thermoelectric method necessitates a
much greater experimental aptitude than the thermometric.
A thermoelectric couple consists of two dissimilar metals, such as German
silver and iron or antimony and bismuth {A and B). These are soldered together
and the binding post upon each couple connected with a low resistance galvanom-
eter (C). In investigating the heat production of muscle, one of these couples is
inserted with its pointed tip in an indifferent muscle, while the other is placed in
the muscle to be experimented upon. As long as this muscle remains inactive, it
generates no heat, and hence, no electric differences are developed at the points of
soldering. The needle of the galvanometer remains stationary. If the muscle is
now made to contract, this system immediately ceases to be isoelectric, because the
heat produced therein generates an electric difference in the corresponding ther-
mopile which in turn leads to a definite deflection of the galvanometric needle.
7
98 PHYSIOLOGY OF MUSCLE AND NERVE
By equipping this indicator with a small mirror, a beam of light may be reflected
from it upon a screen or into a photographic camera. Its excursions are standard-
ized with the help of a very sensitive thermometer.
Becquerel and Bichet (1835) who first employed this method upon the biceps
muscle of a human subject, obtained a rise of 0.5° C. during energetic movements.
In a similar way, Helmholtz (1847) has found that the tetanization of a frog's mus-
cle raises its temperature 0.14-0.18° C, while Heidenhain^ has noted a rise of
0.005° C. during single contractions. It must be remembered, however, that even
a resting muscle serves as a thermogenic organ, because the blood returned from
it possesses a higher temperature than that passing into it (Ludwig, 1881). In
addition, it has been ascertained that the heat production varies directly with the
intensity of the chemical changes. A strong stimulus, therefore, must yield more
heat than a weak one. Tension has a similar influence, because isometric contrac-
tions are followed by a greater liberation of heat than isotonic. Weight acts favor-
ably at first, on account of its initial tendency to augment the mechanical energy;
later on, however, the liberation of heat diminishes more rapidly than the amount
of work. These and other facts tend to show that a muscle works more economic-
ally when acting against a moderate load than when not weighted at all. Further-
more, when a fresh muscle and a fatigued muscle are made to perform the same
amount of work, the former generates more heat than the latt^, because it is
in possession of a greater store of chemical substances.
The Muscle as an Electrogenic Organ. — The electrical current
generated by a battery finds its origin in chemical changes enacted by its
constituents. In quite the same way, the diflferences in electrical poten-
tial developed by muscle and other forms of protoplasm, find their
cause in chemical alterations accompanying their activity, and hence,
are derived from their stored potential energy. The amount of elec-
trical energy developed by muscle is rather small, but it should not be
forgotten that this amount is considerably augmented by the sum
total of the electricity which is evolved by the glands, nervous struc-
tures and other tissues. The final result, therefore, is far from trivial.
It need scarcely be mentioned that certain animals, for example, the electric
fish, possess special organs for the generation of this form of energy to serve as
a weapon of offense and defense. It is stated that Malapterurus electricus inhabit-
ing the rivers of Africa (Nile), is capable of producing a shock equalling 200 volts.
The organ itself is situated directly below the skin on each side of the body and
consists of a number of membranous plates arranged parallel to one another. In
Gymnotus and Malapterurus these plates are placed vertically and in the Torpedo
horizontal to the long axis of the body. Each organ is innervated by a nerve which
subdivides and sends branches to each plate. In Malapterurus this nerye is but a
single giant fiber possessing a very thick investment and derived from a single
large ganglion cell. The long discussions, whether these electrical organs consist of
modified muscle or nerve tissue or whether they are embryologically distinct, have
led to the conclusion that those of Torpedo and Gymnotus have been derived
from muscle tissue, while that of Malapterurus is an outgrowth of the skin glands.
Schonlein has estimated the electromotive force of an entire organ of the Tor-
pedo at 0.08 volt for each plate; hence, it equals that of thirty-one Daniell cells.
This voltage is sufficient to kill other fish and animals and especially because it is
discharged in transverse lines. The discharge results chiefly in a reflex manner up-
on mechanical stimulation. In Malapterurus the shock traverses the conductor
in a direction from the head to the tail of the animal and in Gymnotus from the
1 Mechanische Leistung, etc., Leipzig, 1864; also see: Fick, Myotherm. Unter-
Buchungen, etc., Wiesbaden, 1889.
THE PRODUCTION OF ENERGY IN MUSCLE 99
tail to the head. Peculiarly enough, the fish itself is fully protected against these
shocks, a fact which is generally referred to the extremely low degree of irritability
of its tissues.
Animal electricity, or as it is known in Physics, galvanism was dis-
covered by Alvisio Galvani in 1786. In the course of his experiments
upon the influence of atmospheric electrical discharges upon animal
life, he attached the leg of a frog to a copper hook and placed this
preparation upon the iron railing of the veranda of his house. When
he did so, the muscles twitched violently. He explained this phenome-
non by saying that the muscles themselves generate electricity. Volta,
however, gave a very different and, as it finally proved, more correct
explanation of this reaction. He assumed that whenever two dis-
similar metals are connected with a moist conductor, a difference in
electrical potential is established which is equalized as soon as these
metals are joined. Peculiarly enough, Galvani not only adhered to
his former contention, but endeavored to find further substantiation
for it. He placed a muscle preparation upon a glass plate and brought
the end of a freshly cut nerve in contact with its surface. Whenever
contact was made between them, the muscle twitched violently. He
thus became the discoverer of animal electricity after having just
convincingly recognized contact electricity. •
Methods of Detecting Electrical Variations in Muscle. — The
existence of electrical currents in the tissues of animals and plants
did not find direct proof until the year 1824, when Schweigger dis-
covered the multiplicator and Nobili the galvanometer. A few years
later, Nobili also proved that "natural currents'' occur in the frog,
which pass in a direction from the foot toward the head of the animal.
The ordinary form of galvanometer consists of a ring magnet which is suspended
by means of a silk fiber and rests in relation with a number of vertical coils, each
of which is composed of many windings of fine copper wire. If an electric
current is passed through this system of wires, the neighboring magnetic field is
influenced in such a way that the magnet is deviated from the magnetic meridian
either to the left or right in accordance with the direction of this current. These
deviations are registered as a rule by equipping the pointer or needle of the magnet
with a small mirror, from the surface of which a beam of light may be reflected upon
a screen or upon sensitive paper contained in a photographic camera (Thompson).
In order to protect the galvanometer against the magnetism of the earth, two
magnets of nearly the same strength are placed in opposite directions near the
instrument. As the magnets tend to point toward the poles, they oppose one
another and thus compensate in part for the earth's magnetism. The Deprez
d'Arsonval galvanometer embraces certain modifications whichj in addition to those
just mentioned, diminish the disturbances otherwise prone to result from currents
made to traverse neighboring circuits for purposes of light and electric power. The
principal element of this instrument is a wire which is hung between the poles of an
electromagnet. Inasmuch as this wire is bent upon itself to form a spiral, it is
not deflected laterally but is merely twisted in a rotatory manner. Its movements
are registered by a mirror from which light is reflected.
An instrument of similar construction but capable of a much greater rapidity
of motion, is the string galvanometer, devised by Einthoven. ^ It consists of a power-
1 Arch, intern, de Physiol., iv, 1906, 133, and Pfluger's Archiv, Ixxii, 1908, 517.
100
PHYSIOLOGY OF MUSCLE AND NERVE
ful electromagnet possessing the shape of a horseshoe. A delicate thread of
silvered quartz or platinum is suspended in a vertical direction between its two
iitii " ' 4
Fig. 64. — D'Absonval Galvanometer as Modified by Rowland With Telescope
FOB Obseeving Movements of Needle. (Howell.)
Fig. 55. — Schema of Galvanometer.
n, s. North and south poles of astatic pair of magnets; m, compensating magnet, held
by friction on the staff, and capable of being approached to, or rotated with reference to,
the suspended magnet; X , mirror; /, fiber 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. (American Text-book of Physiology .)
poles. The sides of these poles are perforated so that the shadow of this string may
be reflected upon a screen or upon the sensitive paper of a photographic camera.
THE PRODUCTION OF- ENERGY IN MUSCLE
101
If an electric current is permitted to pass through it, it is moved laterally in a line
parallel to the poles, i.e., perpendicularly to the lines of force passing between the
poles of the magnet. These deflections take place to either side in accordance
with the direction of the current. Contrary to the d'Arsonval galvanometer, the
deflections of this string are not mere twists but actual lateral deviations which can
be increased and decreased by varying the tension placed upon the string. Know-
ing this tension, or, in other words, the resistance of the string, the strength of
the current causing its deviations, may be calculated directly from the size of the
deflections. The string galvanometer permits of a freedom of motion which the
ordinary forms of galvanometer cannot attain, although the actual sensitiveness
of the latter is no doubt greater than that of the former. Thus, its chief character-
FiG. 56. — Einthoven's String Galvanometer, as Modified by Cunningham,
Williams and Hindle.
The front-cover has been removed to show the position of the string between the
poles of the magnet. The conijecting posts lie behind the hood containing the string.
istic is its speed of reaction which enables it to follow the electrical variations with
an almost immeasurable exactness.
A third instrument which is sometimes used for the detection of electrical cur-
rents of animal origin, is the capillary electrometer (Lippmann, 1877). A glass tube
is drawn out at one end into a tube of capillary size and is filled with mercury up to
and beyond the point of entrance of a copper wire {A). This tube is then placed
vertical and is made to dip into a cup-shaped receptacle which is filled with mer-
cury and is pierced by a copper wire {B). A small quantity of dilute sulphuric acid
is now placed over the mercury in the cup. If the capillary is of proper size, the
mercury does not flow out, but is held at a definite level. By compressing a small
rubber bulb which is connected with the upper end of this tube (P), the mercury
is then forced downward and upward a number of times until the lower lumen
of the capillary tube is completely filled with the acid. The level of the mercury or
meniscus {M) is adjusted under the objective of a microscope (L) ', in fact, it may
be projected upon a screen or upon sensitive paper. If an electrical current is now
102
PHYSIOLOGY OF MUSCLE AND NERVE
passed through these conductors by way of the two copper wires, the surface
tension of the mercury is changed, forcing the meniscus to move either upward or
downward in accordance with the direction of the current. If its point of entrance
(anode) is below, the meniscus moves upward, and vice versa.
The strength of this electrical current
may be determined by noting the extent of
the movement of the meniscus, because a
direct relationship exists between these two
factors. It may also be measured by in-
terposing a resistance in the circuit outside
the electrometer or galvanometer which is
just sufficiently powerful to force the menis-
cus or the galvanometric needle to assume
its normal position. At this very moment
the resistance neutraUzes the current, and
hence, the number of ohms necessary to ac-
complish this end must correspond precisely
to the difference in the electrical potential.
Most generally, however, we make use of
the so-called compensation method which re-
quires the use of an artificial current in a
direction opposite to that produced by the
muscle. This end may be attained most
easily with the help of a rheocord (Fig.
58), consisting of a certain length of Ger-
man silver wire. The two binding posts at
the ends of this wire (A and B) are brought
into connection with the poles of a battery
cell. The circuit of the electrometer or gal-
vanometer (C) with its muscle preparation
(M) is then brought into relation with the
resistance wire by a lead from one of its posts,
while the return lead is effected by means
of a post which may be pushed back and forth upon the wire. By moving this
sliding post (D) nearer to or farther away from the end post (B), a greater or
less amount of the current generated by the battery is allowed to oppose the
Fig. 57. — Capillary Electrometer.
A, tube and J5, receptacle filled
with mercury; M, meniscus of mer-
cury; L, lens of microscope; P, tube
leading to small rubber bulb for ad-
justing meniscus.
Fig. 68. — Thb Simple Rheocord.
AB, German silver wire; C, galvanometer; M, muscle; D, sliding post; K, key.
muscle current until an equalization has finally been attained. Knowing the
atrength of the counter current, the strength of the muscle current may be deter-
mined from the resistance which has been interposed, i.e., from the position oc-
cupied by the sliding post. The value of the action current of an ordinary muscle
scarcely exceeds 75 millivolts; its usual strength is 0.06-0.08 volt.^
1 Samjloff, Pfliiger's Archiv, Ixxviii, 1899, 1.
THE PRODUCTION OF ENERGY IN MUSCLE 103
The Character of the Electrical Variations in Muscle. Current
of Injury and Current of Action.^If a perfectly normal resting muscle
is connected with two non-polarizable electrodes which in turn com-
municate with a galvanometer, the indicator of this instrument re-
mains perfectly stationary. The reason for this is that an uninjured
and inactive muscle is isoelectric, i.e., it does not present differences
in electrical potential which could give rise to a current (Hermann).
This condition, however, does not prevail if a muscle is isolated in the
usual way and is then removed from the body, because it is scarcely
possible to do this without: injuring it. On being connected with a
galvanometer, such a muscle immediately deflects the needle, because
it is no longer isoelectric. A current is set up in consequence of these
differences which, in accordance with the direction of the deflection
of the galvanometric indicator, passes from the uninjuried to the in-
771
Fig. 58a. — The Curkent of Injury.
JIf , muscle; G, galvanometer; J, seat of injury.
jured portion of the muscle (Fig. 58). Viewed from the outside, there-
fore, the uninjured portion of a muscle is positive (anode) and the
injured portion negative (cathode). But inside the muscle, the current
passes from the injured portion to the uninjured, so that the former
constitutes its positive and the latter its negative pole. Most com-
monly, however, we characterize this current as galvanometrically
negative, because notice is taken only of its direction outside the
muscle.^ This current' is usually referred to to-day as the current
of injury, although Hermann has called it the demarcation current,
and Matteucci,^ the current of rest. The latter designation has its
origin in the fact that the resting muscles of the thigh of the frog yield
an electrical current whenever they are cut across transversely and
connected with a galvanometer. A few years later, however, Du-
Bois-Reymond^ proved that resting muscles are isoelectric and that
the ciurrent of rest is really a current of injury.
1 Biedermann, Ergebn. der Physiol., ii, 1903, 173.
2 Transact. Acad, des sciences de Paris, 1838-42.
2 Unters. iiber tier. Elektrizitat, Berlin, 1848.
104 PHYSIOLOGY OF MUSCLE AND NERVE
This electrical difference persists as long as the injury. The same
conditions prevail in a degenerating muscle, its degenerated portion
being galvanometrically negative to its normal portion, but naturally,
these differences cease as soon as the degeneration has progressed
evenly throughout its substance. Dead tissue gives no current. In
order to obtain the current of injury in an unmistakable manner, it
is best to employ a cylindrical muscle and to injure it by cutting trans-
versely across one of its ends. One non-polarizable electrode is then
placed against this cross-section, while the other is adjusted externally
upon the equator of the muscle. In 'explanation of this current
DuBois-Reymond has proposed the so-called molecular theory which
assumes that the muscle is built up of a seiies of the smallest possible
molecules which are electrically charged and are surrounded by an
indifferent conducting fluid. These individual molecular elements
are peripolar, i.e., their equatorial zones are positive and their polar
zones negative. The former are directed toward the surface and the
latter toward the cross-section of the muscle. Hermann's^ explana-
tion is based upon the so-called ''alteration theory" which assumes
that muscle tissue develops no electrical current as long as its chemical
constitution remains the same throughout its substance. Electrical
differences, however, arise immediately if the chemical equilibrium of
any of its zones is disturbed either by injury, degeneration or activity.
Oker-Blum^ claims that these differences in the electrical potential of
a muscle are dependent upon its varying concentration and are caused^
therefore, by the speed of movement of its different ionic constituents.
Bernstein^ refers them to a process of dissociation. But these theories,
as well as the one advocated more recently by Overton'* are altogether
too incomplete and indefinite to be made the subject matter of a prof-
itable discussion for students.
In 1842 Matteucci made the observation that if the sciatic nerve
of one leg is placed upon the muscles of the opposite leg, the muscles
of both legs may be made to contract by simply stimulating the sciatic
nerve on the normal side. This experiment, which is known as
the ''induced contraction" or "secondary tetanus," may also be per-
formed in the following manner (Fig. 59). Two muscle-nerve pre pa-
rations. (A and B) are placed near one another upon a glass plate in
such a way that the sciatic nerve of muscle B rests lengthwise upon the
body of muscle A, If the nerve of muscle A is now stimulated with a
weak induction shock, the reaction involves not only muscle A but
also muscle B. The essential point to be remembered about this
experiment which is usually designated as the rheoscopic frog prepara-
tion, is that muscle B is not stimulated directly by the current applied
to nerve A, but indirectly by the ^^ current of action' ' generated in
muscle A in consequence of its contraction.
1 Handb. der Physiol., Leipzig, i, 1879, 235.
2 Pfluger's Archiv, Ixxxiv, 1901, 191.
8 Ibid., xcii, 1902, 521.
* Sitzungsb. der ph.-med. Gesellsch., Wurzburg, 1905.
THE PRODUCTION OF ENERGY IN MUSCLE
105
In explanation of this phenomenon, it should be stated first of all
that the active portion of a muscle possesses a different electrical po-
tential from the resting portion. Thus, if a perfectly normal muscle is
brought into the circuit of a galvanometer by means of non-polarizable
electrodes, the excitation of one of its ends immediately produces a de-
flection of the needle (Fig. 60) . If the direction of this deviation is now
noted, it will be seen that the current flows through the galvanometric
circuit from the unexcited to the excited portion of the muscle. Its
resting part, therefore, is electropositive to its contracting part. In-
side the muscle, of course, the current flows from the contracting to
the resting portion, the former being positive and the latter nega-
tive. But, as has been stated above, we usually designate the direc-
tion of these currents in accordance with their flow through the
galvanometer.
Fig. 59, — The Rheoscopic Frog
Preparation.
Muscle A stimulated through its nerve
at S, generates an action current which
causes muscle B to contract.
Fig. 60. — Current of Action.
M, muscle; G, galvanometer; S, seat^
of stimulation.
In accordance with these results, it must now be evident that the
preceding experiment with the rheoscopic frog preparation, actually
proves the occurrence of an electrical variation in muscle in conse-
quence of its activity. Muscle B serves in this case the purpose of a
galvanometer, because its contraction indicates that such a current is
actually present. It may be concluded, therefore, that the excita-
tion of nerve A gives rise to a contraction of muscle A, in the course of
which an action current is set up in its substance which serves as a
stimulus for nerve B. The impulse generated in the latter produces
a contraction of muscle B. The function of muscle A with regard to
muscle B may therefore be likened to that of a battery. In order to
avoid the possible criticism that the activation of muscle B is caused
by an escape of the current used to stimulate, it is advisable to subject
nerve A to mechanical impacts, or to modify the entire experiment by
placing nerve B lengthwise upon the beating heart of a mammal.^
1 Kollicker, Miiller's Archiv, vi, 1856, 528.
106 PHYSIOLOGY OF MUSCLE AND NERVE
In the latter case the muscle twitches with every systole of this organ,
thereby proving that a current of action is also generated in cardiac
muscle. ^ Similar currents arise in glandular tissue during active secre-
tion and in nerves when made to conduct impulses. This phenom-
enon also manifests itself in the optic nerve when the retina is stimu-
lated by light.
The Different Phases of the Currents in Muscle. — If an injiu-ed
muscle is brought into the circuit of a galvanometer, the needle of
this instrument is deflected almost immediately to indicate a negativity
in the region of the injury. The indicator remains in this position as
long as the injury lasts. The current of injury, therefore, possesses
only one period; in other words, it is monophasic in its nature. The
-Diagram Showing Diphasic Character of Action Current.
Phase I and Phase //.
A, active portion; R, resting portion; ;S, seat of stimulation; G, galvanometer. The
current of action is indicated in each case by the arrows.
current of action, on the other hand, is diphasic, or rather poly phasic,
because the muscle contracts not only in the region stimulated but
successively throughout its substance (Fig. 61). Inasmuch as this
contraction does not involve its different segments simultaneously,
but consecutively in the form of a wave, the electrical variations must
display a similar wave-like character. To begin with, the zone
nearest the seat of the stimulation is electronegative to the resting
zone (Phase I.) A moment thereafter, however, the wave of contrac-
tion has reached the opposite end of the muscle (Phase II), whereas
the area stimulated first has become inactive. The negativity then
becomes centralized in the region far away from the seat of the stimu-
lation. In order to follow this progressive wave accurately, the gal-
vanometer must first execute a deflection in a direction indicating
the negativity of the muscle at the point of stimulation and immedi-
^ The action current of the heart of mammals has also been demonstrated by
A. D. Waller with the help of the capillary electrometer, and by Einthoven by
means of the string galvanometer.
THE PRODUCTION OF ENERGY IN MUSCLE 107
ately thereafter a deflection in the opposite direction, to prove that
the distant pole of the muscle has now become active and negative.
While the ordinary type of galvanometer is sufficiently sensitive
to perceive these electrical variations, its action is altogether too slow
to follow them with accuracy. Although less sensitive, the strong gal-
vanometer is more serviceable for these tests, because it possesses a
much greater motility. There is one way, however, in which even the
ordinary galvanometer may be made to indicate the current of action
and that is, to cause its needle to be deflected first of all by the current
of injury. Thus, if one of the non-polarizable electrodes is placed
against the cross-section of the muscle, while the other is applied to its
equatorial surface, the galvanometric needle will be forced to assume a
fixed lateral position. If the distant non-injured portion of this muscle
is now stimulated, the subsequent contraction of this region must give
rise to a negativity which travels from here toward the other end of
the muscle. As this contraction-wave and its negativity passes the
plus lead of the current of injury, it reduces this positivity and causes
the needle to swing toward and beyond zero. Inasmuch as the needle
is deflected at this time in a direction opposite to that forced upon it by
the initial current of injury, this phenomenon has frequently been
designated as a ^'negative variation" of the primary demarcation
current. This arrangement, therefore, permits the negativity ac-
companying the wave of contraction of muscle, to neutralize the posi-
tivity of the current of injury in the equatorial region of the muscle.
Whether it will do that fully, depends upon the temperature and elas-
tic tension of the muscle, but we might say that under favorable con-
ditions the current of injury may equal 0.04 volt, while the current of
action may amount to as much as 0.08 volt.^ Clearly, the distance to
which the needle will be deflected by the action current depends
upon the strength of the latter, i.e,, upon the measure in which it is
able to neutralize the initial current of injury.
The relationship existing between the wave of contraction and the
current of action has been studied by photographing the variations of
the galvanometric indicator together with the movements of two levers
placed horizontally upon the surface of the muscle near the non-polar-
izable electrodes. It may be inferred that these two factors are very
closely allied to one another, but the records obtained by the method
just mentioned, indicate that the electrical changes antecede the move-
ments of the corresponding lever by a fraction of a second. Two
views may therefore be formulated, namely, (a) the electrical changes
constitute the wave of excitation in consequence of which certain chem-
ical alterations are instigated which eventually give rise to the shorten-
ing of the, muscle, or (6) the electrical differences are the result of the
chemical changes set off by the wave of excitation and are the fore-
runner of the mechanical effects. It is quite impossible at this time to
decide this question one way or another.
^ Piper, Pfluger's Archiv, cxxix, 1909, 145, and Jensen, ibid., Ixxvii, 1899, 137.
SECTION III
THE PHYSIOLOGY OF NERVE
CHAPTER XI
THE NEURON AND ITS CONDUCTING PATHS
The Neuron. — The entire nervous system is an aggregate of an
infinite number of neurons which are held together by a nervous
supporting framework or neurogha, but many parts of it also contain
cells showing a different histological character. Thus, it is found
that the spinal cord and the cerebrum are enveloped by protective
membranes which are made up of connective tissue, and contain in
addition blood vessels and lymph channels for nutritive purposes. The
element which we are chiefly interested in at this time is the neuron
or nerve-cell. It consists of a cell-body and its processes, the latter
being divided into dendrites and the axon or neurit.
In spite of the fact that the neuron is developed from a single
embryonic unit, known as a neuroblast, the adult cell presents a great
variety of forms. It may be pyramidal, oval, round, stellate or
spindle-shaped, and its size may vary from 10-1 50/x. The cyto-
plasm of each cell embraces a nucleus with its nucleolus, and a proto-
plasm which is granular in some places and striated in others. The
latter contains numerous rounded bodies which stain deeply with
methylene-blue and other dyes. These are the so-called Nissl's
granules. Especially at the poles of the cell the cytoplasm is arranged
in a distinct fibrillar manner, and is extended outward in the form of
long processes, which, as has just been stated, are classified as dendrites
and axons. The former divide very frequently and irregularly, and
do not pass far away from the cell-body. Theii terminals are generally
beset with short stubby processes, known as the lateral buds or gem-
mules. They impart a peculiar uneven appearance to these processes.
Each cell-body usually gives rise to several dendrites but only to
one axon. The latter is distinguished from the former by its much
greater length, its uniform caliber, its smoothness and the greater di-
rectness of its course. It gives off very few branches, which are desig-
nated as collaterals, and exhibits a hyaline consistency. The dendrites,
on the other hand, are not sharply differentiated from the cell-body
unless they are long, when they may also acquire a hyaline appearance.
108
THE NEURON AND ITS CONDUCTING PATHS
109
The Function of the Neuron. — We shall see later on that the cell-
body is the nutritive center of the neuron, because its destruction
entails the disintegration of all of its prolongations. Its purpose
is to produce the nerve impulse and to convey it to distant parts. The
arrangement in each neuron, however, is such that it can conduct in
only one direction, namely from the dendrites to the axon. It pos-
sesses, therefore, a distinct polarity,
the former prolongations being the
avenues by which the nerve impulse
is received and the latter the path
by which it is conveyed to other parts.
The general arrangement of the
neuron, therefore, depends in a large
measure upon the connections which
it must establish with neighboring
nerve-cells for functional purposes.
Neurons are usually designated as
afferent or sensory and as efferent or
motor. The former conduct impulses
from the periphery to the center and
the latter from the center to the peri-
phery. Moreover, since several neu-
rons of each type are always required
to cover large distances, they are
commonly arranged in series and are
then differentiated from one another
by characterizing them as neurons of
the first, second, third, and so forth
order. Just how many of them are
required to unite two widely sepa-
rated points of the nervous system
differs greatly. Thus it is said that
some of the efferent neurons of the
spinal cord attain a length of 0.5-1.0
m., so that the distance between the
cortex of the cerebrum and the foot
may be covered by no more than two
neurons, their relay station being
situated in the anterior horn of the
gray matter of the lumbar cord. On the afferent side, the path is
less direct and hence, a more frequent relaying is made necessary.
. Thus, a sensory impulse generated in the foot, generally requires three
or four consecutive neurons for its passage into the cerebrum.
Reflex Action. — The simplest relationship between these afferent
and efferent neurons is presented by the so-called reflex circuit
which permits of the occurrence of the simplest possible reaction,
known as the reflex act. The responses executed with the help of
Fig. 62. — M, motor neuron; S,
sensory neuron; M, motor end-
organ; 5, sensory end-organ; A, axis
cylinder; Af/S, myelin sheath; iV, neuro-
lemma; C, collateral; CB, cell-body;
D, dendrites; Nu, nucleus and nu-
cleolus; R, sensory terminals.
110
THE PHYSIOLOGY OF NERVE
nervous tissue, are divided into reflexes and voluntary reactions. The
former are non- volitional and the latter volitional in their nature;
hence, any action which is performed without the intervention of the
will, is a reflex, while one requiring this amplification, is a voluntary
reaction. As this topic will be dealt with in greater detail in a later
chapter, it may suffice at this time to state that the production of a
reflex necessitates the union of at least one sensory with one motor
neuron. This union, however, is not effected by continuity, because
the distributing terminals of the former merely lie in close contact
with the receptive dendrites of the latter without becoming confluent.
The place where two neighboring
neurons are in this way functionally
united is known as a synapse. Most
generally these synapses appear in
the form of short arborizations of the
sensory terminals around the bushy
dendrite of the adjoining motor cell.
In other cases, the distributing fila-
ments are prolonged into the im-
mediate vicinity of the neighboring
cell-body which they surround in the
form of a closely knitted reticulum.
In still other synapses, the sensory
terminals twine around the neigh-
boring dendrite and invest it closely
for some distance. ^ Attention should
also be called to the fact that the sen-
sory and motor neurons present cer-
tain general peculiarities which render
them better adapted for their manner
of conduction. Thus we find that
the cell-body of the former generally
occupies a central position, while that
of the latter is situated near the end of
the neuron. In fact, in certain sen-
sory neurons, the cell-body lies at
some distance from the main conducting path, this condition being
most clearly in evidence in the ganglia of the posterior spinal roots and
those of the cranial nerves.
Under experimental conditions the reflex circuit may be stimulated
at almost any point, the resulting impulse being propagated from here
toward the axon terminals of the efferent neuron. Under normal con-
ditions, however, the excitation is most generally received by the
radicles of the afferent neuron which are modified into a sense-organ.
A stimulus brought to bear upon the latter gives rise to an impulse
1 Ramon Y. Cajal, Histologie de syst. nerveux, Paris, 1909, and Barker, The
Nervous System and Its Const. Neurones, New York.
SO
Fig. 63. — Reflex Circuit.
SO, sensory end-organ, receptor;
MO motor end-organ, effector; AN,
afferent neuron; EN, efferent neu-
ron; C, center; S, synapse.
THE NEURON AND ITS CONDUCTING PATHS 111
which travels over the afferent conductor to the motor cell, and from
here over the efferent path into the terminals of the axon which are
modified to form a motor end-organ in close alliance with the tissue
effecting the reaction. Thus, it will be seen that a reflex circuit
consists of a receptor, an afferent path, a center, an efferent path and
an effector. In accordance with the different kinds of responses, the
receptors and effectors present different structural and chemical
peculiarities. For example, an afferent impulse may arise in the tactile
corpuscles of the skin and eventually give rise to motion, the effector
being formed in this particular case by the skeletal musculature.
But the impulse may also be generated in the retina of the eye or in
the organ of Corti and nevertheless lead to motion. This list might
be extended almost indefinitely, because besides the ordinary responses
of skeletal muscle, a large number of reactions are also brought about
with the help of smooth muscle. In the latter group are to be placed
the vasomotor and pilomotor actions, as well as the movements re-
sulting in the domain of the stomach, intestine, ureter and bladder.
Another group of very important sensory impulses produce secretory
effects. But quite irrespective of the character of the reaction it
should be kept in mind that any response executed in consequence of
a sensory impression without the intervention of the will, constitutes
a reflex.
The Structure of Nerves. — Each neuron is to be regarded as an
elongated conductor, but naturally, neurons are generally combined
into groups and do not appear singly. In the central nervous system
an aggregation of the cell-bodies of several neurons is known as a
nucleus and, in the peripheral system, as a ganglion. Furthermore, if
a group of cells of this kind regulates a certain function, it is designated
as a center. The former term, therefore, refers to an anatomical
entity and the latter to a functional entity. The nerve-fibers passing
away from these cell-bodies are generally bound together into bundles
which are known as nerves. A nerve, therefore, represents a collection
of nerve-fibers outside the central nervous system. It is formed in
the following manner: the axon passes away from the cone-shaped pro-
jection of the cell-body, and soon becomes enveloped in a tubular
membrane which constitutes the medullary or myelin sheath. In
many cases, a second investment is found externally to this one
which is known as the primitive sheath or neurolemma. Having
acquired these sheaths, the axon, or, as it is now called, the axis-cyl-
inder, becomes the nerve-fiber. Many of these are bound together
to form a bundle, and many bundles to form a nerve. The individual
. fibers are supported by a fine stroma or endoneurium. The connective
tissue investing the individual bundles of fibers, is known as the peri-
neurium, and that surrounding the nerve as a whole, as epineurium.
When a nerve divides, one or more of its bundles of fibers separate
from its main trunk in the form of a branch. It frequently happens,
however, that these branches do not pursue an independent course
112
THE PHYSIOLOGY OF NERVE
but are interwoven with neighboring branches, into an intricate net-
work or plexus. When the individual nerve-fibers reach the end-
organ, they subdivide into finer threads, or fibrils. In the vicinity of
the end-organ the investing membranes disappear.
Fig. 64. — A, nerve fibers stained with osmic acid, showing axis cylinder, medullary
sheath and neurolemma; B, medullated nerve fiber, showing nodes of Ranvier; X 660
times. (Schdfer.)
The thickness of nerve-fibers varies between less than 2/x and more than 20/x.
Those innervating the skeletal muscles are large and possess a diameter of about
14-1 9)U. While these differences are due very largely to the fact that some nerve-
fibers are devoid of a medullary sheath, it must be remembered that even the axis-
cylinders vary greatly in their thickness. Thus, it is easily apparent that the axons
arising from the large ganglion cells of the anterior horn of the spinal cord, possess
an especially large caliber. Nerve-fibers are either medullated or non-medullated
THE NEURON AND ITS CONDUCTING PATHS 113
and may or may not be enveloped by neurolemma. A typical nerve-fiber consists
of the following parts:
1, The axis-cylinder forms the central core of the fiber and about one-half of
its total thickness. It appears as a dim or faintly granular thread which, under
the influence of certain reagents, may become fibrillated. This peculiarity, as
will be shown later on, is one of the important contentions of the fibrillar theory
of nerve action. Each axis-cylinder pursues an unbroken course to the end-organ
where it divides into a number of fibrillse which may at times be closely interwoven
with one another.
2. The medullary substance forms a close-fitting jacket around the axis-cylinder
and consists of a network of neurokeratine, the meshes of which contain a fatty
material. Under normal conditions it appears as a continuous layer of homogeneous
substance which, after fixation or even while still in the body, splits up into seg-
ments possessing a length of about 1 mm. The indentations between these differ-
FiG. 65. — Transverse Section of a Nerve (Median).
ep, epineurium; pe, perineurium; ed, endoneurium. (Landois and Stirling.)
ent segments are known as the nodes of Ranvier. They do not implicate the axis-
cylinder. About midway between two neighboring indentations lies the nucleus,
its long axis being directed parallel to that of the fiber. Immediately surrounding
it is a layer of undifferentiated protoplasm which thus appears as small islands
directly underneath the neurolemma.
3. The neurolemma is a transparent sheath of homogeneous material which
retains a uniform thickness throughout, with the exception of the aforesaid nodes
where it is augmented by cement substance and lies in direct contact with the
axis-cylinder. Staining reagents are prone to enter these indentations and to
progress from here along the axis-cylinder. As far as the relative amounts of these
substances are concerned, it might be mentioned that the median nerve contains
63 per cent, of connective tissue, 28 per cent, of myelin and 9 per cent, of axis-cylin-
der (Ellison).
4. The end-organs to which the axis-cylinders are distributed, vary greatly in
their structure as well as in their chemical composition. They are divided first of
all into receptors and effectors. Among the former might be mentioned the retina
of the eye, the organ of Corti of the internal ear, the olfactory cells, the taste buds,
the cutaneous corpuscles for pressure, pain and temperature and the sensory
spindles of striated muscle tissue. Probably the best known motor end-organ is
the so-called end-plate of striated muscle. It appears as a low, conical or rounded
8
114 THE PHYSIOLOGY OF NERVE
swelling at the junction of the axis-cylinder with the substance of the muscle-fiber.
At this point the former loses its medullary sheath as well as the neurolemma, these
envelopes becoming continuous with the sarcolemma of the muscle fiber. The
plates themselves appear to be made up of fibrillar arborizations and possess a
faintly granular or cloudy appearance. At the point of contact with the myo-
plasm, the arborization is more dense and presents a coarse granular appearance,
forming what is known as the sole or bed of the end-plate.
The Chemistry of Nerves. — The composition of nerves has not
been studied in great detail. Whatever data we possess have been
derived very largely from analyses of the white matter of the cerebrum
which, of course, is composed almost exclusively of nerve-fibers.
Fig. 66. — End-plates; Chlorid of Gold Preparation to Show the Axis Cylin-
ders AND Their Final Ramifications of FibrilluE. X 170. (Szymonowicz.)
The proteins are abundant and especially so in the axis-cylinder. One of these
is a nucleoprotein which coagulates at 56 to 60° C. There are also present certain
globulins. One of these coagulates at 47° C. and the other at 70 to 75° C. Accord-
ing to Halliburton,^ the sciatic nerve is made up of 65.1 per cent, of water and
34.9 per cent, of solids of which the proteins furnish 29.0 per cent. The nerves of
the cold-blooded animals begin to lose their irritability at about 40° C. and shorten
more and more as the temperature rises.
The lipoids are also very abundant. They comprise phosphatides, such as
lecithin and kephalin, galactosids and cholesterin or cholesterol in the following
proportion: 2
Medullated Non-medullated
nerve nerve
Cholesterin 25.0 47.0
Lecithin 2.9 9.8
Kephalin 12.4 23.7
Galactosids 18.2 6.0
1 Arch, of Neurology, ii, 1903, 727.
2 Falk, Bioch. Zeitschr., xiii, 1908, 153; and Bang, Ergebn. der Physiol., vi,
1907, 131.
THE NEURON AND ITS CONDUCTING PATHS 115
The lipoids are found chiefly in the myelin sheath, but as non-meduUated fibers
also contain them, they are not restricted to this particular part of the fiber.
Medullated fibers, moreover, contain a much larger quantity of cerebrosids than
the non-meduUated, while the latter exceed in the lipoids, such as lecithin, kephalin
and cholesterin. Ordinary fat is found in the epineurium, and gelatin in the con-
nective tissue throughout the nerve. Very small amounts of creatin, xanthin,
lactic acid, uric acid and urea have also been detected. The quantity of inorganic
salts is small, amounting to only about 1.0 percent, of the total solids. Potassium
which is most abundant,^ is said to play an important part in conduction. ^
The Function of Nerves. — In the lower forms in which nervous
elements are not present, the wave of excitation is propagated to other
parts of the relatively small organism in a direct way, because proto-
plasm possesses not only the power of irritability but also that of con-
ductivity. In a measure this is also true of the higher animals, but
the conduction of the waves of excitation must here assume a some-
what different character, owing to the minute subdivision of the body
into many colonies of cells which are frequently widely separated from
one another. Previous to the disco veiy of the nerves it was believed
that these impulses pursue a direct course in all directions through the
different tissues, but we now know that long-distance conduction is
effected solely with the help of nervous tissue which is especially
suited for this function on account of its unusual irritability and con-
ductile power. Conduction, therefore, presents itself first of all as an
intracellular propagation of the wave of irritability and secondly, as a
transfer of this wave to other colonies of cells elsewhere in the body.
The result of thi^ transmission of an excitation depends of course upon
the character of the end-organ with which the nerve is connected, as
well as upon the functional qualities of its center. Inasmuch as it is
the function of the nerve to conduct impulses, the character of the
energy evolved in consequence of it, must therefore be wholly dependent
upon the effector with which it is functionally connected.
Irreciprocal Conduction. — The preceding discussion has brought
out the important fact that the conduction in neurons is irreciprocal,
i.e.f it takes place in only one direction. Thus, an impulse passes
with greatest ease across the end-plate into the muscle, but not from
the muscle into the axon and the cell-body. The same conditions
prevail in the synapse, the conduction being from the axon of one
neuron into the dendrites and cell-body of the next. This ''Law
of Forward Direction, '^ as it has been called by Sherrington,^ possesses
a physico-chemical basis, inasmuch as it has been shown that the
different parts of the neuron are not built up of the same chemical
substances. That this is so may be gathered from the fact that
such agents as curare, nicotin, atropin and adrenalin do not affect the
neuron uniformly throughout its substance but only in particular
places. Curare, as has been pointed out previously, selects the motor-
1 Macallum, Ergebn. der Physiol., vii, 1908.
2 Macdonald, Proc. Royal Soc, Ixxvi, 1904-05, 322.
' Proc. Royal Society, London, Hi, and following.
116 THE PHYSIOLOGY OF NEEVE
plates for its point of attack, while nicotin paralyzes the dendritic
processes of the cell-body and atropin the terminals of the axon.
Secondly, it is a well-known fact that the time which an impulse requires
for its passage through a neuron, is largely taken up by its journey
through the cell-body and the end-plate. In the latter, for example,
the delay is appreciable, amounting to more than one thousandth of a
second. Thirdly, it has been demonstrated that the fatigue of muscle,
resulting from excessive indirect stimulation, makes itself felt first
of all in the end-plate and not in the nerve-fiber nor in the muscle
tissue. These and other facts unmistakably point toward the
presence of a third substance which, strictly speaking, is neither nerve
tissue nor muscle tissue but a modification of the former. It is usually
designated as the intermediary or receptor substance. It is conceivable
that the constituents of this substance arrange themselves as electro-
lytes in a way to permit of the passage of the excitation in only one
direction. This is true of the end-plate as well as of the synapse.
The Function of the Different Parts of the Nerve. — The trans-
mission of the wave of excitation is effected by the axis-cylinder, or
rather, by the neurofibrils of which it is composed. The latter, as
has previously been shown, ramify throughout the cytoplasm and
form connections between the different poles of the cell-body and its
processes.
The myelin sheath is said to possess a protective, insulating and
nutritive function. The first assertion finds substantiation in the
fact that the medullary sheath is composed of a spongy network con-
taining a soft fatty material. Thus, if a nerve-fiber is torn, droplets
of a substance will be seen to ooze out which exhibit a double outline
similar to that of the nerve-fiber itself. If subjected to osmic acid,
these globules stain black, owing to the reduction of the osmium.
Moreover, the cross-section of a fiber invariably appears as a heavy
dark ring surrounding a light, faintly stained central area. It is also
a well-known fact that ether and other solvents are capable of removing
this fat at least in part so that the fiber assumes the appearance of a
round tubular space surrounding the axis-cylinder. The latter may
then be stained with carmin and other dyes to render it more conspi-
cuous. It seems, however, that the contention that the myelin sheath
supports and protects the axis-cylinder in a mechanical way, cannot be
emphasized especially, because the non-medullated axons of the
sympathetic system show perfect conduction. Moreover, axons are
never medullated throughout their entire extent but lose their sheath
near the cell-body as well as near the end-organ. In the third place,
while the cerebrospinal nerves are ordinarily in possession of such a
covering, they do not attain it simultaneously but at different periods
of embryonic life. In fact, in some animals, such as the rat, this sheath
is not developed until several days after birth. Meanwhile the new-
born animal shows perfectly coordinated movements.^
1 Donaldson, Jour, of Comp. Neurology, xx, 1910, 119; and Ambronn and Held,
Arch, fur Anat. und Physiol., 1896, 208.
THE NEURON AND ITS CONDUCTING PATHS 117
The same arguments may be advanced against the view that the
myeUn sheath serves as an insulator to prevent the overflow of an
impulse from one axis-cylinder to another. So far no definite proof
has been furnished for the contention that the non-medullated fiber
conducts less efficiently than the meduUated. It is frequently held,
however, that the loss of coordination resulting in the course of mul-
tiple sclerosis of the cord, is due to the destruction of the myelin sheaths
of these fibers, because their axis-cylinders appear to be perfectly nor-
mal. In general, however, it is true that the wave of excitation is
conducted without it spreading to neighboring fibers by contact. Iso-
lated conduction, therefore, is the rule.
The third contention, that the myelin sheath serves as a nutritive
medium for the axis-cylinder, is based upon the following data. It
has been found that its thickness varies directly with the caliber of the
axis-cylinder, and that the axons of the projection system of the cere-
brum are the thickest of all. Moreover, inasmuch as staining reagents
find ready access to the axis cylinder through the different indentations
at the nodes of Ranvier, it has been supposed that the nutritive sub-
stances select the same course. It has also been observed that the
stimulation of a nerve is followed by certain structural changes in the
myelin sheath, consisting in a widening of the meshes of its neurokera-
tin framework.^ Medullated fibers are also said to be more irritable
and to possess greater recuperative powers than non-medullated.
None of these facts, however, is sufficiently definite to constitute an
actual proof of the aforesaid view. In addition, it might be men-
tioned that the axis-cylinder and the myelin sheath have really a
separate origin, because the former is an outgrowth from the cell-
body, and the latter, from the mesoblastic cells surrounding the
axon. This histogenetic peculiarity is also betrayed by the changes
which an adult nerve-fiber undergoes in the course of degeneration
and regeneration. The latter prove conclusively that the axis-cylinder
is nourished from the cell-body, while its investments derive their
nutritive material directly from neighboring blood-vessels.
The neurolemma is generally regarded as a supporting and protect-
ing membrane and plays an important part in the degeneration and
regeneration of nerve tissue. The view that it is also insulating and
nutritive in its function could be met with the objections enumerated
previously.
Degeneration of Nerve. — The nerve-fiber regains its normal appear-
ance and function only as long as it remains in connection with the
cell-body. When its continuity is broken by cutting, crushing, heat-
ing or other means, the fiber loses its irritability and conductivity
and undergoes very characteristic retrogressive changes. Directly
after the injury, however, its excitability is temporarily increased and
especially at the seat of the trauma, owing, in all probability, to the
1 Striibel, Pfluger's Archiv, cxlix, 1912, 1.
118 THE PHYSIOLOGY OF NERVE
development of a current of injury. At this time a gradual retro-
gression sets in which terminates eventually in a complete loss of irri-
tability.^ The interval of time required for the development of these
changes varies in accordance with the type of the animal, the con-
dition of the nervous tissue and the severity of the lesion. In warm-
blooded animals, for example, the excitability is lost in from 2 to 4
days, while in cold-blooded animals it generally takes a much longer
time. For the sciatic nerve of the frog this interval is usually given
as 33 days, although it may be as long as 3 or 4 months. Evidently,
this difference is dependent upon the nutritive condition of the animal
and the temperature, because the degeneration sets in much sooner
during the summer and frequently progresses at this time with a speed
equal to that observed in the mammals. In young and vigorous
animals its progress is more rapid. It should be remembered, how-
ever, that the development of these changes necessitates the complete
separation of the fibers from the cell-body, because if they are merely
divided and their ends left in contact with one another, the degenera-
tion is prone to assume an abortive character. The irritability then
fails to decrease and besides, the morphological changes do not develop
with any degree of definiteness.
Degeneration is classified as primary, secondary, and tertiary.
The primary type involves the nerve-fibers at the seat of the injury
and affects solely those internodal segments which have been directly
exposed to the trauma. Beginning at this point, the degeneration
first progresses outward in the direction of the conduction of these
axis-cylinders until it finally involves their distalmost branches.
This marked implication of their peripheral stumps constitutes sec-
ondary degeneration. As far as the efferent paths are concerned, it may
be inferred that their destruction must render the effector functionally
useless, because its separation from the cell shuts out those central dis-
charges which normally keep it in tonus and activate it. Thus, while
the degeneration of nerve really ceases in the end-plate, it also impli-
cates in an indirect way the tissue with which it is in functional rela-
tion. The latter then suffers a disarrangement of its metabolism in
consequence of the loss of the usual efferent impulses. Thus it may be
observed that the destruction of a musculomotor nerve is invariably
followed by atrophic changes in the muscle innervated by it. It is
noted that the muscle fibers decrease in thickness, and that their cross-
sections lose their sharp contours and fibrillar appearance. They
eventually assume a hyaline appearance and become widely separated
from one another by infiltrated fat. Very similar changes result in
afferent paths. The direction of the degeneration in them may be
either centrifugal or centripetal in accordance with the location of the
cell-bodies.
In either case the destruction of the conducting path must lead to
an isolation of the cell-body and its dendrites, thereby rendering the
1 Waller, Miiller's Archiv, 1852, 392.
THE NEURON AND ITS CONDUCTING PATHS 119
latter functionally useless. This enforced inactivity Causes the cell-
body to lose its irritability and to undergo very characteristic morpho-
logical changes which present themselves as an initial turgescence and
final atrophy of its cytoplasm and nuclear material. The Nissl's gran-
ules become indistinct and finally disappear so that the cytoplasm
assumes a more homogeneous character. It is to be emphasized,
therefore, that the degeneration begins at the seat of the trauma and
advances from here in a peripheral as well as in a central direction.
It involves first of all the entire distal end of the nerve and later on
also its central stump, inclusive of the corresponding cell-bodies and
their dendrites. The degeneration progressing in a central direction,
is commonly designated as retrogressive degeneration. Lastly, it is to
be noted that these retrogressive changes do not stop at the next
synapse, but also implicate those neighboring neurons which are in
functional relation with the neuron primarily affected by the injury.
The cause of this retrogression must again be sought in the inactivity
forced upon the correlating neurons by the trauma to one of their
series This type of degeneration may be characterized as tertiary y
because it is not the direct result of the lesion, but develops only in
the course of time in those neurons which formerly acted in harmony
with the injured neuron.
We have seen that neurons are arranged in such a manner that
their axons conduct either in an efferent or afferent direction. Inas-
much as the degeneration first involves that segment of the fiber which
has been disconnected from the cell-body, the morphological changes
must advance along an efferent fiber in a direction from the center
toward the periphery. In an afferent fiber conditions are not so
simple. The cell-body is situated in between its processes. The de-
generation, therefore, may affect either its distal or its central proc-
esses. This statement will be more easily understood if a brief refer-
ence is made at this time to the so-called Wallerian law of degeneration.
It is a well-known fact that the anterior roots of the spinal cord are
formed by axons which are derived from large ganglion cells situated
in the corresponding horn of the gray matter. These axons, therefore,
conduct toward the periphery and are wholly efferent or motor in
their function. For this reason, a division of this root must be followed
by a degeneration which progresses outward from the level of the cut
until all the terminals have become involved (Fig. 67, 1). The central
stump of this root as well as the corresponding cell-bodies and their
dendrites, will be affected in the course of time by retrogressive degen-
eration. The posterior root of the spinal cord, on the other hand, is
made up of axons which arise in cells situated in the so-called spinal
ganglia. Their function is afferent or sensory, and hence, their direc-
tion of conduction is from the periphery to the center. This fact
implies that the division of this root must give rise to a degeneration
involving the end still connected with the cord (Fig. 67, II), whereas
its other end which has remained in contact with the ganghon, under-
120
THE PHYSIOLOGY OF NERVE
goes merely a gradual retrogression. The peculiar distribution of
these fibers also permits of a third cut being made, namely, at a point
distally to the spinal ganglion. In the latter case, the degeneration
involves the distal axons, leaving the entire posterior root intact until
subsequently affected by retrogressive changes (Fig. 67, III).
Very similar conditions prevail inside the central nervous system.
Thus, it may be noted that the anterior pyramidal tracts of the spinal
cord are formed by axons derived from cells in the motor area of the
cerebral cortex, whereas the posterior columns are made up of axons.
PR
Fig. 67.
Fig. 67. — The Course op the Degeneration in the Roots of the Spinal Cobd.
AR, anterior root; PR, posterior root; /, division of anterior root; II, division of
posterior root centrally to ganglion; ///, division of posterior root distally to spinal
ganglion. The degenerated fibers are indicated in black.
Fig. 68. — Diagram to Illustrate the Direction of Degeneration in Spinal
Neurons.
The degenerated portion is indicated by dotted lines.
the cell-bodies of which lie either in the spinal ganglion or at a low
level of the cord. The former are motor and the latter sensory in
their function. Consequently, a division of the spinal cord, say, at
the level of the first thoracic vertebra must be followed by an outward
degeneration of the pyramidal tracts and an inward degeneration of
the posterior columns. The former is generally called descending
and the latter ascending degeneration.
The Morphological Changes of Degeneration. — The foregoing
discussion must have shown that the cell-body is the nutritive center
THE NEURON AND ITS CONDUCTING PATHS 121
of the neuron. As far as the dendrites and axons are concerned, it is
conceivable that they are nourished by neuroplasmic streams from the
cell-body, whereas the nutritive supply of the investments is derived
from neighboring blood-vessels and lymphatic channels. The metab-
olism of both, however, depends upon the functional capacity of the
neuron as a whole. The cell-body, therefore, constitutes the trophic
center of the neuron and the element chiefly concerned in this func-
tion is the nuclear material. This deduction may be justified by the
analogy that the survival of a cell depends upon the preservation of
its nuclear substance. Thus, if a cell is divided several times, its
different fragments must soon disintegrate, unless a sufficiently larg:e
mass of the nucleus have been apportioned to each of them.
In describing the histological alterations occurring in a disin-
tegrating neuron, attention should first be called to the degeneration
involving the fiber separated from the cell-body and secondly, to the
retrogressive changes affecting the cell-body and its dendrites. Con-
cerning the former it should be noted that the primary degeneration
remains confined to the seat of the injury and advances only as far
as the second or third node centrally and distally to it. The stretch
of fiber so affected measures no more than 3.0 mm. in length. From
here this process spreads so rapidly that it becomes practically
simultaneous throughout the distal stump. ^ A typical Wallerian
degeneration is initiated by a loss of irritability which is associated
with a turgescence and a fiagmentation of the axis-cylinders. These
changes develop two or three days after the injury.^ They are quickly
followed during the next day by a fragmentation of the myelin sheath.
The latter breaks up into ellipsoidal segments and then into smaller
drops, each of which contains a short stretch of the axis-cylinder
appearing as a complex of colorless granules. Naturally, these struc-
tural alterations of the myelin substance are associated with certain
chemical changes which betray themselves by its different staining
qualities.^ This particular phase of the degeneration is followed by
a period during which much of the material thus formed is gradually
absorbed so that at the end of one month the fiber is practically with-
out its medulla. Meanwhile, the nuclei of the neurolemma have
greatly increased in number and have become invested by a layer of
protoplasm which thus partially occupies the place of the absorbed
myelin. This structure is known as the " band fiber. ' * Its appearance
is of course very different from that of a normal nerve-fiber and there
is sufficient evidence at hand to prove that it is non-conductile.
In this connection it should also be mentioned that the distal and
central stumps in the immediate vicinity of the lesion are frequently
beset with neurofibrillar outgrowths from the axis-cylinder. These
rami, however, cannot be considered as indications of regeneration,
^ Ranson, Jour. Comp. Neur. and Psych., xxii, 1912, 487.
2 Bethe and Monkeberg, Arch, fur mikr. Anat., Uv, 1899, 135.
' Mardi's method of staining with osmium after treatment in a chrome solution.
122 THE PHYSIOLOGY OF NERVE
because they again disappear in from three to eight days after the
injury and even if they are well protected by a tubular investment of
fascia. The degeneration, therefore, ceases with the formation of the
band fiber, a functionally inert strand of protoplasm. The central
stump, as has been stated above, degenerates in a typical manner only
for a distance of two or three nodes of Ranvier and hence, only those
segments are involved which have been directly exposed to the trauma.
In addition, it has been noted that the cell-body of this neuron,
as well as such neurons as are in functional relation with it, undergo
certain changes which are arranged collectively under the name of
retrogressive degeneration. It is readily conceivable that an injury to
a chain of neurons must subject all of them to a certain inactivity which
is accompanied by a disturbance of their metabolism. The cell-body
becomes swollen and finally atrophies, this decrease in the quantity of
its cytoplasm being associated as a rule with an irregularity in the
contour of the nucleus and a change in its position to a place nearer
the surface of the cell. The chromatin material gradually disappears
so that the staining power of the cell becomes much diminished,^ and
the more so, because this chromatolysis also affects the Nissl's granules.
It has also been shown by Dickinson ^ that many of these cells become
vacuolar and may indeed be completely destroyed, but these retro-
gressive changes require a relatively long time for their completion.
The Morphological Changes of Regeneration. — The regenerative
processes set in whenever the continuity of the neurons is reestablished,
provided, of course, that not too long a time has elapsed since the in-
jury. Thus, if a nerve is cut and its two ends are again brought into
contact immediately, the resulting changes are so fleeting that they
can scarcely be regarded as typifying Wallerian degeneration. Con-
currently, it may be assumed that a degeneration of long standing
can only be remedied by a regeneration occupying a correspondingly
long time.
In accordance with the view that the neuron is not only the struc-
tural but also the functional unit of the nervous system, it is commonly
believed that the regeneration of the peripheral ends of the different
fibers can only be effected by outgrowths from the axis-cylinders of
the central stump (Ranvier). These neuroplasmic proliferations are
said to seek the old neurolemmal sheaths and to continue through them
into the end-organs. Opposed to this view is the one which holds
that a functional unit necessitates the presence of a number of neurons
arranged in series. In accordance with this conception, it is held by
Bethe and others that the neurolemma is composed of the remnants
of the neuroblasts from which the nerve-cells have originated. The
cutting of a nerve, therefore, would permit these elements to assume
their former characteristics and to give rise to regenerative changes in
the different fibers. While several facts might be mentioned in support
^ Ranson, Jour, of Comp. Neur. and Psych., xvi, 1906, 265.
2 Jour, of Anat. and Physiol., iii, 1869, 176.
THE NEURON AND ITS CONDUCTING PATHS 123
of the second view, it will be shown later on that the former concep-
tion of regeneration is the more correct.
Assuming, therefore, that the regeneration of the fibers results
in consequence of a central proliferation of neuroplasmic material,^
the question may be asked whether this outgrowth takes place from
the axis-cylinder or from its investments. Briefly stated, it appears
Fig. 69. — Histology op a Degenerating Nerve Fiber. (Howell.)
that this process begins with a hyperplasia of the neurolemma at the
site of the section of the nerve, and while the central as well as the
peripheral stumps participate in this reaction, the principal part is
played by the former. ^ The cytoplasm surrounding the nuclei of
this locality, is rapidly increased in amount, as is also the number of
Fig. 70. — Embryonic Fibers in a Regenerating Nerve. (Howell.)
the nuclei themselves. In this way numerous protoplasmic streamers
are developed which become well differentiated in the course of from
foiu" to six days and progress into the distal stump, where they form
thickened bands of cytoplasm within the neurolemmal sheaths. The
axis-cylinders of the central stump follow -along these protoplasmic
bridges and thus close the defect. In many cases they may even be
Fig. 71. — A Newly Developed Fiber in a Regenerating Nerve Fiber.
(Howell.)
seen to penetrate the cicatricial tissue at the site of the injury. To
begin with, these axons are non-medullated but acquire a myelin sheath
in the course of from five to six weeks (dog) — provided, of course, that
they were meduUated previously. This medullation begins proximally
and progresses toward the periphery.
A continuity having been established in this way, the correspond-
ing cell-bodies and their collaborating neurons gradually regain their
1 Purpura, Archivio ed atti della Soc. ital. di, Chirurgia, 1909 and 1911; also
see: Perroncito, Mem. del R. 1st. Lombardo di Sc. et Lett., xx, 1908.
2 Kirk and Lewis, Johns Hopkins Hosp. Bull., xxviii, 1917.
124 THE PHYSIOLOGY OF NERVE
normal appearance and again become functional. It might probably
be mentioned that this regeneration does not always lead to a reunion
of the same axis-cylinders; in fact, a union may be effected between the
central and distal stumps of two different motor nerves or their
branches. Quite similarly, a sensory nerve or a segment thereof may
be brought into functional connection with a motor nerve. Purpura,
for example, has obtained good functional results in cases of paralysis
of the face by joining the distal end of the facial nerve with the central
end of the spinal accessory. In animals the latter nerve has also
been united with the vagus nerve, this crossing enabling an ordinary
musculomotor nerve to produce an inhibition of the heart.
Very important evidence favoring this centro-peripheral manner of
regeneration, has been presented by Harrison.^ It has been shown by
this investigator that the excision of the neural crest in the larvse of
amphibians, from which the cells of Schwann are derived, does not
hinder the development of the axis-cylinders but prevents their ac-
quiring medullary sheaths. It has also been demonstrated that nerve-
cells send out axis-cyhnders when immersed in a favorable nutritive
medium and that nerve-fibers are generated by pieces of cerebellum
and spinal ganglia when kept in a culture of clotted plasma. Many
of these axon processes attain a length of 0.5 mm. in the course of
48 hours.
CHAPTER XII
THE PHENOMENA OF CONDUCTION IN NERVE
Irritability and Conductivity. — Under normal conditions the wave
of excitation arises at one pole of the neuron and traverses it in a
definite direction, either afferently or efferently. Under experimental
conditions, on the other hand, it is possible to bring the stimulus to
bear upon it at almost any point, i.e., either upon its cell-body, its
axon or its end-organ. But the reaction remains the same in all cases^
a motor effect resulting from the excitation of a motor nerve and a
sensation from that of a sensory nerve. The structural element pri-
marily concerned in this transmission of the wave of excitation is the
fibrillated axis-cylinder of the nerve-fiber and its ramifications inside
the cell-body.
It is possible to differentiate between the irritability and conductivity of nerve
in the following manner: A muscle-nerve preparation (M) is placed horizontally
upon a glass plate, the nerve (A^) being drawn through a small glass chamber (D),
which in turn is connected with a Kipp apparatus (C). One pair of electrodes
are adjusted to the nerve inside this chamber (at A) and another pair outside of
1 Harvey Lectures, New York, 1909, 199.
THE PHENOMENA OF CONDUCTION IN NERVE
125
it (at B). A pole changer is made use of so as to be able to divert the current in
the shortest possible time. Provided that the nerve has not been injured, the mus-
cle reacts when stimulated at either point. If carbon dioxid is now permitted to
flow into this chamber, the stimulation at A becomes ineffective, while that at B
persists. This procedure may be repeated a number of times, but the excitability
of the nerve returns very soon after the carbon dioxid hasbeen removed from the
chamber. It seems, therefore, that small quantities of this gas destroy the irrita-
bility of the nerve, but do not affect its conductivity, and hence, these two proper-
ties may be said to occur independently of one another. ^ If vapors of alcohol are
now introduced into this chamber, the nerve
loses even its conductivity, as is evinced by
the fact that the stimulation at B is now
quite ineffective. In a similar way, it may
be shown that ether and chloroform diminish
the irritability as well as the conductivity,
but the former more intensely than the
latter. Furthermore, it may be observed
that when the effect of these depressants
wears off, the conductivity is reestablished
more rapidly than the irritability.
The Direction of Conduction. —
In studying the different phenomena
connected with the conduction of nerve
impulses, it is customary to make
use of a musculomotor nerve which
is still attached to its muscle. Nerves
exhibit no visible signs of their ac-
tivity, i.e.f they do not liberate me-
chanical energy nor do they generate
heat or electricity in amounts suffi-
cient to be recognized by means of
our unaided sense-organs. In this
case, therefore, the muscle serves the
purpose of an indicator of the activity
of the nerve, because under normal
conditions every excitation of the latter gives rise to a muscular con-
traction. But naturally, before this effect can make itself felt, the wave
of excitation must have been transmitted from the seat of the stimula-
tion to the motor end-organ. Conduction, therefore, is the specific
function of nerve, its property of irritability enabling the stimulus to
produce certain chemico-physical changes which are then propagated
onward in the form of a wave of excitation or nerve impulse. It must
also be evident that any other motor mechanism or even a sensory
nerve, may be employed for these experiments. In the latter case,
however, it is necessary to arrange the sensory nerve in such a way
that it can give rise reflexly to a motor effect, because this is the most
convenient way of proving its activity.
The preceding discussion pertaining .to the serial arrangement of
^ Grunhagen, Pfluger's Archiv, vi, 1872, 181; and Luchsinger, ibid., xxiv, 1881,
347.
Fig. 72. — Conductivity and
TABILITY OF NeBVE.
M, muscle; N, nerve; D, glass
chamber; C, Kipp apparatus; A and
B, electrodes inside and outside the
gas chamber.
126 THE PHYSIOLOGY OF NERVE
the motor and sensory neurons, must have shown that the wave of
excitation is propagated along nerve-fibers in a particular direction,
namely from the receptor to the effector. Thus, afferent fibers con-
duct normally in a centripetal direction, and efferent fibers in a cen-
trifugal direction. This constitutes the so-called law of forward con-
duction. An entire nerve, on the other hand, need not be purely
afferent or efferent in character, but may be composed of both types
of fibers. In the latter case, it is designated as a mixed nerve. Its
power of conduction, however, is not interfered with, because a spread-
ing of its impulses from fiber to fiber, is not possible under normal con-
ditions. Mixed nerves, therefore, may convey centripetal and centri-
fugal impulses at the same time.
If the substance of a unicellular organism is stimulated, the wave
of excitation proceeds from the seat of the stimulation in all directions.
In a similar way, it may be noticed that the application of a stimulus
to the center of a single muscle-cell is followed a moment thereafter
by a contraction of its two ends. The results obtained with nerve-
fibers are practically the same, but naturally, this statement applies
only to nerves which are tested under experimental conditions. Thus,
the stimulation of a motor nerve manifests itself solely by a peripheral
reaction in spite of the fact that the wave of excitation is also propa-
gated in a centripetal direction. Quite similarly, the excitation of a
sensory nerve cannot betray itself by a reaction in the receptor, but
only by some central effect which in time may lead to a reflex motor
response. It is evident, therefore, that the law of forward conduction
may be changed by experimental means into a law of double conduc-
tion. The direction of the conduction, however, is not dependent up-
on differences in the substance of the nerve-fiber, but solely upon its
central and peripheral connections. The irreciprocity of conduction,
as we have previously seen, is wholly determined by the conditions
existing at the poles of the neuron.
The fact that the nerve impulse may be propagated in both directions is most
clearly proven by the following experiment (Fig. 73) devised by DuBois-Rey-
mond.i Each end of a long stretch of nerve is connected with the poles of a gal-
vanometer. On stimulating the nerve about midpoint between these instruments,
it is noted that both needles are deflected. For the present this phenomenon
need not be explained further than to state that the passage of a nerve impulse
gives rise to an action current which betrays itself by a galvanometric negativity.
Inasmuch as this negative variation appeared at both ends of the nerve, it must be
concluded that the wave of excitation has progressed in this case in a central as
well as in a peripheral direction. It is also to be noted that this result may be
obtained not only with mixed nerves, but also with pure afferent or efferent nerves.
Gotch and Horsley^ have modified the foregoing experiment by adjusting a galvan-
ometer to the distal end of one of the divided anterior roots of the sciatic nerve
of the cat, and by subjecting the distal trunk of this nerve to repeated stimulations.
The centrifugal conduction was manifested in this case by the contraction of the
leg muscles and the centripetal conduction by the deflection of the needle of the
1 Thierische Elektrizitat, ii, 1849, 587.
2 Philos. Transactions, 1891.
THE PHENOMENA OF CONDUCTION IN NERVE 127
galvanometer. To adjudge this result correctly, it must of course be remembered
that the anterior roots of the cord are motor in their function; i.e., they conduct
under normal conditions in a centrifugal direction. Double Conduction for the
afferent fibers was proved by stimulating the posterior root of the sciatic nerve
and observing the deflections of a galvanometer adjusted to the central end of the
peripheral portion of this nerve. The posterior roots of the spinal nerves are
sensory in their function and conduct under normal conditions in a centripetal
direction.
IT
Fig. 73. — Conduction in Both Directions in Nerve.
N, nerve; *S, point of stimulation; A and B, galvanometers upon the two
ends of the nerve.
Another method of proving double conduction in nerve has been devised by
Kiihnei (Fig. 74). It has previously been stated that several of the long muscles,
such as the gracilis and sartorius, receive their nerve supply at a point about mid-
way between their two extremities. The nerve entering here divides into two
principal branches which innervate the upper and lower ends of the muscle respec-
tively. If the muscular continuity is now broken by a transverse cut into the tip
of the triangle formed by these branches (C), the upper and lower ends of the mus-
cle (A and B) will be practically isolated from one another save for the bridge of
Fig. 74. — Conduction in Both Directions in Ctracilis Muscle.
A and B segments of gracilis muscle divided by cut C; S, point of stimulation;
iV, motor nerve and its branches.
nerve-tissue. If the distalmost filaments of one of the branches of this nerve are
now stimulated (S), the muscular contraction immediately ensuing does not remain
confined to this half of the muscle {A) but also involves the other half (B). This
fact leads us to infer that the excitation advances first of all in a centripetal direc-
tion over the fibers of the corresponding branch (A) and then spreads over the
normally centrifugal fibers to the distant muscle-strip B. Thus, the normally
efferent' fibers innervating the end A, are temporarily converted into afferent
fibers. In order to meet the possible objection that this result may be caused by a
direct spreading of the electrical current from A to B, the stimulation may be
1 Archiv fiir Anat. und Physiol., 1859, 595.
)U.(J.;:M\'i ^' I
128
THE PHYSIOLOGY OF NERVE
effected by simply pinching the distal filaments of the nerve with forceps or by cut-
ting across them with the scissors.
A very similar relationship exists in the electrical organ of Malapterurus. ^ In-
asmuch as its individual membranous plates are innervated by the branches of a
single motor nerve (Fig. 75), the mechanical stimulation of the terminals in a
single plate must invariably be followed by a discharge of the entire organ. Clearly
any impulse arising peripherally in one of these plates (D), can only be trans-
ferred to the adjoining plates (AB and C) at the next bifurcation, and hence, the im-
pulse must first asecnd along the normally efferent branch before it can spread in a
centrifugal direction to the other parts of the organ. This peripheral transfer of
impulses is made possible by the fact that the individual axis-cylinders of the motor
fibers divide when in close proximity to the end-organ and send their fibrillar com-
ponents in different directions into the tissue.
Consequently, it is not necessary that the reversed
impulse be transferred to a neighboring axis-cylin-
der, because it can reach its destination through
the fibrillae of the same axis-cylinder. It will be
seen, therefore, that conduction in both directions
is not contrary to the law of isolated conduction.
Different investigators have also sought to
prove double conduction by the establishment of
a primary union between the central and distal
stumps of different sensory and motor nerves.
I I (I I Thus, it has been shown by Bidder (1865) that
I I |\ j T a union between the distal end of the hypoglossal
' (motor) and the central end of the lingual nerve
(sensory) eventually permits us to effect move-
ments of the tongue by stimulating the sensory
lingual nerve. In a similar way, Budgett and
Green^ have succeeded in cutting the left vagus
nerve between its ganglion and the cranium and
in uniting the peripheral stump of this nerve with
the peripheral end of the hypoglossal. Some
months later the muscles of the tongue could be
made to contract by stimulating the peripheral
end of the vagus. In this connection brief men-
tion should also be made of the well-known experi-
ment of Paul Bert 3 purposing the formation of a
primary union between the tip of the tail of a rat and the subcutaneous tissues
upon the dorsal aspect of its body. The process of healing having been fully com-
pleted, the tail was then cut off near its base. Inasmuch as the stimulation of
the former base of the tail still gave rise to sensations of pain, the conclusion
seemed justified that nerve- fibers conduct centripetally as well as centrifugally.
In all these experiments, however, it must be taken into account that the cutting
of nerves is followed by degeneration which in turn is succeeded by the formation
of new axis-cylinders. For this reason, it cannot be held that the inversion of a
part actually leads to an inversion of the nerve-fibers or to reversed conduction.
These experiments, therefore, cannot be said to be well adapted for proving
double conduction.
Fig. 75. — Conduction in
Both Directions in the
Electric Organ of Malap-
terurus.
N, motor nerve and its
branches, leading to plates A
B C and D; S, stimulation at
D produces discharges of entire
organ.
The Speed of Conduction in Nerve. — Inasmuch as the passage of
the wave of excitation is not associated with visible changes, it was
thought at first that the rate of its progression, in analogy with that of
1 Babuchin, Archiv fiir Anat. und Physiol., 1877, 262.
2 Amer. Jour, of Physiol., iii, 1899, 115.
3 Compt. rend., Ixxxiv, 1877, 173.
THE PHENOMENA OF CONDUCTION IN NERVE 129
light, is immeasurable. But this view, which was first expressed
by Johannes v. Mtiller, in 1844, could not be maintained for any length
of time, because already in 1850 v. Helmholtz^ devised a method which
gave fairly accurate results. In brief, it consisted in determining the
time elapsing between the apphcation of an electrical stimulus to the
nerve of a nerve-muscle preparation and the moment when the result-
ing contraction of the muscle caused the circuit of a galvanic battery
to be broken. Very clearly, however, this interval included not only
the time occupied by the passage of the excitation to the muscle, but
also the time of contraction of the muscle itself. A few months later
Helmholtz devised a second method which is not only much simpler
but also much more accurate than the one just mentioned (Fig. 76).
Fig. 76. — Speed of the Nerve Impulse.
M, muscle and nerve connected with writing lever W and two pairs of electrodes
N and F. The wires from inductorium / are connected with the pole change P, so
that the nerve may be stimulated either near to or far away from the muscle.
A nerve-muscle preparation {M) is connected with a writing lever {W)
in the manner described in one of the earlier chapters. The nerve
is then stimulated either at a point far away from the muscle (F)
or close to it {N). In each case, the contraction of the muscle is re-
corded upon a swiftly revolving kymograph, above the record of a
tuning fork vibrating in hundredths of seconds and the record of an
electromagnetic signal indicating the precise moment of stimulation.
If the lengths of the latent periods of these contractions are compared
with one another, it will be found that those obtained by stimulating
the nerve far away from the muscle {F) , are appreciably longer than those
recorded by stimulating the nerve near the muscle (iV). The differ-
ence between these latent periods corresponds to the time consumed
by the wave of excitation in its passage from F to N. This distance
having been determined with the ruler, the time may then be calculated
1 Monatsber. d. Berliner Akad., 1850.
130 THE PHYSIOLOGY OF NERVE
which the impulse requires for its journey through this particular
stretch of nerve.
The values which Helmholtz obtained varied between 24.6 and
38.4 m. in a second, the determinations being made at temperatures
varying between 11° and 21° C. At the average temperature of the
room, the velocity for the musculo-motor nerves of the frog may there-
fore be said to be about 28 m. in a second. By recording the contrac-
tions of the muscles of the thumb during stimulation of the median
nerve at two widely separated points, Helmholtz and Baxt^ have also
determined the speed of conduction in human nerves. They found it
to be about 34 m. in a second. In the lower animals, the rate of con-
duction varies considerably and even in different nerves of the same
animal. Fredericq and Vandervelde,^ for example, give the value of
6 to 12 m. in a second for the nerve of the claw of the sea-crab, and v.
Uxkiill,^ the value of 0.4 to 1 m. in a second for the nei ve of the mantle
of cephalopods. In the nerve plexus of the heart of Limulus, Carl-
son^ found the speed to be 0.4 m. in a second and in the pedal nerve
of Limax 1.25 m. in a second. The non-medullated olfactory nerve of
the pike conducts at the rate of 0.6 to 0.9 m. in a second.^ According
to Chauveau,® the vagus fibers innervating the smooth musculature of
the esophagus of mammals, conduct with a velocity of 8.2 m. in a
second and those innervating the striated musculature of the larynx,
at the rate of 66.7 m. in a second. The non-medullated fibers, there-
fore, conduct less rapidly than the medullated; moreover, conduction
through the central nervous system is effected at a slower rate than
through the peripheral nerves. It must also be evident that the
speed of the wave of excitation in nerve is much less than that of
certain physical energies. Thus, sound travels with a velocity of
332 m. in a second, whereas hght attains a speed of 332 million meters
and electricity a speed of 464 million meteis per second.
In recent years additional light has been thrown upon this topic
by the use of the string galvanometer. It may be stated at this
time that the passage of the wave of excitation is associated with an
electrical variation which may be accurately followed by a quickly
reacting galvanometer. Piper^ employed the median nerve which he
stimulated either at the elbow or in the axilla. The precise moment of
entrance of the excitation into the distant muscles was indicated by a
string galvanometer adjusted in such a way that it registered the initial
phase of the action current in these muscles. Knowing the length of
the stretch of nerve intervening between the axilla and the elbow, and
also the time elapsing between the moment of the application of the
1 Monatsb. der Berliner Akad., 1870.
2 Bull, de Tacad. de Belgique, C. r., 1875, 91.
' Zeitschr. fiir Biologic, xxx, 1894, 550.
< Am. Jour, of Physiol., xiii, 1905, 217.
^ Nikolai, Pfiiiger's Archiv, Ixxxv, 1901, 65.
* Acad. Scienc, Ixxxvii, 1878.
7 Pfluger's Archiv, cxxiv, 1908, 591.
THE PHENOMENA OF CONDUCTION IN NERVE 131
stimulus at either point and the deflection of the stnng, the velocity
of the wave could easily be calculated. If stimulated in the axilla,
the deflection followed after an interval of 0.00578 second, and if
stimulated at the elbow, after 0.00442 second. As the distance be-
tween these two points amounts in most persons to 160-170 mm.,
the wave must have progressed with a velocity of from 117 to 125 m.
in a second.
Factors Altering the Speed of Conduction in Nerve. — The funda-
mental condition for conduction is the anatomical continuity of the
nerve-fibers. If this has been broken in any way whatever, the excita-
tion must fail to reach the distant segment. An incomplete block
may be established in various ways, for example, by compression, or
by crushing and stretching. Conduction then reappears gradually.
It may also be observed that the sensory fibers are somewhat less
resistant than the motor fibers. Thus, if pressure is brought to bear
upon the ulnar nerve at the elbow, the region supplied by it ''goes to
sleep,'' but while this state is characterized by a simultaneous diminu-
tion of sensory and motor conduction, the former is usually depressed
in a much greater measure. Sensation, therefore, may be destroyed,
while the motor impulses are still able to pass through the block.
The return of conduction following the removal of the pressure is
usually associated with a peculiar pricking sensation in the region
supplied by this nerve. While no adequate explanation of this phe-
nomenon can be given, it is commonly assigned to processes of excita-
tion, i.e. J to a temporary increase in the irritability of the nerve tissue
so affected. In fact, it has been stated by Weber, Schiff, and others
that an increased excitability of the nerve is also experienced directly
after its division. Compression-paralysis is usually ushered in by a
hyperactivity of the distant muscles. It seems, however, that the
development of this initial heightened irritability depends upon the
character of the injury as well as upon the quickness with which it is
effected.
Mechanical influences are prone to give rise to an initial phase of
excitation unless permitted to act gradually,^ while chemical agents
and cold do not. The degree of pressure which may be brought to
bear before conduction is abolished, has been determined by Ducc-
eschi^ and Bethe.^ The former employed a thin silk thread which
was drawn around the nerve and slightly weighted at one end. A
weight of a few grams sufficed to diminish the conduction, while
a reduction of the diameter of the nerve to one-third or one-fourth
of normal abolished it altogether. Naturally, a compression of this
intensity affects the enveloping sheaths and perifibrillar substance
In this category belong the paralyses in the domain of the recurrent nerve
following aneurisms of the branches of the aorta, and the paralysis of the arm
muscles in consequence of the pressure of crutches.
2 Pfluger's Archiv, Ixxxiii, 1901, 38.
^Allg. Anat. und Physiol, des Nervensystemes, Leipzig, 1903.
132 THE PHYSIOLOGY OF NERVE
long before it actually causes an interruption of the fibrillae of the axis-
cylinders.
The fact that temperature influences the speed of conduction has
already been established by the earlj^ experiments of Helmholtz. The
relationship between these two factors is a direct one, ^.6., the higher
the temperature, the more rapid the conduction, but this rule is appH-
cable only within physiological limits. In the case of the motor nerves
of man, variations between 30 and 90 m. per second have been obtained.
This is also true of the nerves of invertebrates, those innervating the
claws of the lobster, showing a velocity of 6 m. at 10° C, and of 12 m.
at 20° C. The motor fibers of the sciatic nerve of the frog cease to
conduct at 41-44° C, but may recover if the temperature is again
lowered. At 50° C. their conductivity is lost altogether. It is also
of some interest to note that the velocity of the nerve impulse follows
the van't Hoff law for chemical reactions, because, as has been shown
by Snyder, 1 a rise in temperature of 10° C. approximately doubles the
conduction. This fact may be employed as a proof that conduction
by nerve entails certain chemical changes, because most physical pro-
cesses present for this range of .temperature a relationship of only 1 :1
or a relationship barely above unity.
Unusual changes in temperature, and especially those beyond
physiological limits, cannot be considered as constituting pure thermal
influences, because they are prone to injure the nerve tissue by bringing
about a loss of water or certain differences in its electrical tension.
In this category belongs the abolition of conduction in consequence of
cauterization and extreme cooling. Thus, the application of ice to
the region of the ulnar nerve at the elbow results at first in sensations
of pain and finally in a complete loss of sensations.
A nerve may be kept in a physiological condition by frequently
moistening it with normal saline solution, but its complete immersion
in this solution (0.6 per cent.) is generally followed by phenomena
of excitation which, however, do not appear if Locke's or Ringer's
solution is employed instead. Overton^ has shown that nerve-
muscle preparations retain their functional qualities in the latter
even after 15 to 20 days. Immersion in water diminishes the irrita-
bility of nerve. Moreover, it is a matter of common observation that
its drying leads to violent contractions of the muscle which, to begin
with, are clonic in character but soon become tetanic. Acids do not
irritate unless concentrated;^ alkalies, on the other hand, stimulate
even in solutions of 0.8-1.0 per cent. According to Mathews,'' the
different solutions of the sodium salts act as exciting agents only in
high concentrations, but some of them also stimulate when isotonic
^ Am. Jour, of Physiol., xxii, 1908, 179; also see: Ranitz, Pfliiger's Archiv,
Ixviii, 1907, 601.
2 Pfluger's Archiv, cv, 1904, 256.
3 Kiihne, Archiv fiir Anat. und Physiol, 1860, 315.
^ Am. Jour, of Physiol., xi, 1904, 455.
THE PHENOMENA OF CONDUCTION IN NERVE 133
to nerve tissue. Potassium salts depress. The same is true of mag-
nesium sulphate. Conduction may be temporarily blocked by means
of this salt and as effectively as by the application of ice or certain
narcotics. As a general anesthetic this salt is useless and dangerous.^
The most important agents influencing the activity of nerve-
tissue belong to the group of the anesthetics. Ether and chloroform
diminish the irritability and conductivity, the latter agent being a
more powerful depressant than the former. In these cases, the con-
ductivity usually persists for sometime after the excitability has been
thoroughly abolished. Alcohol diminishes the conductivity, but does
not materially affect the irritability. Carbon dioxid diminishes the
excitability and finally also the conductivity. Among the narcotics
opium, cocain, curarin and chloral hydrate act as depressants. The
conductivity of nerve may also be gradually destroyed by depriving it
of oxygen. This matter will be more fully discussed later on. Lastly,
the irritability and conductivity of nerve may also be varied by the
galvanic current. As this effect is of fundamental importance in
formulating ''Pfltiger's Law" and the ''Law of Unipolar Stimulation'*
of normal muscle and nerve, it will be more fully discussed later on.
The Nature of Conduction. — In spite of the many views which have
been formulated in explanation of the cause of conduction by nerve, it
cannot be said at this time that the exact nature of this process has
been fully established. Thus, it has been suggested that a nerve-
fiber is a tube containing a liquid or luminiferous ether, which either
flows from place to place or oscillates back and forth. Others,
again, have compared the nerve-fiber to a metal wire and the wave
of excitation to a progressive charge of electricity. Still others have
stated that the excitation arises in consequence of an explosive chem-
ical change which then advances along the nerve-fiber. Without enter-
ing into a detailed discussion of these different views, it may be said
that they are based upon two fundamental conceptions, attaching to
conduction either a purely physical or a purely chemical nature.
The adherents of the former theory claim that the wave of excitation
or nerve impulse is a physical force propagated along nerve-fibers
without the latter undergoing metabolic . changes. It has been sug-
gested, on the one hand, that it consists of a delicate quivering of the
molecular constituents of the nerve, and, on the other, that it is due to
a definite shear along the colloidal substance of the axis-cylinder.
An analogous process is the conduction of electricity along copper,
wires which necessitates no consumption of material. In accordance
with this theory, the nerve impulse consists solely of an electrical
wave which is known to pass along a nerve whenever it is activated.
This entire process may be illustrated very convincingly with the help of the
so-called core-conductor, described by Hermann. ^ A thin platinum wire is
enclosed in a glass tube filled with a solution of zinc sulphate. In the several pairs
^ Meltzer and Peck, Jour, of the Am. Med. Assoc, Ixvii, 1916, 1131.
* Pfliiger's Archiv, v, 1872, 264; also see : Matteucci, Compt. rend., Ivi, 1863, 760.
134
THE PHYSIOLOGY OF NEUVE
of collaterals are placed zinc electrodes which in turn are connected with the wires
leading to a corresponding number of galvanometers. Thus, the central wire is
made to represent the axis-cylinder, and the surrounding zinc solution the less
conductile myelin sheath, but it may also be said that the former corresponds to
one of the fibrilla comprising the axis-cylinder and the latter to the perifibrillar
substance investing it. If the end of this conductor is now stimulated with induction
shocks, the galvanometers along its course will indicate the passage of an electrical
wave in a direction away from the point of stimulation. This model also gives rise
to electrotonic alterations similar to those encountered in normal nerve.
In accordance with the second theory, which assumes that the nerve
impulse consists in progressive chemical changes, it is held that con-
duction necessitates the destruction of some of the constituents of the
nerve. If gun powder is spread out upon a flat surface in the form of a
narrow band and a spark is applied to it at one end, an explosive chem-
ical reaction ensues during which this material is progressively con-
sumed. Very obviously, conduction in nerve is not associated with
changes of this intensity, but it can no longer be doubted that nerve
tissue undergoes certain metabolic alterations in consequence of its
Fig. 77. — Schema to Show the Action of the Core-model.
p, The polarizing current; g' and g, the galvanometers showing the anelectrotonic
and catelectrotonic currents, respectively. {Howell.)
activity which differ from those of other tissues only in a quantitative
way. This point will be proved with absolute certainty by the suc-
ceeding discussion. Consequently, a nerve impulse may be regarded
primarily as a wave of chemical change which is accompanied by a
liberation of chemical energy. In addition, the ensuing electro-
lytic dissociation also permits of the generation of electrical energy.
Under ordinary conditions, the latter is the only means at our disposal
to recognize the nerve impulse as it sweeps over a nerve. But while
this phenomenon may be proved to possess a distinct chemico-physical
basis, its true character has not been established as yet. For the
present it must suffice to characterize it as a chemico-physical disturb-
ance, the most evident product of which is an electrical change, com-
monly called the wave of negativity.
The Liberation of Energy by Nerve. — In accordance with the
preceding statement it must be evident that we cannot ascribe a
chemico-physical basis to the nerve impulse unless it can be shown
that it is actually accompanied by chemical changes such as ordinarily
serve as indications of metabolism and fatigue. We have previously
seen that the contraction of muscle is associated with a liberation of
THE PHENOMENA OF CONDUCTION IN NERVE 135
mechanical energy, heat and electricity, but inasmuch as nerve serves
merely as an instrument of conduction, it cannot be expected to give
rise to considerable amounts of energy. It is a well-known fact that
there is no mechanical change in the active nerve and hence, the only
point for us to determine is whether it presents any indications of the
evolution of heat or electricity. So far it has not been possible to
demonstrate the occurrence of thermic changes with any degree of
certainty. RoUeston, ^ for example, employed a delicate bolometer in-
dicating differences in temperature of Hooo° C, but no increase in
temperature could be detected. Negative results have also been ob-
tained by A. V. HilP who made use of very sensitive thermoelectric
elements, indicating changes of a hundred millionth of a degree.
Cremer,^ on the other hand, does not deny the possibility of thermo-
genesis, but states that the heat liberated by active nerve is less than
the Joule^s heat of the stimulating current. Garten,^ moreover, be-
FiG. 78. — Current of Injury in Nerve.
The cross-section of the nerve is galvanometrically negative to its longitudinal
surface.
lieves it possible that the nerve possesses the power of quickly absorb-
ing the slight amount of heat developed in the course of its metabolism.
In the face of more recent observations, it can scarcely be denied that
nerve undergoes metabolic changes, and hence, in analogy with other
tissues, it may be inferred that nerve also liberates at least a slight
amount of heat.
In contrast to these rather indefinite results, it has been fully
established that nerve Uberates electrical energy. Thus, if the poles
of a galvanometer are connected with two separate regions of an un-
injured nerve, the needle remains perfectly stationary, proving thereby
that a normal nerve at rest is isoelectric or equipotential. But if
one of the non-polarizable electrodes is now adjusted to the cross-
section of this nerve, a deflection of the needle results at once (Fig. 78),
indicating thereby the existence of a demarcation current which we
call the current of injury.^ While its strength equals only 0.02 volt
1 Jour, of Physiol., xi, 1890, 208.
2 Ibid., xliii, 1912, 433.
' Miinchener med. Wochenschr., 1895.
* Physiol, der markl. Nerven, Jena, 1903.
^ Discovered by DuBois-Reymond in 1846 (Arch, fur Anat. u. Physiol.,
1867, 417).
136 THE PHYSIOLOGY OF NERVE
in medullated nerves, it is said to be more intense in non-medullated
nerves. Moreover, its strength diminishes very rapidly and especially
in the nerves of warm-blooded animals, but the previous difference in
potential may again be established by making a new section next to
the first. Injured nerves, therefore, behave in the same manner as
injured or degenerating muscle. In either tissue the current flows
I&fB
Fig. 79. — Current of Action in Nerve.
To begin with the nerve shows the current of injury indicated by the arrows (as
in Fig. 78). When stimulated at >S a negativity passes along the nerve which, on
reaching Pole A, causes a partial reversal of the current of injury, indicated by the
needle.
through the galvanometer from Ihe non-injured to the injured portion,
and inside the nerve from the injured to the non-injured. The latter
we call the axial current. An interesting modification of this axial
current^ has been observed in nerves normally possessing a mixed
direction of conduction. Thus, it has been found that the two cross-
sections of a nerve are equipotential only in a mixed nerve, while
%
JL
Fig. 80. — Schema to indicate the procedure used to prove the diphasic character of
the action current. The isoelectric condition obtained to begin with is destroyed as soon
as the wave of negativity arrives at lead A.
nerves composed either of afferent or efferent fibers, present distinct
differences in potential. In an afferent nerve, the central cross-sec-^
tion is galvanometrically negative to the peripheral, while in an effer-
ent one it is positive to the peripheral. Thus, excised segments of
nerve always exhibit an axial stream in a direction opposite to that
of their normal conduction, namely, descending in afferent nerves and
ascending in efferent nerves.
^ DuBois-Reymond, Unters. iiber tier. Elektrizitat, ii, 252; also see: Weiss,,
Pfliiger's Archiv, cviii, 1905, 416.
THE PHENOMENA OF CONDUCTION IN NERVE
137
When stimulated and made to conduct, nerve tissue invariably
exhibits a current of action, the region of the impulse being galvano-
metrically negative to the resting portion of the nerve. This may be
proved by first deviating the needle of the galvanometer by a current
of injury (Fig. 79) and then stimulating its distant end with an induc-
tion shock {S). As the wave of negativity reaches the plus pole (A)
of the current of injury, it reduces its potential and causes a partial
reversal of the current of injury. The needle of the galvanometer then
swings toward and beyond zero. Immediately, thereafter, the needle
assumes its former position, namely at a time when the wave of nega-
tivity has arrived at the negative injured cross-section of the nerve {B),
Consequently, the current of action in nerve is diphasic.
The diphasic character of the action current may be shown most advanta-
geously by placing both leads of the galvanometer upon the longitudinal surface
of the nerve (Fig. 80). This system is
isoelectric, because both uninjured points
A and B have the same potential. If the
nerve is now excited at S with a single in-
duction shock, the wave of negativity re-
sulting therefrom, will cause a deflection
of the needle when it reaches A, because B
is still positive. A moment, thereafter, a
reversal will take place, B now being
negative and A positive.
In harmony with the results obtained
with the help of the rheoscopic frog pre-
paration, the action current of nerve may
also be employed as a stimulus for a neigh-
boring nerve. If a short segment of a
nerve {A) is placed next to the nerve of a
nerve-muscle preparation {B), the stimu-
lation of A invariably gives rise to a con-
traction of the muscle. In explanation of
this phenomenon it must be mentioned
that the contraction of muscle B is effected in an indirect maner, i.e., the stimu-
lation of nerve A gives rise to an action current which serves as a stimulus for
nerve B. The impulse set up in nerve B then descends to the muscle and causes
it to contract. It is to be noted, therefore, that the impulse in nerve B is not
continuous with the first, but is developed in a manner similar to that of an induced
current in the secondary coil of an inductorium. The impulse (action current)
traversing nerve A, induces an impulse in nerve B.
Action currents may also be detected in peripheral nerves if the corresponding
area of the cerebral cortex is stimulated. This result is also obtained if the corre-
sponding anterior root of the spinal cord is used instead. Sensory nerves are to
be preferred for experiments of this kind, because the stimulation by means of the
electrical current may then be dispensed with. Thus, Kuhne and Steiner^ have
detected negative variations in the optic nerve whenever the retina was exposed to
light, while Steinach^ has noted similar fluctuations in the sciatic nerve of the
frog on stimulation of the tactile receptors of the foot. In the sensory nerves of
the lateral organ of fishes these currents have been observed by Fuchs.^ Records
Fig. 81. — Schema to Show How a
Nerve-muscle Preparation {B) May
BE Stimulated by an Action Current
IN Nerve A.
^ Untersuchungen aus dem physiol.
2 Pfliiger's Archiv, Ixiii, 1896, 495.
3Ibid.,lx, 1895, 173.
Inst, zu Heidelberg, iv, 1881, 64.
138 THE PHYSIOLOGY OF NERVE
have also been taken of the negative variations in the depressor nerve on increasing
the blood-pressure in the aorta^ and of those occurring in the vagus nerve synchro-
nously with the respiratory movements. ^
The Relation of the Nerve Impulse to the Wave of Negativity
and the Action Current. — The preceding discussion must have satis-
factorily proven that the wave of negativity and the nerve impulse
are practically synonymous phenomena, because they advance with the
same velocity and cannot be dissociated by any known means.
A nerve impulse may be generated by mechanical, electrical, ther-
mal, photic and chemical means, and may be the result of either director
indirect (reflex) stimulation. If regarded as a purely physical phe-
nomenon, it will be seen immediately that the impulse must consist
solely of a wave of negativity, while if considered as a chemical phe-
nomenon, it must be the product of certain chemical changes. In
accordance with the second view, which is the more widely accepted
at the present time, the nerve impulse consists of a progressive chem-
ical process entailing catabolism and anabolism. One of the results
of these changes is the wave of negativity which thus assumes the
character of a true current of action. This relationship having been
established, the negative wave is to be regarded as an associative phe-
nomenon of the chemical changes. Hence, the phenomena of conduc-
tion in nerve are very similar to those taking place in muscle whenever
a wave of contraction sweeps over its constituent fibers. The evidence
favoring this chemico-physical explanation of the nerve impulse, is
chiefly derived from the fact that the conduction in nerve entails
certain metabolic changes, which will be more fully discussed in the
succeeding paragraphs.
The Metabolism of Nerve During Activity. — In accordance with
the observation that contracting muscle yields lactic acid, carbon di-
oxid and other fatigue substances, efforts have repeatedly been made
to show that these bodies are also formed in active nerves. Inasmuch
as the functional capacity of nerve varies directly with the carbon
dioxid content of the air surrounding it, A. D. Waller^ assumed at an
early date that this gas is actually liberated in the course of the activity
of this tissue. It has recently been proved by Tashiro^ that this as-
sumption is correct. By employing an extremely delicate indicator
it could be shown that even the resting nerves of frogs produce a
measurable quantity of carbon dioxid, and besides, it was found that
this amount may be greatly increased by stimulation. Positive evi-
dence of nerve metabolism has also been furnished by Bayer ^ and
Frohlich,^ because these investigators have shown that oxygen is abso-
1 Tschermak, Pfliiger's Archiv, xciii, 1903, 24.
2 Lewandowsky, Pfliiger's Archiv, Ixxiii, 1898, 298; also see: Einthoven, Quart.
Jour, of Exp. Physiol., i, 1908, 243.
3 Brain, Ixxvi, 1897, 569, and Proc. R. Soc, London, Ixii, 1897, 80.
* Am. Jour, of Physiol., xxxii, 1913, 137.
6 Zeitschr. fiir allg. physiol., ii, 1903, 169.
6 Ibid., iii, 1904, 131.
THE PHENOMENA OF CONDUCTION IN NERVE
139
iTJp[n||n
71
lutely necessary for the proper function of this tissue. These experi-
ments consisted essentially in enclosing the nerve of a nerve-muscle
preparation in a small glass receptacle so that it could easily be sub-
jected to the influence of an inert gas, such as hydrogen or nitrogen
(Fig. 82). While the effect was never very striking, it could never-
theless be shown that the irritability and conductivity of the nerve
(N) decreased very markedly if kept in this inert medium for a period
of several hours. Moreover, the subsequent displacement of the inert
gas by oxygen was followed within a few minutes by a
complete restoration of the function of the nerve. This
proves that oxygen is one of the prerequisites of nerve
metabolism. As far as the production of acid is con-
cerned, no positive results have been obtained. In this
regard nerves differ very materially from the gray
matter of the central nervous system, because the latter
has been shown to become decidedly acid as a result of
activity.^
The fact that nerve tissue undergoes assimilative
and dissimilative changes, is also betrayed by the high
value of the temperature coefficient of conduction. It
has previously been mentioned that the speed of the
nerve-impulse is greatest in warm-blooded animals
and that even moderate rises in temperature give rise
to a much greater rapidity of conduction. In this re-
gard nerve-tissue behaves in accordance with the van't
Hoff law for chemical reactions. In addition, it should
be mentioned that nerve possesses a very appreciable
refractory period during which it cannot respond to
stimuli. In the case of the sciatic nerve of the frog j^^ ^^^^^ ^^
this period amounts to 0.002 second, but may be in- nerve' muscle
creased by cold, asphyxia, anesthetics and narcotics.
It appears, therefore, that nerve-tissue requires a cer-
tain time for its anabolic changes and hence, if a
second stimulus is brought to bear upon it before it
Fig. 82.—
Fatigue of
Nerve.
preparation
drawn through
glass chamber.
The latter is con-
nected with Kipp
has had sufficient time to complete these processes, it The stimulus is
must necessarily fail to conduct the succeeding impulse, applied at S.
The brevity of the refractory period of nerve sug-
gests that its power of assimilation is unusually great, but this is
rather to be expected, because the conduction in nerve does not re-
quire a considerable expenditure of energy so that the compensation
for the preceding dissimilation can easily be effected without profound
chemical changes. This deduction is in complete harmony with the
structural peculiarities of nerve. Contrary to the gray matter of the
central nervous system, the white matter, as well as the peripheral
nerves, possesses a scanty and ill-defined network of blood capillaries
and lymph channels. This implies that the blood supply of this
1 Funke, Arch, fur Anat. und Physiol., 1859, 835.
140 THE PHYSIOLOGY OF NERVE
tissue is inconsiderable. Contrariwise, however, it is evident that
its storative quahties are excellent, because while the interruption of
its blood supply eventually leads to a reduction of its irritability and
conductivity, this depression is not quickly forthcoming; in fact, the
nerves of the cold-blooded animals may retain these properties for
a surprisingly long period of time after their excision.
Fatigue of Nerve. — Nerve-tissue possesses certain qualities which
fortify it against excessive dissimilation and thus prevent it from
entering the state of fatigue with the same readiness as other tissues.
The earlier experiments pertaining to the development of fatigue in
nerve, were made with nerve-muscle preparations. In all these in-
stances the contraction of the gastrocnemius muscle served as the index
of activity. It is a well-known fact that the repeated stimulation of
any musculomotor nerve eventually leads to a cessation of the contrac-
tions, but this result has been proved to be due to a fatigue of the end-
plates and not to an exhaustion of the nerve itself. Consequently,
experiments of this kind cannot yield reliable results unless the muscle
is protected in some way against these impulses, while the nerve is not.
A block of this kind may be established quite easily with the aid of
curare. To begin with, it must be shown that each stimulation of the
nerve produces a contraction of the muscle. If a solution of curare is
now applied to the latter, the ensuing paralysis of the motor plates
prevents the impulses from reaching the effector^ until the action of
this drug has again weakened. During the interim, therefore, the
nerve may be stimulated without producing a muscular reaction. By
this means it has been found that nerves may be made to conduct
impulses for many hours without becoming fatigued. Similar tests
have been made with the vagus nerve, the inhibition of the heart being
prevented during these repeated stimulations by the administration
of atropin.2 ^g goon as the action of this drug weakened after many
hours, the stimulations again became effective. Very similar results
have been obtained by stimulating the chorda tympani of the sub-
maxillary gland after the administration of atropin. Secretion was
resumed in this instance as soon as the action of this drug diminished
sufficiently to permit the impulses to break through.^ It has also been
shown that a galvanometer connected with a nerve indicates a wave
of negativity with every excitation, and even if these stimulations are
continued for many hours. Thus, Beck'* has stimulated the cervical
sympathetic nerve during seventeen hours without succeeding in
greatly lessening the dilatation of the pupil.
1 Bernstein, Pfliiger's Archiv, xv, 1877, 289; Wedenski, Zentralblatt der med.
Wissensch., 1884, and Bowditch, Jour, of Physiol., vi, 1885, 133. The effect of
curare may be removed within a few minutes by the salicylate of physostigmin.
(Diirig, Zentralbl. fiir Physiol., xv, 1902, 75.)
2 Scana, Arch, fur Anat. u. Physiol., 1891, 315.
2 Lambert, Compt. rend., 1894, 511; also see: Mascheck, Sitzungsber. d.
Wiener Akad., xcv, 1887.
4 Pfluger's Archiv, cxxii, 1908, 585.
THE PHENOMENA OF CONDUCTION IN NERVE
141
A B
These results have led to the early belief that nerve-tissue' cannot
be fatigued and that the nerve impulse is a physical phenomenon.
It should be remembered, however, that these deductions have been
based upon experiments which were made in a medium of air and under
conditions greatly favoring the activity of nerve. Contrary to the
view just expressed, Bayer and Frohlich have shown that the refrac-
tory period of nerve may be considerably lengthened by means of
narcotics or by displacing the air by an inert gas, such as hydrogen or
nitrogen. It was also noticed that the power of conduction of nerve
is markedly diminished in a medium of
this kind and remains so until the nerve
has again been transferred into an atmos-
phere containing oxygen. Thorner^ has
modified this experiment by placing the
nerves of two nerve-muscle preparations
in a chamber containing nitrogen (Fig.
83). One of these nerves was then sub-
jected to a tetanizing current centrally
to this chamber (A). By measuring the
amplitude of the wave of negativity it
was found that the excitability and con-
ductivity decreased very rapidly in the
tetanized nerve, but a similar, although
much slighter, effect was also detected in
the inactive nerve (B). Further evidence
in favor of the view that nerves may be
fatigued, has more recently been pre-
sented by Garten. 2 While testing differ-
ent non-medullated nerves, it was noted
that the action currents sweeping over
the olfactorius of the pike, ceased very Fig. 83.— Fatigue of Nebve.
shortly after the beginning of its tetaniza- ^ ^nd B two nerves placed
.• J Tj J. r-L j.T_ in glass chamber. The latter is
tion and did not reappear even after the connected through c with gas
electrodes had been applied to some other generator, s points of stimuia-
part of this nerve. This fact tends to *i«^: ^' galvanometers placed
, ,i,,i /.,• /. • upon nerves to test their irrita-
snow that the fatigue of nerve is never biiity.
restricted to the segment stimulated but
involves this structure in its entirety. Very similar results have
been obtained by Burian^ in the non-medullated nerves of cephalo-
pods. This investigator, moreover, has proved that these symptoms
of fatigue are not dependent upon electrotonic alterations in the area
stimulated. In summing up, it may be stated that the difficulties
formerly encountered in proving fatigue in nerve must be assigned
1 Zeitschr. fur allg. Physiol., viii, 1908, 530.
2 Beitrage zur Physiol, der markl. Nerven, Jena, 1903; also see: Snowton, Proc.
R. Soc, Ixvi, 1900, 379.
^ Intern. Kongress der Physiol., Heidelberg, 1907;
142
THE PHYSIOLOGY OF NERVE
very largely to the low intensity of the metabolism of this tissue as
well as to its remarkable affinity for oxygen. Nerve-tissue is capable
of assimilating this gas in the briefest possible time from almost any
source. In this regard nerve differs materially from the cell-bodies
of the neurons, because the latter display a very intense metabolism
and may therefore be more easily fatigued.
CHAPTER XIII
THE REACTION OF NORMAL AND ABNORMAL NERVE AND
MUSCLE TO THE CONSTANT AND INTERRUPTED
ELECTRICAL CURRENTS
Electrotonus. — The subsequent discussion should prove of par-
ticular value, because the facts now to be dealt with are absolutely
essential for a thorough understanding of the behavior of human nerve
and muscle when affected by degenerative changes. If we confine our-
selves for the present to the constant or galvanic current, it is to be
noted that the nerve must first be connected with the battery by means
of two non-polarizable electrodes which are placed at a moderate dis-
FiG. 84.
-Schema^ to Show the Arrangement Used for the Stimulation With
THE Descending or Ascending Current.
D, descending; A, ascending.
tance from one another. The electrode joined with the positive pole
of the generator then serves as the point of entrance of the current
into the nerve, and the one united with the negative pole, as its point
of exit. The former constitutes the anode (+) and the latter the
cathode ( — ). Provision must also be made to be able to change the
potential of these electrodes at will. This end is attained by means
of a pole changer. In this way, the anode may be placed either near
to or far away from the central end of the nerve (Fig. 84). If the
former, the current must sweep over the nerve in a direction from cen-
ter to periphery. It is then known as a descending current. If the
i
THE REACTION OF NORMAL AND ABNORMAL NERVE 143
latter adjustment is used, the current must pass from the periphery
toward the center. It is then called an ascending current.
In the second place, attention should be called to the fact that the
passage of a constant current through a nerve gives rise to certain
chemico-physical changes in the regions of the anode and cathode
which have been designated by DuBois-Reymond as electrotonus
(1843). This condition manifests itself in profound alterations in the
irritability and conductivity of the nerve. This change constitutes
physiological electrotombs, the one occurring in the region of the anode
being known as anelectrotonus and the one at the cathode as catelectro-
tonus. The physiological electrotonus finds its origin in the so-called
electrotonic currents which arise in consequence of electrolysis and
polarization. The latter may be designated as physical electrotonus.
Nerve is a moist conductor and hence, it need not surprise us to
find that the passage of the galvanic current induces certain processes
of electrolysis and dissociation which attain their maximal intensity
at the electrodes, i.e., at the points of entrance and exit of the current.
Inasmuch as the acid negative ions of the electrolytes are transferred
to the anode, this region must assume an acid reaction, while the ac-
cumulation of the basic positive ions upon the cathode must render
the latter alkaline. In the course of time, this accumulation of nega-
tive ions upon the anode and of positive ions upon the cathode gives
rise to the so-called polarization current, i.e.; to an electrical inter-
change, the direction of which is opposite to that of the original polar-
izing current.
This polarization becomes most intense if metal electrodes are
employed, but the aforesaid changes then appear to be confined to the
points of contact between the metal and the nerve. If non-polarizable
electrodes are used, this external form of polarization gives way to the
internal form. Although still most conspicuous at the anode and
cathode, these changes are then less closely restricted to the sur-
faces of the electrodes and spread with steadily decreasing density
into the region between these two poles as well as into those situated
immediately outside of them. The distance to which they extend out-
side the poles depends upon the strength of the primary galvanic cur-
rent. Thus, electrotonus may be said to be intrapolar and extrapolar^
in its character.
In this connection emphasis should be placed upon the fact that
these electrotonic currents are absolutely distinct from the nerve im-
pulse, as well as from the wave of negativity or action current and the
current of injury. Thus, it has been proven that their velocity is much
greater than that of the nerve impulse as betrayed by the speed of the
negative variation. ^ In the second place, it has been shown that they
may attain a strength twenty-five times greater than that of the cur-
rent of injury. Their distinctiveness is also indicated by the fact that
^ Pfliiger, Unters. liber die Physiol, des Elektrotonus, Berlin, 1859.
^ Gildermeister and Weis, Pfliiger's Archiv, xciv, 1903, 509.
144 THE PHYSIOLOGY OF NERVE
they persist during the entire period during which the galvanic current
is passed through the nerve and that their direction may be altered
repeatedly by simply reversing the primary current. Action currents,
on the other hand, always retain the same direction and are of momen-
tary duration. They may also be produced by mechanical, thermal
and chemical stimuli, while the electrotonic currents cannot be gene-
rated by these means. Another means of differentiation is furnished
by the fact that the polarization currents are strongest in the extra-
polar regions and that their intensity diminishes with their distance
from the poles. These statements imply that the passage of a galvanic
current through nerve (polarizing current) gives rise first of all to
electrotonic currents (polarization current) which in turn lead to the
production of a nerve impulse. The latter, therefore, is the result of
the first two conditions and is by no means a part of them.
Electrotonic Differences on the Making and Breaking of the Gal-
vanic Current. — If the nerve of a nerve-muscle preparation is stimu-
lated at definite intervals with a constant current of moderate strength,
it will be found that the muscle reacts only on the making and on the
breaking of this current, but not during the interim, in spite of the fact
that the current continues to traverse the nerve. In accordance with
DuBois-Reymond, it may therefore be stated that the stimulating
agent is not the absolute strength of the current, but rather the abrupt
change in its intensity which it suffers when it is made or broken. In
other words, a stimulus invariably fails to stimulate as long as it re-
mains constant, but becomes effective immediately if its striking force
is suddenly altered. Secondly, it has been shown by Pfliiger that
the making of the galvanic current gives rise to electrotonic changes at
the two poles, and that those at the anode are very different from those
at the cathode. The same holds true of the breaking of the current,
but naturally, the changes then occurring, cannot justly be classified
as true anelectrotonic and catelectrotonic phenomena, because they do
not arise during the passage of the current, but immediately after
its cessation. Strictly speaking, therefore, they should be character-
ized as post-anelectrotonic and post-catelectrotonic.
These differences in the functional condition of the nerve at the
points of entrance and exit of the constant current may be briefly
summarized as follows:
(a) On the making of the current the excitability of the nerve is markedly in-
creased at the cathode and decreased at the anode. These changes are most
pronounced at the poles, but also spread with gradually decreasing intensity into
the intrapolar and extrapolar regions. Consequently, an indifferent zone must
exist somewhere between these two poles, namely at the junction between the area
of heightened cathodal excitability and the area of lessened anodal irritability.
(6) On the break of the current this condition is reversed, i.e., the anodal region
then possesses the greater irritability while the cathodal region is depressed. As
has been stated above, this effect appears in reality after the breaking of the cur-
rent, and forms therefore an electrotonic wave in the wake of the galvanic current.
Thus, if the terminology of post-anelectrotonus and post-catelectrotonus is adhered
THE EEACTION OF NORMAL AND ABNORMAL NERVE 145
to, the term anelectrotonus signifies a depression and the term catelectrotonus an
excitation occurring during the passage of the constant current.
(c) It is also essential to remember that the excitatory process developed at the
cathode is always stronger than that developed at the anode.
It appears, therefore, that the wave of excitation constituting the
nerve impulse, is developed at the cathode on the make and at the
anode on the break of the current. This inference may be substan-
tiated with a nerve-muscle preparation by simply recording making
and breaking contractions when the anode is placed far away from the
muscle and the cathode near to it. It will then be noted that the
latent period of the making twitch is much shorter than that of the
breaking twitch. This must necessarily be so, because in the former
instance the nerve impulse arises at the cathode which is situated
in the immediate vicinity of the muscle; while in the latter case it is
produced at the anode which lies at some distance away from it. If
Fia. 85. — Methods Used to Show Electkotonic Changes on Making and
Breaking of Galvanic Current.
K, key for making and breaking of current; P, pole changer for making either
jend of muscle (M) anodic or cathodic; D, clamp applied to muscle to destroy contraction
wave but not wave of excitation; W , weights attached to ends of muscle. These may
be displaced by writing levers.
Ithe current is now reversed so that the anode comes to lie near the
muscle and the cathode far away from it, the latent period will show
a greater length on the making of the current. On the making, the
: cathode serves as the stimulus and this pole is situated in this case far
away from the muscle, while, on breaking, the excitation results at
[the anode which lies very near the muscle.
The preceding statement may also be proved by the procedure of Engelmann
j(Fig. 85). The positive and negative poles of a battery are connected with the
[two ends of along muscle, such as the sartorius. (M). This muscle is then con-
stricted about midpoint between its poles by means of a clamp (D), the com-
pression being just sufficient to prevent the contraction of one-half from being
imparted to the other half without actually hindering the passage of the wave of
10
146
THE PHYSIOLOGY OF NERVE
excitation. The writing levers (W), attached to the two ends of the muscle, are
adjusted in the same ordinate, so that any difference in the onset of the contractions
in the two halves will be indicated in the record. On making the current by closing
the key (k), the contraction invariably begins at that end of the muscle which is
connected with the cathode (C), while on breaking the current the end joined with
the anode (A) is activated first. The polarity of the muscle is then changed by
reversing the bridge of the Pohl commutator (F) interposed in the circuit, so that
the previously cathodic end now becomes anodic. Although reversed as far as
the muscle is concerned, the results will be identical with the preceding. This
experiment may be modified in the following manner. It is a well-known fact that
a much more lasting character may be im-
parted to the contractions by the use of a
strong galvanic current. The one obtained on
making the current is designated as Wendt's
tetanus and the one on opening, as Ritter's
tetanus. Engelmann has proved that these
tetanic contractions remain confined to that
end of the muscle in which they originate,
namely, the making tetanus to the cathodic
and the opening tetanus to the anodic end.
The phenomenon of electrotonus may also
be reproduced with the help of the simple
core-model described in one of the preceding
paragraphs, but naturally, the conditions here
met with are purely physical in their nature
and are not complicated by physiological
changes, as they are in living nerve. Thus, it
has beennoted that an electrolytic dissociation
takes place between the metal core and the
surrounding solution whenever a current is
passed through it. The cathodic ions are
made to move toward the anode and the
anodic toward the cathode until true electro-
tonic currents have been produced.
Pfliiger's Law of Contraction. — In
order to show that the passage of a
galvanic current gives rise to a cathodic
area of excitation and an anodic area
Fig. 86. — Method of Testing
THE ElECTROTONIC CONDITION OF
Nerve.
K, key for making and break-
ing of constant current; P, pole
changer for reversing current so of depression, these regions Hiav be i
that either pole may be made ,• i . j j. i. • i« • j^ ^ 'J^
anodic or cathodic; s, point of stimulated at brief intervals either
stimulation of nerve by means of mechanically or by means of single in-
induction shocks; w, writing lever duction shocks (Fig. 86). In the latter
attached to muscle. ., i , \ / n\ , i -.i
case, the electrodes (o), connected with
the secondary coil of an inductorium, are placed in the immediate
vicinity of either the positive or negative non-polarizable electrode.
By using a strength of induction which, when brought to bear upon the
cathodic region, just barely produces a contraction of the muscle, it
can easily be shown that this same stimulus applied to the anodic
region, fails to incite a reaction. But even if the same minimal
stimulus is employed for both regions, a comparison of the amplitude
of the contractions then resulting will show immediately that the one
obtained by stimulating at the cathode, is the larger of the two. In
THE EEACTION OF NORMAL AND ABNORMAL NERVE 147
this connection reference should also be made to the work of Bethe^
who has shown that the anodic and cathodic regions possess different
staining qualities. At the anode, the neurofibrils of the axis-cylinder
lose their power of absorbing methylene-blue, while those situated at
the cathode, show an abnormally high affinity for this dye.
The relative amplitudes of the contractions obtained by stimu-
lating different points of the anodic and cathodic areas, have been
made use of in the construction of a curve illustrating the manner
in which the excitability of nerve is changed during the passage of
the galvanic current. The following schema of Pfltiger^ (Fig. 87)
shows that the subthreshold anode and suprathreshold cathode lines
Fig. 87. — Electbotonic Alterations of Irbitability Caused by Weak, Medittm,
AND Strong Battery Currents.
A and B indicate the points of application of the electrodes to the nerve, A being
the anode, B the cathode. The horizontal line represents the nerve at normal irrita-
bility; the curved lines illustrate how the irritability is altered at different parts of the
nerve with currents of different strengths. Curve 2/^ shows the effect of a weak current,
the part below the line indicating decreased, and that above the line increased irrita-
bility, at x^ the curve crosses the line, this being the indifferent point at which the
catelectrotonic effects are compensated for by anelectrotonic effects; y"^ gives the effect
of a stronger current, and ^^ 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 cathode. {American Text-hook of Physiology.)
must vary in their position with the irritability of the nerve experi-
mented upon and the strength of the constant (polarizing) current.
This implies first of all that the polarization, or rather, the effect of
the polarizing current must increase with the irritability of the nerve,
and secondly, that the length of nerve so affected must increase with
the strength of the current. At the point of confluency of these anodic
and cathodic fields in the intrapolar region, a conflict arises in conse-
quence of which the irritability remains unchanged. With a weak
polarizing current, this indifferent point lies near the anode, while with
stronger currents it is shifted more and more toward the cathode.
This fact implies that strong currents are more depressant than weak
currents, and hence, a point will eventually be reached when the
depression also involves the cathode. The making increase in excita-
^ AUg. Anat. und Physiol, des Nervensystemes, Leipzig, 1903.
' Unters. iiber die Physiol, des Elektrotonus, Berlin, 1859.
148
THE PHYSIOLOGY OF NERVE
bility at the cathode is then much diminished. Strong currents,
therefore, cause a depression at both poles but the cathodic depression is
always less than that developed at the anode. Werigo^ expresses this
fact by saying that the cathodic depression is initiated by a brief
period of excitation. It is to be remembered, however, that Fig. 87
represents the conditions prevailing during the passage of the constant
current, when the term anelectrotonus is synonymous with depres-
sion and the term catelectrotonus with excitation, and does not portray
the conditions existing subsequent to the breaking of the current.
The post-anelectrotonic and post-catelectrotonic effects are the reverse
of those just described, i.e., while strong currents cause a depression
at both poles, the cathodic region is now more highly depressed.
At this time, the stimulus is derived from the anodic excitation still
remaining.
These electrotonic differences are responsible for the occurrence
of the phenomenon known as ''secondary tetanus of nerve." If a
long piece of the sciatic nerve of a frog {A) is placed beside the nerve
of a nerve-muscle preparation {B), as is indicated in Fig. 81, the
excitation of the central end of nerve {A) with a constant current
invariably results in a contraction of the muscle. By making and
breaking the current more rapidly, the muscle may be thrown into
a complete state of tetanus. In this case, it is the electrotonic current
in nerve (A) which produces the nerve impulse in {B) and the subsequent
muscular reaction. It will be remembered from the previous discus-
sion that this result may also be obtained with the aid of an ordinary
action current.
It has been found by Pflliger that the making and breaking of a
weak galvanic current gives rise to a contraction only on the make. In
this case, it is immaterial whether the anode be situated near to or far
away from the muscle, i.e., the results are the same whether the current
be ascending or descending. With a medium current a contraction
is produced on the make as well as on the break, and this holds true
for the ascending as well as for the descending current. With a
strong current, the results are more complex, because the ascending
current gives a contraction only on the break, and the descending
current only on the make. These effects have been formulated into
what is known as Pfliiger's Law of Contraction which may be summar-
ized as follows:
Current
Ascending
Descending
Make
Break
Make
Break
Weak
c
C
C
C
c
c
c
Medium
c
Strong
Werigo, Pfliiger's Archiv, Ixxxiv, 1901, 547.
THE REACTION OF NORMAL AND ABNORMAL NERVE 149
Clearly, this law is applicable only to excised nerve and muscle
when tested under experimental conditions, but its practical value
will become apparent later on in connection with the stimulation of
normal and degenerating human muscle and nerve. Its explanation
will present no difficulties if the following three fundamental data are
borne in mind, namely:
(a) When a nerve is stimulated with a galvanic current, an excitatory process is
set up at the cathode on the making and at the anode on the breaking of the
current.
(6) The excitatory condition developed at the cathode on the making, is
stronger than the one generated at the anode on the breaking of the current.
(c) The passage of a galvanic current through a nerve entails a decrease in its
power of conduction which, although discernible at both poles, is most strongly
Fig. 88. — Diagram Illustrating Pfluger'
Asc, ascending current; Desc, descending current; W, M
strong current
Law.
*S, weak, medium and
The effective stimulus is indicated in each case by cross marks.
marked in the region of the anode. Immediately upon the breaking of the current,
the anodic conductivity returns to near normal, while the cathodic conductivity is
diminished. With strong currents this anodic depression on the making becomes
so powerful that it actually blocks the nerve impulse and thus prevents it from
reaching its destination. The same holds true of the cathodic depression resulting
after the breaking of the strong constant current.
With a weak ascending or descending current, only the two making
stimuli are effective, because in this case the excitation which gives
rise to the nerve impulse is developed at the cathode (Fig. 88). The
nerve impulse resulting therefrom, reaches the muscle, because the
depression at the anode on the making of the ascending current is not
sufficiently intense to block it. The same holds true of the making
of the descending current, and besides, the stimulating cathode now
lies next to the muscle, so that nothing can prevent the passage of
150 THE PHYSIOLOGY OF NERVE
the impulse into the latter. The breaking contractions are absent,
because both anodic stimulations are as yet too weak. As the strength
of the current is increased to medium (M) , the breaking contractions
also appear, because even the anodic stimulations have now attained
a strength sufficient to generate nerve impulses. The making con-
tractions, however, continue to be larger than the breaking, because
the cathodic stimuli are more powerful than the anodic. With medium
currents no direct blocking effects are obtained, although the anodic-
making and cathodic-breaking depressions are now more powerful
than during the passage of weak currents.
With a strong ascending current (S) , no reaction is obtained on the
making, because the anode is situated next to the muscle. The nerve
impulse generated at this time at the cathode cannot reach the end-
organ, because the strongly depressed and non-conductile anodic region
intervenes. On the break of this current, however, the impulse can
reach the motor organ without hindrance, because the now stimulating
anode is situated near the muscle and the depressed cathodic area far
ajway from it. With a strong descending current a contraction is
obtained only on the making, because the stimulating cathode is
now situated near the muscle and the depressed anode far away from
it. On the breaking of this current, however, the impulse developed
in the anodal region cannot reach the muscle, because the non-conduc-
tile cathode is interposed between it and the end-organ.
The Law of Contraction of Normal Human Nerve and Muscle. —
Pfliiger's Law as such cannot be applied to human muscle and nerve,
because the conditions here met with are entirely different from those
presented by excised muscle. Living human muscle is covered by
skin, adipose tissue, fascia and connective-tissue envelopes, and the
nerves are generally so deeply placed that they are not accessible to
stimulation by means of two widely separated electrodes. For this
reason, their excitation is usually effected with a single electrode ad-
justed as follows: The battery consists of about 25 to 30 cells which
may be quickly joined in series so as to be able to increase the strength
of the current with the least possible loss in time. In this circuit is
inserted a pole changer by means of which the polarity of the elec-
trodes may be reversed at any moment. One of the electrodes con-
sists of a broad metal plate wrapped in a bolster of cotton. The latter
is moistened with saline solution to reduce the resistance of the skin.
The other electrode is pointed and is equipped with a key which may
be closed and opened at will. If a current of a certain voltage is per-
mitted to pass through two electrodes of this construction, it will be
found that the excitation invariably arises at the pointed one, because
the current attains here its greatest density and striking force. At
the broad nietal plate, on the other hand, it is able to scatter more
widely through the tissues without actually acquiring a high stimu-
lating intensity. For this reason, the former is designated as the
stimulating and the latter as the indifferent electrode.
THE REACTION OF NORMAL AND ABNORMAL NERVE 151
This procedure is commonly called the unipolar method of stimula-
tion (Chaveau). To begin with, the indifferent electrode is firmly
appUed to some part of the body, while the stimulating electrode is
brought in contact with the region overlying the nerve or muscle to
be tested. The accompanying Fig. 89 may serve to illustrate the ar-
rangement generally employed in stimulating the muscles of the arm.
But practically every voluntary muscle in our body may be tested
in the same way, although its excitation is usually effected through
its motor nerve by applying the active electrode to the region in which
its nerve becomes most superficial. The location of these different
motor points may be determined with the help of Figs. 90 and 91.
Fig. 89. — Schema to Show the Unipolab Method of Stimulation in Man.
The anode, +, is represented as the stimulating pole, applied over the median nerve.
The cathode, —, is the indifferent pole. (Howell.)
If the stimulating electrode is made anodic, it will be found that
neither the making nor the breaking of a weak galvanic current gives
rise to a contraction. If the active electrode is now made cathodic, a
contraction will be obtained on the making of this current. This re-
action is usually called the cathodic closing contraction (C.C.C.). On
repeating this procedure with a current of medium strength, it will be
noted that the anode also becomes effective, a contraction now resultmg
both on the making and breaking of this type of current. These con-
tractions are designated respectively as the anodic closing (A.C.C.)
and anodic opening contraction (A.O.C.). The cathodic closure con-
152
THE PHYSIOLOGY OF NERVE
traction (C.C.C.) already obtained with the weak current, is, of course,
retained, but no effect is as yet in evidence on the break with the
cathode presenting. This cathodic opening contraction (C.O.C.) ap-
pears only after the strength of the current has been materially in-
creased by the addition of several cells. Attention should also be
called at this time to the fact that strong currents frequently give rise
to contracture-like reactions, which are designated as galvanotonus.
As far as human nerve and muscle are concerned, it will be seen, there-
JV*fll.w!nari*|
M. flexor carpi nlnaris
M. flex, digitor. siib-
Itm, (digit! II et III)
M. flex, digit, subl.
(digit! indicis et
minimi)
Ntrvt ttlnaris
I. flexor digits rain
M. opponens digit
min.
M, lumbricales-
M. flex. poll, brev,
M. adductor polllc. brer-
FiG. 90. — Motor Points in Upper Extremity. {Howell.)
fore, that the gradual increase of the constant current brings forth
these contractions in the order indicated in the succeeding table :
Galvanic current
Weak
Medium
Strong
C.C.C.
C.C.C.
A.C.C.
A.O.C.
C.C.C.
A.C.C.
A.O.C.
C.O.C.
THE REACTION OF NORMAL AND ABNORMAL NERVE
153
In the same manner as the results obtained with excised muscle
and nerve, have been formulated into Pfliiger's law of polar stimulation,
so may the present results upon human muscle and nerve be combined
into the law of unipolar stimulation. But inasmuch as these laws have
a different experimental basis, they cannot really be compared with
one another unless this comparison be restricted to the causes under-
Nerv. ischiadicus
M. biceps fern. (cap. long.)
M. biceps fern, (cap: brev.)
iV. peroneus
M. gastrocnem. (cap. extern.) / #
M. soleus
M. flexor ^hallucis longus
M. gluteus maximus
M. adductor magnus
M. semitendinosus
M. semimembranosus
N. tibialis
M. gastrocnem. (cap. int.)
M. soleus
M. flexor digitor. comm. longus
JV. tibialis
Fig. 91,
-Nerves and Motor Points in Lower Extremity. (Church and
Peterson.)
lying them. A clear understanding of the second law requires first
of all a brief recapitulation of the following three fundamental data :
(o) The making of a galvanic current gives rise to an excitation at the cathode,
and its breaking to an excitation at the anode.
(b) The irritability developed at the cathode on the make of the current, is
always greater than that generated at the anode on the break.
(c) The stimulating power of this current is greatest in its area of greatest
density.
154
THE PHYSIOLOGY OF NERVE
The effects of unipolar stimulation, however, are complicated by
the fact that the electrodes cannot be applied directly to the nerve
but only to the skin overlying, and hence, a number of peripolar re-
gions invariably develop around the actual poles upon the nerve. If
the stimulating electrode is anodic and the indifferent electrode ca-
thodic, the various electrical lines enter the tissues as through a nar-
row gate and then spread out fan-like underneath, constantly seeking
paths of least resistance. At the cathodic pole, these lines again con-
verge and are finally combined into a number of smaller bundles. At
every point where these lines enter the nerve there is established a
secondary anode, and wherever they emerge, a secondary cathode.
In this way, a number of secondary or physiological anodes and ca-
FiG. 92. — Rough Schema op Actitb Threads of Current by the Ordinary
Application of Electrodes to the Skin over a Nerve (Ulnar Nerve).
The inactive threads are given in dotted lines (after Erb) .
thodes are developed beneath the primary or physical anode as well as
below the physical cathode. In brief, therefore, it may be stated that
the results of the stimulation of human muscle and nerve are depen-
dent upon the interaction of these physical and physiological poles.
A fuller explanation must take into account that the contraction,
following the making of the current, is developed at the physiological
cathode, while the one following the breaking of the current, is devel-
oped at the physiological anode. Now, since the stimulating electrode
may be made either anodic or cathodic, and since physiological anodes
and cathodes are developed in either case, four possibilities arise,
namely :
(1) Anodic Stimulation :
(a) On making we obtain the so-called anodic closing contraction in
consequence of excitatory changes resulting at the physiological
cathode beneath the physical anode.
THE REACTION OF NORMAL AND ABNORMAL NERVE 155
(b) On breaking we obtain the so-called anodic opening contraction which
is due to the excitatory process at the physiological anode beneath the
physical anode.
(2) Cathodic Stimulation:
(a) On making we obtain the so-called cathodic closure contraction in
consequence of the excitation developed at the physiological cathode
beneath the physical cathode.
(6) On breaking we obtain the so-called cathodic opening contraction
which is caused by the excitatory alterations at the physiological anode
beneath the physical cathode.
It has been stated repeatedly that the cathodic irritability is
stronger than the anodic. For this reason, the two making or closure
contractions (C.C.C. and A.C.C.) must be stronger than the two break-
FiQ. 93. — Diagram Showing Physical and Physiological Anodes and Cathodes.
A, the physical anode, or positive electrode; K, the physical cathode, or negative
electrode; a, a, a, physiological anodes; k, k, k, physiological cathodes. (American
Text-book of Physiology.)
ing or opening contractions (A.O.C. and C.O.C). Thus, it only
remains for us to see why the cathodic closure contraction precedes
the anodic closure contraction and why the anodic opening contrac-
tion appears before the cathodic opening contraction. In brief,
this sequence of the reactions is dependent upon differences in the den-
sity of the current. On making, the current acquires a greater den-
sity or striking force when the physiological cathode coincides with the
physical cathode than when it lies in relation with the physical anode.
In the first case, we obtain what might be termed a summation of
effects between the inner physiological cathode and the outer physical
cathode. The same explanation may be given for the fact that the
anodic opening contraction develops before the cathodic opening
contraction. The excitation on breaking being developed at the
physiological anode, this stimulation becomes more effective if the
physiological anode and physical anode coincide.
The Law of Contraction of Degenerated Human Nerve and Mus-
cle.— When called upon to ascertain the functional condition of a
certain muscle and its nerve, use should be made not only of the con-
stant current but also of the induced current. It should be noted
156
THE PHYSIOLOGY OF NERVE
first of all that degenerating muscle and nerve is very sensitive to the
galvanic and relatively insensitive to the induced current, so that even
a weak constant current may produce an exaggerated contraction, or
galvanotonus, while strong induction shocks may fail entirely in elicit-
ing a response. This fact in itself is suggestive of degeneration, be-
cause it indicates that the irritability of this particular muscle and
nerve has become more nearly like that of all sluggishly reacting forms
of protoplasm. A further means of differentiation is furnished by the
so-called law of degeneration which is obtained by the same procedure
as the law of unipolar stimulation, the stimulating electrode being
applied either to the region of the muscle or to that of the nerve in-
nervating it (Erb's reaction). For reasons not clearly understood, de-
generated muscle reacts first on the making of the galvanic current
when the anode is the active electrode, while, on breaking, the
cathodic opening contraction is obtained before the anodic opening.^
In advanced cases of degeneration, the galvanic excitabihty is also
diminished, only the first contractions remaining in evidence until
eventually even these disappear. The law of degeneration may be
tabulated as follows:
Galvanic current
Weak
Medium
Strong
A.C.C.
A.C.C.
C.C.C.
C.O.C.
A.C.C.
C.C.C.
C.O.C.
A.O.C.
Chilarducci has suggested to place the stimulating electrode at
some distance below the degenerated muscle, because a contraction
may then be elicited with currents three or four times weaker than
those ordinarily required for indirect excitation. Furthermore, con-
tractions may then be evoked long after the direct stimulation has
ceased to give positive effects. This phenomenon, which is called
''reaction at a distance, " may be used for the diagnosis of degeneration
of long standing and unusual obscurity.
1 Babinski, Compt. rend., 1899, 343.
PART II
THE BLOOD AND LYMPH
IMMUNITY
SECTION IV
THE BLOOD
CHAPTER XIV
GENERAL CHARACTERISTICS OF THE BLOOD
General Consideration. — The general body fluid of the lowest
organisms possesses the simplest possible composition. It is widely
distributed through the intercellular spaces and is separated from the
surrounding medium by a very permeable membrane. Being thus
fully exposed to osmotic influences from without, different nutritive
substances are constantly forced into the organism, while its waste
products are made to pass into the medium. These osmotic condi-
tions, however, are adjusted in such a way that the general fluid of
the body is quite unable to acquire a concentration much above that
of the surrounding medium.
Separate circulatory channels are not present in the lower forms.
Instead, the alimentary canal is called upon to perform a double func-
tion, namely, that of serving as a receptacle in which the nutritive
substances undergo mechanical and chemical reductions, and that of
distributing the assimilated material to the different parts of the body.
A much higher stage of development is attained in those animals in
which the alimentary tract assumes a variegated shape and in which its
different recesses eventually become disconnected from the main chan-
nel to form the beginnings of the circulatory system. In this manner a
number of internal reservoirs are developed, from the contents of which
the tissue-cells derive their nourishment directly. But, while the
body-fluid is thus more thoroughly protected against outside influences,
its isolation is not complete, because it continues to be exposed, on the
one hand, to the osmotic power of the contents of the alimentary
canal and, on the other, to the conditions prevailing in the cells of the
tissues.
With increasing cellular differentiation, this fluid of the celom
gradually assumes the characteristics of real blood. Moreover, as the
interior spaces become more variegated, certain elementary forces are
157
158
THE BLOOD
brought into play which cause the fluid to move in such a manner that
delicate streams or even oscillatory currents are produced. The more
efficient protection against outside influences, which is thus afforded
the "blood," enables it to maintain a much greater complexity with-
out materially hindering the osmotic interchanges.
In the higher animals, the blood assumes all the characteristics
of a tissue, but in order that the cellular units of the body may be
brought into relation with their nutritive source in the shortest pos-
sible tinae, it is made to move rapidly through a system of intricate
and recurrent tubes, the driving force being furnished by a central
muscular organ, the heart. Besides, these animals are equipped with
a fluid known as the lymph ^ which serves the purpose of a medium
Fig. 94. — ^The Development of the Circulatory System.
Osmotic interchanges take place 1, between the medium and the substance of the
cell through the cell wall; 2, between the contents of the alimentary canal {AC) and the
tissue cells (B) ; 3, between the contents of the alimentary canal {AC) and its recesses,
and the tissue cells (JB and C), and 4, at the same two places after the recesses have
become separated from the body canal.
for the osmotic interchanges between the blood and the tissues. Thus,
as the amount of blood present in the body is relatively small whereas
its complexity is great, it must be evident that the lymph forms an
economic factor of greatest importance, because its copiousness and
watery consistency enable it to enter the smallest spaces and to come
in direct contact with practically every cell of the body. The cells,
it is commonly stated, are bathed in lymph, while the blood itself
does not actually touch them. This statement, however, is not in-
tended to imply that these nutritive fluids are quite independent of
one another. On the contrary, the lymph is derived originally from
the blood in accordance with physico-chemical laws. It is diluted
plasma which, however, is not lost to the blood, but is again returned
1 A third circulating fluid is the chyle, but as this is merely lymph loaded with
the products of digestion, it need not be considered separately. The same holds
true of the intraocular fluid and of the liquor cerebrospinalis.
GENERAL CHARACTERISTICS OF THE BLOOD 159
to it. Outside the capillary wall, the lymph serves as the medium with
which the tissue cells interchange their material. This process having
been completed, it then moves onward through the special channels
constituting the lymphatic system, until it again reaches the venous
collecting tubes of the main circulatory system. The lymph, so to
speak, plays the part of a middle man between the blood and the cells.
The lymph is comparable to the general body-fluid of the lower
animals, while the blood forms a much more specialized carrier. Func-
tionally, however, these media must be regarded as fulfilling the same
purpose, because they :
(a) Equip the cells of the tissues with the material necessary for their existence,
and remove from them the substances that are of no further use to them ;
(6) provide the tissues with oxygen in a readily assimilable form, and relieve
them of carbon dioxid, one of the products of their metabolism;
(c) help in the equalization and regulation of the body-temperature;
(d) protect the organism against microbic infection and toxic influences of differ-
ent kinds, and
(e) disseminate the products of the ductless glands, known as atacoids.
The blood is a thick and viscous fluid, containing different bodies
and substances in solution and suspension. It is composed of a fluid
part, commonly designated as plasma, and a relatively large amount
of solids. The latter embrace nutritive particles of all kinds, as well
as formed elements, or corpuscles, which in turn are made up of red
corpuscles or erythrocytes, white corpuscles or leukocytes, and blood
platelets or thrombocytes.
Blood
Water Plasma
Nutritive particles.
Blood dust (hemoconia)
Solids
f red (erythrocytes)
Corpuscles j white (leukocytes)
[ platelets (thrombocytes)
Relative Amount of Plasma and Corpuscles. — Two methods have
been devised for the determination of the amount of the corpuscular
material. The direct method possesses the advantage of being easily
executed. The sample of blood to be examined is mixed with a definite
quantity of potassium bichromate and is centrifugahzed ^ until the
corpuscular elements have been forced to the bottom of the receptacle.
Since the glass-tubes used in this test are calibrated, the amounts of
plasma and corpuscles may be read off directly. This entire procedure
requires no special aptitude nor complicated apparatus and can be
completed before coagulation has set in. It is also possible to ascer-
tain the corpuscular content by measuring the electrical conductivity
of the serum and corpuscles. This method depends upon the fact
that the latter place a considerable resistance in the path of an elec-
trical current which is directly proportional to the thickness of the
^ For clinical purposes a small centrifuge, called a hematocrit, is commonly
employed (Blix and Hedin).
160 THE BLOOD
layer formed by them. The indirect method, suggested by Hoppe-
Seyler, is analytical in its nature and necessitates the following pro-
cedures. To begin with, the total amount of proteins in a definite
quantity of defibrinated blood is determined and secondly, also the
total protein content of the washed corpuscles contained in an equal
amount of the same blood. It must be evident that the value ob-
tained as a difference, corresponds to the amount of proteins contained
in the serum of this sample of blood, and if the quantity of proteins
in a special sample of the same blood is now ascertained, the propor-
tion of serum in the blood as a whole can readily be calculated.
The proportion of plasma and corpuscles differs widely not only
in animals of different species but also in animals of the same group.
As a rule, the volume of the plasma is found to be much greater than
that of the corpuscles, a relationship of 2:1 having been observed at
times. The figures for human blood vary between 48 and 54 per
cent., the average value for the corpuscles being about 50 per cent,
by weight,^ or 35 to 40 per cent, by volume. In the dog, the corpus-
cles constitute 36 per cent, and in the horse 34.5 per cent, by weight.
Color of the Blood. — When present in larger amounts, the blood
exhibits a very characteristic color, varying between scarlet red and
purple. Blood free from oxygen is dichroitic, dark red in reflected
light and green in transmitted light. The color impression, actually
derived from it, is in accord with the amounts of oxygen and carbon
dioxid, or, more correctly speaking, with the amounts of oxyhemo-
globin and reduced hemoglobin present therein.
The blood, or rather, the body-fluid, of the lower forms embraces
pigments of different color. Red, violet, brown, green, and blue
blood has been found. Furthermore, the pigment is not always held
in the corpuscular elements, but may also occur free in suspension
in the plasma. The earthworm, for example, possesses colorless
corpuscles, while the blood-pigment, called hemerythrin, floats in the
plasma. The red coloring material in the echinoderms is known as
echinochrome, while the blue pigment of the molluscs and crusta-
ceans is called hemocyamine, and the green pigment of worms,
chlorocruorine.
The plasma itself is a clear, amber-colored liquid and does not impart
a distinct color to the blood as a whole. Moreover, inasmuch as the
leukocytes and platelets are colorless, the only constituents to which an
influence of this kind may be attributed, are the red corpuscles. It
should be emphasized, however, that single red cells give solely a sen-
sation of very faint yellow, and that a distinct reddish color is obtained
only when many of them are grouped together. The coloring matter
of the red cells is the pigment of the hemoglobin.
On entering the lungs, the blood exhibits a dark red color, while
that leaving them is much lighter. Obviously, therefore, its passage
^Arronet, Maly's Jahresber.; xvii; Schneider, Zentralblatt fur Phvsiol., v,
1891, 362; and Stewart, Jour, of Physiol, xxiv, 1899, 356.
GENERAL CHARACTERISTICS OF THE BLOOD 161
through the capillaries of this organ has enabled it to undergo a
chemical change, which, as will become evident later, consists in an
absorption of oxygen and a loss of carbon dioxid. As far as the color-
ing substance, hemoglobin, is concerned, its sojourn in the lungs ha^
permitted it to acquire a certain amount of oxygen in place of that
which has previously been turned over to the tissues. For this reason,
the color of the blood may be employed as in index betraying the ex-
tent of the molecular union which has been effected between the hemo-
globin and the oxygen of the respired air. In other words, it betrays
the degree of aeration or oxygenation of the blood.
This explanation also accounts for the differences in the color of
the blood in different parts of the vascular system. The most decided
contrast is noted centrally in the large arteries and veins, while periph-
erally all intermediary shades between crimson and purple may be
observed in accordance with the state of oxygenation of the blood in the
region examined. In this connection mention should also be made of
the fact that glandular and muscular activity is always associated
with a greater flow of blood through the active organ, in consequence
of which its venous discharge often assumes a color more like that of
its arterial supply. Thus, it may be noted at times that the blood
returned from the kidney, is much lighter than that of the inferior
vena cava with which it eventually intermingles. A more copious
supply of arterial blood is required by an organ or tissue when acti-
vated, because it needs more material for purposes of oxidation.
The appearance of the different exposed regions of the body, such
as the lips, conjunctiva, nails, and mucous membrane of the mouth,
is frequently employed as an index of the degree of aeration of the
blood. Provided that the capacity of the blood-vessels of these parts
has not been materially altered, a pink color signifies an adequate
supply of oxygen, whereas a bluish hue suggests a poverty in oxygen
and a superfluity in carbon dioxid. A dark blue color may readily
be imparted to the circulating arterial blood by temporarily suspending
the respiratory movements, or by permitting the animal to breathe
air charged with carbon dioxid. Outside the body similar results may
be obtained by removing the oxygen from the arterial blood by means
of an air pump, or with the help of a reducing agent. During asphyxia
the blood assumes an almost chocolate-brown color. This change can
also be brought about locally by obstructing the venous return in a
mechanical way. As the oxygen is gradually abstracted from the
blood, the part experimented upon assumes a much darker appear-
ance. Marked alterations also follow the administration of poisonous
substances. Thus, carbon monoxid gives rise to a cherry-red color,
while phenylhydrazin produces a dark-brown appearance. Quite
similarly, venous blood may be made to assume a much lighter color
by instituting vigorous respirations, or by shaking the shed blood
in atmospheric air. Obviously, this change is brought about by an
absorption of oxygen.
11
162 THE BLOOD
Even in thin layers blood is not transparent, because much of the
light entering it is reflected from the surfaces of the formed elements.
Its opacity, therefore, is caused chiefly by the red corpuscles.
Odor and Taste. — Blood possesses a salty taste and a faint odor.
The latter is caused by volatile fatty acids held in solution, and be-
comes more distinct when concentrated sulphuric acid is added to the
blood. While both factors vary somewhat even in animals of the
same species, the odor of blood is usually sufficiently strong so that
an animal, when wounded, may easily be followed by another pos-
sessing a keen sense of smell.
The Temperature. — The factor responsible for the temperature of
the blood is the metabolism of the tissues. The heat given off by the
cells is retained in full measure by the blood as long
as it traverses well-protected channels, but is dissipated
by it as soOn as it reaches the more exposed parts of
the body. Thus, it is found that the highest tempera-
ture prevails in the intrahepatic veins and the lowest
in the blood-vessels of the fingers, nose and ears.
Differences between 36° C. (97.7° F.) and 39.7° C.
(103° F.) have been recorded; a fair average value for
the blood in central channels is 38° C. (100° F.).
_, j^ Specific Gravity. — This factor may be determined
Pycnometer. by means of a pycnometer. A small flask of glass,
large enough to contain from 3 to 5 c.c. of blood, is
weighed when empty and when filled with distilled water. The
value so obtained is compared later on with the weight of this flask
when flUed with blood. It need scarcely be mentioned that the
temperature must be the same for the two weighings. If the
amount of blood is very small, short capillary tubes of glass may
be employed, and, if large, flasks of a greater capacity than 5 c.c.
The larger pycnometers are equipped with a thermometer as well as
with an extra bulbular enlargement for the reception of that portion
of the blood which is forced out when the flask is filled. A second
method consists in permitting a drop of blood to fall into a fluid
of known speciflc gravity. Various mixtures have been advocated for
this purpose, for example, glycerin and water, or benzol and chloro-
form.^ To begin with, the specific gravity -should be adjusted at about
1.050. The procedure consists in quickly increasing or decreasing the
specific gravity of this medium by the addition of a certain quantity
of one or the other of these liquids, until the individual droplets of
blood are held in the central mass of the mixture. At this moment
their densities may be said to be practically the same. It is then only
necessary to determine the specific gravity of the mixture by means of
an ordinary hydrometer corrected to the mixture used. If a compara-
tive study is made with different samples of blood, care must be taken
to make the collections always from the same blood-vessel and under
» Hammershlag, Zeitschr. fiir klin. Med., xx, 1892, 444.
I
GENERAL CHARACTERISTICS OF THE BLOOD 163
as nearly identical conditions as possible, because, inasmuch as the
internal friction of the blood varies with the size of the channel, its
content in solids must necessarily be subject to fluctuations.
The specific gravity of the blood varies considerably. On the one
hand, it is found that the general body-fluid of the lower forms possesses
a density only slightly greater than that of water, and, on the other,
that the blood of the higher animals represents a complex fluid of
relatively high concentration. Obviously, therefore, the specific
gravity must increase steadily, the highest values being present in the
mammals. It is true, however, that the density of the blood of closely
related animals is subject to only slight variations, so that a rather
definite grouping of animals in accordance with this factor is made
possible. Thus we find that the specific gravity of human blood ex-
ceeds that of the blood of the dog or cat, and that these in turn surpass
that of the blood of the rabbit. The density of turtle's or frog's
blood is much less than that of the mammalian blood. It must be
emphasized, however, that individual variations do occur, as may be
gathered from the fact that the specific gravity of human blood varies
between 1.054 and 1.066. A fair average value is 1.060. In woman
variations between 1.054 and 1.061 have been noted. Blood serum
shows values ranging between 1.028 and 1.032. The red corpuscles
possess a much greater density (1.090), a fact which accounts for the'
rather quick deposition of these bodies in blood to which an anticoagu-
lating agent has been added.
It is also of interest to note that the specific gravity of the blood
of the fetus is usually higher than that of the blood of the mother.
Values, such as 1.066 for the former and 1.054 for the latter, are not
unusual. During the first few days after birth rapid fluctuations
between 1.060 and 1.080 are the rule, which, in all probability, are
caused by a more copious production of tissue-fluid. During the first
few months variations between 1.053 and 1.059 are encountered; a
fair average value at this time being 1.056. A slightly higher figure,
namely 1 .058, is reached after the second and before the fourth year.
Subsequent to the sixth year the average value is 1.061. This is re-
tained throughout childhood.
Similar fluctuations have been recorded in dogs, cats, rabbits, and
other animals. It may be stated, however, that the average value
for dog's blood is somewhat lower (1.055) than that of the blood of
man, but higher than that of the blood of the cat (1.050) or rabbit
(1.045). On the whole, therefore, it is true that the specific gravity in
a particular group of animals displays a certain constancy and that the
minor variations just alluded to are dependent in a large measure upon
such influences as age, sex, exercise, intake of solid food and water, as
well as loss of water by perspiration and otherwise. ^
^ The reader is reminded of the fact that very profound changes in the specific
gravity are frequently encountered during pathological conditions. Very low
values are noted in anemias, and very high values in diseases which are character-
ized by an increase in the number of the red blood cells (polycythemia).
164 THE BLOOD
Reaction. — 'The reaction of the blood as a whole, as well as that of
the plasma, differs with the indicator. The earlier determinations,
which have usually been made with glazed litmus paper, have given an
alkaline reaction, while the more recent determinations, for which
phenolphthalein has been employed, have shown that its reaction is
acid. Its tendency in either direction, however, is so slight that it is
really of very little importance.
Physicochemical researches have shown that the acidity or alkalinity of a fluid
is dependent upon its content in hydrogen ions (+) and hydroxyl ions ( — ). This
impUes that acids are dissociated with a Uberation of H ions, while bodies which
give rise to OH ions, behave like alkalies. In illustration of this statement might be
mentioned the dissociation of HCl into H (+) and CI ( — ), and the dissociation of
NaOH into Na (+) and OH ( — ). Besides, the acidity or alkalinity of the aqueous
solutions of these substances is directly proportional to the number of H ions or
OH ions contained therein.
The number of OH ions contained in the blood and lymph has been determined
by an electrical process^ and has been found to be very small, and hence, as they do
not exceed the H ions, the reaction cannot be decidedly alkaline, nor can it be acid
for the same reason. The number of the H ions in the blood remains very constant,
presumably on account of the presence in the plasma of the salts of carbonic acid,
phosphoric acid and protein which are all very weak in their action. When acid
is added to the blood, it reacts with the carbonates and phosphates. Carbonic
acid and acid phosphates are produced which leave the body, in the first case,
4;hrough the lungs and, in the second, through the kidneys. The tendency,
therefore, is to establish a faint degree of alkalinity as quickly as possible.
Litmus paper gives-a distinct alkaline reaction, because litmus acid which is the
indicator in this particular case, unites with the Na of the NaHCOs present in the
blood, and leaves the carbon dioxid uncombined. The subsequent dissociation of
the Na and litmus acid enables the litmus acid to generate the blue color. Phenol-
phthalein is not sufficiently strong to cause such a displacement of the carbon
dioxid. For this reason, the titration methods cannot give accurate results
concerning the reaction of the blood, but solely regarding the amount of alkalies
available for titration.
In addition to such neutral salts as sodium and potassium chlorid and the
alkali salts of the proteins of the corpuscles and plasma, the blood also contains a
considerable quantity of sodium carbonate. This substance, however, cannot
give rise to a decided alkaline reaction, because it is continuously charged with the
carbon dioxid of the tissues. In this way, the sodium carbonate is retained in the
form of the bicarbonate, during the dissociation of which OH ions are not formed,
as is evident from the formula: NaHCOa = Na and HCO3.
Like other living tissues, blood is practically neutral in reaction and performs its
function best when only very faintly alkaline, but naturally, as it serves as the
reservoir for the products of metabolism, large amounts of carbon dioxid and other
acids are constantly added to it. Under normal conditions, however, any tendency
on its part toward an acid reaction is quickly counteracted in the manner indi-
cated. This property of the blood to neutralize acids without acquiring an acid
reaction to litmus, is designated as its total alkalinity.
Osmotic Pressure. — As the osmotic pressure is the chief regulatory
mechanism by means of which the water content of the tissues is
safeguarded, it constitutes one of the most important properties of the
blood. Obviously, the normal concentration and composition of the
1 Hober, Pfluger's Archiv, Ixxxi, 1900, 522; P. Franckel, ibid., xciv, 1903, 601;
Henderson, Am. Jour, of Physiol., xxi, 1908, 427, and Michaelis and Davidofif, Bioch.
Zeitschrift, xlvi, 1912, 131.
GENERAL CHARACTERISTICS OF THE BLOOD 165
cells can only be retained, if water and nutritive materials are made to
move into them, while their waste-products are made to enter the
lymph and blood. Osmotic streams are produced, the intensity of
which is directly proportional to the difference in the osmotic pressures
between the blood and the tissue-fluid. As these pressures are depen-
dent in turn upon differences in the concentration of the fluids just
mentioned, it is of greatest importance that these differences be
retained without allowing them to become too great. This condition,
however, is not attained without certain changes, because the body is
the frequent recipient of large quantities of water and salts and also
loses much water and other material through the secretions and
excretions.
The osmotic pressure of the blood is determined chiefly by its content in crystal-
loids, namely the inorganic salts, sugar, urea, and other substances. The pro-
teids, however, cannot be said to be without influence. The most convenient
method of measuring the osmotic pressure consists in a comparison of the freezing
point of the blood with that of water (value = A). A 0.1 molecular solution
depresses the freezing point of water 0.186°; and hence, if the depression which a
certain solution is capable of producing, amounts to 0.093°, its concentration
must be 0.05 molecular. Again, as the former possesses an osmotic pressure of
2.24 atmospheres at zero, the latter must exert a pressure of 1.12 atmospheres.
For ordinary purposes, therefore, the osmotic pressure of the blood may be meas-
ured in a simple manner by determining its freezing point-with an apparatus such as
has been described by Hartley.^ The freezing point of mammalian blood is about
—0.6° C, which figure implies that its osmotic pressure equals 0.6/1. 85 X 22.4 = 7.3
atmospheres. Under normal conditions only slight variations are observed, ^ the
values for human blood ranging between -0.52 and -0.60, those for the dog between
-0.55 and -0.64, and those for the rabbit between -0.55 and -0.62.
Curiously enough, some animals are well-protected against the
osmotic pressure of the medium in which they live. The bony fish,
for example, possess an osmotic pressure of their body fluids which,
in the salt water fish, is lower than that of the sea water and, in the
fresh water fish, higher than that of the fresh water. This protection
which must be ascribed to a peculiar impermeability to water of the
lining cells of the gill-plates, enables these animals to migrate. As a
typical example of this kind might be mentioned the salmon which
enters the fresh water during the spawning period without suffering
injury.
Electrical Conductivity.^ — This factor depends upon the amount of
salts present in the blood, because the passage of an electric current
necessitates the presence of dissociated ions. Moreover, as the con-
centration of the blood varies only within very narrow limits, its con-
ductivity must remain almost the same. It should be emphasized,
however, that the corpuscles do not permit the current to pass very
readily, because they tend to prevent the ions of the salts carrying the
^ Archives of Diagnosis, 1913.
2 Hamburger, Osmotischer Druck und Jbnenlehre, Wisbaden, 1902, 456;
Hober, Physik. Chemie der Zelle, 1902, 26; also see : Handb. der Physik. Chemie u.
Medizin by Koranyi u. Richter i, 1907, 338.
166 THE BLOOD
electric charges, from escaping from the plasma. For this reason, the
conductivity of the blood must be attributed largely to the plasma.
This is proven by the fact that clear plasma possesses a greater con-
ducting power than plasma to which corpuscles have been added. ^
Viscosity. — When a fluid traverses a straight tube of sufficient
length, its different constituents arrange themselves eventually paral-
lel to the long axis of the tube. It is also to be noted that the fluid
does not advance as a uniform whole, but unevenly, so that its central
core attains a very great speed, while its more external layers progress
with a velocity which steadily decreases from within outward. For
this reason, the layer next to the wall must remain perfectly stationary
provided, of course, that it moistens the internal surface of the tube.
In the second place, it should be noted that the individual molecules
of the fluid rub against one another, because as the elements in neigh-
boring layers move at different speeds, some of them must be brought
Fig. 96. — Friction of Blood.
E, external friction; J", internal friction.
in contact with one another, while others are separated from one
another. Hence, the movement of a fluid is associated first of all
with an external friction arising between its outermost layer and the
internal surface of the vessel wall, and secondly, with an internal or
intermolecular friction, which, as the name indicates, results between
the different bodies held in solution or suspension.
If several different fluids are forced through a narrow tube under
a constant pressure and temperature, the quantities obtained of each
during a given period of time, varies considerably. For example, if
glycerin, water and ether are used, the quantity of ether collected is
much larger than that of either water or glycerin. This difference in
the readiness with which liquids are capable of traversing a capillary
tube, is ascribed to differences in their internal friction. Quite simi-
larly, if blood and water are employed, the former displays a much
slower movement than the latter. As can readily be surmised, this
tardiness is dependent upon its greater content in solids. Fluids are
commonly described as ''thick" and *'thin," and clearly, the thinner the
fluid, the less must be its internal friction. But, besides these purely
quantitative differences, fluids also possess certain qualitative
peculiarities which impart to them either a ''sticky" or a "non-sticky"
character. The latter kind of fluid, very naturally, possesses a slighter
1 G. N. Stewart, C. Phys., xi, 1897, 332.
GENERAL CHARACTERISTICS OF THE BLOOD 167
internal friction, or viscosity. While frequently used as a synonym
for the general term of internal friction, the term viscosity should in
reality be restricted to that type of friction which has its origin in the
qualitative peculiarity of a fluid.
It has been shown by Burton-Opitz^ that the viscosity of the
blood differs greatly in different animals, but remains rather constant
in the same group of animals. When compared with distilled water
at 37° C.,2 the viscosity of human blood is found to be 5.1 times greater,
while that of dog's blood is 5.0 times greater. The coefficient for
cat's blood is 4.1, for rabbit's blood 3.1, and for the blood of the frog
and turtle 2.5. It is evident, therefore, that the viscosity increases with
the complexity of the blood, and thus, it may also be inferred that the
viscous resistance of the plasma or serum is very much less than that
of whole blood. In fact, it is possible to establish perfectly normal
degrees of viscosity by simply adding definite numbers of washed red
cells to clear serum.
The fact that the viscosity of the blood is subject to variations is
shown by the observation that warm baths decrease it, whereas cold
baths and exposure of the body to hot air increase it. It is also les-
sened by hemorrhage and the injection of small quantities of normal
saline solution. Arterial blood is less viscous than venous blood; and
hence, if a venous character is imparted to the fornier either by tempo-
rarily obstructing the trachea or by permitting the animal to inhale
carbon dioxid, its viscous resistance becomes greater than normal. In
dyspnea it is increased and also during ether and chloroform narcosis,
as well as after the administration of alcohol. It is diminished by
starvation and increased by feeding, more especially by the ingestion
of proteid material.^
1 Pfliiger's Archiv, Ixxxii, 1900; cxii, 1906; and cxix, 1908; also Jour, of Physiol.,
xxxii, 1904 and 1905; Amer. Jour, of Physiol, vii, 1902; and Jour. Exp. Med., viii,
1906.
2 The coefficient of the viscosity for distilled water at 37° C. has been determined
by Poiseuille (Ann. de Chem. et de Phys., Paris, 1843, Sec. 3, p. 7). Its value is
4700.
' For clinical purposes the viscosity of the blood is determined with the help
of a simple instrument, known as a viscosimeter. An instrument of this kind was
first devised by Burton-Opitz (1903). Modifications have been presented more
recently by Hirsch and Beck, Hess and Miinzer, and Bloch.
CHAPTER XV
THE CHEMICAL COMPOSITION OF THE BLOOD
The Composition of Whole Blood. ^ — It must be admitted that it
is almost impossible at the present time to obtain exact analytical
data regarding the composition of the blood on account of its tendency
to coagulate, and, because its composition varies not only in different
species, but also in animals of the same group. Besides, considerable
divergences may be encountered in one and the same animal, in accord-
ance with the location or functional importance of the vessels from
which the blood is withdrawn. Lastly, it is entirely probable that the
methods used at the present time are altogether too crude to allow
us to detect its more intricate chemical peculiarities.
Under ordinary conditions, human blood contains 77 to 82 per cent, of water,
and 18 to 23 per cent, of solids. The latter include 17.3 to 22.0 per cent, of organic
and 0.6 to 1.0 per cent, of inorganic material. Proteins and hemoglobin form by-
far the largest amount of the organic mass; 13 to 15 per cent, being the value for
hemoglobin alone. In the ox, sheep, goat, and rabbit the hemoglobin content is
lower than in man, while in the dog, horse, cat and pig it is equal to it. The
THE COMPOSITION OF DOG'S BLOOD
1000 Parts, by
weight, of blood
contain
1000 Parts, by
weight, of serum
contain
1000 Parts, by
weight, of corpus-
cles contain
810.050
923.980
644 . 260
189.950
76.020
355.750
133 . 400
327.520
39.680
60.140
9.918
1.090
1.820
1.298
0.709
2.155
2.052
1.699
2.568
0.631
1.051
0.759
1.221
0.088
0.054
0.016
0.110
3.675
4.263
2.821
0.251
0.226
0.289
0.641
1.573
0.062
0.113
0.052
0.040
0.071
2.935
4.023
1.352
0.809
0.242
1.635
0.576
0.080
1.298
Water
Solids
Hemoglobin
Protein
Sugar
Cholesterin
Lecithin
Fat
Fatty acids
Phosphoric acid: as nuclein
NazO
K2O
FeaOg
CaO
MgO
CI
P2O5
Inorganic :
P2O5
^ Oppenheimer Handb. der, Biochemie, Jena, 1909.
168
THE CHEMICAL COMPOSITION OF THE BLOOD
169
accompanying table shows the composition of dog's blood as determined by
Abderhalden. ^ In another table are given the values for the blood of the horse.
THE COMPOSITION OF HORSE'S BLOOD
1000 Parts of blood
1000 Parts of serum
1000 Parts of corpuscles
contain by weight
contain by weight
contain by weight
Water
749.020
Water
902.050
Water
613.150
Solids
250 . 980
Solids
97 . 950
Solids
386.840
Hemoglobin
Protein
166 900
Hemoglobin. . . .
315.080
69.700
Protein
84.240
Protein
56 . 780
Sugar
0.526
Sugar .
1.176
Sugar
Cholesterin. ......
0.346
Cholesterin
0.298
Cholesterin
0.388
Lecithin
2.913
Lecithin ,. .
1.720
Lecithin
3.973
Fat
0.611
Fat
1.300
Fat
Phosphoric acid as
Phosphoric acid
Phosphoric acid
nuclein
0.060
as nuclein
0.020
as nuclein . . .
0.095
Soda
2.091
Soda
4.434
Soda
Potash
2.738
Potash
0.263
Potash
4.935
Iron oxid
0.828
Iron oxid
Iron oxid
1.563
Lime
0.051
Lime ■. . .
0.1113
Lime
Magnesia
0.064
Magnesia
0.045
Magnesia
0.0809
Chlorin
2.785
Chlorin
3.726
Chlorin
1.949
Phosphoric acid . .
1.120
Phosphoric acid.
0.240
'Phosphoric acid
1.901
Inorganic phos-
' Inorganic phos-
Inorganic phos-
phoric acid
0.806 phoric acid . . .
0.0715
phoric acid . .
1.458
Sodium chlorid is the chief salt of the serum. It forms 60 per cent, of the ash,
while sodium carbonate constitutes about 30 per cent, of it. Traces of the chlo-
rids and phosphates of potassium, sodium and calcium are also present. The chief
salt of the corpuscles is potassium phosphate, while that of the plasma is sodium
chlorid. In fact, it has been stated that the latter is entirely wanting in the cor-
puscles of some animals. The potassium content of different corpuscles fluctuates
considerably. Chlorin exists in all types of blood, but in greater amounts in the
serum than in the corpuscles. lodin is found only in the serum, while iron appears
principally in the erythrocytes, but in small quantities also in the leukocytes.
Traces of manganese, lithium, copper, and lead have also been obtained.
Traces of fats, cholesterin, lecithin, dextrose, urea, and other nitrogenous
extractives are also present in the serum. The fats in the corpuscles average
0.6 per cent., but this figure may be decreased or increased by feeding. Thus, an
increase of ten times the normal value has been obtained by this means in geese,
while, in diabetic lipemia, as high a value as 18 per cent, has been found. The
fats circulate in the blood in very fine subdivision, the individual globules becom-
ing so numerous at times that a distinct oily or milky appearance is imparted to
the blood or to the serum derived from it.
Cholesterin and lecithin are found chiefly in the erythrocytes, nine-tenths of
the solids of these cells being formed by hemoglobin and one-tenth by the stroma.
In addition to these two substances, the stroma also embraces proteins and salts.
The amount of sugar in the blood varies between 0.1 and 0.15 per cent, and,
although somewhat independent of the character of the food ingested, may be
greatly increased by feeding. As has been pointed out by Claude Bernard, ^ sugar
1 Zeitschr. fur Physiol. Chemie, xxv, 1898, 88.
2 Lecons sur la diabete, Paris, 1877.
170 THE BLOOD
makes its appearance in the urine (glycosuria), when present in the blood in larger
amounts than 0.3 per cent.* Sugar is not a constituent of the corpuscles.
The urea content of the blood varies between 0.02 and 0.15 per cent. It
increases after the ingestion of meat and decreases during starvation. ^ In normal
human blood, von Jaksch,^ found this body in amounts of 0.05 to 0.06 per cent.
An augmented protein metabolism or a retarded elimination of urea leads to an
accumulation of these substances in the blood. Traces of ammonia are also present.
The quantity of lactic acid varies considerably; as much as 0.071 per cent, has
been found.
The Constituents of the Blood Plasma. — The liquid which serves
as the medium for the corpuscles, may be obtained by rapid centrifu-
galization, or by rendering the blood non-coagulable and permitting
the formed elements to settle. The supernatant portion of the blood
may be made to clot at any time by the addition of an agent possessing
the power of inciting coagulation. The clotting of the blood may be
said to be chiefly dependent upon the plasma, because the latter con-
tains all the substances essential for this process.
The plasma is yellowish in color, alkaline in reaction, and possesses
a specific gravity of about 1.026 to 1.029. Its composition per 1000
parts is as follows:
Water 902.90
Solids 97. 10
Proteins :
Fibrin 4. 05
Other proteins 78 . 84
Extractives (including fat) 5 . 66
Inorganic salts 8. 55
Sodium chlorid is most abundant in human blood plasma. It forms 60 to 90
per cent, of the total mineral matter. Schmidt gives the following table for each
1000 parts of plasma :
Mineral matter 8 . 550
Chlorin 3.640
SO, 0. 115
PjOs 0 . 191
Potassium 0. 323
Sodium 3.341
Calcium phosphate 0 . 311
Magnesium phosphate 0 . 222
In general, it may be said that plasma contains 10 per cent, of
solids of which 8 per cent, are in the form of proteins. The latter are
classified as fibrinogen, serum-globulin, paraglobulin and serum-
albumin. Albumoses or peptones are not present. Inasmuch as the
plasma of coagulating blood separates into fibrin and serum, the pro-
teins contained therein, may be divided into those apportioned to the
fibrin and those contained in the serum. Among the former we have
fibrinogen, thrombogen, and kinase. The serum embraces proteins,
^ E. L. Scott, Am. Jour, of Physiol., xxxiv, 1914, 271. (Literature.)
« Sch6ndorff, Pfluger's Archiv, liv, 1893, and Ixiii, 1896, 192.
» Festschrift fur v. Leyden, i, 1901.
THE CHEMICAL COMPOSITION OF THE BLOOD 171
extractives, and salts. The first of these embrace serum-globuUn,
serum-albumin, fibrin-ferment and nucleoprotein.
Blood Serum. — The serum is a sticky liquid, the specific gravity
of which varies between 1.027 and 1.032; its average value is 1.028.
Toward litmus it exhibits an alkaline reaction which is somewhat
greater than that of the plasma. Its color is faintly yellow, shading
into green. While clear under ordinary conditions, it may become
cloudy or milky in consequence of its admixture with varying amounts
of fat. The yellowish coloring material ordinarily present in fats, to
which the appearance of the serum is due, is generally called lutein
or lipochrome.
The quantity of the cellular material ordinarily found in serum, varies between
7.0 and 9.7 per cent. The bulk of the latter is formed by proteins in amounts of
5.5 to 8.4 per cent. The average depression of the freezing point of blood-serum is
given as A = -0.526°, as against that of whole blood which is A = -0.537°. The
following analytical data pertaining to serum have been supplied by Abderhalden :
Water 913 . 64
Solids 86.36
Protein 72.50
Sugar 1.05
Cholesterol. 1 .238
Lecithin 1 . 675
Fat : 0.926
Phosphoric acid as nuclein 0 . 0133
Soda 4.312
Potash 0.255
Iron oxid '.
Lime 0.1194
Magnesia 0 . 0446
Chlorin 3.69
Phosphoric acid 0 . 244
Inorganic phosphoric acid 0 . 0847
The Proteins of the Blood. — Fibrinogen, the mother-substance of
fibrin, is associated with serum-globulin and serum-albumin (page 216).
Serum-globulin is also called paraglobulin, serum-casein, or fibrino-
plastic substance. Besides being present in plasma and serum, it is
also found in lymph, transudates and exudates, as well as in the
corpuscles and several tissues of the body. The probabihty is that
serum-globulin is not a separate substance, but consists of several
protein bodies. Their complete separation, however, has not been
effected as yet. Hammarsten states that its average composition is :
C 52.71, H 7.01, N 1.585, S 1.11, O 23.02. According to Schmiede-
berg, its molecular composition is: Cii7Hi82N3oS038+3^H20. The
blood of different animals contains different amounts of this substance ;
for example, that of the rabbit 1.78 per cent., that of man 3.10 per
cent., and that of the horse 4.56 per cent. Serum is said to contain a
larger amount of this substance than plasma, the surplus being derived
from disintegrated leukocytes.
The globulins are usually obtained by half-saturation of the serum
172 THE BLOOD
with ammonium sulphate. They may also be gotten by dialysis with
distilled water. As globulin is insoluble in distilled water, it is pre-
cipitated. The latter method yields a smaller quantity than the for-
mer, and hence, two types of globulins have really been isolated,
namely euglobulin, and pseudoglobulin. The latter is the one that is
thrown down during half-saturation with ammonium sulphate.
Serum-albumin is found in plasma, serum, lymph, transudates,
exudates, and other animal fluids. It remains in the serum after
half-saturation with ammonium sulphate, but is precipitated by com-
plete saturation. It may also be prepared in crystalline form by the
method of Gtirber. From neutral or acid solutions it is isolated by
heating to 70°-75° C; in fact, it has been stated that three heat pre-
cipitations occur, namely one at 73°, one at 77° and one at 84°C.
This fact has been thought to prove that serum-albumin is a mixture
of three proteins. However that may be, it may be assumed for the
present that two protein bodies enter into its formation. According
to Michel,! its composition is: C 53.08, H 7.10, N 15.93, S 1.90,
O 21.96, and its molecular composition, as represented by Schmiede-
berg:^ C78Hi22N2oS024- The amount of this body ordinarily found in
the blood of the horse equals 3.67 per cent, and in human blood 4.52
per cent.
Thromhogen, or inactive thrombin, is prepared by adding an excess
of alcohol to serurn. A precipitation of the proteins and thrombin
results; the latter, however, is not so easily coagulated by alcohol
as the proteins.
The extractives embrace nitrogenous and non-nitrogenous material.
The former consists of urea and small quantities of uric acid, creatin,
creatinin, xanthin, hypoxanthin, and amino acids. The latter com-
prises fats, soaps, cholesterin, and sugar.
CHAPTER XVI
THE RED BLOOD CORPUSCLES
A. PHYSICAL CHARACTERISTICS
Shape, Size and Color. — With the exception of the camelidse, the
mammalian red corpuscle,^ when placed flat upon the slide, possesses
the shape of a circular platelet, and, when turned on edge, that of a
1 Verh. der phys. med. Gesellsch. zu Wiirzburg, xxix. No. 3.
2 Archiv ftir Exp. Path, und Pharm., xxxix, 1897, 1.
2 The red corpuscles of the frog were first observed by Swammerdam in 1658
and those of the mammal by Malpighi in 1661. They were first described by
van Loewenboek in 1673.
THE RED BLOOD CORPUSCLES
173
dumb-bell.^ Its thin central area is surrounded by a thick marginal
zone. When the latter is brought into focus, the center appears dark,
because its focal point lies at this time at a lower level. When cir-
FiG. 97a. — Human Red Corpus-
cle Placed Flat and on Edge.
Fig. 975. — Red Corpuscle of Frog
Placed Flat and on Edge.
culating through the vascular channels, the fully developed red cell
does not contain a nucleus; in fact, the loss of this constituent very
shortly after the cell has entered the blood-vessels, is generally con-
Fig. 98. — Area of Capillaries.
Showing tubules of different diameter, some so small that the red cells cannot enter
at all and others through which they can only pass by assuming an elliptical outline.
sidered as the cause of the central depression. In the camels, the red
corpuscle presents an elliptical outline, but resembles the preceding
1 Weidenreich, Lewis, Radasch and others hold that the red corpuscles assume
this shape only in shed blood and are cup-shaped or bell-shaped while circulating.
This change is said to be caused by cooling and evaporation. Jordan, who has
reinvestigated this subject more recently, states that a freely moving corpuscle
always shows a central depression. (Proc. Soc. Exp. Biol, and Med., xii, 1915.)
Viewed from the side, however, these biconcave discs give the impression of shallow
oups, because the pressure tends at times to cause them to bulge out centrally.
174
THE BLOOD
type in all other particulars. In other vertebrates/ it is elHpticaP
and contains a very conspicuous nucleus. It is soft and very elastic,
peculiarities which enable it to traverse capillary channels of smaller
diameter than its own. In these minute tubules the otherwise circular
discs often assume a shape approximating the elliptical.
The size of the red cell differs greatly in different animals, but
varies only very slightly in animals of the same group. In man it
measures 7.5/x^ in diameter (7.1 to 7.8/x) and l.Gju in thickness. Its
volume equals 0.000,000,072 c. mm. Variations in size between 6.5
and 9.3ju have been noted even in normal persons. Elliptical cor-
puscles have been found in a few individuals. The following compila-
tion will show that red corpuscles are in existence which are either
very much smaller or larger than the human. ^
Elliptical corpuscles
Lama 7 . 5 X 4 . 2^
Pigeon 14.7 X 6.5/x
Frog 23.0 X 16.3/x
Triton 29.5 X 19. 5m
Proteus 58.2 X 35. 6^
Amphiuma 77.0 X 58.0/*
Circular corpuscles
Musk-deer. 2 . 3m
Goat.. 4.25m
Sheep 5 . Om
Horse 5 . 5m
Pig 6.0m
Cat 6.2m
Rabbit 7.1m
Dog 7.2m
Man 7.5m
Ox 8.0m
Elephant 9 . 4m
If observed under the microscope, a single mammalian red corpus-
cle possesses a yellowish, or even green-
ish color, but if many of them are
grouped together, a distinct sensation of
red is obtained. In shed blood, these
bodies frequently arrange themselves in
the form of rolls, but since these rouleaux
formations are not found in circulating
blood, and rarely in defibrinated blood,
it is assumed that their surfaces must
first be rendered sticky before this ag-
glutination can take place. The agent
which produces this change, must be
derived from the fibrin or its precursor,
because the agglutination may be dimin-
ished or prevented altogether by adding normal saline solution, or
some other non-destructive medium to the blood.
* In lamprey eels the corpuscles are round, biconcave and nucleated.
* Not oval, because this term implies that one of the ends is more pointed
than the other.
' 1m (micron) equals 0.001 mm.
* Monassein, Dissertation, Berlin, 1872; and Schilling — Torgau, Folia hema-
tologica, i, 1912.
Fig. 99. — Circular Red Cor-
puscles Drawn to Scale.
M, musk-deer; G, goat; P, pig; Afi
man; 0, ox; E, elephant.
«
THE RED BLOOD CORPUSCLES
175
Variations in Shape. — Although it is claimed by Schultze^ that the
erythrocytes of the chick possess active motion, it seems that the red
blood cells of the mammals remain perfectly passive as long as the
fluid in which they are kept, retains its normal character. But
their form may be changed at any time by varying the temperature or
the carbon dioxid content of the medium, or by permitting an elec-
trical current to pass through them. Most generally, they react to
Fig. 100. — Human Blood-Corpuscles Arranged in Rouleaux. (Funke.)
these changes by increasing their volume. Moreover, Cavazzani
has shown that if blood is collected in an isotonic or hypotonic solution
of sodium chlorid to which potassium ferrocyanid has been added, the
red corpuscles of man and other animals send out delicate protoplasmic
processes, the rapid motion of which enables them to move about
from place to place. If a drop of cocain hydrochlorid is then added to
this solution, these filaments are retracted within a few moments.
Fig. 101. — PoiKiLOCYTES.
1 and 2, Mulberry shape; 3, prickly pear shape; 4, shadow.
Changes in the size of the red corpuscles are frequently observed
in disease. Cells possessing a diameter of about 6ju are found in
anemia, while cells with a diameter of lO/x and over are encountered in
persons suffering from pernicious anemia, leukemia, chlorosis or cir-
rhosis of the liver. The former are known as microcytes and the latter
as megalocytes or macrocytes. When both their size and shape are
1 Archiv fiir mikr. Anat., i, 18.
176
THE BLOOD
altered, they are designated as poikilocytes. The latter usually
exhibit pointed projections, like burs, or surfaces beset with rounded
elevations.
Number of the Red Blood Corpuscles. — While the method for the
counting of the red cells, devised by Vierordt^ and Welker^ has been
modified by different authors, the principle involved in it has remained
the same. The instrument most commonly used to-day is the hemo-
\^
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Fig. 102. — Hemocytometer. (Thoma-Zeiss.)
A, pipet; B, glass bead; C, counting chamber seen from side; D, counting chamber
seen from above; E, field as seen under microscope.
cytometer of Thoma-Zeiss.^ It consists of a pipet (A), originally
devised by Potain, and a counting chamber (C). Having thoroughly
cleansed the skin upon the tip of the finger or upon the lobule of the ear,
a small wound is made with a lanzette or needle. A portion of the
blood collected upon the integument is then quickly drawn into the
1 Arch, fiir physiol. Heilkunde, xiii, 1854, 259.
^ Prager Viertalj. fiir prakt. Heilkunde, iv, 1854,
2 See Abb6: Sitzungb. d. Jenaischen Gesellsch. f. Med., 1878; also see: Biirker,
Handworterb. der Naturw., Jena, 1912; and Hayem, in Sahli's Lehrb. d. klin.
Untersuchungsmethoden, Leipzig, 1909.
THE RED BLOOD CORPUSCLES 177
pipet until either point 0.5 or 1 has been reached. The end of the
pipet is then dried with filter paper and immediately dipped into
an isotonic solution^ which is intended to dilute the blood previously-
drawn in. The tube is then filled to point 101 above its bulbular
enlargement. Upon its withdrawal from the fluid it is again dried
with filter paper and gently shaken until the blood and the solution
have become thoroughly mixed. The marks upon the tube signify that
if the blood is drawn in as far as point 1 and the diluting fluid as far as
point 101, the original sample of blood is diluted 100 times, whereas,
if the marks 0.5 and 101 are used, a dilution of 200 times is the result.
Having thoroughly mixed the contents of the pipet, a drop or two
are permitted to escape from the tube without being used. The next
droplet, however, is collected upon the stage of the counting chamber
(C) and in such a manner that it does not overflow into the space
next to it. The entire compartment is then closed by placing a cover-
glass over it. The surface of the stage is exactly 0.1 mm. below the-
lower surface of the cover-glass. A series of 20 squares are engraved
upon the former, the sides of which measure 3>^o i^i^- ^^ length, and
hence, each possesses an area of J^oo sq. mm. and a capacity of
Jioo X 0.1 = J^ooo cu. mm. Having counted the number of cor-
puscles in many of these small squares, a fair average value is
obtained from these figures. The value so obtained is then multi-
plied by the degree of dilution and by 4000.
It is only natural to suppose that the size and number of the red
corpuscles must preserve an indirect relationship to one another.
That this is true, is borne out by the following table^ which should be
compared with the one containing the data pertaining to the size of
the different red cells.
1 Various preserving solutions have been recommended, for example :
(a) Hayem's fluid:
Hydrarg. bichlor 0.5 gram,
Sodii sulphat 5.0 grams.
Sodii chlorid 2.0 grams.
Aq. distill 200. 0 c.c.
(&) Gower's fluid:
Sodii. sulphat. gm 104 .0
Acid acetic 5i
Aq. destill g. s. ad. 5iv
(c) Toisson's fluid:
Aq. destill 160. 0 c.c.
Glycerin 30 . 0 c.c.
Sodii sulphat 8.0 grams.
Sodii chlorid 1.0 gram.
Methyl violet 0.025 gram.
2 Storch, Unters. liber den Blutkorperchengehalt des Blutes, etc. Disserta-
tion, Bern, 1901; Musser and Krumbhaar, Folia hematologica, xviii, 1914, 576,
and Wells and Sutton, Am. Jour, of Physiol., xxxix, 1915, 31.
12
178 THE BLOOD
Mill, per c.mm.
Goat 14-19
Lama 13-13 . 2
Sheep 10.3
Cat 9.1
Horse 7.8
Monkeys 6.2
Rabbit 6.8
Dog 6.7
Birds 2.3
Fish (bony) 1.2
Reptiha 0.5-1.6
Amphibia : frog 0.5
Salamander 0 . 09
The average number of red corpuscles in one cubic millimeter of
human blood is given as 5,000,000; in woman, however, their number
is somewhat smaller, namely, about 4,500,000. In infants a higher
•count is usually obtained than in adults. During the first weeks it
averages about 5,580,000, during the first and second years 5,680,000,
and from the second to the sixth year seldom under 5,900,000. Since
the volume of a red cell measures 0.000000072 cu. mm. and its surface
0.000128 sq. mm., the total surface of the red blood corpuscles present
in 1.0 cu. mm. of blood, must equal 640 sq. mm. Moreover, if the
blood contained in a mammal is calculated at Jf 3 of its body weight, an
individual weighing 70 kg. must contain about 5 kg. of blood. The
body as a whole, therefore, gives lodgment to about 25,000,000,000,000
red cells, possessing a total surface of 3200 sq. mm. which equals an area
1500 times greater than that of the surface of the body.^ These figures
clearly betray the surprisingly large size of the ''breathing surface'*
which the red corpuslces present to the air in the lungs or to the cells
of the tissues.
Variations in the Number of the Red Blood Corpuscles. — While
the value of 5,000,000 cells to the cubic millimeter of blood remains
fairly constant under normal conditions, it is subject to certain minor
fluctuations. Ordinary physical influences, for instance, possess
the tendency of diverting the corpuscles into the larger vascular chan-
nels, while the blood in the peripheral vessels contains them in some-
what smaller numbers. This fact should be taken into account when-
ever these bodies are counted in accordance with the method previously
described. It is also to be remembered that a diminution in the quan-
tity of the body-fluids may result at any time in consequence of a
lessened intake of water, or on account of a more copious discharge of
it in the sweat, stools or transudations. In either case, the number of
corpuscles per unit of blood must become greater. The reverse result
is obtained if large quantities of water are taken in, or if smaller
amounts are excreted. In early fetal life the red cells are fewer in
^ Recent investigations have shown that in man the total amount of blood
should be calculated at one-twentieth of the body weight. The total surface of
the red cells, therefore, measures 1700 sq. mm.
THE RED BLOOD CORPUSCLES 179
number; namely, only 0.5 to 1.0 million per cubic millimeter. Their
number increases later on so that infants present higher values than
the average for adults. Pregnancy causes a slight increase and men-
struation a decrease. Physical exertion at low altitudes causes a con-
centration of the blood which Schneider and Havens^ attribute to the
sudden passage into the blood of a large number of red corpuscles
which have been lying dormant in the body, chiefly in the splanchnic
area. Scott^ believes this concentration to be effected by a passage
of fluid from the blood to the tissues, in consequence of the higher
blood-pressure coincident with muscular exercise. Massage,, and
especially massage of the abdomen, produces a similar effect for the
same reason. During hibernation the number of the red corpuscles
is not materially changed. Neither is the specific gravity of the blood,
whereas the number of the white cells is decreased to about one-half
of normal.^
A very interesting phenomenon is the increase in the number of
the erythrocytes, resulting whenever high altitudes are attained.
Bert^ and Viault,^ who first studied this change, have found that the in-
habitants of low lands show this increase whenever they ascend a high
mountain and that persons permanently residing in a mountainous
country, constantly give counts above normal. It is then not unusual
to obtain increases to as much as 7,000,000 or 8,000,000 per cu. mm.,
but in most cases the maximal value is not attained until about twenty-
four hours have been spent at the high altitude. According to Kemp,^
the number of the platelets is also increased, but the leukocyte count
remains the same.
Two possibilities present themselves, namely, it is conceivable
that this increase is dependent upon a greater formation of red cells
by the hematopoietic tissues or secondly, that it is due to changes in
the quantity of the blood plasma. The second view, originally ex-
pressed by Grawitz,^ embodies the possibility that the sojourn in
mountainous regions leads to a concentration of the blood, because
the greater respiratory activity coincident with muscular exertion and
sweating, occasions a loss of a considerable quantity of water.
Gaule, Hallion and Tissot, however, have shown that an increase in
the number of the red cells also appears during balloon ascensions,
and hence, muscular efforts cannot be considered as the cause of this
phenomenon. Abderhalden^ and Bunge,^ who also believe that the
increase is only an apparent one, assert that the blood is really made
1 Am. Jour, of Physiol, xxxvi, 1905, 239.
2 Ibid., xliv, 1917, 298.
2 Rasmussen, Ibid., xli, 1916, 465.
* La pression barometrique, Paris, 1878, or Compt. rend., xciv, 1882, 805.
5 Compt. rend., cxi, 1890, 917.
« Am. Jour, of Physiol., x, 1904, 34.
^ Berliner khn. Wochenschr., xxxii, 1895, 743.
8 Zeitschr. fur Biol, xliii, 1902, 423.
9 Verhandl des Kongr. f. innere Med., xiii, 1895, 192.
180 THE BLOOD
''plasma-poor," because a considerable portion of its fluid mass
is transferred into the perivascular lymph-spaces. ^
The first view, that the increase is real and is caused by a greater
formation of red cells, possesses the advantage of being more closely
in keeping with physiological facts, but it must be admitted that it
has not been possible so far to ascertain the stimulus which gives rise
to the greater activity of the corpuscle-forming organs. Indeed, it
is entirely probable that several factors unite in bringing this change
about. 2 The most interesting of these is the influence which the
barometric pressure exerts upon the interchange of the gases in the
lungs. As the high altitude is reached, the tension of the gases is dimin-
ished and particularly, the pressure which ordinarily forces the oxygen
to combine with the hemoglobin of the red corpuscles. The oxygen
poverty of the tissues resulting in consequence of the deficiency in the
tension of this gas, eventually serves as a stimulus to intensify the
production of these corpuscles. Thus, while each cell is charged with
a somewhat smaller quantity of oxygen than normal, the total amount
of this gas in the body must remain practically the same, because the
number of its carriers has been augmented. In substantiation of this
explanation, it might be mentioned that Dallwig, Kolls and Loeven-
hart^ have succeeded in demonstrating that considerable increases
in the number of the erythrocytes also occur in dogs, rabbits, and cats,
when kept in an atmosphere of low oxygen concentration even at
atmospheric pressure and under conditions which do not require
physical efforts.
A decrease in the number of the red corpuscles is frequently encountered in
disease (oligocythemia). Anemias from all causes are characterized by a change
of this kind, and clearly, this decrease must be due either to a greater destruction
or to a lessened formation of these cells, or both. A very pronounced diminution
in the number of the erythrocytes is frequently observed in pernicious anemia,
counts of 300,000 to 400,000 per cu. mm, being not uncommon. Great numbers of
red corpuscles are lost in hemorrhage, which it may take days and weeks to replace.
Naturally, an acute hemorrhagic anemia, or, more correctly speaking, an oligemia,
is followed by a greater production of red cells, but the activity of the corpuscle-
forming organs has its natural limits and is therefore relatively slow. The fluid
parts of the blood, on the other hand, are replaced very quickly, this end being
attained by a lessened discharge of fluid from the body and a transfer of lymph
into the chief circulatory system. In this way, an initial hydremia is frequently
developed. Furthermore, even if the number of the red cells has again risen
to normal, their hemoglobin content may remain below normal for some time
to come. A chlorotic condition of a temporary kind may thus be developed.
Marked increases in the number of the red cells are noted at times in active patho-
logical conditions, but the hemoglobin content need not be augmented in a corre-
sponding measure. This condition in which counts of 7,000,000 to 8,000,000 per
cu. mm. are encountered, is designated as polycythemia.
^ The assumption that changes in barometric pressure incite variations in
the capacity of the counting chamber, has been disproved by Biirker.
2 As additional exciting causes are regarded changes in temperature and cuta-
neous stimuli (Schumburg and Zuntz; Pfliiger's Archiv, Ixiii, 1896, 461).
^ Am. Jour, of Physiol., xxxix, 1915, 77.
THE RED BLOOD CORPUSCLES 181
B. CHEMICAL PROPERTIES
The Composition of the Red Corpuscles. — Different varieties of
red cells contain between 57 and 65 per cent, of water and between
35 and 43 per cent, of solids. It may be said in general that they
yield 65 per cent, of water and 35 per cent, of solids. The latter con-
sist of hemoglobin, 33 per cent., protein, 0.9 per cent., cholesterin and
lecithin, 0.46 per cent., and inorganic salts, such as potassium phos-
phate and chlorid and sodium chlorid, 1.4 per cent. Hence, the hemo-
globin forms by far the largest portion of the total solids, namely,
94 per cent.
Each ^ red corpuscle is composed of a reticular network, or stroma,
and a fluid or semifluid portion. The former appears as a delicate
spongy and colorless ground substance, in the spaces of which is
deposited the hemoglobin, together with a small quantity of water and
salts. The hemoglobin exists here in a peculiar amorphous condition
and is not held in solution, nor is it deposited in crystalline form.
Separation of the Stroma and Hemoglobin. Hemolysis. — The
procedures usually employed to isolate the hemoglobin are quite
simple. The blood may be frozen and thawed several times in suc-
cession, or it may be diluted with a small quantity of distilled water.
It also suffices to add to it a small amount of ether, chloroform, solanin,
saponin, alkalies or bile acids. Of special interest are those bodies
which are normally present in some animals, and plants and which,
when brought in contact with blood, cause a destruction of the red
cells and a liberation of their hemoglobin. This process is known as
hemolysis, while the agents concerned in it are designated as hemoly-
sins. These bodies are found in the products of bacteria, as well as in
the venoms and irritating secretions of snakes, toads, bees, and spiders.
They also exist in the normal blood-sera of the higher animals in which
they play an important part in the production of immunity. The
hemoglobin is liberated by them either by causing the corpuscles to
rupture or by abstracting this substance from them without marked
injury to their framework. The former change may be produced by
placing the corpuscles in water, and the latter by adding such solvents
as ether or chloroform to the medium in which they are kept. A very
rapid, almost explosive, destruction is had if they are brought in
contact with bile. When subjected to any one of these agents, the
blood gradually assumes a much darker color and becomes more
transparent, this change in its appearance being indicative of the
escape of the hemoglobin and its free dissemination through the plasma.
The stromatic remnants of the corpuscles are then designated as
"shadows," and the blood as a whole as "laked" blood.
In order to retain the volume and shape of the red cells for a long period of time,
it is necessary to place them in a medium which is absolutely isotonic to them, or,
in other words, in a solution which possesses the same concentration and, therefore,
also the same osmotic pressure as the blood-serum. The fluid most commonly
182 THE BLOOD
employed for this purpose is a solution of sodium chlorid, the strength of which
must be varied somewhat in accordance with the type of the red cell to be pre-
served. Thus, it is best to employ it in strengths of 0.85 to 0.9 percent, for the
corpuscles of human blood and in a strength of 0.8 per cent, for those of ox blood;
in fact, the erythrocytes of the frog require an even weaker solution,' namely, 0.70
to 0.75 per cent. It should not be forgotten, however, that it is difficult to keep a
medium of this kind in a perfectly isotonic condition for any length of time, be-
cause a certain loss of water by evaporation cannot be avoided, and naturally, as
the solution becomes more concentrated, it incites such alterations as are usually
produced by hypertonic solutions of any kind.
For purposes of transfusion a 0.75 per cent, solution of sodium chlorid, com-
monly designated as ''normal saline," is generally made use of. More favorable
results may be obtained at times by employing the so-called Ringer's solution
which contains the chlorids of sodium, potassium and calcium in the following
proportions :
Sodium chlorid 0.9 per cent.
Calcium chlorid 0 . 026 per cent.
Potassium chlorid ■ 0 . 03 per cent.
Under normal conditions, therefore, the blood plasma and the corpuscles are
in a state of osmotic equilibrium, and while water passes into them constantly,
an equal amount of the latter is again discharged into the plasma. In this way,
these two neighboring osmotic entities are enabled to retain the same concentration,
and hence, a destruction of the red cells cannot take place. But, naturally, if the
concentration of the plasma is either increased or decreased, the osmotic equilib-
rium is immediately disturbed. If increased, the plasma acts as a hypertonic
solution and if decreased, as a hypotonic solution. In either case, the change in its
concentration insures an alteration in its osmotic pressure, which immediately
gives origin to certain interchanges between it and the contents of the corpuscle.
Obviously, the purpose of this transfer is to reestablish an osmotic balance. Thus,
if the medium is hypertonic, molecules of water will continue to leave the corpus-
cles, until the latter eventually become greatly reduced in size and uneven in outline.
Conversely, a hypotonic medium will cause water to pass into the corpuscles
until they become much distended and finally rupture, giving rise to a great variety
of abnormal shapes.
The red cells are regarded by some authors as small bags containing a concen-
trated solution of hemoglobin. The latter is said to diffuse out whenever the
enveloping membrane is changed in such a way that it becomes more permeable
to this substance. It must be doubted, however, that this explanation is correct,
because the red corpuscles do not possess a true cellular membrane enclosing a free
space, and because the hemoglobin actually forms an intricate part of the stroma.
Hence, the hemoglobin must first be separated from the latter, either by mechan-
ical or chemical means, before its escape from the cell can be effected. Obviously,
a red cell cannot be compared with a receptacle of water which, on breaking,
discharges its contents in all directions.
In order to separate the stroma from the hemoglobin, it is best either to defibri-
nate the sample of blood or to render it non-coagulable by the addition of potassium
oxalate. It is then placed in the centrifuge. When completely separated, the
corpuscular elements are washed repeatedly in 10 to 20 volumes of a 1 to 2 per
cent, saline solution until free from serum. On addition of 5 to 6 volumes of dis-
tilled water containing a small amount of ether, ^ the corpuscles swell up and dis-
charge their hemoglobin into the surrounding medium. Centrifugalization is
resorted to in order to accelerate the deposition of the leukocytes. The supernatant
fluid is treated with a 1.0 per cent, solution of KHSO4 until it acquires the same
1 Wooldridge, Archiv f . Anat. u. Physiol., 1881, 387.
THE RED BLOOD CORPUSCLES 183
density and appearance as the original sample of blood. The stroma is then
thrown down by centrifugalization and may be collected upon a filter and quickly
washed with distilled water. When free from hemoglobin, the stroma possesses
poisonous properties, and gives rise to intravascular clotting.
The constituents of the stroma are lecithin, cholesterin, nucleo-
albumin and a globulin. The stroma protein forms about 4 per cent,
of the total solids of the red cell and is easily dissolved by dilute
alkalies although insoluble in dilute acids.
Great importance is attached to the presence in the red corpuscles
of lecithin and cholesterin which substances constitute as much as
30 per cent, of the dry weight of the stroma. Whether these bodies
are held solely in the surface layers or are contained within the meshes
of the stroma is still doubtful, but it has been ascertained that they
determine the permeability of the corpuscle and are, therefore, directly
responsible for the osmotic interchanges between it and the plasma.
The red cells are completely impermeable to the ordinary varieties of
sugar, mammite and arabite, while water, acids, alkalies, ether, esters,
urea and bile salts are freely admitted. Amino-acids do not enter
very readily.
The Constituents of Hemoglobin. — The normal circulating blood
contains the hemoglobin either in the form of oxyhemoglobin or ''re-
duced" hemoglobin. The latter is generally called hemoglobin,
because the term "reduced" is prone to convey the erroneous impres-
sion that it has been formed by a true chemical decomposition. As the
name indicates, oxyhemoglobin is more fully charged with oxygen and
is found, therefore, in the arterial blood, while hemoglobin proper is
the normal constituent of the blood returned from the tissues.
As the function of hemoglobin is to serve as a storehouse and
carrier of oxygen, it may be inferred that it is widely distributed
throughout the animal kingdom. It really plays the part of the chloro-
phyl of the plants. It is of interest to note that it is not always
confined to the blood, but is also found in several tissues, for example,
in the striated and cardiac muscle cells of mammals, and in several
other tissues of the lower animals. It should also be remembered that
it is not always held in the corpuscular elements but may be dissolved
in the plasma. The ordinary coloring pigments, such as exist in the
hair, choroid coat of the eye, and other structures, are not allied to
hemoglobin, at least not functionally.
Hemoglobin belongs to the compound proteids. When decomposed in the
absence of oxygen, it yields a protein called globin and a coloring matter designated
as hemochromogen. The latter forms about 4 per cent, of the molecule. It
contains iron and may be oxidized into a more stable body, known as hematin.
The latter can also be obtained in a more direct manner by subjecting the hemo-
globin to the action of acids or alkalies.
The composition of oxyhemoglobin differs somewhat in different animals, a
fact which suggests that it is subject to flight modifications. The following
analyses fully illustrate this point:
184
THE BLOOD
Horse
Ox
Pig
Dog
Squirrel
Hen
c
54.87
6.97
17.31
0.65
0.47
19.73
(Kossel)
54.66
7.25
17.70
0.44
0.40
19.54
54.71
7.38
17.43
0.47
0.39
19 60
53.85
7.32
16.17
0.39
0.43
21.84
54.09
7.39
16.09
0.40
0.59
21.44
52.87
H
7.19
N
16 45
S.
0.85
Fe
0.33
0
22.50
(Hiifner)
(Hoppe-
Seyler)
.\,^>
According to Jaquet, the molecular formula of hemoglobin is C758H1203N196-
S3Fe02i8, with a molecular weight of 16.66 grams. Its molecule, therefore, is
extremely large and complex, a peculiarity which Bunge explains by saying that,
as iron is eight times as heavy as water, it must be united with a very large organic
molecule, otherwise it could not be floated by the blood. The p gment substance
hematin, on the other hand, possesses a relatively simple constitution, as may be
gathered from the following formula of Kiister, which reads: C34H34N4Fe05.
The Preparation and Quantity of Oxyhemoglobin. — If blood is
laked and is then allowed to stand, the dissolved hemoglobin is de-
posited in time in the form of crystals. It is to be noted, however, that
Fig. 103. — Hemoglobin Crystals. {After O. Funke.)
the speed with which they are formed varies considerably. Thus,
they appear very rapidly in the laked blood of the horse, dog and
guinea-pig, and especially if the sample of blood is cooled to - 10° C,
or if a small quantity of alcohol is added to it. The blood of the pig,
ox, or man yields them with much greater difficulty. Better results
may be obtained if the sample of blood is first diluted with an equal
quantity of a saturated solution of ammonium sulphate. The pre-
cipitate, which consists of globulins, is then filtered off and the filtrate
permitted to stand. The methods most commonly employed for
<
THE RED BLOOD CORPUSCLES 185
the isolation of these crystals, are those described by Hoppe-Seyler
as well as by Reichert and Brown. ^
The crystals so obtained are red in color and transparent. Although their size
is generally microscopic, they may attain a length of 2 to 3 mm. They appear
as prisms, platelets, tetrahedra and needles of the rhombic system. From the
blood of squirrels six-sided plates of the hexagonal system are usually obtained;
moreover, it is possible to change these into rhombic prisms and tetrahedra by the
process of recrystallization. They may be heated to 110-115° C. without decom-
position, but when subjected to a temperature of about 160° C, a reduction results,
the ash yielded during this process being composed largely of oxid of iron. They
are soluble, but not in an equal measure, because those most difficult to produce
are most readily dissolved. Very dilute solutions of the carbonates of alkalies a e
the most efficient solvents. Hemoglobin is not easily dialy zed. It does not diffuse
through parchment membranes and shows a behavior similar to that of colloidal
bodies.
Reduced hemoglobin is more soluble than oxyhemoglobin. Its crystals are
not easily obtained. They are isomorphous to the corresponding crystals of
oxyhemoglobin and are darker in color and pleochromatic.
The hemoglobin content of the blood amounts to about 14 per cent, in man and
to 13 per cent, in woman. Thus, an individual weighing 70 kilos, contains about
2684 grams of blood and about 491 grams of hemoglobin. This amount is dis-
tributed among 25,000,000,000,000 red corpuscles which present a total surface of
about 3200 square meters. Moreover, as these bodies are usually well scattered
and traverse the capillaries almost "in single file,'' practically all of the hemo-
globin is made available for respiratory purposes. It is also of interest to note
that blood absorbs a much greater quantity of oxygen than water. Thus, while
100 c.c. of the latter take up only 0.7 c.c, 100 c.c. of human blood assimilate
18.5 c.c. of this gas. The amount of hemoglobin present in the blood of the fetus
or infants, is much greater than that found in the blood of adults.
Properties of the Compounds of Hemoglobin with Oxygen. — The
function of hemoglobin, to distribute the oxygen to the different tissues
of the body, depends upon its ability to unite with perfectly definite
amounts of this gas. This union takes place in the lungs, where this
substance is exposed to the full pressure of the oxygen of the atmos-
pheric air. Having absorbed its quota of the gas, it is moved onward
to the distant tissues. Here the oxygen is required for purposes of oxi-
dation, and hence, inasmuch as it is present in smaller amounts in the
cells than in the blood, it must be held under a greater partial pressure
in the blood-vessel than in the tissue. As a direct result of this differ-
ence in its partial pressure, it separates from the hemoglobin and enters
the cells. The oxyhemoglobin is thus converted into its deoxidized
or reduced variety. This property of the hemoglobin to assimilate
and to release a part of its oxygen, forms the basis of the respiratory
activity of the blood.
The compound of hemoglobin and oxygen, known as oxyhemoglobin, can also
be formed and destroyed outside of the body. Thus, if arterial blood is exposed to
a vacuum, it f rothes and its color changes to bluish red in accordance with the
amount of oxygen withdrawn from it. Quite similarly, if venous blood is shaken
^ The characteristics of the crystals of hemoglobin from different animals are
described by Reichert and Brown, in: The Crystallography of Hemoglobins,
Carnegie Inst, of Washington, No. 116, 1909.
186 THE BLOOD
in air or pure oxygen, it gradually assumes a much lighter color, because its hemo-
globin is thereby converted into oxyhemoglobin. These changes may be considera-
bly hastened by warming the blood. The conversion of oxyhemoglobin into
hemoglobin may also be attained by adding a reducing agent to the blood. Such
agents as ammonium sulphid, an ammoniacal solution of ferrous tartrate or hy-
drazin, are commonly employed.^
The power of hemoglobin to combine with oxygen seems to depend upon the iron
which it contains. The figures given above show that the amount of iron varies
only very slightly, and hence, the quantity of hemoglobin may be ascertained by
simply determining the iron content of the blood. One atom of iron corresponds
to about two atoms or one molecule of oxygen.
Methemoglobin.2 — This body is a compound of hemoglobin and
oxygen which does not occur normally in the body. It appears
whenever large amounts of hemoglobin are set free in consequence of
an increased destruction of red cells. The administration of such sub-
stances as acetanilid, antifebrin and the nitrites is said to effect its
formation in the circulating blood. It is also found in the urine and
in the contents of cysts and old extravasates. It may be prepared by
permitting blood or a solution of oxyhemoglobin to stand for a long
time in the air, or by mixing a sample of blood with different oxi-
dizing or reducing substances, such as ozone, potassium permanganate,
ferricyanid or chlorate. Most observers agree that methemoglobin
is a compound of hemoglobin with oxygen in which this gas is held in
a different state of combustion. The compound is thereby rendered
more stable, a change which is clearly betrayed by its greater resist-
ance to vacuum. Not being able to unload its oxygen freely in the
tissues, it is useless as a respiratory agent.
Methemoglobin exhibits a brownish tint and crystallizes in needles. Haldane
.0
suggests for oxyhemoglobin the formula : Hb<^ | and for methemoglobin, the f or-
^O
mula: Hb/^ . The conversion of the former into the latter is not accomplished
^O
directly by a mere shifting of the oxygen, but in an indirect manner, i.e., by first
dissolving all the oxygen and uniting any molecule of this gas that may be available,
with the radicle.
Other Compounds of Hemoglobin.— If blood is freely exposed to
carbon monoxid, a compound is formed between this gas and the
hemoglobin which is known as carbon monoxid hemoglobin (CO — Hb).'
One molecule of the gas combines with one molecule of hemoglobin,
thus effecting a very stable union which strongly resists the action
1 Stokes's solution consists of :
Ferrous sulphate 2.0 per cent.
Tartaric acid 3.0 per cent.
When about to use this solution, add ammonium hydrate until the precipitate
formed at first is redissolved.
2 Discovered by Hoppe-Seyler, Handb. d. physiol. chem. Analyse, 1865, 205.
3 Attention was first called to this fact by CI. Bernard, in 1857.
■I
THE RED BLOOD CORPUSCLES 187
of the different reducing agents. Even air and pure oxygen are quite
unable to destroy this combination with ease. For this reason, the
inhalation of coal gas, or of illuminating gas of which carbon monoxid
is a constituent, gives rise to symptoms of poisoning which are scarcely
less severe than those following the abstraction of oxygen from the in-
spiratory air. Gradually, as the hemoglobin becomes more thoroughly
charged with this gas, it fails in an increasing measure to bind the
necessary amounts of oxygen. The tissues become oxygen-starved
and eventually cease their normal activities. Death results, as a rule,
before all the oxygen has been displaced. About one-fifth of its total
amount most generally remains in the corpuscle. Carbon monoxid
is also capable of uniting with the oxygen of the tissues, thereby de-
stroying the life of the cells themselves.
Hemoglobin exhibits an avidity for carbon monoxid which is 140 times greater
than that for oxygen. Thus, if the oxygen has been displaced by carbon monoxid,
the hemoglobin cannot easily be made to recombine with the former. For this
reason, the forcible introduction of air or pure oxygen into the lungs of an indi-
vidual poisoned with coal gas or water gas, can have no other beneficial effect than
the removal of that portion of the carbon monoxid which has as yet remained
uncombined. To be sure, if a certain number of corpuscles are still present which
have retained their normal capacity to carry oxygen, the metabolism of the tissues
may continue at low ebb until more favorable conditions have been established in
consequence of an active regeneration of the red cells. In severe cases, however,
which necessitate a very quick production of new oxygen-carriers, large quantities
of the carbon monoxid blood must be displaced by the process of blood-transfusion.
The blood of a person poisoned by carbon monoxid gas, possesses a cherry-red
color. The muscles and organs, as well as the integument, exhibit a similar dis-
coloration. The presence of very small quantities of this gas in the respiratory
air (Mooo~Ko>ooo) is sufficient to produce relativelj^ large amounts of CO hemo-
globin. It is for this reason that the admixture of even very slight quantities of
this gas to the air of dwellings is so dangerous to life. It must be admitted,
however, that some animals are more susceptible to it than others, which fact im-
plies that the blood of animals differs somewhat in its power of absorbing this
gas.
Illuminating gas contains another substance, ethylene, which seems to be
strongly toxic to trees and seedlings. Its action upon animals is not known, but as
it is highly toxic, even the slightest escape of illuminating gas should be carefully
guarded against.
A compound of even greater stability results, if nitric oxid (NO) is brought into
contact with hemoglobin. This union, however, cannot be effected in the body,
because the oxygen which under normal conditions is always available, immediately
instigates a reduction. For this reason, the formation of this compound necessi-
tates the removal of the oxygen from the blood by hydrogen. Hydrocyanic acid
(CHN) also enters into combination with hemoglobin, and it is also said that a
typical sulphohemoglobin may be formed.
In accordance with the observations of Buckmaster and Gardner, showing
that ether and chloroform lower the oxygen carrying power of the blood, it may
be surmised that hemoglobin may also form a compound with these agents.
This union is not identical with that ordinarily effected between these anesthetics
and the lecithin or other lipins of the red corpuscles.
Derivative Compounds of Hemoglobin. — The decomposition of
hemoglobin in the absence of oxygen gives rise to hemochromogen^
^ Discovered by Hoppe-Seyler, Zeitschr. fiir physiol. Chemie, xiii, 1889, 477.
188 THE BLOOD
and in the presence of this gas to hematin. Quite similarly, hematin
may be reduced to hemochromogen, while the latter substance may be
oxidized to hematin.
Hemochromogen is responsible for the color of hemoglobin and, therefore, of the
blood. Solutions of this substance exhibit a cherry-red color. It may be prepared
in crystalline form by mixing a drop of defibrinated blood with a drop of pyridin
to which a small quantity of ammonium sulphid is then added. These crystals
possess a stellate shape. ^
Hematin is an amorphous substance which may also appear as rhombic needles
and platelets. 2 It possesses a dark-brown color, and while insoluble in water,
alcohol and ether, is readily soluble in dilute alkalies and acids. It has lost
the properties generally assigned to a proteid body and contains all the iron of the
hemoglobin molecule. Its formula is given as C32H32N4Fe04. It is found in the
Fig. 104. — Hemin Cbystals.
feces after the ingestion of meats and food rich in blood, as well as after hemor-
rhages into the stomach or intestinal canal. The reduction of the hemoglobin
is accomplished in this case by the gastric and pancreatic juices.
A very important derivative of hematin is hemin or chlorhematin, the formula
for which is given by Kiister^ as: C34H3304N4FeCl. One hydroxyl group of the
hematin has been displaced by chlorin. This body is obtained in the form of
crystals, the so-called Teichmann's hemincrystals. As these possess a very charac-
teristic shape and color and may be derived from very small quantities of blood,
the hemin reaction constitutes a most important test for blood. It is possible to
prepare them in large numbers by carefully heating a droplet of blood which has
been placed upon a glass slide. When dry, a drop or two of glacial acetic acid and a
small crystal of sodium chlorid are added, after which a cover-slip is applied and
the acid slowly evaporated by drawing the slide repeatedly through a flame.
For purposes of examination, any dry stain which is suspected of being caused by
blood, must first be thoroughly washed with small amounts of water and the water
evaporated to dryness, while solid particles of blood should first be powdered
with a few crystals of sodium chlorid.
1 Donogamy, Jahresber. fur Tierchemie, xxiii, 1894, 126.
2 Piettra and Vila, Compt. rend., cxli, 1906.
» Zeitschr. fur physiol. Chemie, xl, 1904, 423.
THE RED BLOOD CORPUSCLES 189
On examining the slide under the microscope, the crystals are seen singly or in
clusters. They appear as rhombic platelets and rods belonging to the monoclinic
system. In transmitted light they possess a mahogany-brown color, while in
direct illumination they exhibit a dark bluish tint. They are insoluble in water,
alcohol, ether and chloroform, but soluble in dilute alkalies.
Hematoporphyrin differs from hemochromogen and hematin in that it contains
no iron. Nencki^ gives its composition as C34H38N4O6 = 2C17H19N2O3. It is
prepared by adding crystallized hemin to a saturated solution of hydrobromic acid
in glacial acetic acid. Having permitted this mixture to stand for three or four
days, it is shaken with distilled water and filtered. The hematoporphyrin is then
thrown down by carefully neutralizing with caustic soda. It is insoluble in water
but soluble in acids, alkalies and ethyl alcohol. It appears as a dark, violet powder.
The fact that hematoporphyrin is free from iron is of general interest in so far as
the bile pigments are also iron-free derivatives of hemoglobin; indeed, bilirubin
and biliverdin are commonly regarded as excretory products derived from hemo-
globin. The former pigment is isomeric with hematoporphyrin and both yield
on oxidation acids which are identical with those obtained from hematin. In this
connection, it should also be mentioned that the decomposition of stagnated blood,
as for example that of hemorrhagic extravasations into the brain, gives rise to a red
pigment, called hematoidin (C32H36N4O6) which is also free from iron and crystal-
lizes in clinorhombic prisms. This body is said to be identical with the biliary
pigment bilirubin and to be isomeric with hematoporphyrin. By abstracting one
molecule of oxygen from the latter, a body, called mesoporphyrin, has recently
been produced, which is said to possess the same composition as hematoidin.
Traces of hematoporphyrin are generally present in the urine; greater amounts of
it appear in certain types of poisoning. Crystals of hematoidin have also been
found in the urine after transfusion of blood and during 'icterus, when there is a
marked destruction of red cells. Of general interest is the fact that the green color-
ing matter of plants, known as chlorophyl, possesses a chemical structure similar
to that of hemoglobin. It may be inferred, therefore, that these bodies are closely
related to one another. This is shown, moreover, by the fact that hematoporphyrin
may be reduced to the oxygen-free hemopyrrol which is methylprophlpyrrol. In
a similar way, chlorophyl may be made to yield phylloporphyrin, a body closely
allied to hematoporphyrin which in turn may be changed into hemopyrrol. ^
CLINICAL METHODS FOR THE DETERMINATION OF HEMOGLOBIN
The hemoglobin content of the blood varies very shghtly under
normal conditions, but fluctuates considerably in disease. Two fac-
tors may be held responsible for this inconstancy, namely, a change
in the number of the red cells or a change in their capacity to carry
hemoglobin. While these changes may arise independently of one
another, they are more frequently found to be associated with one
another. In the second place, it should be remembered that they
need not pursue a. perfectly parallel course, because it frequently
happens that a reduction in the hemoglobin content is associated with
an increase in the number of the red cells. Conversely, a decrease in
their number cannot justly be regarded as a certain indication of a
loss in the total amount of hemoglobin, because the individual corpus-
cles may contain larger amounts of it.
1 Monatshefte fiir Chemie, x, 1889, 568; and Zeitschr. fur physiol. Chemie,
XXX, 1900, 384.
2 Nencki and Marchlewski, Ber. der chem. Gesellsch., xxxiv, 1901.
190 * THE BLOOD
As a disturbance in the relationship of these two factors is most
hkely to result in consequence of pathological conditions, it is essential
to be in possession of a quick and accurate method for the quantitative
determination of this substance. It is quite true that a knowledge of
the hemoglobin content of the blood frequently facilitates the diag-
nosis, but, as has just been emphasized, this value must first be brought
into relation with the number of the red cells, otherwise it may give
rise to very erroneous deductions regarding the general condition of
the blood. Two methods have been advocated for the determination
of hemoglobin. One of these has been described by Welker and Hoppe-
Seyler,^ and is known as the chronometric. The other, described by
Vierordt and Glan,^ is known as the spectrophotometric. The various
modifications of the first take the normal quantity of hemoglobin to
be 100 per cent, and the normal number of the red corpuscles (5,000,000
per cu. mm.) also 100 per cent. The color exhibited by a sample of
blood of this quality is regarded as unity; this standard being obtained
by employing the percentage of hemoglobin as the numerator and the
percentage of the corpuscles as the denominator. Thus, if the num-
ber of the red cells remains the same, while their hemoglobin content
is diminished, the color index becomes smaller than 1. A reduction
80
of the hemoglobin to 80 per cent, gives an index of j^ = 0.8, which
g
value implies that, the different corpuscles carry only j^ of the normal
quantity of hemoglobin. Under certain pathological conditions the
decrease in the percentage of hemoglobin is often associated with a
diminution in the percentage of the corpuscles; moreover, the reduc-
tions may or may not be equally great in the two cases. If they are
equal, the color index is 1, and if they are not, the latter is either smaller
or larger than 1. To illustrate, assuming that the percentage of
hemoglobin is 60 and the percentage of corpuscles 80, the index : ^ =
0.75, suggests that the different corpuscles are loaded with only three-
fourths of the amount of hemoglobin ordinarily carried by them.
And again, a percentage of hemoglobin of 60 and a percentage of red
cells of 50 gives the index: ^ = 1.2, which indicates that the hemo-
globin content of the individual corpuscles is greater than normal.
The principle involved in this method is the following: If two solutions in
identical receptacles are exposed to the same source of light and exhibit the same
color, their content 'in coloring matter must be the same. Hence, it should be
possible to prepare a solution of hemoglobin of known concentration and to deter-
mine the hemoglobin content of other samples of blood by simply comparing them
with this standard solution. But, as standard solutions of this kind cannot always
be easily kept, the attempt was made at an early date to find a more permanent
1 Zeitschr. fiir physiol. Chemie, xv, xvi, xxi, 1891, 1892, and 1896.
2Poggend. Ann.,'l877.
THE RED BLOOD CORPUSCLES
191
colometric substitute; for example, solutions of the more stable compounds of
hemoglobin, solutions of picrocarmin and colored glass.
The instruments which have been devised to permit of a comparison of this
kind are called hemoglobinometers, or hemo- ,
meters. Hoppe-Seyler employed two glass
troughs with parallel sides, into one of
which he placed a standard solution of oxy-
hemoglobin of known strength, and in the
other, the blood to be tested. The pro-
cedure consisted in diluting the sample of
blood until its color corresponded precisely
with that of the standard solution. The
quantity of water necessary to attain this
end, enables one to calculate the propor-
tion of hemoglobin in the undiluted blood.
The procedure advocated by Tallqvist,^
consists in permitting a drop of blood to
fall upon white filter paper. When evenly
diffused the color of the stain is compared
with similar permanent stains indicating
the different percentages of hemoglobin
from 10 to 100. The hemophotographic
method of Gartner^ is based upon the fact
that a solution of oxyhemoglobin absorbs
the rays of light in a steadily increasing
measure with its concentration. Fleischl's
instrument^ consists of a short cylindrical receptacle which is divided into two com-
partments by a vertical median partition. Into one of these is placed a measured
Fig. 105. — Hemoglobinometer.
(Fleischl's.)
S, stage; R, reflecting mirror; B,
screw for adjusting position of colori-
metric wedge; A, the cylindrical re-
ceptacle. C, contains two compart-
ments into one of which is placed
the sample of blood to be examined.
r\/7
100
io
C
-•JO
-80
— 70
— so
— 30
— io
— io
^
:
^.
iOimn*
B
D
Fig. 106. — Hemoglobinometer. (Gowers.)
A, tube filled with colored fluid; B, tube for mixing blood; C, receptacle for distilled
water with dropper; D, pipet.
^ Berliner klin. Wochenschr., 1904.
2 Miinchener med. Wochenschr., 1901.
^Wiener med. Jahresb., 1885; modified by Miescher, Korresp. f. Schweizer
Arzte, xxiii, 1893.
192 THE BLOOD
quantity of the blood to be tested plus a definite amount of water. A glass wedge
is situated beneath the other compartment, stained in different reds to correspond
to the color of different solutions of hemoglobin of known concentration. This
scale is then moved onward until its color corresponds precisely with that of the
sample of blood. Thus, if the colors are matched, say, at division 75 of the scale,
the blood contains only 75 per cent, of the normal quantity of hemoglobin, Mies-
cher has endeavored to obviate the use of solutions and has succeeded in producing
an instrument of even greater precision than that of Fleischl. Gower^s hemoglo-
hinometer^ which is the one most commonly employed to-day, consists of two iden-
tical glass tubes, A and B (Fig. 106). Tube A is filled with glycerin-jelly to which
picrocarmin has been added until its color corresponds precisely to that of a 1
per cent, solution of hemoglobin, i.e., to that of normal blood'diluted 100 times.
Tube B is filled with 20 cu. mm. of blood to which a few drops of distilled water
have been added to prevent coagulation. Water is then dropped into this re-
ceptacle by means of a pipet until the color of the diluted blood corresponds pre-
cisely with that of the standard solution in tube A. The gradations upon tube -B
accurately represent the percentage of hemoglobin. It is necessary to transpose
the tubes repeatedly. Thus, if the original 20 cu. mm. of blood are matched at
division 80, the blood contains but 80 per cent, of its normal amount of hemo-
globin. The following modification of this method has been suggested by Hal-
dane.2 In tube A is placed a 1 per cent, solution of blood saturated with carbon
monoxid. Having dropped 20 cu. mm. of blood plus a slight amount of distilled
water into tube B, the hemoglobin contained in it is quickly converted into carbon
monoxid hemoglobin by charging it with pure carbon monoxid or by passing a
mixture containing this gas through it. The dilution of the sample of blood is
then accomplished in the manner described previously. Sahli^ employs a solution
of hematin chlorid and first converts the blood to be tested into hematin chlorid.
SPECTROSCOPIC ANALYSIS OF HEMOGLOBIN AND ITS DERIVATIVE
COMPOUNDS
The most essential part of the spectroscope is a glass prism P,
which receives a bundle of white light through tube A (Fig. 107).
The size of this bundle may be varied by altering the size of the slit-
like opening in the end of this tube, while a biconvex lens interposed in
this place serves to render the rays parallel and to concentrate them
upon the surface of the prism at C. The spectral components of the
white light are observed in magnified form through tube B which is
nothing more than a small telescope. The third tube D contains a
scala M which is illuminated and reflected upon the surface of the
prism at C. In this way, the spectral colors (red to violet) may be
observed in conjunction with the divisions of the scala.
If a colored medium, for example, a solution of hemoglobin is now
placed between the source of light and the opening in tube A, some of
the rays of white light are prevented from entering, i.e., they are ab-
sorbed. In consequence of this absorption, certain sections of the spec-
trum as observed through tube B, appear in different shades of black.
These dark bands situated in between the different colors, are com-
monly called absorption bands. Of greatest importance, however, is
1 The Lancet, 1878.
2 Jour, of Physiol., xxvl, 1901, 497.
3 Lehrbuch der klin. Untersuchungsmeth., 1905.
THE RED BLOOD CORPUSCLES
193
the fact that different substances affect the spectrum in very specific
ways so that it is possible to determine their presence by the number,
intensity and location of the absorption bands. But, as some of these
bands occupy the same or very nearly the same positions, it is desira-
ble to possess certain landmarks in the spectrum for our guidance.
This purpose is served by the Fraunhofer lines. The spectrum of sun-
light extends between the ultra red and ultra violet colors, i.e., between
rays possessing, on the one hand, a wave length of 757^^/ and, on the
other, one of 392^i/x. The Fraunhofer lines traverse the spectrum at
definite distances from one another. Thus, the B-Yme, transects the
red end with a wave length of 686.8/x/x, the D-line the golden yellow
with a length of SSQ/x/x, and the ^-line the green with a length of vibra-
tion of 527 jjLfj..
Fig. 107. — Diagram of Spectroscope.
The spectrum of oxyhemoglobin is a very characteristic one. Two absorption
bands are visible at the border of yellow and green, between the Fraunhofer D- and
£'-lines (Fig. 108). The left band is narrow but dark and sharp and is generally
designated as the "a-band." The one on the right, which is broad and less
clearly outlined, is referred to as the "jS-band." But as the absorption of the
light is dependent upon the thickness and the concentration of the solution, these
bands are not always equally distinct. Thus, if the percentage of oxyhemoglobin is
greater than 0.65, the bands coalesce and the yellow-green color between them
disappears. Greater concentrations eventually give rise to one dark band which
overlaps the D- and £'-lines and causes a darkening of the violet end of the spectrum.
Quite similarly, very dilute solutions (0.01-0.003 per cent.) produce only a single
band, namely, the one nearest the Z>-line. It is essential, therefore, to employ
solely solutions in strengths of from 0.1 to 0.6 per cent., while the layer of the
solution should be 1 cm. in thickness. These bands may also be obtained from
circulating arterial blood. A good object for this purpose is the ear of the rabbit,
a hand spectroscope being applied directly to its surface.
Reduced hemoglobin gives only one absorption band which is commonly
spoken of as the "y- band. " It is situated between the D- and ^-lines, extending
farther toward the red end of the spectrum and slightly beyond the D-line. It
exhibits a considerable width and rather poorly defined margins, but its character-
istics vary somewhat with the strength of the solution.
The spectrum of hemoglobin and its oxygen combination is invariably made use
of in the detection of blood, the suspected substance, smear or stain being first
extracted with a definite quantity of normal saline solution. In these examinations
^ liJLfx = 1 millionth of a millimeter.
13
194
THE BLOOD
the attempt must also be made to convert the oxyhemoglobin into hemoglobin and
the latter into the former. Thus, if a certain solution yields the a- and /3-bands,
a reducing agent should be added to obtain the y-band, because this conversion
establishes the presence of blood with much greater certainty than the presence
of the first two bands alone. Quite similarly, a solution in which hemoglobin has
been proved to exist spectroscopically, should be oxidized by shaking it until the
7-band is eventually displaced by the two bands of oxyhemoglobin.
Solutions of carbon monoxid hemoglobin also give two absorption bands
which may be mistaken at times for those produced by oxyhemoglobin ; however,
a differentiation is readily possible if the solutions are properly diluted. When this
has been done, the superposition of the different spectra so far described, will show
that the bands of carbon monoxid hemoglobin are situated somewhat nearer the
blue end of the spectrum; and besides, they are permanent in character, i.e.,
they cannot be fused into a single one by the addition of a reducing agent.
A f
Lliiiillii lull
^ C L
} E
, . . T 1 1
i i
so
III,
r i
, . , 1 ,
i , , tT
ll
1 »
2 J
1 1
^^■M
n
^g^^l^XJ
'^^^^H.
-im\
13
■■^■^^
s^Hi
m
^^^^n
J"i"'J
!'+;
^-i^r-P^^^M
Fig. 108. — The spectra of oxyhemoglobin in different grades of concentration, of
reduced hemoglobin, and of carbonic oxid hemoglobin. (After Preyer and Ganger.)
1 to 4. Solution of oxyhemoglobin containing: (1) less than .01 per cent., (2) .09 per
cent., (3) .37 per cent., (4) .8 per cent. 5. Solution of (reduced) hemoglobin containing
about .2 per cent. 6. Solution of carbonic oxid hemoglobin. In each case of the six
cases the layer brought before the spectroscope was 1 cm. in thickness. The letters
indicate Fraunhofer lines and the figures wave-lengths expressed in H 00.00 0 millimeter.
Nitric oxid hemoglobin shows two absorption bands which are paler and less
distinct than those of carbon monoxid hemoglobin and furthermore, their charac-
teristics cannot be altered by reducing agents.
The absorption bands of methemoglobin in watery or acidified solutions are very
similar to those of acid hematin, which body gives three to four distinct bands.
A differentiation, however, can easily be effected, because methemoglobin when
mixed with a small quantity of an alkali and a reducing agent, shows the absorp ion
band of reduced hemoglobin, while under precisely the same conditions hematin
exhibits the spectrum of an alkaline hemochromogen solution. In alkaline
solutions this substance shows three bands, two of which are similar to those of
hemoglobin. ' They differ from the latter in that the j8-band is more conspicuous
than the a-band ; moreover, the latter occurs in relation with a third band which is
fainter and occupies a position somewhat to the left of the D-line.
THE RED BLOOD CORPUSCLES 195
Hemochromogen in acid solution has four bands and, in alkaline solution,
two bands. One of the latter is dark and is situated between the D- and £'-lines,
while the other is less intense and covers the ^-line.
Acid hematin possesses a sharply defined absorption band between the C- and D-
lines, the position of which varies somewhat with the type of the solution employed.
A second band, much broader but less intense, is present between the D-and F-lines.
By proper dilution this band may be converted into two. The one nearest the F-line
is dark and broad, and the one nearest E, light and narrow. Another very faint
band may be made out near D by diluting the liquid still further. Hematin in
alkaline solution presents one broad absorption band located principally between
the C- and D-lines, but extending slightly into the space to the right of D.
On addition of a few drops of hydrochloric acid, an alcoholic solution of hema-
toporphyrin presents two bands, namely, one near D which is narrow and faint, and
one between D and E which is broad and sharply outlined. A dilute alkaline
solution of this substance presents four bands, namely, one between C and D, one
between D and E and covering D, one between D and E and very close to E and
lastly, one near F. With the aid of an alkaline zinc chlorid solution these bands
may be made to coalesce into two, namely, into one located at D and one situated
between D and E. In acid solutions this substance frequently shows four
bands, but much depends upon the manner in which the solution is prepared.
THE LIFE HISTORY OF THE RED CORPUSCLES
In the embryo the red cells originate in the so-called vascular
area. The blood-vessels appear at this time as a network of solid
threads, differentiated from the adjoining tissue by a greater opacity.
Their walls are made up of masses of cells which are intermingled
with ameboid corpuscles and of cells which possess a peculiar branched
appearance. Later on, when fluid has forced its way into the different
tubules from without, the cells on the outside arrange themselves in
the form of an endothelial lining, while loose clusters of large globular
cells project from here into the lumen of the vessel. All these cells
multiply very rapidly by indirect division. The cytoplasm of those
fastened to the inside wall is colorless and nucleated at first, but
gradually acquires a certain quantity of hemoglobin. These cells
become yellowish in color and eventually separate to assume a position
in the fluid within the channel. Being still in possession of a nucleus,
they are capable of multiplying by indirect division. Later on, how-
ever, as the individual tubules acquire a larger size and begin to anas-
tomose with one another, these newly developed cells, in which we
recognize the red corpuscles, migrate into the general circuit and hence-
forth lead an independent life.
During the later stages of embryonic development, other organs
enter into the formation of these elements. To begin with, this func-
tion is centralized in the liver; subsequently, however, the spleen,
lymphatic tissues and red marrow of the bones take part in their
production. During the last periods of embryonic existence the im-
portance of the liver and spleen as corpusple-f orming organs decreases
very markedly, while that of the bone marrow increases steadily
until the end of fetal life.
196 THE BLOOD
During the early stages of embryonic existence, the precursors
of the red corpuscles, generally known as erythroblasts, are large
and nucleated, while the non-nucleated cells which are so char-
acteristic of the adult animal, appear at a much later time. In the
human fetus, for example, all the cells are nucleated at the end of the
fourth week, while at the end of the third month only about one-
fourth of their total number is still in possession of a nucleus. The
corpuscles of the latter type become fewer and fewer in number as
gestation advances until at birth practically all the circulating ery-
throcytes are without a nucleus. Only those which are still retained
in the corpuscle-forming, or hematopoietic tissues, remain nucleated.
Naturally, the loss of the nucleus which occurs either by disintegration
or extrusion, implies that they are now fully developed and also, that
they no longer multiply by simple division.
The formation of the red corpuscles does not cease at the end of
intrauterine existence, but is continued throughout the life of the
animal; and furthermore, as their number does not increase, their
formation must be counterbalanced by an adequate destruction.
That this is true may be inferred from many experiments. Thus, if
a loss of red corpuscles is effected by bleeding, the fluid parts of the
blood are quickly replaced by transferring a certain quantity of the
tissue-lymph into the vascular system. Consequently, the blood is
relatively poor in corpuscles directly after the hemorrhage, but ac-
quires them in greater numbers later on as new ones are sent in by the
hematopoietic tissues. An interval of a few days generally suffices
to establish the normal corpuscle count, but naturally, much depends
upon the quantity of blood lost and the activity of the corpuscle-
forming tissues. A second fact that should be mentioned at this time
is the constant outgo of pigmentous material in the feces and urine,
in the form of urochrome, urobilin and stereobilin. It has been shown
that these substances originate in the liver and that their production
is closely dependent upon the amount of hemoglobin available for
this purpose. By inference, therefore, it may be concluded that a
supply of this coloring material must be constantly at hand; i.e.,
it must be brought to this organ by the red cells in undiminishing
quantities.
During extrauterine life the erythrocytes are formed in the red
marrow of the bones. Marrow of this color is found in the flat and
short bones of the head and trunk and in the long bones of the ex-
tremities. The latter, however, contain it solely in their ends. It is
also to be noted that the yellow marrow in the other regions of these
bones may assume the characteristics of red marrow at any time when
a very active regeneration of the red cells is called for. The fatty
marrow in the diaphyses then becomes filled with a red pasty mass
consisting chiefly of red cells and their precursors. This conversion
may readily be induced in animals by bleeding. A similar change has
been observed in hibernating animals. Red marrow is formed very
THE RED BLOOD CORPUSCLES 197
rapidly in the spring, while, at the beginning of the period of hiberna-
tion, the yellow marrow is present in especially large amounts.^
In the frog, lymphoid red marrow appears only in the early summer,
which fact indicates that this animal obtains a considerable supply of
new red cells at this time of the year.^
The precursors of the red cells are called erythroblasts, while the
process by means of which these cells are converted into mature red
corpuscles, is known as hematopoiesis. Their migration into the
blood-stream is greatly facilitated by the circulatory conditions exist-
ing in the marrow. In the first place, it is to be noted that these
channels are protected by unyielding bony walls, while their cellular
lining is thin and rather imperfect. And besides, as the rapidity of
the blood flow is slight and the pressure low, a certain traction is
brought to bear upon them, but naturally, the quickness with which
they are formed and are forced into the circulation, depends in a large
measure upon how greatly the system is in need of them. Thus, it is
possible to retard the production of these elements in such a degree
that the lumen of the vessels becomes practically free from them,
while the region close to their wall is filled with cells in all intermediary
stages of development. It is also possible to stimulate the hemato-
poietic process by causing a greater destruction of the circulating red
cells. This end may be attained either by bleeding, or by the adminis-
tration of toxic substances. The histological picture then obtained
is quite different from that just given, because the lumen of the chan-
nel is now filled with young erythrocytes, many of which are still in
possession of a nucleus. Some of these nucleated cells find their way
into the general circulation, where they are recognized as normoblasts.
Under certain pathological conditions the liver and the spleen seem
to regain the corpuscle-forming power which they possessed during
embryonic life.
While the duration of the life of the red cells has been estimated at
about four weeks, it cannot be said that this point has been definitely
settled. The attempt has been made to arrive at a conclusion by
introducing a limited number of elliptical corpuscles into the circula-
tion of a mammal. It seems, however, that the length of time during
which the cells of the lower forms or of birds continue to live in the
mammalian blood, cannot be regarded as a safe guide, because as they
are thus placed into a medium which is foreign to them, they may go
to pieces much sooner than they would otherwise. Another method
to which brief reference should be made here, depends upon the deter-
mination of the number of red cells which must be destroyed daily
in order to permit of the excretion of the usual amounts of bile pig-
ment. If the quantity of bile is 15 grams per kilo of the body weight
and the percentage of its pigment 0.2, the daily output of pigment
must amount to 1.95 grams. But in order to obtain this quantity of
1 Pappenheim, Zeitschr. fiir klin. Med., xliii, 1901, 363.
2 Marquis, Dissertation, Dorpat, 1892,
198 THE BLOOD
pigment, 48 grams of hemoglobin must be made available, i.e., about
one-tenth of the total amount of this substance ordinarily present in
an individual weighing 65 kilos and possessing about 3500 grams of
blood. Upon the basis of this calculation, the life of the circulating
red corpuscle may be said to be about ten days. Our long cherished
beliefs regarding the production of bile pigments, however, do not
agree with the views of Hooper and Whipple, ^ because it seems that
the liver possesses a certain inherent power to form pigment, thus
quite offsetting the calculation just given. A relatively severe loss of
red corpuscles, which must be compensated for immediately, occurs
during the menstrual flow. Mix^ states that 150 c.c. of blood are lost
during this period which are again reformed in the course of about
twenty-eight days. This necessitates the formation of 5000 cu. mm.
of blood in a day, 208 cu. mm. in an hour or 3.5 cu. mm. in a minute.
The total number of red corpuscles lost during this period, necessitates
the formation of 15,750,000 new cells in a minute.
It seems that the disintegration of the red cells begins while they
traverse the general circulatory channels, but their absolute destruc-
tion and dissolution is restricted to two organs, namely, to the liver
and the spleen. Moreover, it is very probable that the former organ
possesses a much greater disintegrating power than the latter, which
belief may be substantiated by the following facts:
(a) The liver is the place in which the hematin is changed into bile pigment,
and hence, an adequate supply of the former substance must always be kept on
hand.
(6) The hepatic cells contain iron which is normally derived from the red
corpuscles. This fact may be established by treating a cross-section of this
organ with potassium ferrocyanid and acid alcohol, under which condition it
assumes a blue color. While a part of the iron is excreted, a part of it is reabsorbed
and may again be employed in the formation of new corpuscles.
(c) The quantity of the biliary pigment may be increased by injecting hemo-
globin into the blood stream.
{d) The deposition of iron in the liver may be increased experimentally by
inciting a greater destruction of the red cells. This can be done by introducing
, toxic agents into the circulation. A disintegration of red cells also occurs under
pathological conditions, for example, in the course of certain anemias.
(e) A deposition of hemoglobin crystals in the cells of this organ has been
observed.
(/) The blood of the hepatic vein is said to contain fewer red cells than that of
the portal vein.
{g) The endothelial cells lining the capillaries of the liver, the so-called "Stern-
zellen/' possess the power of taking up foreign particles and of rendering the red
corpuscles effete.
A disintegration of the red corpuscles also occurs in the lymphoid
tissues and in the spleen. This conclusion is based upon the observa-
tion that red cells or pieces of them are found at times in the cytoplasm
of certain large cells, or macrophages, which are generally present in
1 Am. Jour, of Physiol., xlii, 1917, 256.
2 Boston Med. and Surg. Journal, 1892.
THE WHITE BLOOD CORPUSCLES 199
these organs. It seems best, however, not to attach too great an im-
portance to this fact, because it can readily be shown that the spleen
is neither the only nor the most important organ for the destruction of
these elements. The evidence which tends to confirm this statement
is as follows:
(a) The removal of the spleen does not seem to lessen the destruction of the
red cells, as is evinced by the quantity of the bile-pigment excreted.
(b) If a marked destruction of red corpuscles actually did occur in the spleen,
the phagocytic cells of this organ should be loaded to their utmost capacity with
these cells or with the substances derived from them. This histological evidence
has not been supplied as yet.
(c) Quite similarly, the blood emerging from this organ should show a cor-
puscle count below that of the arterial blood, and, furthermore, should also con-
tain those bodies which are ordinarily derived from the red corpuscles. That the
splenic blood undergpes these changes has not been definitely established.
CHAPTER XVII
THE WHITE BLOOD CORPUSCLES
PHYSICAL AND CHEMICAL PROPERTIES
Color, Shape and Size. — The white corpuscles appear as small
globules of protoplasm, measuring from 4 to 14/x in diameter. Some
of them, therefore, are much larger and some much smaller than the
red cells. Their substance is soft and sticky, grayish in color, homo-
geneous or granular, and not surrounded by a clearly recognizable
membrane. Their surface is often quite uneven and shows at times
irregular projections which break off and float free in the blood. Al-
though these cells are strongly refracting, their nuclear portion does
not become sharply differentiated until they have been brought in
contact either with suitable stains or with water and solutions of acetic
acid. These agents serve to contrast them more sharply against the
medium, because water tends to render the granules more conspicuous,
while acetic acid lessens the opacity of their cytoplasm.
The Classification of the White Corpuscles. — The white cells may be
arranged in groups in accordance with the shape and size of their
cell-bodies and nuclei, as well as in accordance with certain differences
in the behavior of their granular constituents toward anilin dyes.
Ehrlich^ found that some of these granules react only toward acid
dyes, while others can only be stained with basic or neutral pigments.
For this reason, the white corpuscles have been described as acido-
philes,^ basophiles and neutrophiles. In accordance with their general
characteristics, they are divided into two principal groups and these
again into several others, as follows:
1 Archiv f. (Anat. u.) Physiol., 1879, 571, and "Die Anemie," 1898.
2 Also called oxiphiles or eosinophiles.
200
THE BLOOD
1. Lymphocytes, are not granular^ and do not show a very pronounced shifting
of their substance.
(a) Small Type. — These cells possess a small amount of cytoplasm and a
relatively large and symmetrical nucleus. They are about as large as the red
corpuscles. and constitute about 25 per cent, of all the white corpuscles.
(6) Large Type. — These cells are much larger than the preceding and display a
broader margin of cytoplasm around a somewhat eccentric nucleus. They are
few in number and often exhibit a granular, irregularly stained network simu-
lating true granulations.
2. Leukocytes, are granular and exhibit a very characteristic ameboid motion.
(a) Transitional Type. — These cells are few in number (2 to 10 per cent.)
and contain a large quantity of protoplasm in which a few neutrophilic granules
are suspended. The nucleus is shaped like a horseshoe or an hour-glass, but is
not divided into smaller masses.
5 E F
Fig. 109. — Different Varieties of Human White Corpuscles.
A, lymphocyte; B, mononuclear leukocyte; C, transitional form; D, polynuclear
leukocyte; E, eosinophile leukocyte; F, mast-cell. (After Szymonowicz.)
(b) Polymorphonuclear Type. — The protoplasm of these cells is abundant
and embraces many fine neutrophile granules. The nucleus is lobulated, its different
segments being connected by strands. They form about 70 per cent, of the total
number of the leukocytes. To this group also belong the eosinophilic leukocytes
which, as the name indicates, stain with acid dyes, such as eosin. They are
characterized by their coarse and strongly refracting granules, and show a most
active ameboid motion.
(c) Basophile Type. — These cells are frequently called mast-cells. ^ They are
present in small numbers under normal conditions (less than 1 per cent.) and
embrace a nucleus consisting of two or three segments. Their granules stain
deeply with basic dyes, such as thionin.
The Number of the White Corpuscles. — It is generally given as
6000 to 10,000 per cu. mm., which figure indicates a proportion of one
white to about 700 red corpuscles. The total number of white cor-
^ True granules are present in severe anemias, but rarely in health.
2 Discovered by Bonders and Molischott in 1848; also see: Hirt, Dissertation^
Leipzig, 1855.
ii
THE WHITE BLOOD CORPUSCLES 201
puscles has been estimated at 19-32,000,000,000. They are especially
numerous in the new-born, counts of 15,000-19,000 per cu. mm. being
not infrequent. They become fewer in number shortly after birth,
but again increase during infancy, when a value of 30,000 per cu. mm.
cannot be regarded as abnormal. From the first to the sixth year the
values range between 13,000 and 7000 per cu. mm. A second decrease
takes place in adult life. This is again followed by an increase in
old age. The ingestion of food rich in protein raises the count, but
maximal values are not obtained until two or three hours after meals.
Very pronounced increases of this character constitute the so-called
assimilation or digestion leukocytosis. Fasting lowers the count,
while muscular activity^ and massage^ raise it.
A transitory increase above the physiological maximal value is
designated as leukocytosis, while a reduction below the minimal value
is called hypoleukocytosis or leukopenia. In accordance with the
data given above, it is advisable to classify leukocytosis as physio-
logical and pathological, this division being based solely upon the cause
of the increase. A pathological leukocytosis, for example, arises in
the course of many febrile reactions and especially after hemorrhages
and in consequence of suppurative processes. It is also possible to
produce this condition by the administration of quinin, turpentine,
albumose, nucleic acid, bacterial products and extracts of thymus,
spleen and bone-marrow. A leukopenia of marked degree frequently
follows exposure to the Rontgen rays.
The method employed in determining the number of the leukocytes is the
same as that made use of in counting the red cells, but as a larger drop of blood
is needed in this case, the pipet and counting chamber must be somewhat larger
in size. 3 In order to render the white corpuscles more conspicuous, the red cor-
puscles must first be destroyed by adding a small quantity of acetic acid to the
diluting fluid. It is also possible to add some coloring material to the latter so that
the total count may at the same time be amplified by a differential count.* In
general, however, it is advisable to differentiate these cells in a stained smear,
because abnormal forms of leukocytes are difficult to recognize in the counting
chamber.
The Chemical Composition of the White Corpuscles. — The direct
chemical analysis of the white corpuscles meets with the difficulty that
it is quite impossible to secure these cells in sufficient numbers.
Their chemical characteristics, however, have been studied in an
indirect way by making use of the so-called pus-corpuscles which are
always present in tissues which have been invaded by pus-producing
^Zuntz, Physiologie des Marsches, Berlin, 1901.
2 Zangemeister and Wagner, Deutsche med. Wochenschr., xxviii, 1902, 549.
' A special counting cell has been devised by Brener (Berliner klin. Wochen-
schr., xxxix, 1902, 954.
^ Tiirk (Wiener klin. Wochenschr., xv, 1902, 715) recommends a mixture of:
Glacial acetic acid 3 c.c.
Distilled water „ 300 c.c.
Gentian violet, 1 per cent, aqueous solution 2 to 3 c.c.
Also see: Zollikofer, Zeitschr. f. wissensch. Mikr., xvii, 1900, 313.
202 THE BLOOD
bacteria. It is also possible to obtain large numbers of lymphocytes
from lymphatic glands. As will be explained more fully later on,
the pus-corpuscles are the remnants of destroyed leukocytes. They
show a content in water of 90 per cent. The solids (10 per cent.)
consist chiefly of albumin, globulin, nuclein, nucleoproteid and nucleo-
histon. Neutral fats appear in their cytoplasm as strongly refracting
granules. Cholesterin, lecithin, glycogen and alkaline phosphates
are also present.
The Origin and Fate of the White Blood Corpuscles. — The different
views regarding the formation of the white corpuscles may be said to
advocate either a monophyletic or a dualistic origin. In accordance
with the former, the different varieties of white corpuscles are regarded
as having arisen from a single mother-cell.^ To be sure, the facts
favoring this unitarian mode of generation are insufficient, at least
when applied to the adult animal, but it is also true that the objections
commonly raised against it, lose much of their weight when the condi-
tions existing in the embryo are more fully considered. The dualistic
theory is based upon the contention that the lymphocytic white cells
arise from the so-called lymphoblasts which are present in the adenoid
tissue of the lymphatic glands and lymph nodules, and that the larger
ameboid types, or leukocytes, are descended from the myeloblasts of
the bone-marrow. This view, which was first expressed by Ehrlich,
is the most favored at the present time.
The lymph nodule consists of a dark peripheral and a clear inner
zone, or germ center. The latter is formed by large cells which
divide and give rise to the lymphocytes. The largest number of these
then escape into the lymph channel situated at the periphery of the
nodule, but a few of them also enter the blood stream directly. Those
white corpuscles which originate in the marrow of the bones, have as
their precursors the so-called myelocytes which present themselves
as granular or non-granular protoplasmic masses with rounded nuclei.
By transition these elements finally assume the characteristics of the
leukocytes, and eventually escape into the blood capillaries of the
marrow, whence they are distributed to all parts of the body.
The duration of the Hfe of these colorless corpuscles has not been
determined with accuracy. They undergo dissolution and disappear.
Many of them are destroyed while engaged upon their mission of
ridding the body of toxic substances.
THE FUNCTION OF THE WHITE BLOOD CORPUSCLES
Contractility and Motion. — A molecular movement of the cyto-
plasm has been observed in all white corpuscles, but with the exception
of the polynuclear and mononuclear varieties, this movement is not
sufficiently strong to cause motion. "White cells may be obtained
without much difficulty by placing a drop of blood upon a glass slide
1 Weidenreich, Ergebn. der Anat. und Entwickelungsgeschichte, xix, 1911, 2.
THE WHITE BLOOD CORPUSCLES 203
end removing from it the red corpuscles by means of a lateral drainage
stream of slight force. The white cells then stick to the surface of the
slide and, if kept in a warm isotonic solution, may be studied for some
time thereafter. They may also be obtained from the frog by insert-
ing a platelet of porous wood under the skin covering the dorsal aspect
of its body. If permitted to remain in this position for several
hours, the meshes of the wood will be filled with many leukocytes, the
removal of which can easily be effected by washings with normal saline
solution. They may be studied in a more plastic manner by placing
the frog's mesentery or bladder under the microscope. In the cir-
culating blood they appear as translucent globular bodies, which, on
account of their lesser specific gravity, leave the swift axial stream and
enter the more slowly moving peripheral layers of the current. They
attach themselves here or there to the vessel wall, but soon pass on-
ward again by executing a peculiar rotary motion.
Under favorable conditions the leukocytes exhibit a movement
of their cytoplasm^ which is very similar to that displayed by the
ameba. Their substance contracts and relaxes alternately, while their
nuclear constituents remain rather stationary and serve, so to speak,
as a center for this movement. Prolongations, commonly designated
as pseudopodia, are sent out in different directions into the surrounding
medium to be again retracted later on with varying swiftness.^ Thus,
a leukocyte may extend and retract its pseudopodia repeatedly without
altering its position, but it may also happen that one of its prolonga-
tions becomes attached to the surface and that the remaining mass of
the cell is slowly moved onward in the direction of this fixed point.
This propertj^ of the leukocytes to adhere to surfaces is attributed by
Verworn to the extrusion of a mucous secretion. When freely moving
they usually present a globular outline which implies that they are in
a state of contraction.
Phagocytosis. — Whether the leukocyte remains stationary or
moves onward to a different place, the molecular shifting of its sub-
stance is instrumental in bringing it into relation with various particles
of food and other extraneous material. As is true of other low forms
of life, the leukocyte behaves in a very characteristic manner toward
these substances, being either attracted or repelled by them. This
orientation is brought about largely by chemical means, and hence, the
leukocytes may be said to possess the property of chemotropism or
chemotaxis of a positive and negative kind.
The chemotropic qualities of the leukocytes must be held responsible
for their power of taking up nutritive particles and of englobing and
digesting all that material which is foreign or injurious to the body.
^ First observed by Wharton Jones in 1846, and proved for the human leuko-
cyte by Davaine in 1850. Lieberkiihn gave an adequate description of this
movement in 1854.
2 Verworn, Pfliiger's Archiv, li, 1891; also see: Maximow, Ziegler's Beitrage,
Ixxiii, 1909 and Ixxvi, 1910.
204 THE BLOOD
For this reason, they are frequently spoken of as devouring cells or
phagocytes (to eat-cell), and are further characterized as the "police-
men of the blood." In illustration of their function the following
phenomenon may be cited: As the larva of the fly changes into the
mature insect — a metamorphosis which occurs rather rapidly — such
structures as the creeping muscles become superfluous and undergo
degenerative changes. The substances which are formed during this
catabolic process, exert a strong chemotactic influence upon the
leukocytes with the result that this tissue soon becomes overcrowded
with them. The ensuing phagocytosis soon leads to the removal of
these now useless parts. The absorption of the tail of the tadpole is
accomplished in a similar manner. It is also known that they invade
injured tissues and help in the removal of the superfluous cellular
material, but whether they actually take part in the process of recon-
struction, is still doubtful. To be sure, Metchnikoff ^ has expressed
^%-
Fig. 110. — Leukocytes Engolfinq Particles of India Ink.
the idea that the emigrated leukocytes undergo certain changes which
enable them to become connective-tissue cells, but most authors
believe that this regeneration is accomplished solely by the plasma cells
of the tissues.
Of even greater importance and interest are the phagocytic quali-
ties displayed by the leukocytes when brought in relation with patho-
genic bacteria. But while capable of ridding the body of different
dead and living germs, the leukocytes are not capable of destroying
all varieties of them. They seem to be attracted especially by the
ordinary pus microbes or by the products of their metabolism, which
fact is well proven by an experiment described by Pfeffer. A capillary
tube, closed at one end, is filled with a culture of staphylococcus pyo-
genes albus or aureus. It is then placed under the skin or into the
abdominal cavity of a rabbit. On removing it 10 to 12 hours later,
the microscopical examination reveals great numbers of leukocytes in
the culture, actively engaged in ingesting the bacteria. The fact that
the bacteria, and not the culture, are responsible for the migration of
the leukocytes into the tube, can readily be proven by employing a
1 PathoL compar. de F inflammation, Paris, 1892.
THE WHITE BLOOD CORPUSCLES 205
medium containing no germs. Under this condition the leukocytes
do not enter the tube.
Opsonins. — It was observed at an early date that the leukocytes
behave at times in a very indifferent manner toward certain types
of bacteria, and hence, it was thought likely that these germs must
first be killed before the phagocytosis can take its regular course.
Metchnikoff then expressed the view that the leukocytes are capable
of surrounding living material under ordinary conditions, but that
the complete destruction of the latter necessitates the presence of a
specific intermediary agent. It was assumed, therefore, that the
fluids of the body contain special activators which stimulate the leuko-
cjrtes to greater activity.
Leishman^ and Wright and Douglass^ showed later on that the
phagocytosis may be greatly augmented by blood plasma or serum
which has been treated in a particular way.
It could be proved by the centrifugalization ,<:?^^t^.
of bacterial mixtures that this process tends |i^;- •.•:;' J^
to diminish the reinforcing power of the ;:-:|-
serum, while the bacteria are "sensitized ^^
thereby,'' i.e., they are rendered especially ^^<^c^0^^?::^$i^
vulnerable to the leukocytes. In this way, 'fe.Di :■?••:?
it has been established that the bacteria in- - K"^.' -.-*'*/%•>•
teract with certain specific bodies of the blood. }rf.' ../vlVj.'r^N r\
These bodies which, so to speak, render the ^i>""-*3iJ»' /-'r--^
bacteria palatable to the leukocytes, are called '^?/'i^'^..>v^^MSii
opsonins (prepare for a meal). K'£-' •••:•%•'' "%
The function of the opsonins, therefore, is ^li-i''--5\ ^
to produce certain physicochemical changes '^^'^
in the substance of the bacteria so that the ■'•'■•■'
leukocytic material is able to react with it. ^'V.'^;-''ZT.:^:J'^-
Paint applied to window glass will soon q, indicates part played by
crumble off, but will stick to it for an indefi- opsonin,
nite period if the glass is first eroded with a
fluoride. The opsonins are comparable to the eroding fluid. They
attack the bacterial substance and lessen its power of resistance so
that the leukocytic material is able to combine with it.
The resistance and immunity of an animal against microbic in-
fections depends in a measure upon the phagocytic properties of its
leukocytes. But in order to attain this power it is necessary to have
at hand not only a sufficient number of leukocytes, but also leukocytes
of the proper quality. In addition, it is essential that it be in posses-
sion of opsonins, because without these bodies a reaction between the
protecting cells and the invading bacteria cannot always be brought
about. Conversely, it is true that a large content in opsonins cannot
- British Med. Jour., Ixxiii, 1902.
^ Proc. Royal Soc, London, Ixxii, 1904. A brief discussion of opsonins has
been given by Hektoen, in Science, February 12, 1909.
206
THE BLOOD
serve as an adequate protection if the leukocytes are inferior in num-
ber or power. The best results can only be obtained if these two
factors are properly balanced. The opsonin content may be deter-
mined experimentally, the result being the so-called opsonin-index of
the body. By treating an animal in a specific way, the number of its
leukocytes and opsonin-content may be increased so that its power of
resistance becomes much greater than ever before.
Diapedesis. — This term was originally applied to the passage of
the blood or of its formed elements, chiefly the red cells, through the
wall of a blood-vessel. Cohnheim, however, has shown in 1869 that
this power of migration into the neighboring tissues is a distinct
characteristic of the leukocytes. In contradistinction to the passive
behavior of the red corpuscles, the latter are aided
in their escape from the vascular system by their
ameboid properties. A delicate pseudopodium is
first protruded through a perforation in the vessel
wall, after which the principal mass of the cell is
slowly drawn through the opening until entirely
I xs^:nJ^ U outside the vascular channel. An assemblage of
*^^^^_ ^ great numbers of these corpuscles outside the main
circulatory system results whenever a tissue has
been injured or has become the seat of an infective
process.^ Under these circumstances, their migra-
tion is greatly facilitated by certain changes in the
flow of the blood, namely:
(a) A relaxation of the capillaries in the area affected
so that the size of the blood-bed becomes larger; (6) an
accumulation of a larger quantity of blood in this par-
ticular region which tends to produce a local rise in tem-
perature ; and (c) a diminution in the velocity of the blood
flow which enables the white corpuscles to assemble in
numbers and to attach themselves more securely to the
vessel wall. These dynamical changes indicating an inflammatory reaction,
may be studied under the microscope in such tissues as the mesentery, tongue,
lung or web of the frog, if they are first moistened with normal saline to which a
few drops of alcohol or a small amount of mustard has been added.
Having invaded the tissue, the leukocytes immediately display their
phagocytic properties. Supposing that the inflammatory reaction has
been produced by bacteria, the outcome of this interaction depends
upon the relative strengths of the leukocytes and invading cell. If
the latter is the more powerful factor, the infection will gradually
extend to neighboring areas of the tissue, while if the former is the
stronger, the bacteria will eventually be encircled and eliminated.
But, in either case, large numbers of leukocytes will be destroyed in
the course of this process, their remnants appearing in the extrava-
sation in the form of pus-corpuscles. The foregoing discussion
Fig. 112. — Diapede-
sis OF Leukocytes.
^Adami, Inflammation, Macmillan, New York, 1909.
THE BLOOD PLATELETS 207
clearly shows that the leukocytes constitute a most important safe-
guard against bacterial invasion. They are therefore directly con-
cerned with the production of immunity.
In this connection mention should also be made of the fact that the
mammalian body contains other types of phagocytes to which differ-
ent names have been given. Contrary to the white corpuscles,
which are migratory phagocytic entities, the cells now referred to
remain "stationary.^' They are found, for example, in bony tissue
where they have to do with the absorption and removal of all super-
fluous material, or in the spleen and liver where they take up the
worn out red corpuscles and destroy them. To the first type of cells
belong the myeloplaxes of the bone-marrow, while the second group is
represented by the so-called giant cells and the third, by the endothelial
lining cells of the hepatic capillaries, generally known as the ''Stern-
zellen" of Kupfer. Since the aforesaid cells are so closely related in
function, it is quite probable that they are also allied to the leuko-
cytes in structure as well as embryologically.
Allied Functions. — Certain other functions have been ascribed to
the white corpuscles, the most important of which is their power of
taking up nutritive material and of carrying it to different parts of the
body. Thus, the lymphocytes are said to absorb fat globules and to
convey them into the lymph channels. They are also supposed to
aid in the absorption of the peptones and to help in maintaining a
proper protein content of the blood. Both functions are in keeping
with their phagocytic properties. Sufficient evidence is also at hand
to show that the leukocytes contain a substance which, when liberated,
plays an important part in the coagulation of the blood.
CHAPTER XVIII
THE BLOOD PLATELETS
Physical Characteristics. — While the blood platelets are usually
described as rounded biconvex discs, it must be granted that their
shape varies considerably from almost globular to flat. They have
also been observed to assume a spindle shape; in fact, it is stated that
they possess this form normally in the horse. They give no particu-
lar color impression. Their granular centers refract very strongly,
and stain deeply with basic dyes. For this reason, they are said to
contain a real nucleus, and may therefore be regarded as true cells.
They display ameboid movements, and if collected in a favorable
medium, present a number of variegated processes. Their specific grav-
ity is less than that of the other formed elements of the blood, which
fact accounts for their occupying the outermost layers of the blood
stream. As their diameter naeasures as a rule no more than 3/x, they
1^-
208
THE BLOOD
are scarcely half as large as the red corpuscles, but cells considerably
larger or smaller than these are not uncommon. Their number is
usually given as 180,000 to 800,000 per cu. mm., which means that they
are more numerous than the leukocytes.
Methods of Examination. — A few platelets can always be secured
by carefully collecting a drop of blood in normal saline solution; much
better results, however, are obtained with Haymen's fluid. ^ Bizzozero^
recomniends a solution of 30 per cent, gentian violet in a 0.75 per cent,
sodium chlorid solution. Their immediate fixation may be achieved
by drawing the blood into a 1 per cent, solution of osmic acid, or better
still, by previously moistening the tip of the finger from which the
blood is to be taken with this solution.^ Deetjen preserves them by
permitting a droplet of blood to flow upon agar jelly. ^ By making use
of their slight specific gravity, Biirker^ sepa-
rates them from the other formed elements in
the following manner. A drop of blood is
collected upon a thin sheet of paraffin and is
allowed to stand for a short time. The lighter
platelets collect near the surface of the drop
and may be removed by drawing a cover-glass
through its upper layers.
Origin and Fate of the Blood Platelets. —
Haymen, their discoverer, regarded the throm-
bocytes as carriers of hemoglobin and there-
fore as transitional types of the red corpuscles.
He designated them as hematoblasts. Bizzo-
zero, on the other hand, first expressed the
view that they are independent elements and
are therefore neither embryonic red cells nor the remnants of destroyed
corpuscles. To be sure, fragmented red cells may'appear in the blood
at times, but a differentiation between these bodies and the blood
platelets, as described by Bizzozero, is readily possible upon the basis
of their histological characteristics. The supposition that the throm-
bocytes are fragmentary white corpuscles also lacks satisfactory con-
firmation. Thus, it is a well-known fact that the latter do not dis-
integrate in great numbers in the circulating blood and neither do
they break up with undue rapidity in shed blood. It may indeed
be concluded that they are relatively resistant, because they are often
preserved in extra vascular and intravascular coagula of long standing.
The conclusion, that the thrombocytes are not derived from the
1 Archives de physiol. norm, et pathol., x, 1878.
2 Virchow's Arch, fur path. Anat., xc, 1882.
3 Kemp, Stud., Biol. Lab., J. Hopkins Univ., iii, 1886.
^ Made by dissolving 5 gr. of agar-agar in 500 c.c. of distilled water. To 100
c.c. of the filtrate are added 0.6 gr. NaCl solution, 6 to 8 c.c. of a 10 per cent.
NaPOa solution and 5 c.c. of a 10 per cent. K2HPO4 solution. See: Deetjen, Vir-
chow's Archiv, clxiv, 1901, 260.
^ Pfluger's Archiv, cii, 1904, 36.
Fig. 113. — Thrombocytes
Highly Magnified.
THE COAGULATION OF THE BLOOD 209
other formed elements of the blood, makes it necessary to examine
the evidence pertaining to their origin somewhat more closely. It
is believed (a) that they are not present in the normal circulating blood,
and appear only if the latter is brought in contact with a foreign body,
and (6) that they are preexisting and constant constituents of the
blood. The former view contends that the thrombocytes do not be-
long to the class of the formed elements, but appear together with
those chemicophysical alterations which indicate the beginning of the
coagulation of the blood. They constitute, so to speak, condensation
or precipitation products of the globulin constituents of the blood.
This view^ has found support in the following observations. It is
true that the platelets are absent from the blood of several animals,
for example, from that of the frog, fishes and birds. It is also conceded
that they are not very conspicuous in the blood of several mammals,
but may be rendered more prominent in these animals by first injuring
the wall of one of their blood-vessels or by introducing a foreign body
into their circulatory system. Under these conditions they may be
seen to collect upon the injured area in the form of a deposit. More-
over, Buckmaster has shown that blood drawn into the sterile serum
of another animal, does not always display these bodies, but exhibits
them very promptly if it is collected in the loop of a platinum wire.
Furthermore, while they are not present in fresh plasma which has
been rendered non-coagulable by sodium oxalate or peptone, they ap-
pear in this plasma in large numbers after it has been cooled for a
period of about 24 hours. Lastly, blood which has been treated with
an anticoagulating agent while still in the circulatory system, does
not show them, nor do they appear in it later on after its withdrawal
from the body.
The evidence which may be submitted in favor of the second view,
advocating the preexistence and independency of the thrombocytes,
is as follows: Quite aside from the fact that we are in possession of
definite methods for their isolation, we possess in the mesentery of the
guinea-pig and in the wings of the bat preparations in which it is possi-
ble to observe them directly. Moreover, they are present in large
numbers in the blood-vessels of the subcutaneous connective tissue of
various animals and particularly in that of the new-born rat. If to
these facts are added the observations regarding their ameboid
motion,^ as well as certain observations pertaining to their physical
and chemical characteristics, such as their stickiness, their great vul-
nerability and their very manifest power to incite the coagulation of
the blood, ^ it cannot be doubted that they are preformed and function-
ally distinct constituents of the blood.
1 Wooldridge, Die Gerinnung des Blutes, Veit and Co., Leipzig, 1894, and
Loswit, Virchow's Archiv fiir path. Anat., cxvii, 1889.
2Deetjen: Yirchow's Archiv fur path. Anat., cxlvi, 1901, and Deckhuysen,
Anatom. Anzeiger, xix, 1901.
3 Eberth and Schimmelbusch, Die Thrombose, Stuttgart, 1888, and Klopsch,
Anat. Anzeiger, xix, 1901.
14 .
210 THE BLOOD
The red and white corpuscles having been excluded as possible
sources of the thrombocytes, their origin remains much in. the dark.
Wright, however, has suggested that they arise from the cytoplasm
of the giant cells, the so-called megakaryocytes, which are found in,
the marrow of the bones. It is believed that these cells send out
pseudopodia which become detached and are carried away in the blood-
stream. The observations of Duke^ and others tend to show that the
life of the thrombocytes is very short.
When the blood is shed, the platelets quickly agglutinate, forming
globular or irregular masses. Their formerly pointed processes be-
come stubby and break off, while their central portions swell up and
rupture. Eventually, therefore, the platelets are reduced to chips
of insignificant size, many of which soon disappear altogether by dis-
solution, but the regions in which the thrombocytes have undergone
this disintegration, soon become the seats of active fibrin-proliferation.
In this way definite centers of coagulation are formed, from which the
different shreds of fibrin gradually extend through the blood in all
directions. Practically all the platelets take part in this process so
that they finally become intricate constituents of the network of fibrin.
The red and white corpuscles, on the other hand, remain normal,
because the shreds of fibrin pass by them without actually imbibing
them. It has been proven by Biirker^ that the number of the throm-
bocytes is proportional to the mass of the fibrin formed, and that this
reaction may be varied by changes in temperature as well as by the
addition of chemicals. Thus, any agent tending to cause a destruc-
tion of the thrombocytes, also hastens the coagulation of the blood,
while any substance possessing preservative qualities, not only retards
this process, but actually prevents it. The latter end may be attained
very readily by the addition of hirudin,^ because this substance pre-
serves the thrombocytes. It must be conceded, therefore, that, quite
irrespective of the red and white corpuscles, the disintegration of the
platelets gives rise to an agent which plays a most important part in
the coagulation of the blood. This activating substance is designated
as thrombokinase.
1 Jour, of the Amer. Med. Assoc, Iv, 1910.
2 Pfltiger's Archiv, cii, 1904, 36.
3 A crystallized form of the extract of leeches. The heads of these animals
contain the active principle, an albuminous body.
THE COAGULATION OF THE BLOOD
211
CHAPTER XIX
THE COAGULATION OF THE BLOOD
A. EXTRAVASCULAR CLOTTING
Physical Changes in Coagulating Blood. — Possibly the most strik-
ing characteristic of the mammalian blood is its power of changing its
fluid state into one of semisolidity. As this conversion, designated as
coagulation, may set in either after the blood has escaped from the
blood-vessels, or while still within them, two forms of clotting are
obtained, namely, the extravascular and the intravascular.
A
,-.:,:
-,==-
- ~-
^g^
^^
-^^^jT-i^^^^*-
®^
p^^^^g
\i^,/^^^n^
^P^)-«=->
Fig. 114. — The Coagulation of the Blood.
A, Normal blood; B, the formation of fibrin from colonies of thrombocytes envelop-
ing the formed elements; C, the separation into the coagulum and supernatant serum.
In normal blood the different corpuscular elements are freely sus-
pended in the plasma. When coagulation sets in, dehcate shreds of
fibrin are formed which advance from certain fixed points and traverse
the blood in different directions, encircling large colonies of corpuscles.
In accordance with the view of Wooldridge, these filaments arise in
consequence of a deposition of fine crystals which become confluent and
are finally united into an extensive network. The production of fibrin,
therefore, is essentially a process of crystallization, so that the coagula-
tion of the blood may be said to be based upon the crystallization of
fibrin from a supersaturated solution. The physical characteristics
of these crystals, as well as their functional properties, make it certain
that they are retained in a liquid state and should therefore not be
considered as solids. The meshes of this network are gradually drawn
more closely together so that the corpuscular elements become more
tightly packed. The entire mass finally gravitates to the bottom of
the receptacle. This gelatinous deposit is known as the coagulum.
It is composed of fibrin, the different types of corpuscles, and nutritive
material.
If the blood is permitted to clot slowly, so that a complete deposi-
tion of the red cells is had, the coagulum presents a marginal zone,
212
THE BLOOD
the color of which varies between yellowish gray and reddish gray.
It is composed in the main of fibrin and colorless corpuscles and seems
to originate in any blood in consequence of certain peculiarities in
its manner of coagulating. The name of "buffy coat" or crusta
inflammatoria, has been applied to this region.
The liquid which separates from the clot in constantly increasing
quantity, is known as the serum. While its immediate source is the
plasma, it differs from it materially, because it contains no corpuscular
nor larger nutritive elements. The separation of the blood into the
clot and the serum begins as soon as coagulation sets in, but is not
completed as a rule until about 24 hours later. During this time the
Figs. 115 and 116. — The Fibrin Needles Formed in the Clotting of Blood.
Plasma of Oxalated Dog's Blood Clotted by Thrombin. The Photographs Show
the Needles as Seen With the Ultramicroscope.
Af photographed by sun-light; B, by arc-light. Only the needles lying in the focal
plane are seen distinctly. (Howell.)
fibrin shreds contract more and more and squeeze additional amounts
of serum out of the clot. If the vessel into which the blood is with-
drawn is kept in a cool place and is not disturbed, the serum separates
as a clear, straw-colored fluid. It frequently happens, however, that
the clot adheres to the walls of the receptacle and is torn, releasing
varying numbers of red and white corpuscles. The serum then
assumes a reddish color and acquires a specific gravity which is
much greater than that of clear serum.
Chemical Changes in Coagulating Blood. — While the final and most
important change effected during coagulation is the formation of fibrin,
this body cannot be obtained unless several preliminary reactions have
first been completed. Indeed, the process of clotting may be divided
THE COAGULATION OF THE BLOOD
213
into two stages, the first ending with the formation of thrombin and
the second with the production of fibrin. Fibrin as such is not present
in the circulating blood, but is derived from a precursor through the
intervention of thrombin. The substance from which fibrin arises, is
known as fibrinogen and is present as such in the plasmatic portion of
normal blood. Fibrinogen, however, is an inert body and must first
be activated before its conversion into the final product, fibrin, can be
achieved. This activation is made possible solely with the help of a
fibrin "ferment," commonly designated as thrombin.
Thrombin as such is not present in normal blood, but is formed from
an inactive precursor, called thrombogen or prothrombin. The con-
version of the latter into its active form is accomplished by means of
an organic thromboplastic agent, called thrombokinase, in the pres-
ence of soluble calcium. The kinase is furnished by the cellular
elements of the blood, principally the thrombocytes. To recapitu-
late, the circulating blood contains fibrinogen, thrombogen and solu-
ble calcium salts. If the blood is brought in contact with a foreign
body so that a destruction of the thrombocytes results, thrombokinase
is liberated which, with the help of ionic calcium, activates the throm-
bogen into thrombin. This process constitutes the first phase of
coagulation. Its completion in turn insures the second phase which
consists in the conversion of fibrinogen into fibrin.
Blood
Plasma
Fibrinogen Thrombogen Calcium
••Thrombin*
Solids
(Thrombocytes)
Thrombokinase
►Fibrin*
This explanation of the process of clotting is in accordance with
the views expressed by Moravitz,^ Fuld and Spiro,^ and is based upon
data which have been furnished in large part by Schmidt, Wooldridge,
Pekelharing, and Hammarsten. While this view is open to several
objections, especially in regard to the action of thrombin, it is the one
commonly accepted to-day. A second explanation, which is in part
1 Hofmeister's Beitrage, iv, 1903, 381; also see: A. Schmidt, Zur Blutlehre,
Leipzig, 1892 and Wiesbaden, 1895.
2 Ibid., V, 1904, 171.
214 THE BLOOD
dependent upon the work of Wooldridge and others, has recently been
advocated by Nolf ^ and Howell.^ It is held that prothrombin may be
changed into thrombin by means of calcium alone, but this reaction
is prevented ordinarily by an antithrombin^ which is always present
in the blood. If the blood is injured, a thromboplastic substance is
liberated by the corpuscles (platelets), which neutralizes the action of
the antithrombin and allows the activation of the prothrombin by the
calcium. The second stage of coagulation takes place as described
previously. The theories just outlined, therefore, differ only in
regard to the action of the '' kinase" which, on the one hand, is said to
act as a ferment which actually takes part in the activation of the pro-
thrombin, and, on the other, is believed to inhibit the anticoagulating
substance so that the calcium is able to incite the reaction.
Thrombokinase. — As it has not been possible so far to demonstrate an organic
kinase in the plasma of the blood, it is commonly held that this clotting agent is
contained in the formed elements. For this reason, a disintegration of the latter
must necessarily precede the liberation of this substance, but as relatively few red
cells are destroyed during the shedding of the blood, it may be concluded that
these elements cannot possibly harbor the coagulating agent. It has also been
observed that these cells are quite ineffective under ordinary conditions, but
may be changed into a coagulating agent if the hemoglobin is thoroughly separated
from the stroma. With the help of the latter even intravascular clotting can
readily be effected. Practically the same statement may be made regarding the
white corpuscles. It is true, however, that under experimental conditions clot-
ting may be greatly accelerated by the addition of leukocytic material. But this
fact cannot be employed as a strong argument in favor of the view that they do
play a part in normal clotting, because they are found in large numbers in exudates
in which coagulation has not taken place. And furthermore, plasma from which
the leukocytes and red cells have been removed by centrifugalization, may be made
to clot by the addition of water or by passing a current of carbon dioxid through it.
Wooldridge, moreover, has shown that the white cells of lymph, when washed in
salt solution, are quite unable to clot the lymph from which they have been taken
and neither can they coagulate peptone-plasma in the absence of platelets or their
derivatives.
The thrombocytes, on the contrary, have been shown to exert a most important
influence upon coagulation, because they disintegrate very rapidly in shed blood
and the amount of fibrin formed is nearly proportional to the number of platelets
destroyed. Various experiments may be cited in support of this statement.
Thus, it is possible to increase or to decrease their destruction by subjecting them
to different temperatures or to different mechanical and chemical influences.
In general, it holds true that a medium which tends to preserve them, delays the
coagulation, while a medium which is injurious to them, hastens this process.
For example, if a drop of a solution of ammonium oxalate (1/100 N) is added to a
drop of blood, coagulation fails to take place. If this sample of blood is examined
later on, it will be found to contain the thrombocytes in a state of perfect preserva-
tion, while the red and white corpuscles are thoroughly fragmented. Moreover,
Schmidt has called attention to the fact that the plasma derived from sedimented
horse-blood, exhibits a difference in its coagulability in so far as its upper portion
clots more readily than its lower, but may be made to remain fluid for a much
longer time than the latter by passing it through a filter. In explanation of this
* Archives intern, de physiol., ix, 1910, 407.
2 Am. Jour, of Physiol., xxix, 1911, 29.
' Called hepatothrombin by Nolf .
THE COAGITLATION OF THE BLOOD 215
phenomenon, it may be stated that the thrombocytes, on account of their lesser
specific gravity, collect in much greater numbers near the surface of the plasma and
that they may then be removed from it by filtration. Bizzozero beat freshly
drawn blood with cotton threads until they were thoroughly covered with plate-
lets. They were then washed in a 0.7 per cent, solution of sodium chlorid to
remove the red corpuscles. If desired, a rapid coagulation of artificial pro-
thrombin could then be effected by suspending these threads in solutions of this
substance. To prove his point more conclusively, he showed subsequently that
this result cannot be obtained with the cotton threads alone, while threads covered
with red cells or with leukocytes, gave rise, at best, to only a very slow type of
coagulation. Moreover, it has been observed repeatedly that the disintegrating
thrombocytes act as centers for the formation of fibrin, and that the injection of
platelets into the circulation produces intravascular clotting. It must be con-
cluded, therefore, that the platelets yield a substance which serves as the exciting
agent of the coagulation.
Morawitz calls this agent thrombokinase, but it is also referred to as cytocym.
If it is assumed that the platelets are not real cells but merely fluid crystals, the
liberation of the thrombokinase would correspond to the deposition of these
crystals as insoluble threads of fibrin. For the present, however, it seems best to
adhere to the view of Morawitz, Fuld and Spiro as previously outlined. In
accordance with this explanation, it becomes necessary to assume further that the
blood of those animals which does not clot when collected directly from the blood-
vessel, contains no thrombokinase. The absence of this agent is readily accounted
for, because these animals are not in possession of thrombocytes. Instead,
their tissues contain a very effective thromboplastic substance which takes the
place of thrombokinase and which is brought in contact with the blood as it
flows across the opened surface. But, the mere fact that 'in us and allied animals
the principal coagulating agent is held in the blood itself, does not preclude the
possibility of a similar substance being present in our tissues; in fact, it seems
entirely probable that we are thus doubly protected.
Thrombogen is a normal constituent of the plasma. Only a part of it is used
up during coagulation. The remaining portion escapes activation either because a
sufficient quantity of thromboplastic material to cause its complete conversion is
not at hand, or because its formation is stopped as soon as the coagulation has
advanced to a certain stage. It is not present in the tissues, and the indications
are that it is not derived from the cellular elements of the blood, but is held in
solution in the plasma. Drinker^ believes that it arises in the bone-marrow,
because it may be removed from the latter in considerable amounts by perfusion.
It is very stable and is capable of withstanding the temperature of boiling water
for a brief period of time. Although calcium is necessary to incite its conversion
into thrombin, this salt is by no means the precursor of thrombin. Thrombogen
is also known as prothrombin, proferment or plasmozym.
Thrombin, or fibrin ferment is not a preexisting constituent of the blood nor
of any one of the fluids of the body. Thus, if blood is withdrawn directly into an
excess of alcohol, the precipitate, when dried, pulverized, and extracted with
water, yields practically no thrombin. While it is usually regarded (Schmidt)
as an enzyme or ferment, it must be remembered that an agent of this kind possesses
the property of producing maximal reactions even when present in minute
amounts. Another peculiarity of enzymes is their power of producing a chemical
reaction without losing any of their substance. But as Wooldridge, Nolf and Rett-
ger2 have failed to observe these peculiarities in thrombin, its ferment nature has
not been definitely established. Indeed, the evidence seems to point rather the
other way, because it has been found that the amount of thrombin is directly pro-
portional to the amount of fibrin formed, as the following compilation will show :
1 Am. Jour, of Physiol., xli, 1916, 5.
2 Am. Jour, of Physiology, xxiv, 1909, 429.
216 THE BLOOD
5 drops of thrombin yield 0.2046 gm. of fibrin.
10 drops of thrombin yield 0.3575 gm. of fibrin.
20 drops of thrombin yield 0.6089 gm. of fibrin.
40 drops of thrombin yield 1.5872 gm. of fibrin.
Besides, it has been noted that thrombin actually becomes a part of the final
product, and that this reaction does not vary with the temperature, i.e., it takes
place at 17° C. as well as at 40° C. Rettger, therefore, draws the conclusion that
fibrin is not derived exclusively by a progressive conversion of the fibrinogen,
but may also be produced by a direct combination of these bodies. The product,
however, is unstable, because the thrombin may be separated from it with relative
ease. Thrombin may also be prepared in accordance with the directions given by
Schmidt. 1 A certain quantity of blood having beien permitted to clot, the serum
is precipitated by the addition of 15 to 20 volumes of alcohol, in excess. The pre-
cipitate is removed after several days or months and is dried, pulverized and ex-
tracted with water. While this solution contains different protein bodies and salts,
it may be concluded that the coagulation which it induces when added to solutions
of pure fibrinogen, is caused by its thrombin constituent. Buchanan and Gamgee
advise to extract the ordinary washed fibrin for several days with an 8 per cent,
solution of sodium chlorid. The filtrate is not pure, but contains dissolved
proteins in addition to much thrombin. HowelP purifies this extract by shaking
it repeatedly with chloroform. In this way, the coagulable proteins are removed,
while the thrombin is left behind in a pure state, although somewhat diminished
in quantity. This author states that it is easily soluble in water and is not coagu-
lated by boiling. Moreover, while it is difficult to precipitate it with alcohol in
excess, it may be precipitated with ammonium sulphate in half saturation. As
it gives positive results with several of the ordinary protein reagents, it must be
regarded as a protein substance.
Fibrinogen exists as an independent body in the plasma of the circulating
blood. It is also present in lymph, chyle, and certain transudates and exudates,
but not in the blood serum, inasmuch as it is used up in the process of clotting.
While its place of origin is not definitely known, it is certain that it is not derived
from the corpuscular elements of the blood. It should be mentioned, however,
that some evidence is at hand to show that it may be formed in the liver and in the
myeloid tissue of the bone-marrow. Thus, Nolf has found that the quantity of
fibrinogen in the blood may be greatly diminished by extirpating the former organ
or by the administration of poisonous amounts of phosphorus or chloroform. Men-
tion should also be made of the observation of Dastre that the blood of the mesen-
teric vein is richer in fibrinogen than that of the corresponding artery. This fact
has been interpreted as showing that the intestinal wall is one of the sources of
this substance.
Fibrinogen may be obtained in solution and free from other proteins in the
following manner: A quantity of fresh blood is mixed with a solution of sodium
oxalate in amounts sufficient to give a 0.1 per cent, oxalate mixture. The latter
is then centrifugalized and its plasma portion precipitated by the addition of an
equal amount of a saturated solution of sodium chlorid. The resulting precipitate
of fibrinogen is pressed out or centrifugalized, redissolved in an 8 per cent, salt
solution, and the filtrate precipitated by a saturated salt solution. Having been
subjected to this process three times, the final precipitate is pressed between filter
paper and is then finely divided in water. The precipitate may be dissolved
in a 1 per cent, solution of sodium chlorid. If it does not dissolve readily, a few
drops of a 0.5 per cent, solution of sodium bicarbonate should be added. The
traces of sodium oxalate may be removed by dialysis in a colloidin sac, against a
1 per ceQt. solution of sodium chlorid.
1 Pfliiger's Archiv, xi, 1887, 515.
2 Am. Jour, of Physiol., xxvi, 1910, 26.
THE COAGULATION OF THE BLOOD 217
A pure solution of fibrinogen may be kept at ordinary temperatures for an
indefinte period of time without its yielding even traces of fibrin. A perfectly
typical coagulum, however, may be produced, if either a washed fibrin-clot, a small
quantity of blood serum, or a solution containing thrombin is added to it.
Fibrinogen is a protein. It belongs to the group of the globulins. From para-
globulin, it may be distinguished in several ways ; viz. : it coagulates at a lower tem-
perature (55° to 60°), is completely precipitated by saturation with sodium chlorid
or magnesium sulphate, and may be converted into the insoluble protein, fibrin.
Its percentage composition has been given by Hammarsten as: C 52.93, H 6.90,
N 16.66, S 1.25, O 22.26. According to Schmiedeberg its molecular composition
is: Cl08Hi62N3oS034.
Fibrin. — In accordance with the analyses of Hammarsten, fibrin possesses the
same composition as fibrinogen. This similarity, however, is only an apparent
one, because as both substances are extracted with alcohol and ether, the fat and
lipoid are not included inj the analysis, and hence, the remaining substance
appears as a protein of the composition just given. Wooldridge, ^ in fact, believes
that these bodies are not identical at all but show certain differences in the lipin
part of their molecules. Fibrinogen as it exists in the plasma is regarded as a
iecithoprotein or as a substance containing much phospholipin. Fibrin is similarly
constituted, but contains less phospholipin. The chemical process underlying the
formation of the relatively insoluble fibrin is not clearly understood. Fibrinogen
is said to change first into soluble fibrin, and later on into fibrin proper. In accord-
ance with Hammarsten, 2 a hydrolysis results which splits the molecule of the fibrin-
ogen into fibrin and fibrinoglobulin. Other investigators, however, assume that
physicochemical alterations are incited which lead to an intramolecular rearrange-
ment of the fibrinogen. Thus, fibrinogen is regarded as the hydrosol, and fibrin as
the hydrogel of one and the same globulin. ^ It is also supposed that a precipita-
tion of the fibrinogen by electrolytes takes place soon after the thrombin has incited
its decomposition.*
If the blood is beaten with a rough piece of wood while it is being withdrawn
from the blood-vessel, the fibrin accumulates upon the stick in the form of an
elastic fibrous mass, the springiness of which is lessened as soon as the shreds are
torn or are separated from their attachments. This deposit is always contamin-
ated with red corpuscles and lymphoid cells. If it is essential to obtain this sub-
stance in a pure form, it should be prepared from filtered plasma, or from filtered
transudates; moreover, it should be noted that if it is allowed to remain in contact
with the blood from which it has been removed, it dissolves in part. While the
factors which are responsible for this fibrinolysis are not known, it is believed that
they are of enzymic origin. Fibrin derived from the blood of different animals,
exhibits somewhat different properties. It is insoluble in water, alcohol and ether,
but may be dissolved in dilute salt solutions at a temperature of 40° C.
B. INTRAVASCULAR CLOTTING
It has been found that the blood retains its fluid condition only as
long as it is permitted to remain in contact with the normal intima of
the blood-vessels. This statement implies that coagulation must set
in as soon as the blood is brought in relation with a foreign body,
whether this be outside or inside the vascular channels. Intravascular
1 Collected papers, Rep. to the Scient. Comm. of the Grocer's Assoc, i, 201;
ii, 266.
2 This view is also held by Schmiedeberg (Archiv fiir Exp. Path, und Pharm.,
xxxix) and Heubner (ibid., xlix, 1903, 229). '
2 Iscovesco, Soc. Biol., Ix andlxi, 1906.
* Friedemann and Friedenthal, Zeitschr. fiir exp. Path., iii, 1906, 73.
218 THE BLOOD
clotting may be incited by introducing a solid object directly into the
blood-stream, or by causing a trauma of the blood-vessel and surround-
ing tissue so that these will be changed into destructive agents. A
thin layer of fibrin is then deposited upon the injured area, more and
more material being gathered in gradually until a clot has been formed
which may occlude the entire lumen of the blood-vessel. When fully
formed, a clot of this kind is known as a thrombus. After the blood
current has played against this intravascular coagulum for some time,
pieces of it may be broken off and carried to distant parts of the cir-
culatory system, where they may obstruct the blood flow and give rise
to an anemia and functional uselessness of the tissues situated distally
to the block. A floating thrombus is known as an embolus.^ The
ultimate outcome of a condition of this kind depends upon the freedom
with which the tissues so cut off may be supplied with blood by anas-
tomosing vessels. It need scarcely be mentioned that the lining of
the blood-vessels may also be changed into a destructive agent by the
products of bacteria, and other toxic substances circulating through
the system.
Intravascular clotting may also be incited experimentally by the
injection of solutions of various substances. In accordance with the
statements made previously, it might be supposed that thrombin or
thromboplastic substance would act as very powerful coagulating agents
when introduced into the circulation, but, curiously enough, the system
possesses the power of protecting itself against them. Howell believes
that the action of thrombin is neutralized in this case by a greater
production of antithrombin.
The effects obtained with tissue extracts and solutions of thrombo-
plastic substance are rather perplexing. Extensive clotting most
frequently results in consequence of the injection of moderate amounts
of thrombokinase and extracts of organs rich in cellular elements, such
as the thymus and lymph glands. It has been suggested by Wool-
dridge that these extracts contain thrombokinase. Their injection,
therefore, leads to the same results as the liberation of this body in
shed blood. It is to be noted, however, that small quantities of these
extracts diminish the coagulability of the blood. The former reaction
is usually designated as the positive and the latter as the negative
phase of the injection, but as a lessening of the coagulability cannot be
obtained in this manner during extravascular clotting, it must find its
origin in certain functional pecuHarities of the tissue cells, analogous
to their behavior toward toxins. It is a well-known fact that the
injection of diphtheria toxin gives rise to a certain amount of antitoxin
in the course of two or three days. Additional injections, however,
most generally produce a complete disappearance of the antitoxin
until, a day or two later, it again makes its appearance in quantities
much larger than those present before the second injection. It should
1 The circulation may also be obstructed by embolisms of different origin, for
example, by droplets of fat or bubbles of air.
THE COAGULATION OF THE BLOOD 219
also be mentioned that the effects of Witte's peptone, or of hirudin are
only temporary. It seems, therefore, that certain tissue cells possess
the power of rendering these substances inert, the probabiUty being
that this neutrahzation is brought about by the discharge of an anti-
coagulating agent.
The fact that the blood does not clot while traversing the normal
circulatory channels, may therefore be explained in two ways, namely:
(a) by saying that thrombokinase is not liberated as long as the blood
is prevented from coming in contact with a destructive agent and (6),
that a certain amount of an anticoagulating substance is always pres-
ent in the blood which serves the purpose of retaining the thrombin
in its inactive condition.
THE TIME OF COAGULATION
The period intervening between the moment of the withdrawal of
the blood and the moment when it has assumed a jelly-Hke consistency,
is known as the coagulation time. Various methods have been devised
to determine its length, but none of them gives absolutely reliable
results. Vierordt^ employed a glass tube possessing a diameter of 1
mm. and a length of 5 cm. A white horse hair
having been placed lengthwise in this tube, the* [ j
latter was then filled with the blood to be tested.
After a few moments the hair was withdrawn ' — i r\ B Tr"
at intervals and a short distance each time, until
small coagula began to adhere to it. Possibly
the simplest procedure is to collect a small quan-
tity of blood in a test tube of ordinary size, ^'""'TiMETF^Bro'L^™''
noting the time of its withdrawal, and to deter- ^^ chamber in which
mine again the moment when it is possible to drop is suspended from
invert this tube without causing the blood to """^,^''^ f "?^^ (^^ "^^^^
no 1 ocular of microscope.
flow out. Brodie and RusselP advocate the
following method: A drop of freshly drawn blood is placed upon
the poHshed tip of a conical piece of glass (Fig. 117). The latter is
then inverted and placed in a small compartment underneath a lens
magnifying thirty diameters. Very weak currents of air are brought to
bear upon the lateral surface of this suspended drop at intervals of
thirty seconds until the corpuscles cease to spin around and the ex-
ternal layers have assumed a gelatinous consistency. Btirker^ employs
a glass sHde the central area of which is depressed and surrounded by
a low wall of glass. A drop of boiled water is then placed in this com-
partment, to which is added a drop of fresh blood. The time of mixing
these fluids is accurately recorded by means of a kymograph and
1 Archiv fur Heilkunde, 1878, 193.
2 Jour, of Physiol, xxi, 1897, 403; also see^ Pratt, Archiv fur Exp. Path,
und Pharm., xlix, 1903, 299.
3 Pfluger's Archiv, cii, 1904, 57.
220
THE BLOOD
Jaquet chronometer. At intervals of half a minute the hair-like end
of a glass rod is drawn through this mixture from side to side until it
catches the first shreds of fibrin. This moment is again noted. Can-
non and MendenhalP have devised a small instrument, known as a
graphic coagulometer, consisting of a horizontal writing lever and a
vertical glass tube containing the blood to be tested (Fig. 118). A
coil of very thin copper wire is suspended in this blood, its other end
being attached to the tip of the lever. The latter is counterpoised
in such a manner that it retains its horizontal position without supports
as soon as the blood is coagulated. This procedure, therefore, con-
sists in releasing the lever at intervals of 30 seconds until its pointer
fails to rise.
The experiments of Vierordl have shown at an early date that the
coagulation time of human blood is subject to considerable daily varia-
tions. During the morning hours, he found its value to be 9.6 minutes.
»v, C.
Fig. 122. — Diagram Illustrating
Interaction Between Complement C
AND AntigeIst a.
Am, amboceptor; Cy, cytophile
and Co, complementophile part
amboceptor.
252 RESISTANCE AND IMMUNITY
sickness. Arthus/ moreover, had proved that a second injection of
horse serum into rabbits frequently causes a very intense reaction, so
much so that this formerly perfectly harmless procedure becomes dis-
tinctly injurious. Quite similarly, it had been observed that a tuber-
culous person is hypersensitive to tuberculin and that injections of
cocain eventually give rise to an increased susceptibility, as evinced
by undue rises in the body temperature.^ A similar hypersensitiveness
follows the repeated administration of apomorphin.^ Anaphylaxis,
therefore, may be active and passive, because it is possible to render
an animal anaphylactic by these injections and also to transfer this
state from a sensitized to a normal animal. The latter process
requires the injection of the serum of an anaphylactic animal which is
then followed, say 24 hours later, by an injection of the antigen origi-
nally used to produce this condition in the first animal.
Numerous theories have been advanced to explain anaphylaxis.
In general it may be said to be a reaction between the antigen and the
specific antibody. In the same way as antibodies are developed after
a definite period of incubation, a certain antigen may eventually give
rise to anaphylactic bodies, such as toxogenin (Richet) anaphylactin
or sensibiHn. This complex formed by the antigen and antibody be-
comes poisonous in the course of this reaction, but it may also be true
that the reaction affects the medium (blood-serum) in such a way
that it assumes toxic properties.
iSoc. biolog., Iv, 1903, 817.
2 Adnico, Arch. ital. de bioL, xx, 1894.
3 Richet, Soc. biolog., Iviii, 1905, 955.
PART III
THE CIRCULATION OF THE BLOOD
SECTION VII
THE MECHANICS OF THE HEART
CHAPTER XXIII
A COMPARATIVE STUDY OF THE CIRCULATORY SYSTEM
General Arrangement of the Vascular System. — In its simplest
form the circulatory system consists of two parts, namely, a fluid
and a circular tube, the caliber of which is greatly increased at one
point to represent the pumping mechanism, or heart. The latter
first appears in the form of a simple bulbular enlargement of the gen-
eral vascular channel and finds its origin in the deposition of large
numbers of muscle cells possessing automatic properties. This enables
the walls of this organ to contract at intervals and to place the fluid
within under a higher pressure than that prevailing in the tubes with-
out. In consequence of this difference in pressure, the fluid is forced
through orifices (A) and (B) into the distal channel (C), but as every
phase of contraction of the musculature must necessarily be followed
by a phase of relaxation, the fall in pressure then resulting within the
heart must permit the fluid to return into the central cavity (H).
A simple arrangement of this kind, however, is not adapted for
anything dynamically more perfect than an oscillatory to and fro
motion of the fluid. A true circular motion can only be imparted to
the fluid within this system by guarding the aforesaid orifices {A and
B) of the heart (H) by valves which open only in the direction of the
flow. These valves having been put in their proper, places, the con-
traction of the cardiac musculature now forces the fluid across the
yielding valve flap (A) into the distal channel (C), but is unable to drive
it through the opposite orifice (5), because this valve closes immediately
upon the first increase in the central pressure. A moment thereafter,
however, when the relaxation of the cardiac musculature has led to
the establishment of a lower central pressure, the valve at (B) is opened,
allowing the fluid to reenter the central compartment. Inasmuch
253
254
THE MECHANICS OF THE HEART
as valve (A) is firmly closed at this time, a definite direction of
flow is now imparted to the fluid. It leaves the heart (H) through
the arterial orifice . (A) and cannot return to this organ until it has
traversed the entire tube (C) .
The channel which conveys the blood away from the heart is
known as an artery, while the one returning the blood to this organ is
called a vein.^ In a true circulatory system these two divisions are
joined by a multitude of fine tubules, designated as capillaries, so that
the- entire vascular system is really com-
posed of three parts, namely of arteries,
capillaries, and veins. In accordance with
certain structural pecuHarities, these chan-
nels may be subdivided further so that in
final analysis the circulatory system con-
sists of arteries, arterioles, arterial capil-
laries, capillaries proper, venous capillaries,
venules, and veins. The central arterial
tube is commonly spoken of as the aorta,
and the central collecting channel as the
vena cava.
The Circulatory System in the Lower
Animals. — In the lowest forms the nutri-
tion of the outlying colonies of cells is
effected by progressive and oscillatory
streams which are brought into existence
by differences in pressure as well as by
the processes of diffusion and osmosis. In
the highest animals, on the other hand,
these simple movements give way eventu-
ally to a complex roundabout motion of
the body fluid, but this end is not attained
until the circulatory mechanism has passed
through several intermediary stages of de-
velopment. In order to be able to follow these changes more closely,
it seems advisable to initiate this discussion with a study of the con-
ditions existing in such forms as the sponges which may be said to
possess a circulation of the most elementary kind. We find here
that the water enters through numerous pores of the derma and is
then returned to the surrounding medium by way of the central canal
and the osculum. The power necessary to produce this flow is fur-
nished by the cilia with which the aforesaid passage is beset. The
higher ccelenterates are in possession of an alimentary canal, the
smaller recesses of which extend far into the substance of their
bodies. In this way, these saccular extensions are enabled to serve
1 For this reason, the pulmonary artery is known as an artery, although it
contains venous blood, and the pulmonary vein as a vein, in spite of the fact that
it contains freshly aerated blood.
Fig. 123. — Schema op Simple
clbculatoky system.
I, phase of contraction; II,
phase of relaxation of heart; A
and B, valves guarding cardiac
orifices; D, arteries; C, capil-
laries; E, veins.
A COMPARATIVE STUDY OF THE CIRCULATORY SYSTEM 255
as intermediary agents between the distant cells and the nutritive
material in the alimentary passage. In the medusa well-marked
gastrovascular streams may be observed. The lower vermes ex-
hibit an arrangement very similar to that found in the ccelenterates.
In the slightly higher forms, however, the alimentary tract is com-
pletely separated from the general body cavity, so that the gas-
tric prolongations are enabled to assume the function of true cir-
culatory channels. The fluid within them is albuminous in character,
and is moved from place to place by differences in pressure produced
by the general movements of the body. In some anneUds, the cir-
culatory system is fully differentiated and consists of a dorsal and a
ventral tube which are connected with one another
by several branches. As the latter, as well as the
adjoining segments of the dorsal tube, are- auto-
matically active, these forms may be said to be in
possession of a real heart which, however, presents
a most rudimentary structure. Its most essential
characteristic is its tubular shape. In Arenicola,
the main cardiac cavity is constricted at one point
so that the cardiac tube as a whole appears as two
distinct compartments.
Similar differences are to be noted among the
vertebrates. Amphioxus, for example, does not
possess a distinct heart, a portion of its posterior
aorta being equipped with automatic power. It
should be remembered, however, that this animal
presents the first indications of a portal circuit, be-
cause the dorsal aorta gives off certain branches to
the intestine, from which organ the blood is then
collected by a single tube, which is known as the
portal vein. Having traversed the capillaries of
the liver, the blood is eventually returned into the
ventral aorta.
In the lower animals, the power of rhythmic activity extends over
relatively long segments of the dorsal and lateral blood-vessels; but
in the fishes the heart loses its diffuse tubular character, and the power
of contraction becomes restricted to a particular area of the vascular
system. These animals are in possession of a cardiac mechanism which
occupies the ventral extent of the body-cavity and presents a structure
very similar to that found in the higher animals. It is protected on
aU sides by a membrane which is reflected from its base to form a pouch,
the so-called pericardial sac. The organ, as a whole, is composed of
two compartments, an antechamber or auricle, and a main chamber
or ventricle. Moreover, as the veins do not unite with the auricle as
separate tubes, but become confluent, a vestibular chamber is formed
which is commonly designated as the sinus venosus. Quite similarly,
the aorta does not arise from the ventricle itself , but from an appendage,
Fia 124.— Dia-
gram TO Show the
Course of the Blood
Through the Fish
Heart.
SV, sinus venosus;
A, auricle; V, ven-
tricle; BA, bulbus ar-
teriosus; A, aorta
with (C) arteries to
gill plates.
256
THE MECHANICS OF THE HEART
known as the conus arteriosus. All these different parts of the heart
possess contractile powers, their action being coordinated in such a
manner that the sinus contracts first, the auricle next and the ventricle
and conus last of all. The blood traverses the chambers of the heart
in the same direction. An oscillatory flow is made impossible by : (a)
the proper sequence of contraction of the different segments of the
heart and (6) the fact that the cardiac orifices are guarded by valves
which open only in the direction from sinus to ventricle.
In accordance with the force which the different parts of the heart
must develop in order to propel the blood, the ventricle contains a
^^^
much greater amount of muscle tissue than
the auricle or sinus. It must be remem-
bered that the ventricle produces the pres-
sure which is necessary to drive the blood
through the entire vascular system. In ac-
complishing this end it must overcome the
relatively high resistance prevaihng in the
peripheral blood-vessels. The sinus and
auricle, on the other hand, pump the blood
merely into the adjoining ventricle and, as
this transfer is effected at a time when the
latter is in a condition of rest, the ante-
chambers need not develop anything more
than very moderate degrees of pressure.
A peculiar modification of the circula-
tory system is found in fish. Inasmuch
as the respiratory interchange in these
animals is effected by means of the gills,
this particular circuit is most highly de-
veloped, while the lungs with their pulmo-
nary system of blood-vessels are, of course,
absent. The circulation of the gills is
made possible by a number of afferent
branches which are given off from the ven-
tral aorta and lead to the different gill-
plates. From here the blood is conveyed
to the dorsal aorta by way of the efferent vessels. In this way, only a
part of the blood discharged by the heart finds its way into the gills,
where it is aerated and is distributed subsequently to all parts of the
body. It is returned to the heart thoroughly charged with carbon
dioxid. The fourth subclass of the fishes, the Dipnoi, present rather
complicated conditions, because they are equipped with lungs as
well as with gills and hence, are in possession of a pulmonary and a
gill-circuit.
The heart of the amphibians is situated in the fore part of the body
ventrally to the first vertebrae, and consists of a sinus venosus, two
auricles, and a ventricle with its bulbus arteriosus. The blood which
Fig. 125. — Diagram to Show
THE Course of the Blood
Through the Amphibian Heart.
SV, sinus venosus; RA,
right auricle; LA, left auricle;
V, ventricle; BA, bulbus arte-
riosus; A, aorta; PA, pulmo-
nary arteries; PV, pulmonary-
veins. The striated portion
contains venous blood, the
dotted portion mixed blood,
and the clear space, arterial
blood.
A COMPARATIVE STUDY OF THE CIRCULATORY SYSTEM 257
is returned from the system, flows into the right auricle, while the
blood which has just been aerated in the lungs, enters the left auricle.
When these parts contract, both types of blood are simultaneously
forced into the ventricular cavity, where they must intermingle
somewhat, because they are not kept apart by partitions. It must be
emphasized, however, that a thorough mixture of the aerated with the
venous blood cannot take place, because the interval between the
auricular and ventricular contractions is extremely brief, and because
the ventricular wall contains numerous recesses, in which at least a
part of the venous and oxygenated types of blood finds separate lodg-
ment. It is only natural to suppose that these types of blood will be
forced into those parts of the ventricle
which lie directly below their respective
auricular orifices. It is also true that
the venous blood reaches the conus
arteriosus ahead of the oxygenated, be-
cause the right expanse of the ventricular
cavity lies nearest this structure. More-
over, as the resistance in the pulmonary
circuit is less than that in the systemic
blood-vessels, the first gush of ventricular
blood, venous in character, must find its
way into the lungs by way of the pulmo-
nary artery, while the aerated portion
following it must necessarily be diverted
into the peripheral channels. A special
system of blood-vessels for the muscula-
ture of the heart is not present in amphi-
bians. These animals, however, are in
possession of a hepatic portal system and
a peculiar renal portal system. The
latter modification of the vascular mechan-
ism finds its origin in the double blood-
supply of the amphibian kidney. It will be
remembered that its glomeruli receive their
Fig. 126. — Diagram to Show
THE Course op the Blood
Through the Reptilian Heart.
SV, sinus venosus; RA, right
auricle; LA, left auricle; V, ven-
tricle incompletely divided by a
septum; A, aorta; PA, pulmo-
nary arteries; PV, pulmonary
vein. The striated portion con-
blood from the aorta directly, while the re- tains venous blood, the non-
maining portions of the urinary tubules striated arterial blood,
are supplied by the renal portal vein.
The heart of the reptiles resembles that of the amphibians in
several particulars. It also consists of a sinus, two auricles, and a
ventricle. A two-lipped valve is situated in the sino-auricular orifice
and a right and left semilunar valve in the corresponding auriculo-
ventricular openings. The ventricle, from which the aorta and pul-
monary artery emerge separately, is divided into two compartments
by a muscular septum. The separation is complete in the crocodiles,
but incomplete in the snakes, lizards,- and turtles. In the animals
named last, the tendency is to keep the venous blood separated from
17
258
THE MECHANICS OF THE HEART
the aerated, the former being held in the compartment to the right^
and the latter largely in the space to the left of this septimi. During
the contraction of the ventricle, the edges of the septal flaps are brought
together so that the largest amount of the venous blood is forced into
the pulmonary artery, while the oxygenated blood is diverted chiefly
into the aorta. But while definite provision has been made in these
animals to prevent a complete mixture of the venous with the aerated
blood, a certain degree of intermingling is still possible in several places
outside the heart. Excepting certain fish, the reptilian heart is the
first to exhibit a system of blood-vessels for the nutrition of the cardiac
musculature. The hepatic portal is
associated with a renal portal system.
The heart of birds possesses four
chambers, namely two auricles and two
ventricles. A distinct vestibular por-
tion is not present. The blood is re-
turned from the tissues by the right
and left post, cavae. It enters the right
auricle and then the right ventricle,
whence it is conveyed to the lungs
through the pulmonary artery. Four
pulmonary veins conduct it from here
to the left auricle and left ventricle,
whence it again attains the peripheral
tissues by way of the aorta and its
branches. Thus, for the first time, the
aerated blood is completely separated
from the venous blood by a longitudinal
septum which divides the heart into a
right and a left side. Each side in
turn embraces an antechamber, or
auricle, and a main chamber, or ven-
tricle. The auriculoventricular orifices
are guarded by membranous valve
flaps, the right being large and muscular. The aortic and pulmonary
orifices are beset with three cup-shaped valve-flaps. Owing to the
functional importance of the wings and the corresponding massive-
ness of the pectoral muscles, the arteries supplying these parts are very
large in caliber. Moreover, in agreement with the position of the legs,
the femoral blood-vessels are found far forward in the body.
The Circulatory System in Mammals. — In mammals, the heart
is divided into a right and left half and each half in turn into an ante-
chamber, or auricle, and a main chamber, or ventricle. The blood
which is returned from the tissues, enters the right auricle by way of
the superior and inferior venae cavae, while the blood from the lungs
is conducted into the left auricle by way of the pulmonary veins.
Two distributing channels leave the heart, namely, the pulmonary
Fig. 127. — Diagram to Show
THE Course of the Blood Through
THE Heart of Birds.
PC, post, cavae; /2A, right auricle;
LA, left auricle; RV, right ventricle;
LV, left ventricle; PA, pulmonary
artery; PV, pulmonary vein; A,
aorta.
A COMPARATIVE STUDY OF THE CIRCULATORY SYSTEM 259
r
artery and the aorta. The former conveys the blood from the right
ventricle to the lungs, and the latter from
the left ventricle to all parts of the body.
If the multitude of blood-vessels con-
stituting the different divisions of the cir-
culatory system are taken and moulded
into single channels, a system of tubes is
formed such as is represented in the ad-
joining schema (Fig. 128). In studying
this diagram more closely, we find that
a droplet of blood leaving the left ven-
tricle first enters the central arterial
trunk, or aorta, whence it escapes into
either the blood-vessels of the head or
those of the trunk and lower extremities.
In either case, it must first traverse the
arteries, then the arterioles and finally,
the capillaries. Having attained the
other side of these extremely fine tubules,
it enters the venules and then the veins
to be eventually conveyed into the right
auricle. The venous trunks in the vi-
cinity of the heart are designated as the
superior and inferior cava respectively.
This extensive system of blood-vessels
which suppHes all the tissues of the body
with the exception of the lungs, consti-
tutes the greater, or systemic circuit. It
embraces two specialized smaller divi-
sions, namely, the coronary and portal
circuits. The former arises from the
root of the aorta as the coronary artery
and ends in the right auricle as the
coronary vein or sinus. The coronary
blood-vessels have to do solely with the
nutrition of the heart. The portal cir-
cuit begins with the arteries supplying
the so-called portal organs, namely, the
spleen, pancreas, liver, stomach, and in-
testine. Having traversed the different
capillary networks of these organs, the
blood is collected by a single channel,
known as the portal vein, and is then
conducted to the liver, whence the he-
patic veins convey it into the inferior
vena cava. The portal circuit, therefore; is concerned chiefly with the
processes of digestion and absorption.
Fig. 128. — Schema of the
Circulation.
A, aorta; Ar, arteries; Art,
arterioles; AC, arterial capillaries;
C, capillaries; VC, venous capil-
laries; Ven, venules, Ve, veins;
VCS, vena cava superior; VCJ,
vena cava inferior; RA, right
auricle; RV, right ventricle; LA,
left auricle; LV, left ventricle; 1,
tricuspid valve; 2, mitral valve;
3, pulmonary semil. valve; 4, aortic
semil. valve; PA, pulmonary-
artery; L, lungs; PV, pulmonary
veins ; PO, portal organs ; PV, por-
tal vein; HA, hepatic artery; Li,
liver; HV, hepatic vein.
260 THE MECHANICS OF THE HEART
The second principal division of the circulatory system is fonned
by the lesser or pulmonary circuit. It consists of the pulmonary artery
and its branches which conduct the blood from the right ventricle into
the capillaries of the lungs, and of the pulmonary veins which collect
the aerated blood and return it into the left auricle. Thus, while
every drop of blood is forced to traverse the greater and lesser circuits
successively, the course which it may pursue is not restricted to one
and the same channel, because it may pass either into the capillaries
of the head or into those of the heart, portal organs and posterior ex-
tremities. In other words, a large number of shorter and longer
paths are open to it.
In perfect agreement with the circulation in the lower forms, the
blood of the mammal is made to flow in the direction indicated,
because the contraction of the auricles antecedes that of the ventricles
by a definite period of time, and because the circulatory channel is
beset with valves which open only in one particular direction. As far
as the second factor is concerned, it should be stated at this time that
there are three sets of valves to be considered, namely: (a) the auriculo-
ventricular which guard the openings between the auricles and ven-
tricles, (6) the semilunar which are situated in the orifices of the aorta
and pulmonary artery, and (c) numerous venous valves which are
placed as a rule at the points of confluency of small and large veins.
The first set of valves comprises the tricuspid and mitral, the former
being placed in the right and the latter in the left orifice. Both open
downward into the cavities of the ventricles. The second set con-
sists of the pulmonary and aortic semilunar valves. Their flaps yield
outward, i.e., in a direction away from the ventricles. The venous
valves open only toward the heart.
The Circulatory System During Fetal Life. — The circulatory
system of the adult human being finds its origin in the system which is
present during the last months of intra-uterine life. The complete
separation of the young from the mother effected at birth, necessitates
first of all the presence of a heart that is capable of developing an
adequate driving force, and secondly, several very definite alterations
in the distribution of certain blood-vessels which insure a perfect con-
tinuity of the vascular channels. It should be emphasized, however,
that the changes effected at birth, are not the only ones to which the
circulation of the human embryo is subject to. Thus, it has been
established that the early vitelline system which is fully developed
during the third week, is modified several times to meet new conditions,
and its shortcomings are soon compensated for by the formation
of the allantoic vessels which are specialized further into the placental
circulation. The following peculiarities are evident during the last
months of gestation. The blood spaces of the placenta which he in
contact with the enormously enlarged capillaries of the uterus, unite
eventually to form two blood-vessels, commonly known as the
umbilical artery and vein. The latter conveys the blood from the
A COMPARATIVE STUDY OF THE CIRCULATORY SYSTEM 261
placenta to the fetus. Very soon after it enters the fetus through the
umbiHcal perforation, it divides into two channels, one of which
unites directly with the inferior vena cava, and the other with the
portal vein in the immediate vicinity of the liver. The portal branch
Fig. 129. — The Fetal, Cibculation.
P, placenta; UV, umbilical vein carries oxygenated blood and unites with the
vena cava inferior (JVC) and portal vein {PV). This blood mixes with the venous
blood and enters the right atrium, (RA) being here diverted largely through the fora-
men ovale into the left auricle {LA). From here it passes into the left ventricle {LV),
aorta (A) and either into head circuit or abdominal aorta {A A). Here it may be
diverted into the portal organs (PO) or continue onward into the common iliac {CJA),
external iliac (EJA) or hypogastric arteries (HA). In the latter case the blood again
reaches the placenta by way of the umbilical arteries (UA). The blood from the head
enters the superior vena cava (SVC) and right auricle (RA), where it is diverted into
the right ventricle (RV) and pulmonary artery (PA). From here it passes chiefly
through the ductus arteriosus (DA) into the aorta. A small portion of its traverses
the lungs proper (L) to be returned to the left auricle (LA) by way of the pulmonary
vein (PV). The striated vessels contain venous blood and the dotted vessels, mixed
blood.
is known as the ductus venosus. Whichever course the placental
blood selects, it eventually reaches the right auricle. It is to be noted,
however, that it is immediately mixed with the blood of the inferior
262 THE MECHANICS OF THE HEART
cava which in all probabiUty is fully loaded with the waste products
of the fetal tissues.
On account of the peculiar position of the orifice of the inferior
cava and the presence of a lip-like membrane, known as the Eustachian
valve, the blood entering the right auricle is immediately directed
through an opening in the interauricular septum into the cavity of the
left auricle. This orifice which thus grants a free passage to a portion
of the venous blood into the arterial side of the heart, is called the
foramen ovale. Under normal conditions this defect is closed very
shortly after birth, its place being taken by a tense fibrous membrane
which forever thereafter remains sharply differentiated from the
much thicker muscular portion of this septum. In certain infants,
however, it does not become patent until several weeks after birth;
in fact, in some it never becomes completely impervious. The venous
blood then continues to intermingle with the arterial and the more so,
the larger the size of the opening remaining. In indication of the
poor aeration of the tissues resulting in consequence of this condition,
the skin and mucous membranes of these children retain a bluish
appearance.
From the left auricle, the blood passes into the left ventricle and
from here into the aorta. If it is now diverted into the blood-vessels
of the head, it eventually reaches the right auricle by way of the supe-
rior vena cava. Peculiarly enough, the stream from this blood-vessel
is directed in such a way that it flows directly through the right
auriculoventricular opening into the ventricle of the same side without
seriously interfering with the cross-current through the foramen ovale.
The pulmonary artery then conducts the blood into the lungs, but as
these organs are inactive and are merely a slowly growing mass of
tissue, they do not require much blood. For this reason, by far the
largest quantity of the blood of the pulmonary artery is not distributed
to the lungs at all, but escapes into the aorta by way of a special chan-
nel, commonly called the ductus arteriosus. Only an insignificant
portion of the blood of the pulmonary artery actually reaches the capil-
laries of the lungs, whence it again attains the left auricle by way of
the pulmonary veins. This blood, of course, serves solely the purpose
of supplying nutritive material to the growing lung tissue.
A droplet of blood may pursue the course just outlined a number of
times, but it may also happen that it is forced into the posterior parts
of the body, i.e.., into the portal circuit or into the blood-vessels of the
legs, and eventually regain the heart by way of the inferior cava. Last
of all, it may leave the fetus altogether and return to the placenta by
way of the hypogastric branches and the umbilical artery. Clearly,
therefore, the paths which a drop of blood may follow, are even more
numerous and diverse in the fetus than they are in the adult. It may
be said, however, that a very considerable portion of the blood allotted
to the posterior part of the body, constantly leaves the fetal channels
to be replenished in the placenta. Considered in a general way, it is
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART 263
obvious that the circulation of the fetus greatly favors the head
region, the proper growth of the nervous system being of much greater
importance than that of the other tissues and organs.
The distinctive features of the fetal system may, therefore, be
said to be the ductus venosus, the foramen ovale, the ductus arteriosus,
the hypogastric arteries, and the umbilical artery and vein. The
obliteration of these blood-vessels is initiated immediately after birth,
but several days usually elapse before this process has been completed.
Thus, the distal portions of the hypogastric arteries are usually found
to be impervious at the end of the third or fourth day, while the
obliteration of the ductus venosus and umbilical vein is not effected
until the end of the first week and that of the ductus arteriosus not
until the end of the third or fourth week.
CHAPTER XXIV
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART
THE VALVES OF THE HEART
The Structure of the Auricles and Ventricles. — The adult human
heart measures about 125 mm. in length, 87 mm. in breadth, and 62
mm. in thickness. Its volume exhibits the following variations:
22 c.c. at birth, 155 c.c. during the fifteenth, 250 c.c. during the
twentieth, and 280 c.c. during the fiftieth year. Thus, it will be seen
that its growth is most rapid during early life. Beginning with about
the fifteenth year, the heart of the male becomes larger than that of
the female. At birth the organ weighs about 24 grams, at puberty
250 grams, and in adult life 310 grams. The heart of the adult female
weighs about 255 grams. To begin with, the ventricles are equally
heavy, but at the end of the second year the left weighs about twice
as much as the right, this relationship of 2 : 1 being retained until
death.
The wall of the heart is composed of three layers, namely a lining
membrane, or endocardium, a median coat, or myocardium, and an outer
investment, or epicardium. The outermost layer forms at the same
time the inner or visceral half of the pericardium which is then reflected
from the base of the heart to serve as the parietal half of this capsular
investment. The space which is thus cut off from the general cavity
of the thorax, is known as the pericardial sac. Its opposing surfaces
are moistened with a few drops of a lymph-like fluid, called the peri-
cardial fluid. The function of the latter is to lessen the friction which
must necessarily be associated with the changes in the volume of the
heart. The pericardium contains many elastic fibers which coalesce
264 THE MECHANICS OF THE HEART
with the adventitia of the large veins. Elastic fibers and a few smooth
muscle cells are also scattered through the endocardium, and espe-
cially through the lining of the auricles. As far as the function of the
pericardium is concerned, it may be stated that it exerts a restraining
influence upon the musculature of the heart, insuring a certain com-
pactness of its substance, and serving to counteract the effects of un-
usual degrees of pressure within its chambers. Thus, any defect in
this enveloping membrane generally permits of a decided outward
bulging of the cardiac substance which in turn may lead to an in-
competency of the valves.
It is very suggestive that the heart of mammals is composed of a
type of muscle tissue which occupies an intermediate position between
the primitive smooth muscle and the specialized striated muscle. In
fact, its high content in sarcoplasm would tend to ally it more closely
with the former tissue. It is also of interest to note that in the lower
forms the cardiac muscle is composed of actual cells possessing a spindle-
like shape and an elongated nucleus. In these animals, the heart
appears essentially as a simple tubular muscle, the different parts of
which are intimately connected with one another by bridges of muscle
tissue.
In the mammals, on the other hand, the mass of the ventricular
musculature is completely separated from the auricles by a heavy
deposit of connective tissue situated in the domain of the auriculo-
ventricular groove. It is to be noted that the perimysium enveloping
the muscle fibers increases very markedly at this level of the heart,
while the muscle fibers decrease in number, their places being taken
eventually by strong fibrotendinous rings, the so-called annuli fibrosi.
These structures which occupy the auriculoventricular furrow,
serve as the framework to which the different strands of muscle-tissue
are fastened. But, while the auricles and ventricles of the mammalian
heart are not united by direct bridges of muscle, they are brought
into functional relation by a strand of musculonervous tissue which is
known as the auriculoventricular bundle or the bundle of His.
In. accordance with the low degree of pressure developed by the
auricles, the musculature of these chambers appears as a thin capsule
to which, however, a seemingly disproportionate strength is given by
the musculi pectinati. These projecting strands of muscle tissue are
especially numerous in the domain of the appendix auriculae, where
they encroach upon the main cavity in such a manner that saccular
recesses are formed which are known as the foramina Thebesii. In
this way, the capacity of the central expanse of the auricular cavity,
which lies directly above the auriculoventricular orifice, may be greatly
increased at any time without incurring the danger of over-distending
and rupturing its wall. A circular depression upon the interauricular
septum indicates the location of the foramen ovale of intra-uterine life.
In addition, the right auricular cavity presents the orifice of the coro-
nary sinus, guarded by the dehcate valve of Thebesius. In the left
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART 265
cavity, we observe the orifices of the pulmonary veins, generally four
in number.
The musculature of the principal mass of the auricles is arranged
as an outer transverse and an inner longitudinal layer. ^ Moreover,
while each auricle really constitutes an anatomical and functional
entity, a number of fibers of the superficial coat always pass from one
side to the other, thus joining the two. In this way, a coordinated
activity of the two chambers is assured. Circular fibers are much
in evidence at the orifices of the larger veins and at the coronary sinus.
It should be emphasized, however, that these muscular rings do not
act as sphincters, but merely tend to lessen the size of the opening.
A more complicated relationship is presented by the musculature
of the ventricles. As these parts are called upon to develop the force
necessary to drive the blood through the
distant vascular channels, it cannot sur-
prise us to find that their walls possess
a great massiveness and strength. Fur-
thermore, as the left ventricle is destined
to supply the blood-vessels of the greater
circuit and thus to perform by far the
greatest amount of work, it may be as-
sumed that its wall is much thicker and
stronger than that of the right cavity.
In cross-section, the left cavity appears t:. ,or. rr. a
, , . ^ - 1 1 T Fig. 130. — Transverse Sec-
as a rounded ormce enveloped by a heavy tion Through Heart of Dog, 3
frame of muscle-tissue, while the right cm. Above Apex to Show Shape
compartment presents itself as a cres- ^^^^.^^^^^'^^^ °^ Ventricular
cent-shaped slit limited externally as by
a relatively thin layer of muscle (Fig. 130). It should be remembered,
however, that the basal portion of the right cavity gradually assumes
a more conical outline, and that the apex of the heart is formed ex-
clusively by the left ventricle. Thus, if the heart is divided trans-
versely beginning at its apex, the left ventricular cavity is opened
first and the right cavity only after another section at a much higher
level has been made.
Although the ventricular muscle fibers do not exhibit definite
points of origin and insertion, it is permissible to assume that they
begin in the fibrous tissue at the auriculoventricular junction;
indeed, the entire ventricular network may be likened to a muscular
basket fastened above to the annuli fibrosi. Three distinct layers
are discernible, namely, an outer, a middle, and an inner. The fibers
of the outer and inner layers are arranged longitudinally, while those
of the median coat are directed transversely to the long axis of the
heart and pass, therefore, circularly around the lumen of the ventricu-
lar cavity. Beginning at the base of the heart, the outer fibers
extend spirally toward the apex, but in such a way that their general
1 Krehl, Abhandl. der sachs. Gesellsch. der Wissenschaften, xvii, 1891, 346.
266 THE MECHANICS OF THE HEART
direction is oblique. Rather numerous on the left side, they form
merely a thin superficial layer in the right ventricle. At the apex
they again curve upward and are finally inserted in the septimi and
adjoining papillary muscles. The inner fibers begin in the apical
whorl and extend almost in a straight line toward the base, but it is
not quite correct to look upon them merely as continuations of the
outer fibers.
MalP divides the superficial fibers into the bulbospiral and sino-
spiral. The former begin at the conus, the left side of the aorta and
FiQ. 131. — Schema to Show the Course of the Superficial and Deep Fibers of the
Bulbospiral and Sinospiral Systems. The Heart is Viewed From the Dorsal Side.
BS, superficial bulbospiral system; BS', deep bulbospiral system; SS, superficial
spinospiral system; *S*S', deep sinospiral system; C, circular fibers round the conus;
C, circular fibers round the base of the aorta and the left ostium; LRV, longitudinal
bundle of right ventricle, from membranous septum to right ventricle; IV, interven-
tricular or interpapillary layer. (Mall.)
the left side of the left ostium venosum and pursue a spiral course to
the apex, where they enter into the formation of the posterior horn
of the vortex. Some of these fibers end in the septum and some in
the posterior wall of the left ventricle where they terminate in the
basal portion of this papillary muscle. The fibers of the sinospiral
system originate from the posterior aspect of the heart in the vicinity
of the right venous ostium. They pursue a spiral course to the apex,
where they form the anterior horn of the vortex and terminate in the
anterior wall of the left ventricle and corresponding papillary muscle.
. In addition, Mall recognizes a deep bulbospiral and sinospiral system
^ Am. Jour, of Anatomy, ii, 1911, 211.
b
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART 267
of fibers. Both are directed more transversely then the superficial
layers. The former encircle the left cavity and the latter the right
cavity, and finally surround the large blood-vessels at the base of the
heart.
These two longitudinal layers, form, so to speak, a sling-like
support for the circular fibers which are especially numerous on the
left side, and give an unusual volume and strength to this compart-
ment. It must be evident that the circular coat is the most important
dynamic factor, because its constrictor action serves to lessen the
lumen of the ventricular cavity in a most decided manner, thus giving
rise to the pressure which is required to drive the blood through the
system. It should be emphasized, however, that although each ven-
tricle is constructed in such a way that it forms a muscular unit, the
joint action of the two is assured by certain strands of fibers which pass
from side to side and envelop both compartments.
On contraction, each ventricular mass of tissue assumes a rounded
outline so that the two compartments become sharply differentiated
from one another by a groove which extends obliquely downward
-from a point above and on the right side to a point below and on the
Mt. Moreover, in accordance with the general direction of the fibers
of the outer coat, the entire ventricular mass is turned at this time
slightly around its longitudinal axis so that the apical center is rotated
from left to right and forward. For this reason, a more extensive
area of the left side of the heart is brought into view during this period ;
and naturally, only the left ventricle then presents itself below the
interventricular groove, because the apex is formed solely by the mus-
culature belonging to this compartment.
The Arrangement of the Valves. — With the exception of the ap-
pendix auriculae, the cavity of the auricle presents a perfectly smooth
internal surface. In the ventricles, on the other hand, open spaces
are encountered solely below the orifices of the aorta and pulmonary
artery. The former is designated as a rule as the aortic vestibule
and the latter as the conus arteriosus. The remaining space of each
ventricle is rendered i^igose and uneven by numerous projecting bundles
of muscle-tissue which appear in the shape of (a) columns raised in
relief from the wall, (6) as isolated cords of tissue stretching directly
through the cavity, and (c) as free conical and nipple-shaped elevations
projecting for a short distance into the lumen of the cavity. The first
are known as columnce carneoe. Their function seems to coincide with
that of the general mass of the cardiac tissue. The second, called
moderator hands, are found most frequently in the right cavity. They
arise as a rule from the interventricular septum and are inserted in
the outer wall. Obviously, their purpose is to prevent an excessive
outward movement of the latter and an undue distention of the cavity
as a whole. The third, commonly referred to as the papillary muscles ,
are in functional relation with the principal mass of the cardiac mus-
culature and serve as points of attachment for the chordce tendineoe,
268 THE MECHANICS OF THE HEART
which, as the name indicates, are tendinous cords extending from
here to the overlying valve flaps.
The Auriculoventricular Valves. — It has been stated above that
the blood flows through the heart in a perfectly definite direction,
because the contraction of the ventricles does not take place until the
contraction of the auricles has been completed, and because the orifices
connecting the different chambers of this organ are opened and
closed in perfect harmony with the activity of the cardiac muscle.
There are really two ways in which the cardiac orifices could be closed :
namely, by heavy rings of muscle tissue which by their sphincter-like
action obliterate the passage in the manner of the diaphragm of a
photographic camera, or by membranous flaps which, in the manner of
a door, swing directly across the openings. Clearly, the closure of an
orifice by a layer of circular musculature is an action which requires
power and, therefore, necessitates the expenditure of a considerable
amount of energy. If this mechanism were actually in use in our
heart, it would mean that the pressure developed by this organ would
have to be apportioned in part to the closure of its orifices, and in part
to the blood as driving force. For this reason, the use of valves must
be considered as a much more economical means, inasmuch as it does
not necessitate a division of the cardiac energy. The different valve
flaps are moved into place passively by the relative degrees of pressure
upon their two surfaces, and hence, all the power developed by the
heart may be directed to the single purpose of propelling the blood.
In this way, the closure of the valves is accomplished, so to speak,
incidentally in the course of the general muscular contraction.
The auriculoventricular openings are large and are especially
adapted for a quick transfer of blood. The left is oval in shape and
smaller than the right which possesses a rounded triangular outline.
Both orifices are surrounded by fibrous rings which are connected
with the mass of the fibrocartilaginous tissue situated at the auriculo-
ventricular junction. The different valve flaps are composed of double
folds of endocardium, strengthened by fibrous tissue and containing a
few elastic fibers and muscle cells. The latter are arranged radially
and are connected with the auricular musculature. The basal por-
tions of the fiaps are fastened to the walls of the orifice, while their
tips and thin margins are free and project far into the cavity.
The left valve, known as the mitral, is composed of two triangular
flaps of unequal size, while the right, or tricuspid, consists of three
flaps. Both valves yield solely in a downward direction and on closure
assume a position transversely across the opening. A perfect approxi-
mation of the different flaps is made possible, on the one hand, by the
muscle tissue forming the wall of the orifice, and, on the other, by the
chordae tendinese'with which their lower surfaces are connected. Ob-
viously, the contraction of the former gives a certain firmness to the
frame in which the valve flaps are hung so that their basal portions
become flxed, while their tips attain a wide range of movement. In
I
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART 269
addition, this firmness and greater prominence of the wall of the orifice
must tend to lessen the size of the passage. The arrangement of the
chordce tendinece must seem very perplexing to the casual observer.
On closer examination, however, it will be seen that they arise from
the papillary muscles which are situated at some distance below the
basal portions of the different valvei flaps. A very clear picture of
the course pursued by them may be obtained in the left ventricle, in
which only two papillary prominences are present. In the right cavity,
on the other hand, the condi-
tions are less simple, because we
find here three papillary projec-
tions and, in addition, also a
number of chordae which origi-
FiQ. 132. Fig. 133.
Fig. 132. — Heart of the Cow, With Left Auricle and Ventricle Laid Open.
{MiiLler.)
a, Root of the aorta; h, spaces in the wall of the auricle; c, c, orifices of the pulmonary
veins; Z, Z, pulmonary veins; p, p, papillary muscles; q, q, columnse carnese. A, orifice
of the aorta; K, left ventricle; S, septum; V, left auricle; W, lateral wall of left ventricle;
1, 1, 2, leaflets of mitral valve.
Fig. 133. — Schema to Show Fan-like Distribution op Chordae Tendinece (C) from
A Single Papillary Muscle (P), Situated Underneath (V), Two Adjoining Valve
Flaps.
nate from the septum itself. Very soon after they leave their places
of origin, the individual chordae divide into smaller strings which ex-
tend fan-like through the cavity to be inserted eventually upon the
free margins and more centrally located areas of the flaps above them.
Moreover, as the papillary muscles are placed as a rule almost ver-
tically below the points of union between two neighboring flaps, each
colony of chordae concerns itself chiefly with the two margins nearest
to them. In reaching their points of insertion they frequently cross
one another, but without impairing their movement.
The structure and general arrangement of the chordae prove very
270 THE MECHANICS OF THE HEART
convincingly that they are instrumental in approximating the different
valve flaps. Thus, by permitting the different flaps to be moved into
a position transversely across the orifices and no farther, they serve
a purpose very similar to that of the guy-ropes of a sail. Secondly, as
a number of chordae are always inserted upon the central area or body
of the flaps, they prevent the bulging or bellying of the entire valve
into the auricular cavity. Thirdly, as the papillary projections from
which the chordae arise are usually placed vertically below the space
between two adjoining flaps, and as the individual strings are inserted
upon the margins of both, they must necessarily exert a traction toward
a common center which is situated midway below the planes of the two
flaps. In this way the margins of the different flaps are pulled together
transversely and are then held firmly in place. It may be assumed
that the papillary muscles take part in the general contraction of the
ventricles, thereby furnishing a more solid basis for the chordae to act
upon; in fact, it may be said that the contraction of these projections
exerts a certain traction upon them which facilitates their unfolding
and the approximation of the valve-flaps.
The auriculoventricular valves are opened very soon after the ces-
sation of the contraction of the ventricles. Gradually, as the blood
flows into the auricles from the central veins, the intra-auricular pres-
sure is raised above that prevailing in the now passive ventricles.
In consequence of the higher pressure exerted upon their upper sur-
faces, the flaps are forced slightly apart with the result that the blood
now rushes into the ventricular cavity. It should be remembered,
however, that the flaps are not moved as a door would be on opening
it, because their basal portions are attached to a rather rigid cushion
of tissue and remain, therefore, relatively fixed. Their tips, on the
other hand, are bent sharply downward so that each flap assumes the
shape of a crescent, the concavity of which faces the ventricle.
The auricular contraction following very shortly after the initial
opening of the auriculoventricular valve, renders the orifice between
these chambers more funnel-shaped. The blood being driven directly
into the narrowest part of this passage opposite the tilted tips of the
flaps, is thus directed into the central expanse of the ventricles without
being able to form secondary currents or whorls which might seriously
impair its flow. Quite naturally, when this column of blood traverses
the ostium, the flaps are pushed far apart, but are not brought into
actual contact with the ventricular wall. The space between them
and the surface of the latter is filled with blood. This is of great dynam-
ical importance, because if thefiaps were forced against the wall, it
would be difficult to dislodge them and to move them into the position
of closure. Obviously, the latter movement can only be effected if
their under surfaces remain exposed to the ventricular pressure.
The contraction of the auricles fills the ventricles to their utmost
capacity so that their walls become fully distended and remain so
until the end of the auricular contraction. Directly thereafter,
THE ARRANGEMENT OF THE MUSCULATURE OF THE HEART 271
however, the ventricular wall recoils and exerts a static pressure upon
the blood with which this cavity is now filled. Secondary currents
are set up which strike the surfaces of the valve flaps and push them
upward in the direction of their position of closure. This static
back pressure, however, is not the only factor upon which the approxi-
mation of the valve flaps depends ; in fact, it merely serves the purpose
of *' floating" them into their initial position of closure, while the actual
snapping together of their marginal areas is accomphshed by the
suction which must necessarily result in the wake of the column of
auricular blood as it clears the auriculo ventricular orifice.^ When
the contraction of the auricles ceases, the driving force is suddenly
withdrawn. The column of blood, however, rushes on, with the
result that an area of negative pressure is developed in the rear of it
which immediately draws the flaps
almost transversely across the center
of the oriflce. Thus, it will be seen
that the final closure of the valves is
accomplished by the "breaking" of
the column of auricular blood and
clearly, as the flaps swing in from the
side, the blood is cut off very sharply
so that a backward movement of it is
impossible under ordinary conditions. Fig. 134.— Longitudinal Section
The Semilunar Valves. — The con- Through the Root of the Aorta to
,.,. , .,, , ,1 ,- 1 Show Cup-like Shape of Semilunar
ditions met with at tne aortic and valve Flaps.
pulmonary orifices, are quite different
from those encountered at the auriculoventricular openings. In ac-
cordance with the high degree of pressure developed by the ventricles,
their exits are narrow and surrounded by solid walls. Each orifice is
guarded by three separate segments which are fastened end to end
against the internal surface of these blood-vessels. Each segment
exhibits a cup-like shape, its convex surface being directed toward the
heart. The basal portions of the flaps rest upon a solid cushion of
the ventricular substance, while their free ends project far into the
lumen of the blood-vessel. No special structures are present to hold
them in place.
When the ventricles contract and drive the blood through these
slit-like orifices into the arteries, the tips of the different valve-flaps
are pushed far apart, but it should be emphasized that they are not
forced into contact with the wall of the blood-vessel. ^ Such a result
is practically impossible, because the basal portions of the flaps are
well protected against the ventricular stream by the heavy cushion
of muscle tissue to which they are fastened, and because the beginning
segment of each blood-vessel is very much larger than its more periph-
1 Henderson, Am. Jour, of Physiol., xvi, 1906, 325; also see: Henderson and
Johnson, Heart, iv, 1912, 69.
2 Ceradini, Der Mechanismus der halbmondf . Klappen, Leipzig, 1872.
272
THE MECHANICS OF THE HEART
eral segment. The latter peculiarity is dependent upon the fact
that the wall opposite each valvular segment is distended to form a
pKDcket, the so-called sinus of Valsalva.^ A certain quantity of residual
blood is always retained in these enlargements. From the right and
left fossae arise the two coronary arteries which supply the substance
of the heart.
The semilunar valves are closed directly after the completion of
the contraction of the ventricles. The mechanism involved in this
process is similar to that described previously. As the basal portions
of the different segments are relatively
fixed, their free tips are snapped to-
gether by the ''breaking" of the ven-
tricular jet of blood. The flaps are
then held firmly together by the pres-
sure existing in the arteries. As is
indicated in Fig. 135, this force is di-
rected not only in a straight line
against their outer surfaces, but also
transversely against- their marginal
zones. In this way, the under sur-
faces of their tips are forced firmly
against one another so that a displace-
ment and inversion of the segments
is quite impossible. Moreover, it is
of interest to note that the marginal
area of the tip of each flap gives lodgment to a fibrous thickening
which rises above the general surface and is adjusted in such a way
that it closely fits into the neighboring nodules. In this way, even
the most central regions of these arterial orifices are made perfectly
secure when the valves are closed. These granular bodies are known
as the corpora Arantii.^
Fig. 135. — Diagram to Show Posi-
tion OF Semilunar Valve Flaps on
Closure.
/, longitudinal section; II, trans-
verse section; V, ventricle; A, aorta;
FV, fossa of Valsalva; C, corpora
arantii.
CHAPTER XXV
THE CARDIAC CYCLE (REVOLUTIO CORDIS)
The Niunber of Cardiac Cycles. — The blood reaches the venous
vestibule of the heart under a very low pressure and leaves its arterial
orifices under a relatively high pressure. This fact shows that this
organ acts as a pump. It develops one of the fundamental attributes
of the circulation, namely, the pressure necessary to drive the blood
1 Named after the Italian anatomist Valsalva of Bologna, born in 1666.
2 Named after Julius Caesar Aranzi of Bologna, an Italian anatomist, born
in 1530.
THE CARDIAC CYCLE (rEVOLUTIO CORDIS) 273
through the system. Its action, however, is not comparable to that
of a piston-pump, but rather to that of a rubber bulb when compressed
by the hand. The contraction of its muscular substance diminishes
the size of its cavities so that the blood contained therein is subjected
temporarily to a high degree of pressure. Each contraction of the
heart, or systole, is immediately followed by a period of relaxation, or
diastole, and the latter in turn by a period of rest. These three phases
together constitute the cardiac cycle.
The general rule, that the frequency of the heart is indirectly
proportional to the size of the body, finds its application throughout
the animal kingdom, but particularly among the warm-blooded ani-
mals. This fact is clearly brought out by the following compilation:
Elephant 25 cycles in a minute
Camel 30 cycles in a minute
Lion, horse, ox 40 cycles in a minute
Donkey 50 cycles in a minute
Panther 60 cycles in a minute
Sheep 70 cycles in a minute
Man 70 cycles in a minute
Dog 100 cycles in a minute
Rabbit 150 cycles in a minute
Mouse 175 cycles in a minute'
Among the cold-blooded animals this relationship is not always
apparent, because their bodily functions are more markedly influenced
by outside conditions. The heart of the frog or turtle beats 40 to 50
times in a minute, a rather slight frequency for such small animals.
The fact that the cardiac frequency is greater in small animals, need not
surprise, because their metaboHsm is greater on the whole than that of
larger animals. This must necessarily be so, because as the former
present a proportionately larger surface to the medium in comparison
with their mass, they must lose larger amounts of heat. This greater
loss is counteracted by more intense metaboUc changes.
The human heart is subject to various influences, such as age, sex,
temperature, barometric pressure, posture, muscular movements,
emotions, etc. Before birth, the heart of the female beats about 140
to 145 times in a minute,' and that of the male about 130 to 135 per
minute. Conditions being favorable, it is posible to make use of this
fact in foretelHng the sex of the fetus. It is still very frequent at
birth, but its rate is markedly decreased during the first year of extra-
uterine life and more gradually during the subsequent years. Late in
life its frequency is again increased.
At birth 140
Infancy 120
Childhood 100
Youth 90
Adult age 75
Old age 70
Extreme old age 75-80
18
274 THE MECHANICS OF THE HEART
On account of the larger size of the male body, the heart of the
male is less frequent than that of the female, but if a comparison
is made between men and women of equal size, no significant differ-
ences will be found. The figures ordinarily given for man are: 70
beats in the male, 80 in the female, and 90 in children. Even very
slight muscular movements increase the rate, while rest decreases
it, the lowest value being found after continued quietude in the hori-
zontal position. On assuming the erect position the heart beats some-
what faster. The figures frequently given are: 75 on lying down, 77
on sitting up, and 85 on standing erect. Its frequency is also aug-
mented by warm food, or by increasing the temperature of the sur-
rounding medium. The same result is obtained if the temperature of
the body, as a whole, is raised, as in fever. This augmentation may
be shown very clearly by perfusing the heart of a cold-blooded animal
with Ringer's solution which it is possible to heat gradually. The
force and rate of the heart beat then increase with the temperature
until a maximum has been reached at about 30° C. Beyond this point
the beats become slower and assume an irregular and fibrillar character
until they stop entirely. Very similar tests have been made by N.
Martin upon the heart of the cat. This organ ceases to beat at about
17° C. and also if the temperature of the perfusing hquid is raised to
44° or 45° C. The acceleration obtained during fever may, therefore,
be due in large part to the direct action of the blood as it traverses
the cardiac chambers. Most generally, the heart of warm-blooded
animals beats more quickly and more strongly during the cold seasons
of the year, which change is in agreement with the fact that their
metabolic activity is greater in winter than in summer. The reduced
metaboUsm and heat production coincident with low degrees of tem-
perature must be held responsible for the decided decrease in the fre-
quency of the heart of hibernating animals. In the bat, for example,
a frequency of 28 in a minute during this period gives way to 200
per minute during the summer months. Muscular exercise increases
the frequency of the heart, because the tissues then undergo more in-
tense metabolic changes and require a more copious supply of blood.
Decreases in the oxygen content or increases in the carbon dioxid con-
tent of the blood increase the rate.
The Character of the Contraction. — Attention has already been
called to the fact that the different segments of the heart do not con-
tract simultaneously, but successively, the musculature nearest the
venous vestibule being activated first and that nearest the apex last
of all. Thus, the contraction of this organ presents several of the
characteristics of a peristaltic wave, progressing from its base to its
apex. For this reason, it has been said to be similar in character to the
curve recorded by skeletal muscle when stimulated with a tetanic
current. This fact proves that the cardiac musculature remains in
the state of systole for some moments before it again relaxes. Clearly,
this peculiarity in the manner of its contraction must tend to produce a
THE CAKDIAC CYCLE (rEVOLUTIO CORDIS) 275
thorough emptying of the different chambers of the heart. But, as it
has been shown that single narrow segments of cardiac muscle give
typical twitch-Uke contractions, it must be concluded that the tetanic
character of the systoUc movement of the entire organ can only be
due to the fact that its different segments contract successively in
the direction from base to apex.^
The Speed of the Contraction Wave. — The progressive character
of the contraction of the heart may be studied best in the lower forms
in which the systole of the sinus antecedes that of the auricle, and the
systole of the latter that of the ventricle. In a similar way it may be
observed in the mammaUan heart that the auricular contraction is
separated from the ventricular by a definite interval which becomes
especially noticeable in an organ shortly before it ceases to beat.
A graphic record of the contraction wave may be made by placing
long writing levers upon the basal and apical portions of an exposed
heart. If these levers are permitted to write in the same vertical line
and in relation with a chronograph registering the time in seconds, it
is a simple matter to compute its speed, because the distance between
the levers can be measured directly with a ruler. In this way, it has
been found by Reid and Waller^ that the velocity of this wave is 10 cm.
in a second in the heart of the frog and 80 cm. per second in that of the
sheep. Bayhss and StarUng^ give the value of 300 cm. in a second for
the dog's heart. In accordance with these figures, it must be con-
cluded that the wave consumes at least 0.05 sec. in its passage across
the human heart. In fact, upon the basis of electrical measurements
made by Kraus and Nicolai,^ an even longer time seems to be required,
namely about 0.2 sec, before the distalmost segments of the ventricles
beconie involved.
The Path of the Contraction Wave. — In the mammalian heart, the
musculature of the ventricles is completely separated from that of the
auricles by a zone of fibrous tissue.^ At one point, however, the two
masses are connected by a strand of modified muscle tissue which is
known as the bundle of His® or the auriculoventricular bundle. This
bridge begins in the basal portion of the interauricular septum, di-
rectly above the septum fibrosum atrioventriculare. It arises in a
complex nodular accumulation of cells and fibers which is usually re-
1 Walther, Pfliiger's Archiv, Ixxviii, 1900, 597.
2Phila. transactions, 198, 1888, 230.
3 Proc. Royal Soc, 1892, 211.
^ Berliner Klin. Wochenschr., 1907, Nr. 25 and 27.
^ It has been known for some time that muscular connections between the
auricles and ventricles are present in the fish, reptiles and amphibians. The
existence of similar connections in mammals has been denied until 1893, when
G. Paladino and Stanley Kent put forth the claim that a path of this kind exists.
Their observations, however, cannot be regarded as valid, because their descriptions
are very indefinite, while the illustrations, showing certain connections between the
left auricle and ventricle, apparently do not picture the conditions as they actually
are.
« Named after W. His, Jr. (1893), Professor of Anatomy at Leipzig (1863).
276 THE MECHANICS OF THE HEAET
ferred to as the auriculoventricular node. Having pierced the fibrous
tissue of the groove, it passes along the interventricular septum immedi-
ately below the endocardium, and divides eventually into two branches.
This bifurcation takes place at about the point where the posterior
and median flaps of the aortic valve are joined. The main bundle of
the average human heart is about 18 mm. in length and 1.5 to 2.5 mm.
in width. One of its branches is distributed to the right, and the other
to the left ventricle, but before the distant musculature is reached, the
bundle spreads out fan-Hke and forms an intricate network of fibers.
This peripheral ramification was clearly recognized by Pur kin je, but
no particular attention was paid to it until Tawara^ proved that its
constituents are intimately connected with the bundle of His.
Fig. 136. — Left Ventricle Laid Open to Display the Interventbicular Septum.
The Course of the Auriculoventricular Bundle and Its Ramifications are Shown
IN Black. {After Tawara.)
It has previously been stated that in the lower animals the contrac-
tion wave originates in the sinus venosus, and eventually reaches the
apex of the ventricle by travelHng across bridges of muscle tissue.
The sinus, therefore, must give lodgment to a certain group of cells
in which the wave of excitation is generated. For this reason, this
particular area of the sinus has been designated as the pacemaker of
the heart.
Very similar conditions are met with in the mammals. Thus, the
embryonic heart presents the sinus venosus as a separate cavity which
is bounded by the orifices of the venae cavse, the Eustachian valve and
the interauricular septum. The adult organ, on the other hand, does
not possess a distinct vestibular enlargement, because the sinus has
been incorporated in the main cavity of the auricle. The remnants
of the Eustachian and venous yalves, however, are still discernible
in conjunction with the taenia terminalis. Even a very casual observa-
1 Pfliiger's Archiv, cii, 1906, 300.
THE CARDIAC CYCLE (rEVOLUTIO CORDIs)
277
tion of the beating mammalian heart must show that the contractions
begin in the tissue situated at the junction of the superior vena cava
with the right auricle. This region which corresponds to the sinus
reuniens of the embryonic organ, constitutes the pacemaker of the
higher type of hearts. One of these veno-auricular accumulations
of tissue has been adequately described by Wenkelbach. In confirma-
tion of this work, Flack and Keith ^ have applied to this area the name
of sino-auricular node, the further assertion being made by these in-
vestigators that it is intimately connected with the bundle of His.
It must be concluded, therefore, that the stimulus to contract
arises in the specialized tissue forming the sino-auricular node. When
Fig. 137. — The Auriculoventricular Bundle and its Terminal Ramifications
IN THE Interior or the Ventricles (from Model Constructed by Miss De Witt
ON Basis of Dissections).
The division of the bundle into right and left branches is shown, and the ramifications
of each of these branches in the interior of the right and left ventricles. The branching
system in the left ventricle is incomplete in the model, as the outer wall of this ventricle
had been removed in the dissection. (Howell.)
this area is warmed or cooled, the frequency of the heart as a whole is
either increased or decreased; and this effect cannot be produced if
other regions of this organ are subjected to changes in temperature.^
Furthermore, it has been found by GaskelP that the rhythmic power
of the muscle tissue of the venous vestibule is greater than that of the
ventricular musculature.
The wave of excitation is propagated from the sino-auricular node
to the different segments of the auricles as well as to the auriculoven-
tricular node. Although the statement is generally made that the
1 Jour, of Anat. and Physiol., xli, 1906, 172, and M. Flack, Jour, of Physiol.,
xli, 1910, 64.
^Erlanger and Blackman, Am. Jour, of Physiol., xix, 1907, 125; also see:
Schlomovitz and Chase, Am. Jour, of Physiol., xli, 1916, 112.
3 Schafer's Textbook of Physiol., 1900.
278 THE MECHANICS OF THE HEART
auricles contract together, accurate measurements have shown that
the left one lags somewhat behind the right. The interval, of course,
is extremely brief; it amounts to only 0.01 to 0.03 sec. The excitation
wave finally reaches the papillary bases of the ventricles by way of the
bundle of His and its distal ramifications. The wave itself is accur-
ately timed so that a perfect coordination between the different seg-
ments of the heart is assured. We have previously noted that a period
of almost 0.2 sec. elapses before the wave arrives in the distalmost
muscle strands of the ventricle, but naturally, the conduction is not
equally rapid in all parts of the heart. Thus, it has been found that
the bundle of, His conducts rather slowly, because the wave attains
here a velocity of only 10 to 15 cm. in a second. This fact is of interest,
because, as has previously been shown, the ventricle contracts after
the auricle, the interval between their systoles amounting to 0.12-0.2
sec. Hence, the resistance in this bridge of tissue has been adjusted
in such a way that a perfect sequence of contraction is obtained.
Two views are held regarding the manner in which the ventricular
musculature is activated. It was formerly believed that the segments
situated nearest the auriculoventricular groove, contract first, while
those closest to the apex are involved last. The results of electrical
measurements and of cinematographic records of the beating heart,
taken by Nicolai and others,^ however, have shown that the excitation
wave is conducted directly to the papillary projections, and hence,- it
must be concluded that this particular system of the ventricles is
activated first. The contraction wave spreads from here to the oblique
and circular muscle fibers. Clearly, this view is entirely in accord with
the anatomical arrangement of the conducting path, because, as has
been stated above, the main bundle of His is enveloped in a sheath of
fibrous tissue, while its terminals, the fibers of Pur kin je, are directly
traceable to the papillary muscles.
Heart-block. — The preceding statements find ampHfication in the
observations of Gaskell,^ showing that the passage of the wave of excita-
tion through the hearts of frogs and turtles may be greatly retarded by
compressing the tissue forming the auriculoventricular groove. While
this end may be attained with the help of a pair of forceps, a better way
is to adjust a screw-clamp to this region, which enables the experimenter
to grade the pressure more accurately and to obtain different degrees
of blocking. Under ordiniary conditions every contraction of the auri-
cles is followed by a contraction of the ventricles, because the wave
of excitation meets with no obstacle in its passage through the bundle.
If the latter is now thoroughly compressed by the closure of the clamp,
the impulse is blocked at the seat of the injury and cannot reach the
ventricles. This particular segment of the heart now ceases to beat,
while the auricular portion continues its activity as previously estab-
1 Braun (Herzbewegung und Herzstoss, Fisher, Jena, 1898), and Rehfish
(Berliner klin. Wochenschr., 1908, Nr. 26).
2 Jour, of Physiol., iv, 1883, 66.
THE CARDIAC CYCLE (rEVOLUTIO CORDIS) 279
lished. Eventually, however, the ventricle develops a rhythm of its
own which is made possible by its inherent power of contraction.
This condition constitutes total heart-block. It must be remembered,
however, that there are also certain intermediate stages of this affec-
tion which arise whenever the obstruction is not complete. This en-
ables the wave of excitation to break through at intervals. Thus, it
may come to pass that only every second, or every third or fourth
auricular systole is able to elicit a regular ventricular contraction,
thus establishing a2:l, 3:1, or4:l rhythm. In other words, while
one single wave may not be sufficiently powerful to overcome the re-
sistance placed in the path of conduction, the sum total of two or three
or more may suffice to break through this obstruction. And naturally,
whenever the ventricle is thus made to respond to an auricular beat,
the resulting systole must exhibit the characteristics of a normal
contraction, because under ordinary conditions, the activity of cardiac
muscle does not vary with the strength of the stimulus, but remains
constant.
It has been stated by Kent^ that these observations, although origi-
nally made upon the heart of the frog, may be duplicated in mammals,
but the evidence submitted in support of this statement cannot be re-
garded as at all convincing. In conformity with the work of Wool-
dridge and Tigerstedt,^ it has been found by His that the auricles and
ventricles may be functionally dissociated not only by destroying the
inter auricular septum, but also by causing a local injury to the auric-
uloventricular bundle. These results have been confirmed and much
extended by Erlanger.^ In man, heart-block commonly arises in con-
sequence of endocardial lesions or tumors involving the origin and main
strand in the bundle of His. It may also be caused by a general
diminution in the irritability of the ventricular musculature, a con-
dition which may result in the course of syphilis and septic infections
and intoxications.
Fibrillation of the Cardiac Muscle (Delirium Cordis). — When
in fibrillation, the musculature does not respond with strong and
unified contractions, but with a continuous wavy and oscillatory
motion. This condition may be more or less localized or may affect
the organ as a whole. When restricted to the auricles, as it frequently
is, it is designated as auricular fibrillation, and when involving the
ventricles, as ventricular fibrillation. It follows strong electrical,
thermal, or mechanical stimulation of the cardiac muscle as well as
obstructions to the coronary circulation. It is scarcely possible to
relieve this condition after it has been firmly established. In this
regard, it differs from the so-called flutter which signifies an extreme
increase in frequency, sometimes to 300 or 400 in a minute without
marked alteration in the character of the individual beats.
1 Jour, of Physiol., xiv, 1893, 233.
2 Archiv fur Physiol., 1883 and 1884.
. 3 Am. Jour, of Physiol., xvi, 1906, 160; and xxx, 1912, 395.
280 ^ THE MECHANICS OF THE HEART
The cause of this sudden loss of regularity of contraction is not
fully understood. Kronecker^ beheves that it is due to the destruction
of the coordinating cardiac center, while McWilliam^ states that it is
dependent upon an interference with conduction. The work of Gar-
rey^ has greatly strengthened the block-hypothesis of Porter^ which
proposes that the fibrillation is due to an interruption of the contrac-
tion wave. In consequence of this blocking, this wave is prevented
from running its usual course until the normal coordinated action of
the cardiac musculature gives way to the confused ^'circus" motions
of fibrillation. A similar confusion of contraction may be produced
in the tongue by reestablishing the circulation after it has been inter-
rupted for some time. As this organ embraces muscle fibers which are
arranged in different directions, it has been thought that this peculiar
motion is caused by a loss of functional continuity between the adjoin-
ing areas of tissue. It is possible that a similar dissociation takes
place in the fibrillating heart.
A fibrillating heart, or ventricle, is, of course, quite unable to expel
the blood and to sustain the circulation. Death results very sud-
denly. A fibrillating auricle, on the other hand, is not necessarily
incompatible with life, because the ventricles are still in a condition of
responding. To be sure, the contractions of the latter become irregu-
lar, because they are now played upon by numerous impulses derived
from the fibrillating auricles. This condition is characterized by an
irregular arterial pulse and an absence of the auricular summit from
the venous pulse, as recorded from the external jugular vein. The
electrocardiogram taken at this time does not show the P-wave which
represents the electrical variation produced by the normally acting
auricles.
CHAPTER XXVI
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE
The different cardiac cycles follow one another in rapid succession,
every additional one adding another unit of work to that already
accomplished. Like any other mass of Uving substance, cardiac
muscle generates mechanical, thermal, and electrical energy. The
first of these is at present of greatest interest to us, because it furnishes
the basis for the dynamics of the circulation. While the heart is en-
gaged in this process of kinetically innervating the blood, it exhibits
1 Compt. rend., Soc. de Biol., 1891.
2 Jour, of Physiol., viii, 1887.
3 Am. Jour, of Physiol., xxi, 1908, 283.
* Ibid., vi, 1902, 25.
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE 281
a number of phenomena which may be conveniently dealt with under
the following headings : (a) the changes in its form, (h) the generation
of electrical energy, (c) the production of sounds, {d) the variations
in pressure within its chambers, and (e) the changes in the position of
its valves.
A. THE CHANGES IN THE FORM OF THE HEART
Methods of Registration. — The procedures most frequently em-
ployed for determining the changes which the heart undergoes during
its systoUc and diastolic phases, may be arranged in the following
manner :
(a) Observation with the help of linear measuring instruments. (Ludwig,
1843.)
(6) Graphic registration by means of ordinary writing levers which are placed
horizontally upon different parts of the heart (von Frey), or with the help of
suspended levers which are connected with the cardiac musculature by strings.
(Gaskell, 1882, and Engelmann, 1892.)
(c) Photographic, cinematographic, and radiographic registration. Ortho-
diagraph. (Zuntz and Schumberg, 1896, Buchard, 1898, and Braun, 1898.)
(d) Acupuncture, the insertion of long needles into different regions of the
heart while the chest remains closed. (Jung, 1836, and Haycroft, 1890.)
Nearly all investigations of this kind have been made either upon
the excised heart or upon the heart while freely exposed to the view
Fig. 138. — Diagram to Show How the Beating Frog's Heart Adapts Itself to the
Surface Upon Which It Rests. The Dotted Line Indicates Diastole.
by removing the ventral wall of the thorax. Quite obviously, either
one of these procedures cannot be regarded as perfect, because it
places this organ under abnormal conditions and tends, therefore,
to disturb its normal activity. At the present time, however, this diffi-
culty cannot be avoided and hence, it becomes necessary to correct
any errors from this source by indirect evidence. Inasmuch as the
consistency of the cardiac substance is soft during diastole and firm
during systole, the organ as a whole must necessarily adapt itself to
its surroundings and undergo certain changes in its form which, so to
speak, are forced upon it. Even the normal heart in situ is not fully
protected against the different degrees of traction which are brought
to bear upon it whenever the body as a whole is made to assume an
unusual position.
In endeavoring to obtain a composite picture of the changes in the
form of the beating heart, attention should first be called to the altera-
282
THE MECHANICS OF THE HEART
tions in its shape, and secondly, to the alterations in its position.
Concerning the former, the general statement may be made that its
longitudinal and transverse diameters are decreased during systole,
while its anteroposterior diameter is increased. In this way, the base
and apex of the organ are brought closer together, while the outhne
of its basal portion is changed from an ellipse to a circle. For this
reason, a diastolic heart always appears to be thicker along its borders'
than near its center, while the organ as a whole more nearly conforms
to the general outline of the surface upon which it is resting. It is
also evident that the systolic heart executes a rotatory movement
which under ordinary conditions of experimentation remains more
closely confined to its apical portion. In accordance with our previous
Fig. 139. — Showing Location of Apex Beat.
The position of the aortic semilunar ( +) and mitral (A) valves are indicated in red
and that of the pulmonary semilunar ( +) and tricuspid (A) in blue.
observation that the superficial fibers of the ventricle pursue in general
an S-shaped course and form a whorl at the apex, it may be inferred
that the rotation takes place from left to right.
The Cardiac Impulse (Impulsus Cordis). — On observing the exter-
nal surface of the chest in the region of the apex of the heart, it is
noticed that the thoracic wall is made to bulge outward with every
systohc movement. In men, the greatest prominence is attained in
the fifth intercostal space slightly to the right of the left mammillary
line, which represents the perpendicular drawn through the left
nipple. In woman, this impulse is more frequently observed in the
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE 283
Fig. 140. — Transverse Section
Through the Chest to Show the
Changes in the Shape of the Base
OF THE Heart on Systole.
The systolic heart (dotted line) lies
closer to the chest wall.
fourth intercostal space and is not so clearly betrayed on account of
the interposition of a layer of mammary tissue. The area so affected
measures about 2 cm. in diameter.
In accordance with the statements
just made, it is possible to assign
three causes to this impulse, namely:
(a) the change in the outline of the
basal portion of the heart, (h) the
elevation or erection of the ventricle,
and (c) the spiral rotation of the apex
from left to right and from behind
forward. We have seen that the
cross-section of the base of the dias-
tolic heart is elliptical while that of
the systolic organ is circular. This
change, as is clearly portrayed in the
accompanying schema (Fig. 140),
tends to decrease the distance between
the wall of the thorax and the anterior surface of the heart. The base
of the organ is thus moved nearer the chest wall. It
should also be remembered that, in man, the space
intervening between the heart and the wall of the
thorax, is filled by the marginal area of the left lung.
As this organ is more fully distended during inspira-
tion, its border is forced farther forward in the direc-
tion of the median line, while during the subsequent
expiration it again recedes laterally. It may be in-
ferred, therefore, that the layer of pulmonary tissue in-
terposed between the heart and the thoracic wall, is
thinner during expiration than during inspiration and
that the organ as a whole approaches the thoracic
wall more closely during the former period. For this
reason, the cardiac impulse, or apex beat, is more con-
spicuous during expiration. In the second place, it
need scarcely be emphasized that the ventricle is more
flaccid when relaxed than when contracted, so that its
apex must assume a more dependent position during
the former period. The contraction of the ventricle,
therefore, must lead to an elevation of the apex for-
ward and upward,^ because the base of the organ is
naturally more firmly anchored than its apex (Fig. 141).
Thirdly, this upward kick of the ventricle is intensi-
fied by the fact that the apex turns slightly around
its longitudinal axis, bringing a more extensive por-
tion of its left side into view.^
Fig. 141.—
Longitudinal
Section Through
THE Chest to
Show the For-
ward and Upward
Movement of the
Apex During the
Systole (Dotted
Line) of the Ven-
tricles.
^ W. Harvey,
^ W. Harvey,
'Cor sese erigere."
■lateralem inclinationem.
284 THE MECHANICS OF THE HEART
In accordance with the observations made upon the excised heart,
it may seem surprising that the changes in the different diameters of
the heart do not cause the apex to be displaced in an ahnost straight
Hne upward toward the base. Different reasons may be given for its
relative immobility. While it must be granted that the heart is more
firmly anchored at its base on account of the firm support afforded it
by the large blood-vessels, it must be remembered that the pericardial
sac, together with its mediastinal fastenings to the diaphragm, pos-
sesses the tendency of counteracting any distinct displacement of the
apex. . It is also claimed that the discharging heart suffers a recoil in
the manner of a cannon on being fired, ^ and secondly, that the sudden
distention and straightening out of the aorta and pulmonary artery
by the escaping ventricular blood causes the basal region to recede
somewhat in a downward direction. The ventricle being thus opposed
by a resistance above, must remain in its former position. ^
Fig. 142. — Cardiograph.
This is strapped around the chest, the central button is applied to the "apex-beat"
and its pressure on the chest wall regulated by means of the three screws at the sides.
The tube at the upper part of the instrument serves to connect the drum of the cardio-
graph with a registering tambour, such as is shown in Fig. 143. (Sanderson.)
The Cardiogram. — A graphic record of the cardiac impulse or
apex beat may be obtained with the help of two Marey tambours,
one of which is fastened to the surface of the chest (Fig. 142) in the area
previously designated, and the other upon a stand in relation with the
smoked paper of a kymograph (Fig. 143). When connected by means
of rubber tubing, the membranes of these tambours must oscillate in
unison. If the membrane upon the receiving tambour is pressed in-
ward by the bulging chest wall, the writing lever attached to the re-
cording drum must move upward, and vice versa.
This instrument is known as the cardiograph, and the record made
by it as the cardiogram. Not much importance can be attached to it
^ Skoda, Abh. iiber Perc. und Auskultation, Wien, 1847, also see : Feuerbach,
Pfliiger's Archiv, xiv, 1877.
^ Sena, Traite de la struct, du coeur., Paris, 1849, or Aufrecht, Deutsch. Arch,
fiir klin. Med., Nr. 19, 1877.
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE 285
as a means of diagnosis, because it frequently fails to represent the
conditions as they actually are. It must be granted, however, that the
fault does not always lie with the instrument, but more frequently
with the experimenter. If properly, applied, it registers the different
beats with accuracy, but does not allow definite conclusions being
made regarding the character of the contractions, because its mechan-
ism is easily affected by various factors such as changes in the position
of the body, or alterations in the resistance under which it is made to act.
Fig. 143. — Marey's Tambour.
a. Axis of lever; b, metal tray covered with rubber membrane, and communicating
by tube / with the receiving drum shown in Fig. 142. (Starling.)
Moreover, the conspicuousness of the impulse differs even in perfectly
normal individuals, owing to differences in the thickness of the chest
wall.
Under ordinary conditions, the cardiogram consists of a series of
upstrokes and downstrokes. The former indicate the successive sys-
tolic and the latter the successive diastolic movements of the ventricles.
In complete agreement with the general character of the contraction
of the cardiac muscle, these two limbs of the curve are generally joined
Stc
Fig. 144. — Cardiogram.
AB, Systole ;BC, plateau; CD, diastole; DA, pause; time in seconds.
by a "plateau," the implication being that this muscle does not relax
immediately upon having attained its state of maximal shortening,
but remains in this condition for a brief period of time. The curve
may also present an initial slight rise which is caused by the systole of
the auricles, and a small peak upon its downstroke which occurs
synchronously with the closure of the semilunar valves.^
1 For purposes of diagnosis, it is necessary to ascertain not only the location
of the impulse but also its strength. A displacement of it is brought about by
accumulations of air (pneumothorax), serum (hydrothorax), blood, and pus, as
well as by tumors of the thoracic and abdominal viscera. Hypertrophy and
286 THE MECHANICS OF THE HEART
B. THE ELECTRICAL VARIATIONS
The Action Current of the Heart. Electrocardiography. — The
activity of any form of living substance is accompanied by the produc-
tion of electrical energy. We have found this to be true in striated
as well as in smooth muscle tissue. Cardiac muscle forms no exception
to this rule, because, if the heart of a frog or turtle is exposed to the
view and the nerve of a gastrocnemius preparation is placed upon it, the
muscle is seen to twitch with every systole. In this particular case,
the heart acts as a battery, and generates an impulse in the adjoining
nerve which then causes the muscle to contract. The electrical current
generated by the beating heart may be registered by means of suitable
instruments, such as the capillary electrometer, or the galvanometer.
Thus, if the two terminals of the former are placed upon the active
organ, preferably upon its base and apex, the meniscus of the mercury
in the capillary tube moves first in one direction and then in the other
in synchronism with the successive periods of activity. The same
result may be obtained with the help of the galvanometer, the reflecting
mirror of this instrument being doubly deviated with each contraction.
The current rendered recognizable by this means is known as the
current of action of the heart. It is dependent upon the fact that the
active portion of this organ is electronegative to the resting portion.
Inasmuch as the cardiac contractions begin at the base, this particular
area of the heart is of a lower electrical potential than its still inactive
apical portion. A moment thereafter, however, conditions are re-
versed. The apical region now having been activated, exhibits a
galvanometric negativity, while the basal zone which is in the state
of rest at this very time, becomes electropositive. In perfect analogy
with skeletal muscle, the action current of the heart exhibits a diphasic
character. This is indicated very clearly by the deflections of the in-
dicator of the recording instrument which occurs first in one direction
and then in the other. It should be added, however, that this current is
somewhat different from the ordinary action current of skeletal muscle,
its peculiarities being no doubt attributable to the much greater com-
plexity of the cardiac musculature. These electrical changes are
developed with great rapidity, so that the capillary electrometer and
the ordinary type of galvanometer are not sufficiently motile to follow
the different phases of this wave with accuracy. This difficulty has
been almost entirely overcome by the very sensitive string galvanom-
eter, invented by Ader^ and modified by Einthoven.^ The indicator
of this instrument is a filament of quartz or platinum covered with a
thin coating of silver and suspended between the poles of a powerful
dilatation of any part of the heart also change its position. The strength of the
apex beat is indicative of the condition of the cardiac musculature, but only
when the factors previously enumerated have been properly controlled.
^ Compt. rend., Ac. Sci., Paris, cxxiv, 1897.
» Ann. der Physik, xii, 1903, and.Pfliiger's Archiv., cxxx, 1909, 287.
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE 287
electromagnet. The deviations which the string of this instrument
suffers in the course of each cardiac cycle, may be projected and photo-
graphed upon sensitive paper moved with proper rapidity. The
record so obtained is known as the electrocardiogram, and the complex
apparatus necessary to take these \racii^s, as the electrocardiograph.
This method of studying the chaM^- of the cardiac contractions
has attracted much attention in recSit years; in fact, it has been so
highly developed that it may be employed as an important diagnostic
aid in ascertaining the functional
capacity of even the human heart.
While the currents produced by
this organ are of very moderate
strength, the modern type of elec-
trocardiograph has been renderied
sufficiently sensitive to detect them
with ease. As Waller^ has shown
years ago, it is quite unnecessary
to expose the heart to the view,
because the current generated by it
can be led off to the galvanometer
by simply applying the terminals of
this instrument to the integument.
In the human subject, the elec-
trodes are usually connected with
the body in three ways, designated
as leads, namely:
Lead I. — Right arm and left arm.
Lead IL — Right arm and left leg.
Lead III. — ^Left arm and left leg.
Fig. 145. — Distribution of Poten-
tial Differences Due to Electrical
Variations in the Beating Heart.
(Waller.)
To record the variations any of the
points a may be led ofiE, together with
any of the points b.
In the first case in which the two
hands are connected with the poles
of the string galvanometer, the
right one may be regarded as the
conductor which leads off from the base, and the left one, as the con-
ductor which leads off from the apex of the heart.
Regarding the general outline of the normal electrocardiogram and
the causes of its different minor phases, some uncertainty still prevails.
Figure 146 represents the electrocardiogram most commonly obtained
from normal human subjects. It is readily observed in the curve of
Lead I that each cardiac cycle begins with a slight wave which has been
designated by Einthoven as the P-wave (presystolic). Subsequent
to this point, the string either retains its position of zero or is deviated
somewhat below the base line. This primary deflection is due to the
contraction of the auricles and is spoken of, inclusive of the presystolic,
1 Philos. Transact., 1889, 180.
288
THE MECHANICS OF THE HEART
as the "auricular complex of the electrocardiogram."^ The ''ven-
tricular complex" of the curve is much more complex. When fully
developed, it consists of a deflection below the abscissa, called the Q-
wave, a very conspicuous upward deviation or i^-wave, a second
depression or S-wave, and ^ broad rounded elevation or T-wave.
The largest variation at R dlhyies 0.02 to 0.04 sec. and the one at
T, 0.1 sec. The total time of thft complex corresponds approximately
to the duration of the ventricular contraction, which has been proved
lllllllliii
ojSee.
Fig. 146. — Electrocardiogram Obtained by Photographing the Movements of the
Thread of a String-galvanometer.
The upper figure shows the photographed curve while the lower one is a diagram
constructed from the photograph to show the electrical changes occurring during a single
cardiac cycle. To obtain this record the electrodes were connected with the right and
left hands. Waves with the apex upward indicate that the base of the heart (or the
right ventricle) is negative to the apex (or left ventricle) . Waves with the apex down-
ward have the opposite significance. Wave P is due to the contraction of the auricle.
Waves Q, R, S, and T occur during the systole of the ventricle. The curve seems to
show that the contraction in the ventricles begins first toward the apex (or in the left
ventricle), since the negativity first appears toward that side (waveQ). (Einthoven.)
to begin very shortly after the onset of the deflection at R and to con-
tinue to about the end of the T-wave.
A detailed discussion of the individual variations in the electro-
cardiogram ^ cannot prove of much value, because many matters
pertaining to it must first be thoroughly investigated. Its complexity,
however, clearly betrays the segmental arrangement of the cardiac
musculature as well as the wave-like character of its contraction. It
appears that the excitation wave, on being distributed to the different
areas of the heart, gives rise to a muscular activity which is not at all
^ Lewis, Clinic. Electrocardiography, London, 1913.
2 Einthoven, Pfliiger's Archiv, cxlix, 1913, 65; Meek and Eyster, Am. Jour, of
Physiol., XXX, 1912, 271; James and Williams, Am. Jour, of the Medical Sciences,
1910, and Kraus and Nicolai, "Das Electrocardiogram," Leipzig, 1910.
THE PHENOMENA NOTED DURING EACH CARDIAC CYCLE 289
simultaneous. For this reason, the different zones of the cardiac
musculature must present different electrical potentials toward one
another. As far as the significance of the general details of the electro-
cardiogram are concerned, it might be mentioned in brief that an auricu-
lar complex of the form previously described, indicates that the wave
of excitation arises in its proper place at the venous vestibule and is
propagated in normal sequence through the whole of the auricular tissue.
As far as the ventricular complex is concerned, it should be noted that
the deviations at R and T are always present in normal records and
that the deflections at Q and S differ greatly in amplitude. Their
presence signifies that the auricular impulse has traversed the auriculo-
ventricular bundle and its ramifications in a proper manner and
direction. Age usually lessens the conspicuousness of the T-wave, while
exercise increases it. Curiously enough, the electrocardiogram secured
from the hearts of the lower forms, coincides very closely with that
obtained in -mammals.
C THE HEART SOUNDS
First, Second and Third Sounds. — All contracting muscle tissue
emits a sound, which is caused by the molecular shifting of its sub-
stance and the displacement of its fibers. The intensity of this sound
must therefore be proportional to the mass of the tissue involved as
well as to its power of contraction. In the case of the heart, three
additional factors must be taken into account, namely (a) the play of
the fibrous flaps forming the valves, (6) the friction of the blood upon
the endocardial lining of the narrowed orifices, and (c) the friction of
the organ as a whole against the chest wall and neighboring viscera.
Clearly, therefore, the sounds heard in the region of an active heart
may be said to be of intracardiac and extracardiac origin.^ While
both types deserve recognition, the former are of much greater physio-
logical importance.
If the unaided ear is applied to the surface of the chest in the
region of the heart and preferably over its apex, two very distinct
sounds are heard during each cardiac cycle which may be represented
phonetically by the syllables *4ubb-dup" or ta-ta. The first
possesses a rather low pitch and is fuller and longer than the snappy
and sharp second sound. They may be rendered more audible by
means of resonators, such as are contained in some of the monaural
or binaural forms of stethoscopes. But if an instrument of this kind
is employed, a certain care must be exercised, because diverse errors in
auscultation may arise in consequence of poorly fitting ear pieces, or
in consequence of the improper apphcation of the bell-shaped receptor
to the thorax. 2
' Noises are frequently heard in other parts of the vascular system, generally
at the points where the channels deviate from their former course or are con-
stricted. Venous bruits are not at all uncommon.
2 The cardiac sounds are modified in their intensity by any factor (respiratory
movements, pulmonary infiltrations," pericardial effusions, etc.) producing a change
19
290 THE MECHANICS OF THE HEART
The cardiac sounds have been recognized &t an early date. Harvey,
for example, states that the delivery of a quantity of blood into the
arteries produces a pulse which can be heard within the chest, but
Laennec^ was the first to describe the character of the sounds and to
make use of them for clinical purposes. Graphic records of them have
been obtained by Donders (185G), Martin (1888) and Hurthle (1892),
but the first really satisfactory method of registration has been devised
by Einthoven and Geluk.^ The sounds transmitted by a stethoscope
were caught upon a microphone. The currents were then led off to a
capillary electrometer, and photographed by projecting the move-
ments of the mercurial column of this instrument upon sensitive paper
moved with a certain velocity. In recent years, this means of regis-
tration has been displaced by the string galvanometer. Frank^.
has devised an instrument without a microphone, the sounds being
transferred directly from a stethoscope onto a membrane carrying a
reflecting mirror. It should be mentioned, however, that the records
so obtained are not always satisfactory, because they really represent
a combination of phonogram and cardiogram. Under ordinary con-
ditions, however, it is not difficult to differentiate between the rapid
oscillations caused by the cardiac sounds, and the slow deflections
produced by the contraction of the cardiac musculature. By means
of the method described previously, Einthoven* has succeeded in
registering a third heart sound which, however, cannot usually be
heard with the stethoscope.
The first sound occurs during ventricular systole. It begins with
the "setting" of the ventricles and continues until the highest intra-
ventricular pressure has been produced. This point coincides with
the beginning of the plateau, when the semilunar valves are forced
open. It is loud at first, but becomes less intense toward the end
of the ventricular contraction. It lasts 0.07 to 0.10 sec.
It may be concluded that the first sound of the heart is due very
largely to the friction noises emitted by the contracting ventricular
musculature,^ because:
(a) It is also produced by the exposed and bloodless heart, and also by excised
portions of the ventricle and by apex preparations.
(6) The sound begins before the closure of the auriculoventricular valves
and continues practically throughout ventricular systole until the muscle fibers
have attained their maximal degree of shortening.
in the tissue situated between the heart and the chest wall, as well as by structural
alterations in the musculature of the organ itself (hypertrophy and dilatation).
Moreover, when one or several of the valves become incompetent, the resulting
murmurs seriously impair the normal character of these sounds.
1 De r auscultation, Paris, 1819.
2 Pfluger's Archiv, Ivii, 1894, 617.
^Kongr. fur inn. Med., Wiesbaden, xxv, 1908; also see: Weiss, Das Phono-
scope, Med. nat. Arch., Berlin and Wien, i, 1908.
* Pfluger's Archiv, cxx, 1907, 31.
6 Q, j_ B. Williams, Rep. Brit. Assoc, for the Adv. of Science, London, 1836.
THE PHENOMENA NOTED DUKING EACH CARDIAC CYCLE 291
(c) The auriculoventricular valve flaps may be hooked back without markedly
impairing the quality of the sound.
(d) The character of the sound is decrescent.
(e) The contracting auricles also emit a sound which, however, remains below
the threshold of audibility, owing to the small mass of tissue involved.
It is generally conceded, however, that the first sound also contains a
sUght valvular element, because if the play of the valve flaps is re-
stricted or prevented, it displays a somewhat different character. We
know that the ventricular systole insures first of all the closure of the
auriculoventricular valves (Fig. 147 a), and shortly thereafter, the open-
ing of the semilunar valves (6). As the outward movement of the latter
is accomplished practically without noise, it must be concluded that
the modification imparted to the muscular element of the first sound
must be dependent upon the initial contact and the subsequent after-
vibration of the closed mitral and tricuspid valves.
Fig. 147. — Schema to Show the Relationship Between the Heart Sounds and
THE Curve of Intraventricular Pressure.
AB, systole; BC plateau; and CD, diastole; a, closure of auriculoventricular valve;
6, opening of semilunar valve; c, closure of semilunar valve; d, opening of auriculo-
ventricular valve; /, // and ///, heart sounds.
The second sound occurs at the beginning of ventricular diastole
and follows immediately upon the closure of the semilunar valves.
It lasts 0.05-0.11 sec, while the interval between it and the first
sound amounts to 0.15-0.25 sec. It is most intense when the blood
pressure is high and when the arterial system is very elastic.
In contradistinction to the first sound, the second sound possesses
no muscular element. It is purely valvular in its origin and is caused
by the tension and after-vibration of the closed semilunar valves.
This can be shown in the following way:
(a) If the tension in the aorta and pulmonary artery is lessened by permitting
a quick escape of the arterial blood, the intensity of the second sound is greatly
diminished.
(6) If the heart is rendered bloodless, it ceases to give a clear second sound.
(c) If the semilunar valve-flaps are hooked back, the second sound gives way
to a murmur, due to the regurgitation of the blood into the ventricular cavity.
(d) A sound very similar in character to the second sound may be produced in
292
THE MECHANICS OF THE HEART
an excised segment of aorta by quickly forcing a column of water through the
semilunar orifice toward the ventricular cavity.
The third sound is diastolic in its nature and occurs 0.13 sec. after
the beginning of the second. It is soft and low in pitch. Two causes
have been assigned to it. As it appears to follow in the wake of the
second, Einthoven has suggested that it is dependent upon the after-
vibration of the closed semilunar. valves. It is also claimed that it
is due to the vibration of the auriculoventricular valves^ which are
opened at this moment of diastole, and to the friction-noises occasioned
by the blood as it rushes int6 the ventricles {d).
D. THE CHANGES IN INTRACARDIAC PRESSURE
The Filling of the Heart
Methods of Registration. — By the term intracardiac pressure is
meant the pressure to which the blood is subjected while traversing
the different chambers of the heart.
To begin with, it is to be noted that
the general character of the pressure
variations in the auricles is quite
different from that of the variations
taking place in the ventricles, but that
the two ante-chambers as well as the
two main chambers show an almost
complete correspondence. In addition
it should be remembered that the
former develop equal degrees of pres-
sure, while the latter do not, because
the pressure encountered in the left
ventricle, is much higher than that pre-
vailing in the right.
The methods employed to determine
the intracardiac pressures may be ar-
ranged in two groups, the first em-
bracing those procedures which are
practicable only when the heart is fully
exposed to the view, and the second,
those which are also practicable when
the chest is still closed. In the first
instance, the cardiac chamber is con-
nected directly with a manometer. En-
trance to the auricular cavity is effected
through its appendage into which a cannula may be inserted without
causing the slightest disturbance in the heart's action. The right
auricular cavity may also be reached by introducing a hollow probe
through the superior vena cava, and the left cavity by introducing
1 Thayer and Gibson, Boston Med. and Surg. Jour., 1908.
Fig. 148. — Schema to Illus-
trate THE Method of Recording
THE Blood Pressure in the Right
Auricle and Ventricle.
A probe (^
the result that the pressure now falls somewhat below its normal level.
Subsequent to this point normal conditions are again established.
As might be expected, these compensatory changes are not always
of the same intensity, because the irritability of the vasomotor mech-
anism differs in the same degree as that of the entire nervous system.
It is obvious, however, that a close reflex correlation exists between the
cardiac and vasomotor centers, so that a reduction in the ventricular
output may be compensated for immediately by a constriction of
the blood-vessels. This is of greatest importance, because the functions
of the different colonies of cells in our body
must necessarily cease, if the pressure under
which they obtain their nutritive material
falls below a certain minimal value. For
this reason, even a relatively brief inhibi-
tion of the heart must be associated with
a general depression of function which
makes itself felt most strikingly by a loss of
our psychic activities. If continued for an
undue length of time, the inhibition must
necessarily be followed by certain disturb-
ances of function which are not so easily
compensated for and remedied. The '^ es-
cape of inhibition" may be said to consti-
tute a safety device of the body to prevent
fatal consequences from this source.
The Character and Nature of the Ac-
celeration.— The action of the accelerator
fibers may be tested experimentally in
mammals as well as in lower forms. In
the former, these fibers may be isolated dis-
tally to the thoracic sympathetic ganglia,
while in the frog and aUied animals, they
may be rendered accessible directly beside
the vertebral column. As is indicated in
Fig. 171, the latter eventually unite with
those of the vagus and finally terminate
in the heart. The cardiomotor fibers, therefore, may be reached in
this animal in three different places. Their stimulation at A, where
the vagus alone is affected, results in an inhibition, while the stimula-
tion of the sympathetic chain at B gives acceleration. For reasons
discussed previously, the excitation of the vagosympathetic at C is
followed by an inhibition.
The accelerators produce their effect after a considerable latent
period, but when once established, the acceleration continues as a rule
for some moments after the cessation of the excitation. Ten or
twenty seconds- frequently elapse before a marked increase in the
cardiac rhythm is observed, while, in the case of the vagus, the latent
Fig. 171. — Schema to
Show the Course of the Car-
diac Nerves in the Frog.
A, vagal fibers are still
separate; B, sympathetic fibers
are still separate; C, both
types of fibers have combined
to form the vagosympathetic
nerve. 2, Remak's ganglion;
B, Bidder's ganglion.
324 THE NERVOUS REGULATION OF THE HEART
period is less than one second. Clearly, therefore, the sympathetic or
accelerator fibers react more sluggishly but are less easily fatigued
than the inhibitor. The effect of their excitation consists either in an
acceleration or in an augmentation; in fact, in some cases both changes
are obtained simultaneously, the contractions becoming more frequent
as well as more forcible. In explaining this result, it is generally
stated that the accelerator mechanism is adjusted in such a way
that it may give rise to two reactions, namely, an increase in the
frequency, and an augmentation in the amplitude of the individual
beats. In analogy with this functional dissociation, it is also held that
the inhibitor mechanism is adjusted in such a way that the inhibition
may be accomplished either by lessening the frequency, or by decreas-
ing the amplitude of the cardiac contractions.^
While the experimental evidence is not very conclusive, it has been
suggested that the accelerator center discharges its impulses in rhyth-
mic succession, thereby establishing the so-called accelerator tonus in
antagonism to the inhibitor tonus. The removal of the former influ-
ence, ♦therefore, places the inhibitor discharges in complete control.
A slowing of the heart is the result of this disturbance of the cardio-
motor equilibrium. This end can be attained either by dividing the
accelerator fibers themselves, or by removing the intrathoracic ganglia.
Upon this basis cardio-acceleration may be explained by assuming that
the inhibitor tonus is temporarily diminished. ^
The increase in the rate of the heart is made possible by a shorten-
ing of each cardiac cycle, the duration of the diastolic period being
reduced first of all. It may be stated in general that the simultaneous
occurrence of accelerator and augmentor influences gives rise to a higher
blood pressure and more effective circulatory conditions than one
of these reactions alone could possibly produce. Thus, a simple
acceleration may fail absolutely in improving hemodynamical condi-
tions for the obvious reason that a greater number of ventricular
discharges alone does not suffice to increase the cardiac output per unit
of time, because the filling power or power of relaxation of the heart
may have been diminished in a measure to offset the increased rate.
The Afferent or Cardiosensory Fibers. — These fibers are divided into
two groups, namely, those which bring the cardiac center into relation
with the various regions of the body, and those which connect it with
the heart and neighboring pericardial and mediastinal membranes.
The first group embraces a large number of nerves, because practically
any one of the afferent paths in our body may at times convey impulses
to central parts which here affect the activity of the heart in a reflex
manner. The second group includes the ordinary sensory nerves
1 Bayliss and Starling, Jour, of Physiol., xiii, 1892, 407.
2 Several cases have been recorded of persons who could voluntarily increase
their heart rate (West and Savage, Arch. Int. Med., 1918, 298). The acceleration
was accompanied by an augmentation of the respiratory movements and a dilatation
of the pupils.
CARDIAC INHIBITION AND ACCELERATION
325
of the cardiac region and also a number of inherent fibers which are
commonly designated as the depressor nerve. The latter arise in the
plexus cardiacus and use the highway of the vagus nerve in reaching
the medulla oblongata. In the rabbit, they pursue a separate course,
entering the vagus by two rami, one of which unites with the superior
laryngeal nerve.
If we confine ourselves for the present to the general type of
cardio-afferent nerves, it will be noted that the cardiac center is con-
stantly played upon by various impulses which
reach it through the different afferent channels
of our body and are then transferred either to
the cardio-accelerator or cardio-inhibitor mechan-
ism. Thus, while the heart is capable of con-
tracting independently of its center as well as of
the rest of the body, its activity is regulated
under normal conditions in such a manner that
it fully conforms to the functions of other organs
and tissues. Naturally, this correlation can only
be attained with the aid of diverse afferent im-
pulses which are poured into the cardiac center
at different times and vary its automatic dis-
charges so as to give the results previously de-
scribed. We are deahng, therefore, at this time
with typical cardiac reflexes.
This statement raises the question of whether
the automatic activity of the cardiac center is
maintained by stimuli which are generated by its
constituents, or whether these stimuli are con-
veyed to it from other parts of the body. Al-
though little is known regarding the peculiar pro-
cesses occurring in ganglion cells, it may be
assumed that nervous impulses result in con-
sequence of certain physicochemical alterations
within the cell. It is a well-known fact, how-
ever, that intracellular reactions of this kind
cannot continue for an indefinite period of time
unless extraneous influences are at hand to cause
these internal changes to be repeated. Cellular
retrogression and disintegration always follow in
the wake of loss of stimulation. The constit-
uents of the cardiac center do not form an exception to this rule,
because the permanent removal of these afferent stimuli soon reduces
them to a state of inactivity. For this reason, it may justly be as-
sumed that the normal tone of these ganglion cells is largely dependent
upon reflex stimulation.
To summarize, the activity of the heart is normally regulated by
the cardiac center, the discharges of which are constantly varied in
Fig. 172 — Diaqbam
TO Show the Course
OF THE Depressor
Nerve in the Rabbit.
L, larynx; T, thyroid
gland; J, int. jugular
vein; C, carotid artery;
S, sympathetic nerve
extending between the
superior and inferior
cervical ganglia ; V,
vagus nerve; SL, sup.
laryngeal nerve; D, de-
pressor nerve, entering
the vagus by two
branches. The vagus
is pulled over, permit-
ting the sympathetic to
appear next to the caro-
tid artery.
326 THE NEEVOUS REGULATION OF THE HEART
accordance with the character of the afferent impulses received by it.
Two views are held regarding the nature of this control. In the pres-
ence of an accelerator and inhibitor mechanism, it is believed that the
cardiac musculature is constantly under the influence of two types of
impulses which are antagonistic to one another in so far as the first
tends to increase, and the second to decrease the contractions. Con-
sequently, the cardiac frequency must be regarded as the product of
the interaction between these two factors. The afferent impressions
received by the center shift the balance either in the direction of accel-
eration or inhibition. They, accomplish this end by causing a greater
number of impulses of either the former or latter kind to be generated
and to be conducted to the heart. In accordance with the second
view, it is held that the activity of the heart can only be increased by
a depression of the inhibitor mechanism.^ Thus, it is assumed that
the afferent impulses, on reaching the cardiac center, lessen the re-
straint under which the heart is constantly held, and thereby permit
the accelerator influences to gain full power. In the absence of defi-
nite facts, it is somewhat difficult to decide which of these two processes
is normally at work. It would seem, however, that the frequency of
the heart is regulated under normal conditions solely by the inhibitor
center, slight changes in the rate of contraction being effected by altera-
tions in the tonus of the latter. Greater variations as well as aug-
mentor effects, however, necessitate an active opposition to the in-
hibitor influences by the accelerator center. For this reason, the
latter may really be regarded as an aid to the former; its active
participation being required whenever especially marked results are
to be obtained.
It has been stated above that almost all sensory nerves convey
afferent impulses to the cardiac center and hence, practically all recep-
tors are in communication with the cardiomotor mechanism. Chief
among these are the retina, the organ of Corti, the semicircular canals,
the olfactory cells, the taste-buds, as well as the cutaneous and visceral
end-organs for touch, pain, and temperature. The impressions de-
rived from these sources, become operative either directly after their
reception or some time later after they have been associated in their
respective intracerebral centers. In the latter case, the stored im-
pulses which serve as expressions of our psychic fife or belong to the
group of the emotions, need not affect solely the activity of the heart,
but may also involve respiration, secretion, as well as the responsive-
ness of smooth and striated muscle-tissue. In general, it may be stated
that pleasurable experiences decrease and annoying impressions
increase the cardiac rate. It should also be noted that these afferent
impulses may give rise to effects which actually endanger the life of
the individual. As an example of this kind might be mentioned the
so-called ''reflex cardiac death" which may result whenever the in-
hibitor center is excessively stimulated. It should also be mentioned
1 Hunt, Am. Jour, of Physiol., ii, 1899, 395.
CARDIAC INHIBITION AND ACCELERATION 327
that while the action of the heart cannot usually be influenced by
volition, certain cases are on record which clearly prove that a marked
voluntary control over this organ may be acquired at times quite inde-
pendently of emotional states or remote sensory impressions.^
These volitional efforts most commonly produce an acceleration, but
may also induce a slowing of the heart.
The frequency of the heart may also be lessened by exerting a slight
pressure upon the vagus at any point of its course along the neck.^
As this procedure is not without danger, it should only be practised
with the greatest care. Augmentor or inhibitor effects frequently
result from tumors or serous effusions affecting either the medulla or
the cardiac nerves themselv^es. It should also be remembered that
the activity of the cardiac center is closely related to that of the
neighboring respiratory center, as is shown by the fact that the fre-
quency of the heart increases during inspiration.^ This reaction ap-
pears in the nature of a reflex which seems to have its origin in a central
stimulus rather than in one generated in the lungs themselves. Two
or three reasons may be given for this view. Thus, it has been found
that it persists during the spasmodic respiratory attempts following
the division of the cervical portion of the spinal cord,* and that it is not
in evidence in certain animals. This acceleration may be made more
striking by increasing the amplitude of the respiratory motions or by
heightening the general irritability of the central nervous system.^
It has been suggested by Spalitta® that the stimuli upon which this
reflex depends, arise in the muscles normally employed in inspiration.
Deglutition possesses a similar influence, the cardiac acceleration be-
coming the more marked, the greaterthefrequency of these movements.
The opposite result may be produced by stimulating the mucous mem-
brane of the nasal cavity with the vapors of chloroform or other irri-
tants. This constitutes the so-called cardiac trigeminus reflex.
An intimate functional connection also exists between the heart
and the systemic blood-vessels, because a higher arterial tension is
generally compensated for by a lessening of the activity of this organ,
while a low pressure gives rise to augmentor effects. Although the reflex
character of these changes cannot be questioned, some doubt exists
as to the precise locality in which these primary stimuli are produced.
Thus, it may be assumed that they arise in consequence of the varying
distention of the blood-vessels, but it is also possible that they are
generated in the heart itself, because this organ is equipped with sen-
sory corpuscles similar to those found in other structures.^ It is more
than probable that the high arterial pressure tends to stimulate these
1 Tarchanoff, Pfluger's Archiv., xxxv, 1885, and van de Velde, ibid., Ixvi, 1897.
2 Thanhoffer, Centralbl. fiir die med. Wissensch., 1875.
3 First observed by C. Ludwig (Miiller's Archiv., 1847).
^ Fredericq, Archiv de Biol., iii, 1882.
^ Henderson, Am. Jour, of Physiol., xxxi, 1913, 399.
^ Arch. ital. de Biol., xxxv, 1901.
' Smirnow, Anat. Anzeiger, x, 1895.
328 THE NERVOUS REGULATION OF THE HEART
end-organs by causing an overdistention of the ventricular cavities
or at least of the root of the aorta. This conception finds support in
the fact that even a moderate compression of the heart, as results
during the act of coughing or laughing, is usually associated with an
acceleration,' while the irritation of the endocardium most generally
gives rise to inhibitor effects.^ Less probable is the view that these
changes are occasioned by a direct action of the blood pressure upon
the constituents of the cardiac center. ^
One of the first proofs of the existence of these cardiovascular
reflexes has been furnished by Goltz^ who found that the frequency
of the heart may be reduced by simply tapping upon the surface of
the abdomen of a frog with a flat instrument. As this effect is not
obtained after the vagi nerves have been divided, there can be no ques-
tion regarding the reflex character of these impulses. On the afferent
side, their course may be either over the nerves of the cutaneous
sensations or over those relegating deep sensibilities from the viscera.
The latter contention seems the more probable. Very similar results
are obtained in mammals in consequence of the mechanical, thermal,
electrical or chemical stimulation of the abdominal viscera. Among
the large number of causes for this reflex may be mentioned the accumu-
lation of gas in the stomach or intestine,* inflammatory processes or
irritations of these organs by substances contained in the food, and
strokes upon the region of the solar ganglia.
The cardiac acceleration commonly associated with increases in
the activity of the skeletal musculature, may be explained in different
ways. Thus, it may be held that the volitional impulses which are
generated in the cerebral hemispheres and are then conducted to the
muscles, overflow and affect the cardiac center directly. It may also
be assumed that the contractions of the muscles give rise to mechan-
ical impulses which influence the center reflexly. In the third place,
it has been thought possible that the activity of the center may be
varied by certain chemical substances formed in the course of muscular
exercise. This view finds confirmation in the fact that the function
of the center may be influenced either by varying the amounts of blood
supplied to it, or by altering the oxygen content of the circulating
blood. Thus, it has been found that the occlusion of the carotid and
vertebral arteries, as practised by Kussmaul and Tanner, is followed
invariably by a slowing of the heart. This reaction, however, does
not result if the vagi nerves have been divided beforehand. Very
similar effects may be obtained by lessening the oxygen content or
by increasing the carbon dioxid content of the blood. Even a slight
dyspneic condition suffices to augment the cardiac beats and rate,
while a more intense dyspnea invariably leads to partial and complete
^ Pagano, Archiv ital. de Biol., xxxiii, 1900.
2 Bie(ji and Reiner, Pfluger's Archiv, Ixxiii, 1898, 385.
3 Virchow's Archiv fiir path. Anat., xxvi, 1863.
* Burton-Opitz, Pfluger's Archiv, cxxxv, 1908, 205.
CARDIAC INHIBITION AND ACCELERATION 329
inhibition. Very decided changes in the frequency of the heart may
also be produced with the aid of the cutaneous end-organs, their
activation being effected either by cold or warm water, mechanical
impacts, massage, effervescent water, and other stimuli. The fact that
some of these afferent impulses most easily elicit inhibitor and others
accelerator phenomena, has been explained by assuniing that they may
be more intimately connected either with the cardio-inhibitor or
with the cardio-accelerator mechanism. In the case of the carbonated
water bath, however, the mechanical stimulus, consisting in the bump-
ing of the globules of the gas against the integument, may be aug-
mented by a direct effect of the carbon dipxid upon the cardiac center.
It seems entirely probable that some of it may be absorbed and then
act as a stimulant not only to the respiratory but also to the cardio-
vascular system.
As has been emphasized above, the cardiac center is also the re-
cipient of sensory impulses which arise either in the membranous
Fig. 173, — Record of the Caeotid Blood-pressure in Rabbit During Stimulation
OF THE Depressor Nerve.
structures enveloping the heart, or in this organ itself. The fibers
conducting the impulses from the heart are attributes of the vagus
system, and have been designated by Ludwig and Cyon,^ their dis-
coverers, as the depressor nerve. These fibers become clearly recogniz-
able upon the arch of the aorta, whence they reach the vagus center
either by pursuing an independent course along the carotid artery
(rabbit), or by intermingling with the vagosympathetic fibers (dog).
In the rabbit, this nerve is isolated most easily in the neck, where it
forms an anatomical entity next to the inner border of the cervical
sympathetic and the trunk of the vagus. Centrally to this point
it divides into two slender bundles, one of which enters the cervical
portion of the va^us directly, and the other, the superior laryngeal
branch of this nerve. The fibers of both branches then intermingle
with the other vagal fibers.
1 Berichte der sachs. Akad. der Wissensch., 1866.
330 THE NERVOUS REGULATION OF THE HEART
The depressor nerve possesses a very characteristic and important
function. It is sensory in its nature and conducts impulses solely from
the heart to the nucleus of the vagus and the cardiac and vasomotor
centers. It must be obvious, therefore, that the effects ordinarily
obtained with the help of this nerve, can only be elicited by stimulat-
ing either the intact nerve or its central end. Concerning its function,
it may be stated in brief that it gives rise to reflexes which are centered
upon the cardiac and vasomotor mechanisms. The former produce
a reduction in the frequency of the heart and the latter, a fall in arterial
blood pressure. But their action upon the heart may be destroyed
by dividing the vagus distally to its point of union with the depressor
fibers. Naturally, the drop in pressure persists even after the division
and is then frequently associated with an increase in the frequency
of the heart. ^
The foregoing data show very clearly that the depressor nerve
plays an important part in varying the resistance in the vascular
channels against which the heart must act. To illustrate, if the ar-
terial tension is too high, an impulse is set up in this organ which, on
being relayed to the cardiac and vasomotor centers, produces a re-
duction in the rate of the heart and a fall in the blood pressure. Ob-
viously, this reflex lessening of the peripheral resistance places the
cardiac muscle in a much more favorable position to contract with-
out strain.
By connecting this nerve with a string galvanometer, Einthoven^
has shown that sensory impulses are generated synchronously with
every contraction of the heart, but naturally, this fact does not signify
that the ''depressor-reflex" is elicited an equal number of times. No
doubt, these impulses remain subminimal as a rule, and although trans-
mittejd to the medulla, serve here merely the purpose of maintaining the
tonicity of the cardiac center. It has also been proved by Koster
and Tschermak^ that electrical variations may be produced in this
nerve by increasing the intra-aortic pressure artificially. Inasmuch
as this nerve ramifies extensively upon the ascending portion of the
aorta, it may be surmised that these sensory impulses arise chiefly in
consequence of the mechanical stimulation resulting from the disten-
tion of this blood-vessel and, in a lesser degree, also from the disten-
tion of the heart itself.
1 Bayliss, Jour, of Physiol., xiv, 1893, 303.
2 Pfliiger's Archiv, cxxiv, 1908, 246.
3 Ibid., xciii, 1903, 24; also see: Eyster and Hooker, Am. Jour, of Physiol., xxi,
1908, 373.
SECTION IX
FUNCTIONAL PECULIARITIES OF THE CARDIAC
MUSCLE TISSUE
CHAPTER XXVIII
THE ORIGIN OF THE HEART BEAT
The Excised Heart. — If the heart of a cold-blooded animal is re-
moved from the body and is placed in a nutritive medium under proper
conditions of moisture and temperature, it will continue to beat
rhythmically for many hours, and even for days. Essentially the same
result may be obtained with the hearts of warm-blooded animals, but
inasmuch as their storative power is slight, they require a constant
supply of nutritive material. Thus, it will be found that the mamma-
lian heart ceases to beat very soon after the circulation has been inter-
rupted, but may be made to resume its activity later on by perfusing
it through its coronary blood-vessels. This procedure consists in
connecting the aorta with a pressure reservoir containing an 0.8
per cent, solution of sodium chlorid. Ringer's fluid, or defibrinated
blood through which bubbles of oxygen are passed at a constant rate.
Under the most favorable conditions an excised heart may be kept
beating rhythmically for many hours ; moreover, if it is merely intended
to incite the contractions without having them continue for any length
of time, it is sufficient to use oil or paraffin in place of the nutritive
fluids just mentioned. Evidently, the mechanical stimulus derived
from the distention of the coronary vessels suffices to activate the
musculature and to keep it in this condition for a moderately long
time. These experiments may be repeated with smaller segments of
the heart as well as with narrow strips of the ventricles. In the latter
case, it is sufficient to immerse them in solutions of certain inorganic
salts. Larger pieces of the ventricles may be made to beat rhythmi-
cally by perfusing them through their supply channel.
The conclusion to be drawn from experiments of this kind is that
the power of rhythmic contraction is inherent in the hearts of all
vertebrates.^ Their connection with the central nervous system, there-
fore, is not essential to their activity and merely serves the purpose of
bringing them into functional relation with the other organs and tissues.
It has previously been shown that various conditions may arise in
1 First taught by Haller in 1757.
331
332 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
different parts of the body which influence the activity of the heart
by way of these connecting channels. These correlating impulses,
however, have nothing to do with the actual cause of the contractions.
In the second place, it must be evident that even if it has been demon-
strated that the beat originates in the heart, it still remains to be de-
termined whether the impetus to contract is given by the muscle
substance or by the nervous elements contained therein. The views
held pertaining to this question have been embodied in the so-called
neurogenic and myogenic theories of the heart beat.
Closely related to this problem is another which pertains more
directly to the cause of the orderly sequence of the contractions of the
different segments of the heart. Thus, it may be asserted that the
rhythm of the heart is associated either with the nervous elements or
with the muscle tissue. With reference to the automaticity of this
organ, the question may then be raised whether its power of remaining
active by a self -inducing cause is contained in the first or in the second
component? At the present time it is quite impossible to give a
definite answer to these questions. We are, however, in possession of
certain fundamental facts relating to this topic which may best be pre-
sented separately under the headings of the theories just mentioned.
The Neurogenic Theory of the Heart Beat. — This theory which has
been proposed by Volkmann, was strengthened considerably by the
discovery of Remak that the heart of the frog gives lodgment to nerve
fibers as well as to ganglion cells (1849). Upon entering the sinus
venosus, the two vagi nerves unite to form a plexus which is situated
below the pericardium and embraces numerous ganglion cells. Re-
mak's ganglion is connected by means of two septal nerves with another
network of nerve tissue which is situated in the vicinity of the auriculo-
ventricular groove and is known as Bidder's ganglion. Both ganglia
send non-medullated fibers to the neighboring regions of the auricles
and ventricle, a few isolated nerve cells being interposed here and there.
It was also noted that the apical portion of the heart, embracing the
lower one-half to two-thirds of the ventricle, is free from cellular
elements. Even more favorable conditions for experimentation
prevail in the turtle, because the heart of these animals is larger and its
nervous elements are more easily accessible.
In accordance with this theory, it is assumed that the successive
cardiac contractions result in consequence of excitations which are sent
out at regular intervals by the cells composing the aforesaid ganglia.
Moreover, as each contraction begins near the venous entrance to the
right auricle, and progresses from here toward the apex, Remak's
gangUon is generally regarded as the motor center of the entire organ.
It is held, therefore, that the cause of the automaticity lies within these
cells, while the peripheral fibers and cellular elements serve merely as
adjuncts which are made use of in the conduction of the wave of
excitation to other parts of this organ. It is granted, however, that the
separation of these outlying elements from the "pace-maker, " enables
THE ORIGIN OF THE HEART BEAT
333
them to assume certain automatic properties of their own and to acti-
vate that portion of the musculature with which they are normally
connected. Essentially the same explanation is given for the mode of
contraction of the mammalian heart, although the location of its
nervous elements has not been fully ascertained as yet.
It should be stated at this time that the neurogenic theory in its
extreme form is untenable, and while a number of experiments could
be cited, tending to emphasize the importance of the nervous elements
as the controlling factor of the heart's action, the evidence is not suffi-
ciently definite to prevent us from interpreting it in a way to favor the
myogenic theory. The same objection, however, may be raised against
several of the experiments which will be mentioned later on in support
of the latter theory, because they permit of a two-fold interpretation,
thus favoring one view as much as the other. The experimental
evidence so far presented may be arranged as follows :
1. If the heart of a frog is removed in its entirety, it will continue to beat for a
long period of time, provided, of course, that it is placed in a proper nutritive medium.
If it is then cut across at the sino-auricular groove, its sinus continues to contract
Fig. 174. — Heart op Limulus prom Dorsal Surface. (Carlson.)
mnc, Median nerve-cord; In, lateral nerve-trunks.
at regular intervals, while its auricles and ventricle cease beating at least for some
time. The latter then resume their activity, the beat seemingly originating in the
auricle. Their frequency of contraction, however, rarely equals the normal. If the
ventricle is then separated from the auricles by a cut across the auriculoventricular
groove, the latter continue to beat, while the former soon ceases its activity. A
certain time having elapsed, the ventricle again contracts but now quite independ-
ently of the rhythm of the other segments of this organ.
2. Very similar results may be obtained by applying two ligatures to the heart
in such a way that one comes to lie in the sino-auricular groove and the other, in
the n.n r if. 1 iln ypin trj p,] d a.r groove, (Stannius experiment, 1852.) After the applica-
tion of the first, the auricles and ventricle cease beating, while the sinus continues
to contract. All three divisions, however, beat at regular intervals as soon as
the second ligature has been properly placed and tightened. As Heidenhain has
stated, the first ligature seems to exert a mechanical stimulus upon the inhibitor
ganglion, while the second serves as a stimulant for the accelerator elements. It is
to be noted, however, that the different segments of the heart now beat inde-
pendently of one another, and that the regular progression of the wave of con-
traction from the sinus to the apex is no longer in evidence. These experiments
tend to show that the different portions of the heart are imbibed with a certain
automatic power of their own which diminishes gradually in the direction from
sinus to apex. This dormant power enables the. more distant ganglia to originate
impulses at any time after the more central elements have been destroyed or have
been separated from them. Since the property of automaticity seems to be
associated exclusively with nerve cells, the muscle cells find themselves in the
position of mere executors of the will of a higher controlling factor.
334 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
3. By cutting and removing the nerve cord which passes along the tubular
heart of the horseshoe crab, Carlson^ has succeeded in showing that the cause of
the contraction of this organ lies in the ganglion cells of the median cord, and that
the conduction is effected by the nervous and not by the muscular elements. In
this particular case, therefore, it would appear that the cessation of the heart beat
is brought about by an interference with the automatic discharges of the ganghon
cells (Weber) and not by an inhibition of the activity of the cardiac musculature
(Engelmann). These results, however, do not permit of generalizations, because
they cannot justly be applied to the vertebrate heart without certain modifications.
The reason for this is that the heart of vertebrates may possess certain physiological
properties which are very different from those displayed by the heart of the
crustaceans.
4. It has been found by Kronecker and Schmey^ that the regular and forceful
contractions of the ventricle may be changed into mere fibrillary undulations
(delirium cordis) at any time by puncturing the interventricular septum at a
point near the junction of its upper and middle thirds. While this phenomenon
has been interpreted as proving that the coordinated action of the ventricle is de-
pendent upon a center situated in the aforesaid region, this hypothesis can scarcely
be defended in the light of our present knowledge regarding the conduction paths
of the heart. Moreover, it has been shown subsequently by McWilliams^ that
the cardiac musculature may also be made to fibrillate in other ways, for example,
by mechanical, thermal, and electrical stimulation of the surface of the heart in
the vicinity of the apex.
5. The contractions of the mammalian heart may also be incited by perfusing
the coronary circuit with non-nutritive fluids. It seems that in this particular
case the distention of the coronary blood-vessels suffices to stimulate the nervous
receptors in a mechanical way.
The Myogenic Theory of the Heart Beat. — This theory has been
more fully developed in recent years by the work of Gaskell and
Engelmann. It is held that the wave of excitation arises in the muscle
tissue and that the nervous elements serve the sole purpose of cor-
relating the action of the different parts of the heart, and secondly, of
bringing the activity of this organ into functional relation with other
structures. Furthermore, as the beat originates in the venous vesti-
bule, the tissue composing this particular area, is said to possess
certain functional peculiarities which render it especially suitable for
the generation of those impulses which later on give rise to the con-
traction. The arguments favoring the myogenic theory may be cited
as follows: — *--
1. Bernstein's Experiment. — If the apical portion of the heart of a frog or
turtle is separated by a ligature which is tightly drawn around the ventricle, it
ceases to contract almost immediately. When isolated in this way, it may be made
to beat again by applying electrical or mechanical stimuli to its surface or by raising
the pressure within its cavity. The latter end may be attained at times by tem-
porarily compressing the aortse.
2. Strips of tissue may be cut from the apex which may be made to beat
rhythmically by placing them in an isotonic solution of sodium chlorid or in
Ringer's fluid. These strips frequently continue their activity for several hours.
These experiments become especially significant, if it is remembered that the apex
of these hearts contains no ganglion cells.
. 1 Am. Jour, of Physiol., xiii, 1905, 217.
^ Sitzungsber. der Akad. der Wissensch., Berlin, 1884.
3 Jour, of Physiol., viii, 1887, 296.
THE ORIGIN OF THE HEART BEAT 335
3. In the frog and turtle it is possible to remove practically the entire inter-
auricular septum, together with its ganglia and connecting paths, without inter-
fering with the character or rhythm of the cardiac contractions.
4. A still stronger argument is contained in the fact that the embryonic heart
of the chick (2 to 5 days) or shark beat with perfect regularity at a time when as
yet no ganglion cells can be made out. If segments of the embryonic heart are
kept in a medium of blood plasma, ^ they will continue to beat for a long time ;
indeed, the muscular units usually multiply under this condition and give rise to
new cells which possess rhythmic activity. While this fact clearly proves that
the cardiac muscle is automatic, it may be contended that this property is primi-
tive and of short duration, and that it is eventually superseded by the auto-
maticity of the newly developed nervous elements.
5. The excised bulbus aortse of the frog, and even portions thereof, usually con-
tinue to contract rhythmically. The same result may be obtained with small
segments of the veins entering the sinus venosus.
6. Rhythmic contractions may be observed in the veins of the wing of the bat,
as well as in certain segments of the lymphatic system. Nervous elements have
not been demonstrated in these tissues.
7. In the lower forms, the wave of contraction v/hich normally starts in the
sinus portion of the heart, is propagated to the auricles and ventricles by means
of clearly recognizable strands of muscle tissue. Moreover, while the conducting
path in the mammalian heart, as represented by the bundle of His, is formed by a
type of tissue which cannot justly be classified as muscle tissue, it does not at all
possess the characteristics of nerve tissue.
8. Waves of contraction may also be incited in other parts.of the heart. Thus,
the stimulation of the apex most generally gives rise to a contraction in a direction
opposite to normal, namely, from ventricle to sinus.
9. Engelmann has shown that the continuity of the nerve fibers of the heart
may be destroyed without materially changing the sequence of its contractions.
Thus, it is possible to convert the auricle of the frog's heart by several transverse
cuts into a zig-zag strip without blocking the wave of contraction as it passes
from the sinus to the ventricle. Very similar results may be obtained with the
ventricular muscle. If changed into a zig-zag strip by transverse incisions, a
contraction started in its basal portion eventually reaches the apex, while a
contraction incited at the apex also progresses to the base.
The results of the experiments just enumerated indicate with
certainty that the nervous elements of the heart possess the power of
discharging rhythmic impulses and that cardiac muscle tissue is
equipped with rhythmic properties similar to those of other tissues.
Smooth muscle and, in a slight degree, also striated muscle are in
possession of this power. It may be contended, however, that this
primitive functional characteristic of cardiac muscle prevails only
as long as no nervous tissue is present, and that it gradually loses its
dominating influence in the course of the development of the latter.
Thus, it may be said that the separation of the adult heart from the
central nervous system or the destruction of its nervous elements
again permits this primitive property of the cardiac musculature to
assert itself. Arguments of this kind are difficult to meet, because,
while an adequate proof of a supersedence or transfer of function of
this kind is not at hand, no perfectly definite reasons can be given
against this occurrence. It seems best, therefore, to leave this matter
1 Burrows, Science, xxxvi, 1912.
336 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
in abeyance, with the understanding, however, that the evidence so far
submitted favors the myogenic theory.
The Nature of the "Internal" Stimulus.— Even if the cause of
the heart beat should finally be localized either in the nervous tissue or
in the muscle tissue, the nature of the exciting agent must still remain
doubtful. It is customary to evade this question by saying that the
cardiac muscle possesses the power of automaticity, the implication
contained in this statement being that this tissue embraces certain
excitatory agents which are capable of acting independently of outside
influences. Strictly speaking, however, this cannot be true, because
all reactions of living substance are dependent upon material brought
to it from the outside. Without stimuli of this kind life is impossible.
In seeking to discover the nature of the ''inner" stimulus, it is
fair to assume that the cardiac contractions result in consequence of
an interaction between the chemical constituents of the blood and those
of the substance of the heart. If this problem is restricted in this
way, further advance in this direction necessitates the determination
of those substances which act as exciting agents either individually
or when combined with others. In what measure we have succeeded
in isolating these agents will be brought out in the succeeding
paragraphs.
It is a well-known fact that the hearts of the cold-blooded animals
continue to beat for some time after their excision, while the hearts of
the warm-blooded animals cease their activity very soon after the
interruption of the circulation. Both types of organs, however, may
be kept in an active condition outside the body by supplying them
with defibrinated blood or some other nutritive fluid. This difference
in their behavior may best be explained upon the basis of metabolism.
As the mammalian heart possesses a more vivid metabolism, it requires
a more constant supply of nutritive material, and especially, because
its storative power is altogether too slight in comparison with the work
demanded of it. It is essential, therefore, that it be in possession of
an extensive coronary system which enables even its most remote cellu-
lar constituents to obtain fresh substances in a very brief time. The
heart of the lower animals, on the other hand, does not require a sys-
tem of local blood-vessels, because its metabolic processes are less in-
tense and are amply safeguarded by direct interchanges with the blood
as it traverses its cavities. The cells of the lower hearts also seem to
be able to store a considerable portion of their nutritive material, so
that it may be made use of whenever the blood supply is cut off.
It has been found by Merunowicz that an aqueous extract of the ash of the
blood exerts a stimulating action upon cardiac muscle. In continuation of these
experiments Ringer^ has proven in 1882 that certain inorganic salts, namely the
chlorids of sodium, calcium and potassium, affect this tissue in a very specific
manner, because they are especially adapted for maintaining the beat. In the case of
the heart of the frog, these salts act most efficiently in the following concentration:
1 Jour, of Physiol., iv, 1883, 222.
THE ORIGIN OF THE HEART BEAT 337
NaCl 0.65 percent.
KCl 0.03 per cent.
CaCl2 0 . 25 per cent.
Even the mammalian heart may be kept beating for many hours by perfusing it
with this solution. The best results, however, are obtained if the solution is first
charged with oxygen before it is allowed to enter the coronary vessels. Locke'-
recommends a perfusion fluid containing 0.9 per cent, of NaCl, 0.024 per cent, of
CaCla, 0.042 per cent: of KCl, 0.01-0.03 per cent, of NaHCOs, and 0.1 per cent,
of dextrose. This fluid should be warmed to 35° C. and charged with oxygen.
The dextrose is said to prolong the -period of contraction and to renew the vigor
of those hearts which have ceased to beat while still being perfused with the pure
solutions of the aforesaid salts. With the aid of this solution, Locke and Rosen-
heim^ have succeeded in reviving the isolated heart of a rabbit on four consecutive
days, keeping it in activity each* time for several hours. In a similar way, Kuli-
abko^ has been able to incite contractions in a rabbit's heart three and four days
after its removal from the body. Hering^ revived the heart of a monkey 28 and 54
hours after the death of the animal. Very similar results have been obtained with
human hearts.
jwmjwmljwwwMmMBMM
Fig. 175. — Tracing op Contracti6ns of a Frog's Heart, Showing Effect of
Adding a Trace of CaCl2 to the NaCl Solution Used Previously for Perfusion.
(Ringer.)
It is evident, therefore, that these salts give rise to an osmotic environment
which is well adapted for cardiac muscle. The action possessed by each salt
individually, has been brought out by the work of Kronecker,^ Howell,^ Loeb^
and others. By making use of strips of the ventricle of the frog or turtle, it has
been shown that the preceding solution is capable of inciting a rhythmic activity
which may last for niany hours. The same end may be attained by immersing
these preparations in a 0.7 per cent, solution of sodium chlorid. The contractions
appear as a rule after a latent period lasting from 5-20 minutes, and attain a
maximal height and length in the course of a few minutes. It is to be noted,
however, that while this salt excites the contractions, it does not maintain the
beats for any considerable length of time. The muscle presently ceases its activity
in the state of relaxation. " The sodium salt, therefore, favors contractility and
irritability. If a small quantity of a solution of calcium chlorid is now added
to the former in slight excess of the sodium, the strip of muscle again begins to
contract. Later on, however, its contractions become more and more forced until
it remains in a condition of tonic shortening, known as calcium rigor. By the
addition of a small amount of potassium chlorid, this strip may then be activated
again. An excess of potassium, however, leads to a slowing and a possible cessa-
tion of the contractions. The muscle is then retained in a state of extreme
relaxation.
1 Jour, of Physiol., xviii, 1895, 332; also see: Mines, Ibid., xxxvii, 1908, 408,
and xlii, 1911, 251.
2 Ibid., xxxvi, 1907, 205.
3 Pfluger's Archiv, xcvii, 1903, 539.
4 ibid.^ cxvi, 1907, 143.
^ Festschr. fur C. Ludwig, 1874.
6 Am. Jour, of Physiol., ii, 1898, 47.
"^ Festschr. fiir Fick, 1899.
22
338 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
While the sodium, calcium, and potassium may not be the only agents con-
cerned in this excitation, it must be evident that they play a most important part
in the formation of a molecular concentration of the blood which favors the
activity of cardiac tissue. It must also be apparent that these salts are specific
in their action. The sodium, for example, stimulates contraction, while the
calcium maintains the tonus and the potassium favors relaxation. Obviously,
therefore, a proper activity of the heart can only be secured by means of a solution
which contains these salts in perfectly definite proportions. Howell, in fact,
believes that the states of contraction and relaxation of cardiac muscle are depend-
ent upon an alternate and opposing interaction of these substances with the
contractile elements of this tissue. In this connection, it is of interest to note
Fig. 176. — A Frog's Heart Poisoned by Excess of Calcium Salts, Recovers
Its Spontaneous Rhythm on Adding a trace of KCl to the Perfusion Fluid.
{Ringer.)
that Biedermann^ and Loeb have succeeded in eliciting rhythmic contractions
in striated muscle by subjecting it to the influence of isotonic solutions of sodium
and lithium. Solutions of calcium, on the other hand, have been proved to
possess an inhibitor action.
As far as the nature of the ''inner stimulus" of the heart is con-
cerned, it may be held that the substances just enumerated, actually
constitute the exciting agent (Howell), or that they merely furnish a
medium in which the true stimulus is then capable of unfolding its action
(Engelmann). If the latter view is adhered to, the stimulating agent,
whether it be chemical, electrical, or enzymotic in its nature, has not
been discovered as yet.
CHAPTER XXIX
THE PHYSIOLOGICAL PROPERTIES OF CARDIAC
MUSCLE
Refractory Period. Extrasystole. — The heart of the lower animals
may be made to register its contractions upon the paper of a kymo-
graph by connecting its apex with the free end of a writing lever. A
thread and small hook are used to make this connection. Another
procedure is to place a delicate rod upon the ventricle and to permit it
to act against the long arm of a writing lever. The lower end of this
rod should be equipped with a cup-shaped platelet serving to retain
the former more firmly upon the surface of the heart. A third method
1 Wiener Sitzungsber., Ixxxii, 1880.
PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE
339
consists in fastening the apex of the ventricle to the long arm of a
writing lever, which is pulled upward beyond its horizontal position
by a counter spring (Fig. 177). In the latter case, the contracting
ventricle pulls the lever downward, while in the first two instances the
lever moves upward during systole and downward during diastole.
Under normal conditions, the successive up and down strokes are
of equal size, but assume a smaller amplitude as soon as the prepara-
FiG. 177. — Schema to Illustrate the Methods of Recording the Contractions of
THE Frog's Heart.
The writing lever (W) is pulled upward by a spring (S) against the action of the
heart.
tion becomes fatigued or when it is made to act under less favorable
circumstances (Fig. 178). Very similar records may be obtained with
apex-preparations subjected to electrical stimuli or with strips of
ventricular muscle tissue immersed in a solution of the inorganic salts.
It is to be noted, however, that the amplitude of the contractions can-
not be changed by varying the strength of the stimuli. This fact
Fig. 178. — Record of the Contractions of the Frog's Heart.
The time is registered in seconds.
implies that a heart always contracts with full vigor irrespective of
the character of the stimulation. This result is somewhat different
from that ordinarily obtained with striated and non-striated muscle,
because the reactions of these tissues are directly proportional to the
strength of the stimuU. Cardiac muscle, therefore, is said to behave in
accordance with the "all or none'' law, i.e., it always reacts maximally,
whether the stimulus be shght or strong.
340 PECULIAKITIES OF THE CARDIAC MUSCLE TISSUE
In explanation of this phenomenon, it should be mentioned that
Gotch and K. Lucas^ have shown that the amplitude of the contrac-
tions of striated muscle is determined by the number of fibers actually-
involved in this process. In other words, while a slight stimulus
activates only a relatively small portion of the total mass of the muscle,
a strong stimulus causes a much more general reaction. The cellular
components of heart muscle, however, are not functionally independent
of one another, and hence, are not adapted to give graded reactions.
Thus, even the slightest stimulus must produce a wave of excitation
which spreads far and wide through its different rows of cells and
involves even its most distant constituents. This explanation of the
''all or none" law permits of the conclusion that the mode of contrac-
tion of cardiac muscle is not at variance with that of other contractile
tissues. It must be evident, therefore, that the functional difference
to which attention has just been called, is dependent upon the number
of the cellular units involved and not upon any chemicophysical
differences in the muscle substance. Consequently, the all or none
law merely serves to show that the different components of cardiac
muscle are more closely allied with one another than those of skeletal
muscle. It is easily noted, however, that this continuity is not the
same in all hearts, as is shown by the fact that the effects in those of
the frog, turtle and different mammals always possess a disseminating
character, while those obtained in the crustacean heart do not.
Regarded from the standpoint of hemodynamics,^ a maximally contract-
ing heart is of course to be preferred, because it gives rise to more
uniform discharges and more constant pressures.
The assumption that cardiac muscle is a functional curiosity, is
disproved further by the fact that it gives rise to the phenomena of
summation of stimuli and summation of contractions, both of which are
conspicuous characteristics of skeletal muscle. Thus, it has been
found that if several subminimal shocks are sent into a quiescent
strip of frog's ventricle in rapid succession, these individual stimuU
are added to one another until they finally give rise to a contraction.
Furthermore, if the ventricle of a Stannius-heart is stimulated with
single shocks at the rate of one in every ten seconds, the first reactions
frequently tend to be somewhat smaller than those obtained later on,
so that an ascending series is produced, resembhng the ''staircase
contractions" of striated muscle. This result is obtained only under
experimental conditions and, hence, does not run counter to the "all
or none" law.
In accordance with the well-established fact, that a mf.ss of living
substance cannot continue to react unless a sufficient time be allowed
it during which to replenish the material destroyed during its pre-
ceding period of activity, it may justly be assumed that the
successive systolic and diastolic phases of the heart represent period-
1 Jour, of Physiol., xxxviii, 1909, 113.
2 Woodworth, Am. Jour, of Physiol., viii, 1902, 213.
PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE 341
ically recurring catabolic and anabolic phenomena. No doubt, the
systolic movements necessitate the utilization of the largest store of
its energy-yielding material which must first be replaced before the
next contraction can take place. The systole, therefore, must be con-
sidered as the period of decomposition of the contractile substance and
the diastole as the period of assimilation. Moreover, as the irritabiUty
of all tissues depends upon a proper store of energy-yielding substances,
the power of cardiac muscle to respond to stimuli must be at a mini-
mum when catabolic processes are going on. This is the case during
systole. The stimulus to contract is given immediately preceding this
period. This implies that certain chemicophysical changes result at
this moment which eventually give rise to the visible contraction.
During systole, however, while the heart is thus engaged in converting
practically all its potential energy into kinetic energy, no other exci-
tation can be brought to bear upon it effectively. This means that it
is then in a non-responsive state and is, so to speak, imperrneable or
refractory to outside influences. Immediately upon the completion of
its refractory period, it again becomes receptive and more so later on
in the course of diastole. Its greatest irritabiUty it attains just before
the next contraction.
These changes in irritability may be detected very easily if single in-
duction shocks are passed through the heart of a frog or turtle at any
time while it registers its contractions upon the paper of a kymograph. ^
It will be noticed that a stimulus which reaches it during its systolic
state, does not alter the sequence nor the general character of its con-
tractions, whereas a stimulus which enters at the very beginning or at
any time during the diastolic period is followed by an extrasystole.
This- extra contraction, however, does not appear until the succeeding
normal one has been completed. In accordance with what has just
been said, it must be clear that a greater strength of stimulus is re-
quired to produce this second reaction when applied at the beginning
of the period of relaxation than when applied near its end. This dif-
ference, as we have just seen, is accounted for by the fact that the
restoration of the contractile substances has been practically completed
at the end of diastole. The height of these extrasystoles corresponds
very closely to that of the normal contractions.
After the completion of an extrasystole, the heart most generally
remains in a condition of relaxation during the interim of one beat. It
then exhibits a so-called compensatory pause. This designation, how-
ever, is not especially pertinent, because this temporary inhibition does
not serve the purpose of compensating for the preceding hyper-effort,
but only to correct the disturbance in the rhythm. The correctness
of this statement may be proved without much trouble by studying
these extra contractions when generated in an isolated ventricle.
If this portion of the heart, or a strip thereof, is activated by subjecting
it to the stimulating influence of a solution of the inorganic salts, these
1 Marey, Trav. du laboratoire, 1876.
342 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
extra contractions may then be incited without giving rise to compen-
satory pauses, nor do we then obtain a significant disturbance of the
rhythm. It seems, therefore, that this phenomenon can only develop
in the spontaneously beating heart, the activity of which, as we have
seen above, is dependent upon rhythmic discharges from the "pace-
maker" situated at the venous vestibule. Under normal conditions,
these stimuli are generated at regular intervals and activate the auricles
and ventricles in quick succession. The latter in particular are well
Fig. 179.— Tracings of Spontaneous Contractions of Frog's Ventricle, to Show
Refractory Period.
In each series the surface of the ventricle was stimulated by an induction shock at e,
as indicated by the tracing of the signal. In 1, 2 and 3 this stimulus had absolutely no
effect, since it fell during the refractory period. In 4, 5, 6, 7 the effect of the shock was
to interpolate an extra contraction in the series, the latent period (shaded part) gradually
diminishing from 4 to 7 (diastolic rise of irritability). In 8 the irritability of the prepa-
ration was already considerable, and the latent period inappreciable. The " compensa-
tory pause " after the extra beat is also well shown in 4, 5, 6, 7, 8. (Marey.)
supplied with contractile substances, and are therefore very irritable
and responsive. If they are now made to give an extrasystole, the
subsequent normal wave of excitation must arrive in them at a time
when they are just engaged in producing this contraction. Conse-
quently, they are impermeable to this stimulus and refractory. Inas-
much as this excitation remains without results, the ventricles continue
inactive during the period ordinarily occupied by the next normal
contraction. The succeeding normal wave of irritability, however,
PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE 343
finds the ventricle again in a receptive state and is therefore able to
incite a contraction. No further disturbance takes place until another
extrasystole is interposed.
The refractory period and compensatory pause serve as a protective
mechanism which prevents any interference with the cardiac rhythm.
But if such a condition has actually arisen (arhythmia), their tendency
will be to reestablish normal relationships as quickly as possible. In
addition, the refractory period serves lo check off the individual
discharges of the ''pace-maker" and to regulate the length of the
successive systoles. Under ordinary conditions, therefore, the latter
must retain a twitch-like character and cannot become tetanic. It is
possible, however, to prolong them unduly either by stimulating the
heart with a . series of strong induction shocks, or by exposing it to
heat.
E- '^'^^'^'-^
Fig. 180. — Electrocardiogram Showing an Intrasystole at e, and Compensatory
Pause at C. (Cunningham.)
Extrasystoles are frequently encountered in the human heart
without being able to recognize a distinct lesion of the myocardium or
of the conducting paths. No special importance need be attached to
them as long as they remain infrequent. Most commonly they find
their origin in a hyperirritability of the local or general nervous ele-
ments. Two types of extrasystoles are recognized clinically, namely,
those which are followed by a distinct compensa;tory pause and those
which are not. The former are more common and are often designated
as premature beats. They result in consequence of impulses which
start either in the pace-maker itself or high up in the conducting paths
and adjoining auricular tissue. The latter are generally called inter-
polated systoles, and seem to be due to stimuli which originate either in
the substance of the ventricles or in the more distal segment of the
conducting bundle. For this reason, they cannot seriously interfere
with the regular waves of excitation conveyed downward from the
auricle and, hence, cannot give rise to a distinct compensatory pause or
344 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
a disturbance of the rhythm. It might also be mentioned that a large
number of the so-called ''premature" beats are caused by impulses
which arise in a hypersensitive auricular tissue. Whether these stimuli
originate in this particular area or nearer the pace-maker, can readily
be determined by noting the length of time intervening between them
and the next systole, because a compensatory pause must arise as soon
as the distance between their place of origin and the ventricle becomes
sufficiently great to allow them to reach the latter while in systole.
The method of auscultation is not well adapted for the detection of
these irregularities in rhythm, and especially not if they are of the inter-
polated type, but it is possible to recognize them without difficulty with
the aid of the electrocardiograph.^
The Tonus of Cardiac Muscle. — The functional capacity of the
heart depends upon the tonus of its muscular elements. This fact
implies that the latter are normally held under a certain physiological
tension, i.e,, they are retained in a state intermediate between com-
plete relaxation and contraction. The tonus, however, does not re-
main the same for a long period of time, but varies with the character
of the internal stimuli. This fact may readily be deduced from any
continuous record of the beating heart of a frog, because the curve
as a whole does not follow along a straight horizontal line, but shows
long wave-like oscillations. In this respect, cardiac muscle does not
differ from striated or non-striated muscle tissue, because both of these
are continuously exposed to tonic impulses and are able to relax fully
only if separated from the central nervous system. It need scarcely
be emphasized that a muscle when held in a position of partial contrac-
tion, can reach the condition of maximal shortening with much greater
rapidity. This statement also applies to the arteries and other tubular
organs, because their walls are ordinarily kept in a position intermedi-
ate between constriction and dilatation.
The property of tonicity of a tissue is dependent upon the activity
of the nervous elements with which it is connected. It is believed that
the nervous centers give origin to a series of subminimal impulses which
tend to keep the tissue continually in a condition of functional alertness.
Concurrently, it may be reasoned that if these impulses are prevented
from reaching their destination for any length of time, the tissue
loses its tonicity and eventually becomes functionally useless. In
the case of the isolated heart, however, the tonus is retained in a meas-
ure, because its intrinsic nervous elements are capable of generating
those impulses which under normal conditions are derived from its
extrinsic centers.
The nature of the stimuli upon which the tonus depends is still
unknown. It is commonly held that the tonicity is due to the same
stimuli which produce the contractions. In the former case, however,
they remain subminimal, while in the latter case they become supra-
^ Lewis, Clinical Disorders of the Heart Beat, London, 1913.
PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE 345
minimal. Fano/ on the other hand, beHeves that there are two dif-
derent kinds of excitatory agents at work. In support of this conten-
tion, Gaskell and Mines ^ have found that weak acids and carbon
dioxid diminish the power of contraction as well as the tonus, whereas
an increased alkahnity gives rise to just the opposite effect. It seems
certain, however, that an optimum degree of tonus can only be obtained
if the body fluid possesses a perfectly definite reaction. As the re-
action of the blood depends chiefly upon the tension of carbon dioxid,
it may be inferred that this gas plays a most important part in the
production of tonicity.^
It must be clear that the tonicity of cardiac muscle furnishes a
means of determining its functional capacity. Under ordinary con-
ditions it is sufficient to note the amplitude and force of the contrac-
tions of the exposed or isolated heart, or to measure the pressure which
the normally beating organ is capable of developing in the blood-vessels.
To begin with, the individual cells must of course be capable of entering
the state of complete relaxation, as well as that of maximal contrac-
tion. Hence, they must possess a wide range of movability. The
former quality is as important as the latter, because it determines the
capaciousness or power of filling of the entire organ. It must be
evident that a loss of the relaxing power of the muscular units must
place the heart under a certain disadvantage, because it lessens the
capacity of its chambers. Quite similarly, it may be said that an
unusual degree of relaxation must act unfavorably, because it tends to
invite an undue distention and imperfect emptying of the cardiac
chambers. The latter condition indicates a loss of tonus approaching
fatigue, and may lead to a general dilatation of the organ when called
upon to perform an extra amount of work. It stands to reason that a
muscular unit which is not tonically set is not in a favorable position
to resist those strains which 'frequently arise in the vascular system
in consequence of physical exertions and emotions. A loss of tonus^
therefore, exposes the heart to the danger of becoming hyperdistended
and dilated.
Opposed to the condition of dilatation is the condition of hypertrophy, which
presents itself in the form of either a deposition of perfectly new cells or an increase
in the volume of those already present. In either case, an organ larger and heavier
than normal is the result. Hypertrophy finds its origin in the fact that the cardiac
cells are in a tonic condition and react to excessive stimulation by increasing
their power of contraction. This change eventually produces a compensatory
increase in the size and massiveness of the heart, while the condition of dilatation
is a simple distention without a deposition of new material. But it is not always
true that these changes affect the organ as a whole, in fact, in many instances only
single compartments are involved. Thus, mitral stenosis is usually associated
with a hypertrophy of the left auricle and aortic stenosis with a hypertrophy of
the left ventricle.
^ Festschr. fiir C. Ludwig, Leipzig, 1887.
2 Jour, of Physiol., xlvi, 1913, 23.
3 Patterson, Piper and Starling, Jour, of Physiol., xlviii, 1914, 465.
346 PECULIARITIES OF THE CARDIAC MUSCLE TISSUE
The ability of cardiac muscle to increase its substance is of great dynamical
importance, because in the absence of this compensation grave circulatory dis-
orders would result. In illustration of this statement, attention might briefly be
called to the different lesions of the cardiac valves, which may persist for many
years without serious impairment of the circulation. A stenotic condition of one
or the other of the cardiac orifices commonly produces a hypertrophic condition of
that part of the heart which forces the blood through this opening. In this way,
the supply of blood to the compartment situated distally to the obstruction may
be kept practically the same for many years. This is also true in a way of regur-
gitation, because the continuous stretching of the cardiac chamber by the regurgi-
tating blood serves as a stimulus for its elements to contract more forcibly. In
both cases the arterial pressure and flow remain practically normal until the
primary lesion has developed sufficiently to exceed the limit of this physiological
compensation.
SECTION X
THE MECHANICS OF TH& CIRCULATION.
HEMODYNAMICS
CHAPTER XXX
PHYSICAL CONSIDERATION
The Sources of Pressure. — If considered from the kinetic or dy-
namic standpoint, the movements of fluids may be said to be dependent
upon the force of pressure, which in turn is derived from three sources,
namely from :
1. An outside factor (hydraulic pressure).
2. Imparted motion (hydrodynamic pressure).
3. The weight of the fluid (hydrostatic pressure).
In a similar manner it may be stated that the flow of the blood finds its
cause in the pressure to which it is subjected while traversing the
vascular channels. This force, as has just been emphasized, must be
regarded as the product of three factors, although it cannot be doubted
that in this case the dynamical action of the heart is the most important
of the three.
Hydraulic influences are brought to bear upon a fluid from without. A con-
dition of this kind may be produced either by permitting oil or mercury to press
upon water or by subjecting the fluid contents of a syringe or of a hydraulic pump
to pressure by means of a piston. In all these cases, the fluid must be confined in
a closed receptacle, or must be kept under such conditions that its chances of
escaping to the outside are so slight that a general displacement of it cannot result.
The vascular system fulfills these mechanical requirements very efficiently, because
its channels are closed and are sufficiently elastic to yield to pressure. The degree
of their distention, however, is not sufficiently great to neutralize the pressure.
In this case, the heart takes the place of the piston and the capillary bloodbed, that
of the narrow outlet. Hydrodynamic influences are brought into play in so far
as every moving fluid is in possession of a certain kinetic energy which tends to
drive it onward, even at a time when the external force has ceased to act upon it.
At this moment, one component of the fluid presses upon the one ahead of it, and
so on, until the end of the column has been reached. Hydrostatic influences are
also present, because every fluid possesses weight, and hence, its lower layers are
always subjected to the pressure of its overlying strata.
In determining the degree of pressure exerted by these forces, the following
facts should be kept in mind. The pressure of the air resting upon the surface
of the earth, amounts to about 1 kg. per square cm. of area. This volume of air
weighs 1033 gm. This pressure which is designated as one atmosphere, may be
347
348 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
counterbalanced by any factor capable of exerting precisely the same degree of
pressure. If wateris used for this purpose, it would have to be 1033 cm. in height,
provided its specific gravity is unity. If mercury is employed instead, a column
only 76 cm. in height would be required, because the specific gravity of this element
is 13.55 times greater than that of water. When a pressure exceeds that of the
atmosphere, it is rated as positive, and when it is less than the atmospheric, as
negative. Thus, the values of the pressures prevailing in the different channels
and cavities of our body, are always rated in accordance with the line of the atmos-
pheric pressure (760 mm.). This constitutes the zero line or abscissa.
Dynamically considered, blood behaves in much the same way as water.
It flows through the vascular channels in agreement with certain laws which are
derived from those regulating the flow of other practically incompressible liquids.
One difficulty, however, is met with and that is the distensible and elastic char-
acter of the blood-vessels and spaces. For this reason, it must be admitted that
the general physical data given above, may not be ap-
plicable to the conditions encountered in a circulatory
system built up of living matter. In spite of this prob-
ability, however, it seems advisable to give a brief dis-
cussion of the factors controlling the flow of a fluid
through rigid tubes, because many of the problems con-
nected with the circulation of the blood are founded
*\ upon them. But as our knowledge regarding the dyna-
mics of the movement of liquids, or hydrodynamics, is
still very incomplete, the present discussion must be re-
stricted to the simplest of the facts known.
Toricelli's Theorem (1643).— If a fluid is
placed in a receptacle possessing vertical and
parallel walls, it exerts a pressure upon the lower
surface of this vessel equal to the weight of any
other mass of fluid of the same cross-section and
height. If a round opening is now made in the
bottom of this reservoir, while the quantity of
fluid within it is replenished sufficiently to remain at the level (h) , the
fluid escapes with a velocity (v) which may be expressed by the formula :
V = \^2gh, g being the acceleration produced by the gravity. It is a
well-known fact that the speed attained by a falling body equals 2g/i,
and hence, the velocity of a fluid flowing through a hole in the bottom
or side of a receptacle, is the same as that attained by the fluid when
falling in vacuo through the distance (h). Thus, it should be possible to
determine with accuracy the volume of the fluid escaping in a unit of
time, by contrasting the velocity with the cross-section of the outlet.
It has been shown, however, that the quantity of fluid which may be
expected to escape upon theoretical grounds, does not quite equal the
quantity obtained. This discrepancy is caused by the resistance en-
countered by the fluid at the brim of the orifice (r). As only a limited
number of columns of fluid lie in straight lines vertically above the open-
ing, the others must occupy positions lateral to these. But as the latter
tend to escape together with the former, they must converge toward the
center of the orifice, so that a conical and not a cylindrical outline is
imparted to the entire mass of outflowing liquid. Consequently, the
total energy Qi) cannot be spent to produce velocity, because some of
Fig. 181. — Diagram
Illustrating Tori-
CELLi's Theorem.
h, height of pressure; R,
resistance at orifice.
PHYSICAL CONSIDERATION 349
it is required to overcome the resistance at the outlet. Obviously,
therefore, the formula deduced by Toricelli, holds true only if the
resistance to the outflow is so slight that it can justly be neglected.
Flow of a Liquid Through Rigid Tubes. — Further modifications
of the previous contention are made necessary if the orifice of the
receptacle is equipped with a round tube of uniform diameter, adjusted
in a horizontal direction. It must be evident that this addition places
an even greater resistance in the path of the escaping fluid, thereby
insuring a still greater reduction in the outflow. It is essential, how-
ever, that the size of the tube do not exceed a certain limit, because,
if it possesses a very large diameter, the conditions of flow become so
complicated that they cannot be brought in accord with our present
knowledge pertaining to this matter. Moreover, theoretical specula-
tions of this kind seem uncalled for at this time, because channels of
exceptional diameter are not encountered in the vascular system.
A liquid flowing through a tube, always meets with a certain resistance which
is dependent, on the one hand, upon the cohesion of its molecules, and, on the
other, upon the adhesion of its outer layer to the walls of the vessel. The former
constitutes the internal friction or viscosity, and the latter, the external friction.
Provided, therefore, that a liquid moistens the vessel wall, an adhesion results, in
consequence of which its outermost layers become stationary. The molecules
of the layers of fluid situated next to the outermost, are also retarded by cohesion,
but they are not stopped altogether. The more centrally situated layers are
slowed in quite the same manner until the axial column is reached which, however,
is retarded least of all and possesses therefore the greatest speed of flow. When
speaking of velocity, we generally refer to the average speed attained by a liquid
irrespective of the differences shown by its various layers. Furthermore when
dealing with straight tubes which impart a parallel motion to the different particles
of the liquid, the general velocity of the flow is only one-half as great as that of
the axial stream. Obviously, therefore, the pressure of the liquid in the reservoir
is constantly made use of in overcoming the peripheral resistance composed
of the forces of adhesion and cohesion. Thus, while a part of the static energy
produced by the mere position of the liquid, is consumed in antagonizing this
hindrance to the flow, the remainder is converted into kinetic energy, as evinced
by the escape of the liquid from the tube.
The resistance to the flow is betrayed by the lateral or side pressure prevailing
at the different points of a system of tubes. Thus, if a number of vertical tubes,
or piezometers, are connected in series with the main horizontal channel, some
of the liquid escapes from here and enters these branches to a height corresponding
to the pressure prevailing at these points. In other words, the level of the liquid
in these laterals is accurately adjusted to the peripheral resistance encountered by
the liquid as it passes these points. It must be clear that the liquid exerts a certain
pressure upon the internal wall of the main tube which is evenly distributed in all
directions. Besides, if the main channel is equipped with a branch, the pressure
prevailing in the former, is propagated outward through the orifice in its wall in
strict agreement with the cross-section of the collateral. Under this condition,
the internal pressure is capable of supporting in the side-tube a column of liquid
of a certain height or weight. By determining the latter (^), an accurate measure
is obtained of the pressure prevailing at the point where the branch joins the main
tube. Furthermore, since the resistance in a tube of uniform diameter is pro-
portional to its length, and since the resistance still to be overcome diminishes
with the proximity of the outlet, the pressure must decrease gradually in a direc-
tion from the reservoir to the outlet. For this reason, the occlusion of the latter
350 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
is immediately followed by a rise of the liquid all the way to the reservoir, because
under this condition the collaterals are converted into mere recesses of the main
vessel.
It must be clear, therefore, that the power furnished by the liquid in the
reservoir {H) is the downward pressure of its constituents. A large, portion of it
(h) is utilized in overcoming the resistance and is therefore known as the resistance-
-pressure. The remainder (h^) constitutes the actual driving force and is com-
m.only spoken of as velocity-pressure. The amount of each may be determined
very readily by joining the levels of the liquid in the piezometers by a straight
line and by extending this line until it meets the reservoir (y-n). It should be
noted, however, that their sum total is not absolutely equal to the head-pressure
{H). This discrepancy indicates that a fraction of the latter {x) is used up in
overcoming the friction encountered by the liquid in its passage through the
orifice of the reservoir. The initial energy (H) may also be produced in other
ways than by means of the position or ''head" of the liquid in a reservoir, for
example, by the movement of a piston within a cylinder. But the results remain
the same irrespective of the source of the pressure.
t
I I
; i
? h
h
^^
1
^"^^
.^^^
3
^^ — ■ 1
m
^
^^»
FiQ. 182. — A Pressure Vessel, P, With A Horizontal Outflow Tube, 0-n, into
Which Vertical Tubes or Manometers are Inserted (a, 6, c, d, e, and /) .
If the tube attached to the reservoir, does not retain the same diameter through-
out, but changes from large to small, or from small to large, the dynamical con-
ditions resulting therefrom may readily be deduced from the foregoing data.
Thus, if the median portion is the larger, the speed of flow is diminished in this
particular segment, because the velocity is inversely proportional to the cross-
section. Moreover, in as much as the resistance is less here, the initial energy or
head-pressure is used up more slowly in this section. Consequently, the lateral
pressure declines less rapidly here than nearer the reservoir. On entering the
third segment which possesses the same diameter as the first, the original velocity
is again established, while the increased resistance in turn insures a more rapid
fall in pressure.
If a tube is now used, the second segment of which is narrower than the first
and third, the speed of flow is increased in the central one. This implies that the
resistance is also increased, while the head pressure is considerably diminished.
This change is clearly indicated by the fall in the lateral pressure. On reaching the
third section of the tube, the velocity and resistance are decreased as is betrayed
by a less rapid fall in the pressure. In the preceding experiments the head-
pressure has always been kept constant by making provision for a steady influx
of water into the reservoir to compensate for its outflow. But if the initial energy
PHYSICAL CONSIDERATION 351
is not exerted continuously, the fluid will escape from the distant orifice of the
tube only when a definite quantity has been forced into its central end. Under this
condition, the outflow becomes intermittent, although it does not cease as yet
at the very moment when the pressure is discontinued. It lags behind, because
its inherent sluggishness causes it to escape with a rapidity which is less than that
of the influx.
Flow of a Liquid Through Elastic Tubes. — If the rigid tube is dis-
placed by one possessing elastic walls, a condition of flow will be estab-
lished in time which is practically the same as that described pre-
viously. To begin with the walls of the tube move outward in the
direction of the lateral pressure exerted by the liquid, and this disten-
tion continues until the elastic power of the walls exactly counter-
balances the internal pressure. At this time, the elastic tube really
displays the same phenomena as those previously observed in the rigid
system, but naturally, only as long as the head-pressure remains con-
stant. If the latter is diminished, the vessel wall must first recoil to
adapt itself to the new conditions.
If the head-pressure is now permitted to act intermittently, the conditions
of pressure and flow must be the result of the force and frequency with which
the primary power is applied and secondly, of the resistance which this primary
power encounters in the system of tubes. To begin with, let Us suppose that the
pressure acts at long intervals and that the resistance is slight. The latter con-
dition may be produced without difficulty by using a short tube of relatively large
diameter. In this case, the entrance of the fluid is associated with a distention
of the walls of this tube and a discharge from its outlet which is greatest during
the period of highest pressure, and becomes less and less as the driving force is
diminished. A flow of this kind is characterized as intermittent. If the pressure
is now allowed to act more frequently, or if the resistance is heightened, or
both, the outflow becomes smaller during the interims, but does not cease altogether.
The flow is then said to be remittent. By continuing to increase the force and
frequency of the pressure, as well as the resistance, a point will finally be reached
when the outflow ceases to fluctuate. It is then constant in its character.
If a certain quantity of liquid is permitted to escape from the reservoir into the
elastic tube, the walls of the latter are forced apart. The influx having ceased,
the walls tend to come together again. This recoil is a property of all elastic
bodies. If the pressure is now applied more frequently, while the resistance is
permitted to remain the same or is increased, the mass of the liquid in the tube
increases steadily. This is made possible by the steady yielding of the walls of
the tube in an outward direction. The tube is distended. Eventually, however,
its elastic recoil effectively counteracts all further distention and storage of liquid.
It must be evident, therefore, that the quantity of fluid which is present in the
tube in excess of that constantly escaping through the outlet, is sufficient to main-
tain a certain pressure even during the intervals of time when the head pressure
is not being exerted. In this way, the fluid is held under a continuous pressure
with the result that the outflow remains practically constant. Thus, it will be
seen that the property of elasticity by means of which the walls of the tube en-
deavor to regain their original position, is of greatest importance to the agent
producing the pressure, because it helps to preserve normal conditions of flow
even during the periods when the latter is at rest. Obviously, therefore, the
energy developed by the generator is stored each time in the walls of the tube
in the form of elastic tension. It is then spent during the periods when the pri-
mary force is not acting. In this way, the flow is kept constant in spite of the fact
that a new supply of fluid is had only every now and then.
352 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
Analogous Features of the Circulation of the Blood. — Essentially
the same conditions prevail in the vascular system. The heart which
here assumes the function of the rhythmically discharging reservoir
or piston pump, contracts and forces a certain quantity of blood into
the vascular channels. The frequency of this organ, as well as the
peripheral resistance, is adjusted in such a way that the blood-vessels
are constantly retained in a condition of hyperfilling, made possible
by the elastic tonicity of their walls. In this way, the intermittent
ventricular discharge is converted into a continuous flow. The power
of the heart is transferred each time into elastic tension. The latter
acts while the heart is at rest.
Fig. 183. — Pressube Vessel with Progressively Branching Tubes Which are Again
United into One Collecting Channel.
This arrangement illustrates the conditions prevailing in the vascular system.
(Brubaker.)
If it were not for the fact that the diameters of the different blood-
vessels vary considerably, the pressure prevailing in the vascular
system would be practically identical with that existing in a system of
tubes such as has been represented in the preceding schema. In
reahty, however, the central arterial trunk or aorta, divides again and
again into much smaller branches which eventually give rise to the
capillaries. Beyond this point, these fine tubules constantly unite
into larger ones until the venae cavse and right side of the heart
have been reached. This multiple division brings it about that the
total cross-area of the vascular system is steadily increased from the
arteries to the capillaries, while beyond these tubules, it is again gradu-
ally diminished. For this reason, these conditions of pressure and
flow must closely resemble those described in one of the earlier para-
graphs dealing with the dynamics in tubes of varying diameter. To
PHYSICAL CONSIDERATION
353
illustrate, as the cross-section of all the capillaries put together is larger
than that of either the arteries or veins when combined into single
tubes, the lateral pressure as well as the velocity of flow must be much
less in these tubules than in the latter channels. Besides, as the fric-
tion in these exceedingly fine tubules is considerable, they really serve
the purpose of a resistance which is interposed at this point of the vas-
cular system to retard the flow of the blood. On account of this hin-
drance, the arterial blood is held back, thereby establishing a much
higher degree of pressure on the arterial side of the capillaries than
could possibly be produced if the ofl^low were not restricted at all.
Furthermore, as the arterioles are capable of actively varying their
calibre, this resistance may be augmented or diminished at any time, so
that smaller or larger quantities of arterial blood may be allowed to
escape into the capillaries and veins.
These changes in the peripheral resistance may be imitated with the help of the
accompanying schema (Fig. 184) by equipping the horizontal tube with a stopcock
possessing the same diameter as the main tube. If the latter is widely open, the
pressure shows a gradual decline in the direction from the reservoir to the outlet.
\
"**-
-"•'-
.
m
Fig. 184. — A Stopcock is Inserted at the Middle of the Outflow Tube in Illustra-
tion OF THE Resistance Furnished by the Capillaries.
Its partial closure, however, interposes a high resistance, in consequence of which
the fluid accumulates between this point and the reservoir, while it declines on
the side toward the outlet (Fig. 184). Concurrently, the lateral pressure exhibits
a decided increase in the central section of this tube, and a fall in its distal portion.
In our circulatory system changes of this kind are brought about by the con-
traction of the smooth muscle cells situated in the walls of the arterioles. The
constriction of the lumen of these tubules increases the resistance placed in
the path of the arterial blood, and prevents its free escape into the capillaries
and veins.
The influence which the peripheral resistance is capable of exerting upon
the flow of the blood, may be illustrated in a very convincing manner by con-
necting a piece of elastic band-tubing with an ordinary valved syringe. The
outlet of this elastic tube should be diminished somewhat by equipping it with a
narrow piece of glass tubing. If the syringe is now dipped in water and is com-
pressed at frequent intervals, the band-tubing is distended by each influx of
water, but collapses as soon as this central force ceases and allows all the water to
escape through the outlet. The flow is then intermittent. If the syringe is now
compressed at shorter intervals, the tubing remains more fully distended and the
flow becomes remittent and finally constant. At this time the entire stretch of
23
354 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
tubing is under the greatest possible elastic tension and subjects the fluid within
to the steady pressure of its recoiling walls. Each compression of the syringe
increases the pressure slightly, while during the interims it is somewhat decreased
owing to the continuous escape of fluid. It is to be emphasized, however, that this
system must always be kept in a hyperfilled condition, otherwise the flow cannot
remain constant.
Fig. 185. — Simple Schema to Illustrate the Factors Producing a Constant Head of
Pressure in the Arterial System.
o, A syringe bulb with valves, representing the heart; 6, glass tube with fine point
representing a path with resistance alone, but no extensibihty (the outflow is in spurts
synchronous with the strokes of the pump) ; c, outflow with resistance and also extensible
and elastic walls represented by the large rubber bag, e; the outflow is a steady stream due
to the elastic recoil of the distended bag, e. (Howell.)
CHAPTER XXXI
BLOOD PRESSURE
The Factors Responsible for Blood pressure. — In order to prove
that the blood flows from the arteries into the veins and thus completes
the circuit of the body, Harvey placed loose ligatures upon an artery
and neighboring vein and raised them gently out of the wound until
their lumina became fully constricted. It was then found that the
central end of the artery and the distal end of the vein were highly
distended, while their other ends were collapsed. If the walls of the
distended segments were then pierced with the point of a needle, the
blood spurted out in fine jets, but with a much greater force from
the artery than from the vein. The same observation was made during
capillary bleeding, because the blood oozes from these opened blood-
vessels in small droplets which presently coalesce to form a sheet-like
covering over the injured area. These and other observations read-
ily prove that the blood is held in the vascular system under a certain
pressure.
The term blood pressure is often used to denote the general pres-
sure existing in the vascular system, while at other times it is intended
to indicate merely the pressure prevaihng in the arterial channels.
This ambiguity mav easily be avoided by making specific reference to
BLOOD PRESSURE
355
either the arterial, capillary or venous pressure, because the blood
pressure really presents definite differences in accordance with the
three divisions of the vascular system.
The pressure to which the circulating blood is subjected is the prod-
uct of a reaction participated in by four factors; namely by: (a)
the energy of the heart, (b) the quantity of the circulating blood, (c)
the elasticity of the blood-vessels, and (d} the peripheral resistance.
Under ordinary conditions, this pressure displays a certain constancy,
and retains a level considerably above zero throughout the circu-
latory system with the exception of the central veins. In addition
it is to be noted that it is subject to cer-
tain minor variations which are de-
pendent chiefly upon the action of the
heart and the respiratory movements.
These details will be brought out more
fully by the subsequent discussion.
The Energy of the Heart. — Each
ventricular systole forces a definite
quantity of blood into the arteries.
Assuming that the other three factors
remain unchanged, it may be concluded
that the pressure must rise whenever
a new amount of blood is added to
that already existing in these channels,
and that the pressure must fall when-
ever the ventricles enter the state of
diastole. This relationship implies that
the energy of the heart must be pro-
portional to the ventricular output and
must embrace the following minor fac-
tors:
(a) The volume of the cardiac out-
put,
(6) The frequency with which these
discharges are repeated, and
(c) The force with which the blood is ejected.
The first condition is determined by the capaciousness of the cardiac
chambers, ol* better, by the power of filling of the heart, the second by
the number of the discharges occurring in a given period of time, and
the third by the force with which the emptying of the ventricles is
effected. Right here it should be emphasize^ that the energy of the
heart which, as has just been stated, is only one of the factors upon which
blood pressure depends, is subject to fluctuations, because the condi-
tions previously cited, do not always act in unison, but may actually
counteract each other. Thus, the volume of the different ventricular
outputs may be increased owing to a greater filling power or relaxa-
bility of the cardiac musculature, without being associated with a rise
Fig. 186. — Record of Blood-
pressure Showing the Cardiac and
Respiratory Variations.
The time registered in seconds,
serves as the abscissa.
356 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
in the blood pressure. The cause of this discrepancy most frequently
lies in a lessened rate of the heart. For very similar reasons it cannot
be taken for granted that a rapid heart always gives rise to a higher
blood pressure, because the filling power of this organ may be decreased
in a measure to compensate for the increase in the frequency. More-
over, as a diminution in the power of contraction of the cardiac muscle
must be followed by a reduction in the force of ejection, the blood pres-
sure must fall even when the frequency and the filling power of the
heart remain practically unaltered. And again, while an increase in
the power of contraction of the cardiac musculature generally raises
the pressure, this result cannot be attained if the frequency or the
filling power of this organ is diminished.
In further illustration of these complex interactions between the
factors giving rise to the energy of the heart, it might be mentioned that
the stimulation of the vagus nerve leads to a fall in the general blood
pressure, because the ventricular outputs are either diminished in
number or are stopped altogether. ^ But if a strength of current
is employed which is just sufficient to cause a moderate reduction in
the cardiac rate, the 'filling power of the organ may thereby be aug-
mented in such a measure that the blood pressure is enabled to retain
its former level. Quite similarly, the cutting of the vagi nerves most
generally produces a rise in blood pressure, because the removal of
the inhibitory impulses permits the heart to increase its frequency,
so that the number of ventricular outputs in a unit of time becomes
greater. But it also happens at times that this procedure produces no
augmentation at all, because a proper relaxation of the cardiac muscle
cannot be effected, owing to the high frequency of contraction. Under
this condition, the heart is quite unable to eject a greater quantity
of blood. Similar compensations occur at times during the stimulation
of the acceleratory nerves so that the rises in pressure ordinarily
resulting from this procedure, cannot attain their full development.
These variations are not mere theoretical possibilities, but are fre-
quently observed under pathological conditions. They have been
cited here somewhat at length, in order that they may be made use of
in explaining some of the peculiar changes in the blood-pressure occur-
ring in the course of cardiac diseases.
It has previously been stated that the height of the blood pressure
most commonly bears a direct relationship to the cardiac energy as
expressed in terms of the ventricular output. This means that an in-
crease in the latter, is followed by a rise in the blood pressure, and vice
versa. In the second place, we have seen that the blood pressure is the
product of four different factors, namely, the energy of the heart, the
total quantity of the circulating blood, the elasticity of the blood-
vessels and the peripheral resistance. In view of this fact, the pre-
ceding general rule should therefore be amplified to include the provi-
sion that the other three factors must remain constant. If they do not
1 O. Frank, Zeitschr. fiir Biologie, xxiii, 1901, 1.
BLOOD PRESSURE 357
remain constant, their influence upon the cardiac energy may be ma-
terially modified by the changes in the other three factors. It would
lead altogether too far to give a complete analysis of these interactions
and hence,;^1i must suffice to illustrate them with the help of a single
example, namely the relationship existing between the energy of the
heart and the peripheral resistance. It should be stated first of all
that the peripheral resistance may be increased or decreased. The
former change gives rise to a lessened escape of arterial blood into
the capillaries, and the latter to a more copious arterial offlow. Sup-
posing now that the cardiac energy is agumented, we would expect to
obtain a rise in the arterial blood pressure. This result, however, may
be nullified by a vasodilatation, i.e., by a diminution of the peripheral
resistance and a greater ofliow of the arterial blood. In a similar
manner, it may be reasoned that a lessened ventricular discharge
must lead to a fall in blood pressure. But this effect is not always
obtained, because the diminution in the cardiac output may be com-
pensated for by an increase in the peripheral resistance occasioned
by a vasoconstriction. The simultaneous appearance of an increased
cardiac energy and peripheral resistance would, of course, raise the
blood pressure. The opposite result would be obtained after a simul-
taneous depression of these two factors.
The Total Quantity of the Circulating Blood. — This factor bears
a direct relationship to the blood pressure, because different degrees
of pressure may be established very readily by simply varying the
volume of the blood, provided, of course, that the other three factors
remain unchanged. Conditions of this kind invariably result in the
course of hemorrhages, and during the infusion of isotonic solutions and
the transfusion of blood. Under normal conditions, the vascular sys-
tem possesses the power of adapting itself very quickly to different
quantities of blood- by (a) varying the size of the bloodbed, (6) forcing
the fluid elements of the blood into the lymphatic channels, and (c)
transferring the lymph into the bloodstream. Thus, slight losses of
blood are quickly compensated for by a vasoconstrictor reaction and a
transfer of lymph into the vascular channels. For this reason, a de-
cided fall in blood pressure cannot develop under these circumstances,
unless the hemorrhage has been sufficiently severe to offset this com-
pensation. A similar reaction takes place whenever the amount of the
circulating blood is increased. The blood-vessels then relax, and a
certain portion of the blood seeks the lymph spaces.^ These changes
are often followed by an extra discharge of water from the body in the
excretions. It is true, however, that any extraordinary increase in
the amount of the circulating blood gives rise to a more decided and
more permanent rise in the pressure. It need scarcely be emphasized
that these alterations frequently assume a local character and remain
1 Worm-Muller (Ber. der. sachs. Gesellsch. der Wissensch., 1873), Stolnikow
(Arch, fiir Anat. und Physiol., 1886), and Johansson and Tigerstedt (Skand.
Arch, fur Physiol., ii, 1889).
358 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
confined to particular divisions of the vascular system. These local
hyperemias and anemias may be neutralized by vasomotor changes and
a transfer of the plasma, insuring a continuance of the normal circu-
latory conditions. ^\
The Elasticity of the Blood-vessels. — This factor betrays itself by a
distention of the walls of the blood-vessels whenever the pressure
within them rises. This elastic play is most clearly in evidence on the
arterial side and particularly in the central arteries, where we find the
largest number of elastic fibers. In the more distal channels, the
elastic tissue is gradually displaced by smooth muscle cells, which ap-
pear here chiefly in the form of a thick layer arranged circularly
around the lumen of the vessel. Some of these cells are also arranged
in a longitudinal direction and in such a way that they form a thin
coat externally to the circular. The peripheral arteries and arterioles,
therefore, contain practically no elastic fibers, but are made up of a
heavy layer of smooth muscle tissue. This difference in the structural
character of the arterial system leads us to infer that the elastic
forces have full sway centrally, while peripherally the prevailing factor
is muscular contraction. Hence, the aorta may be regarded as an
elastic pouch, the walls of which are forced outward with every ven-
tricular output. Directly thereafter a recoil sets in at a moment when
the elastic power of the arterial wall is capable of overcoming the
internal pressure. This means that they accomplish their work
during the diastolic interim, and constitute therefore a most important
aid to the heart, because the power generated by this organ during
each systole, is immediately stored in their walls as elastic tension to
be made use of during the period of cardiac rest. Inasmuch as the
blood is thus held under a constant pressure, the arteries serve the
same purpose as the air-bladder of a bag-pipe from which the air
may be drawn in a continuous stream.
The energy of the heart, the quantity of the blood and the periph-
eral resistance are adjusted in such a way that the arterial system
is constantly retained in a state of hyperfilling. This implies that the
escape of the blood into the capillaries is regulated in such a way
that it is always exceeded by the ventricular output. In this way, a
definite head of pressure is established which cannot be nullified
during the diastolic period of the heart. It is true, however, that the
pressure is somewhat greater during the systolic inrush of blood, than
during the diastolic phase of gradual emptying. The offlow must
necessarily be limited, because the peripheral resistance and the
frequency of the heart are so accurately balanced that more than
a moderate recoil of the arterial walls cannot result. Only in case
the heart ceases to beat altogether do we obtain a complete collapse
of these channels, the blood then accumulating on the venous side
and principally in the central veins and right side of the heart.
This is the condition prevailing after death.
The preceding statement leads us to infer that the diastolic fall
BLOOD PRESSURE 359
in the arterial blood pressure must become the greater, the longer
the interval between two successive ventricular discharges. This
rule, however, is not infallible, because in many cases a fall in pressure
resulting from an undue slowness of the heart, may be effectively
counteracted by an increase in the peripheral resistance. A com-
pensation of this kind takes place very frequently, but naturally, it
cannot overcome the dynamical disturbances produced by an exces-
sively infrequent heart.
The elastic power of the vascular system lessens the work of the
cardiac musculature very materially, because it insures a constancy of
flow without necessitating an extra expenditure of energy on the part
of the heart. As each cardiac output is accommodated in the arteries,
their walls are forced outward. In this way, a large part of the work
of the heart is converted into potential energy in the form of elastic
tension which is utilized later on during the diastolic interim, and hence,
the work of this organ is actually distributed over more than twice
the time actually consumed in its muscular contraction. This enables
the heart to obtain the rest required for its anabolism. The importance
of the elasticity is also elucidated by the fact that a rigid vascular
system immediately converts the otherwise constant flow into one
possessing remittent and intermittent qualities. Each systole then
gives rise to a quick onrush of blood which is soon followed by a slowing
and a cessation of the flow. Very high and very low pressures are
then obtained alternately.
The property of elasticity is possessed in a slight measure by all
types of cells and not only by those composing the elastic tissues. For
this reason, it cannot be said to be wholly lacking in other segments of the
vascular system, although we have just seen that it becomes of greatest
dynamical importance in the central arteries. The structure of the
capillaries is such that varying quantities of arterial blood can readily
be accommodated in them by simply changing the size of their lumen.
These perfectly passive changes are made possible by the fact that
they are distensible, although their elastic power is insignificant.. In
this connection, mention should also be made of the claim of Strieker
and others,^ that the capillary lining cells possess contractile
qualities which betray themselves in active variations of their
thickness at the sites of the different nuclei. The evidence so far
presented in favor of this view, does not seem sufficiently conclu-
sive to warrant further discussion of this subject. Somewhat dif-
ferent conditions are met with in the veins. Here the elasticity again
plays a more important part, because these channels are large and
are structurally in a position to oppose the pressure by a very moderate
recoil. It is to be noted especially, however, that the size of the venous
bloodbed is very largely dependent upon the quantity of the blood
transferred to them by the arteries. They themselves cannot vary
their caliber in an active way by vasomotor activity.
^ Berichte, Akad. der Wissensch., Wien, 1865.
360 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
The early determinations of the elasticity of the blood-vessels,
were made upon excised segments which were suspended from a
hook and loaded with different weights. In as much as the curve
obtained by this method resembled a hyperbole, the conclusion was
drawn that the coefficient of the elasticity does not possess a constant
value but increases with the distention. It seems, however, that the
degree of distensibility obtained under this condition, is not comparable
to the distensibility produced by an internal
pressure, but merely gives us an idea regarding
the compactness or strength of the blood-
vessels. Mareyi sought to establish more
perfect experimental conditions by placing seg-
ments of arteries in plethysmographs and by
subjecting their walls to a steady internal pres-
sure. This end he attained by connecting the
lumen of the segment with a bottle filled with
saline solution which he could raise to a certain
level above the preparation. Roy^ and others
state that a steadily rising pressure leads to a
gradual increase in the caliber of the blood-
vessel, but a limit is soon reached beyond which
the distention diminishes very rapidly. In
rabbits the normal distensibility is reached with
a pressure of 70 mm. Hg, in dogs at 75 to 125
mm. Hg, and in the ox at 100 to 150 mm. Hg.
A much higher pressure is required to cause a
, normal artery to rupture. In accordance with
RANGEMENT FOR TESTING the determinations of Grehant and Quinquaud,*
THE Elastic Power op the carotid artery of the dog can withstand an
Blood-vessels. internal pressure of 600 mm. Hg, while the lowest
pende^d InT gfass'%X Pressure necessary to burst the carotid artery of
fiUed with saline solution man amounts to 1.29 m. Hg. As the smaller
(T). Its ends are closed arteries are even stronger than the larger ones
with discs of rubber and , ,, , • i i i • i
its lumen connected with and as the arterial pressure seldom rises above
a pressure bulb (B). The 150 mm. Hg, the margin of safety is more than
meniscus of the saline solu- Qjvjr^lp
tion M in tube C indicates K ' i e • i i •
the degree of distention of It IS also 01 interest to note that the opti-
the artery. mum degree of movability of the vessel wall is
had at a pressure most closely approaching the
normal. At this time the most perfect elastic play is obtained. If the
pressure is raised much beyond this point, the distensibility becomes less
and less. Supposing, therefore, that the quantity of the circulating
blood is increased, the power of the vascular system to accommodate
1 Trav. de Lab., iv, 1880, 253.
2 Jour, of Physiol., iii, 1881, 125; also see: Zwardemaker (Neterl. Tijdschr. vor
Jencesk., xxiv, 1888, 61), and Frank (Ann. der Physik., 1906).
3 Jour, de I'anat. et de la Physiol., xxvi, 1885.
BLOOD PRESSURE 361
this extra amount of blood must become the less, the higher the pressure
already established. Concurrently, it may be reasoned that the energy
of the heart may be most seriously impaired by forcing it to increase
its activity at a time when the tension in the vascular system is high,
because the vascular channels cannot then yield so readily to the internal
pressure. The veins attain their maximal cubic distention at much
lower pressures than the arteries, and their extensibility is much less.
They are more easily torn when manipulated, but are more yielding
than the arteries. This may well be so, because the pressures which
they are called upon to withstand, scarcely exceed 20 mm. Hg even
under pathological conditions.
The Peripheral Resistance. — This factor serves as an expression
of the size of the "blood-gate" at the arteriocapillary junction. It
may be inferred that the resistance placed in the path of the arterial
blood, must become the less the larger this orifice. The friction which
is responsible for the production of this resistance, is composed in
reality of two types of frictions which may be designated respectively
as the "externar' and the "internal." The former is produced by the
blood as a whole as it rubs against the internal surface of the vessel
wall and the latter, by the bumping together of the different con-
stituents of the blood. The term viscosity is usually applied to this
intermolecular friction. It is evident that the hindrance placed in
the path of the arterial blood, must increase whenever the "blood-
gate" is made smaller and decrease whenever it is made larger. In
the first instance, the arterial influx into the capillaries is diminished,
and in the second increased. Supposing, therefore, that the other
three factors remain the same, the first change must lead to a rise and
the second, to a fall in the arterial pressure.
Special emphasis has been placed upon the conditions existing at
the arteriocapillary junction, because the distalmost branches of the
arterial system are equipped with especially powerful rings of smooth
muscle cells, which enable them to influence the blood stream most
decisively. This statement, however, is not meant to imply that the
peripheral resistance is formed in the arterioles and not in the capil-
laries. A deduction of this kind could not possibly be correct, because
it is a well-known fact that no segment of the vascular system pro-
duces a greater amount of friction than the capillaries. This must be
so, because the column of blood is divided by them into the finest
possible streams, many of which are no broader than the diameter of
a single red cell. Although generators of the peripheral resistance, it is
evident that the capillaries as such are quite unable to vary this
resistance, because they are not in possession of an active means for
influencing the blood-stream. This function is relegated to the arter-
ioles which, as we have j ust seen, act as powerful sphincters, permitting
larger and smaller quantities of arterial blood to escape. Conse-
quently, the state of filling of the capillaries is determined very largely
by the arterioles. In view of their decided vasomotor qualities, it
362 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
may also be concluded that they are the chief factor regulating the
peripheral resistance.
Reference has repeatedly been made to the close functional relation-
ship existing between the peripheral resistance and the energy of the
heart. Thus, it has been said that a high blood pressure resulting from
vasoconstriction, is commonly associated with a decrease in the fre-
quency of the heart, and vice versa. Although not wishing to over-
emphasize this reflex compensation, the foregoing facts will go far to
show that the blood pressure is more closely dependent upon the inter-
action of the two factors just mentioned than upon the quantity of the
circulating blood or the elasticity of the blood-vessels. No doubt, the
former are subject to more frequent changes than the latter, i.e., under
normal conditions the quantity of the blood and the elasticity remain
the same for much longer periods of time.
THE DIRECT AND INDIRECT METHODS OF RECORDING BLOOD
PRESSURE
Methods for Determining the Arterial Blood Pressure. — The pro-
cedures employed to ascertain the pressures in the different parts of the
Fig. 188. — Diagram Illustrating the Indirect Method of Measuring Blood-
pressure.
A, arm surrounded by a flat rubber pouch, R\ by means of a rubber bulb, B, a pressure
is set up in this system of tubing sufficient to compress the artery. This moment is
indicated by the manometer (M).
vascular system, differ somewhat in accordance with the nature o
the blood-vessel. If the direct method is resorted to, the vascular chan-
nel is opened and the blood brought into immediate contact with
the recording instrument. If, on the other hand, the indirect method
is employed, the blood-vessel is left intact, while the pressure existing
therein is accurately balanced by a known pressure set up in an arti-
ficial system immediately adjoining it (Fig. 188). Obviously, there-
fore, the direct procedure is applicable only to animals and to blood-
vessels of larger caliber, whereas the indirect or bloodless method
may be practised upon animals as well as upon man.
The first attempt to ascertain the pressure of the blood, was made
in 1732 by the Rev. Stephen Hales, ^ an English clergyman. A long
1 Statical Essays, 1733.
BLOOD PRESSURE
363
I
Carotfd
Aorto^
as<
copper cannula was inserted in the artery in the groin of a horse which
in turn was connected with a vertical tube of glass, measuring nine
feet in height and one-sixth of an inch in diameter. On removing the
ligature from the artery, the blood was seen to enter the tube to a
height of eight feet and three inches above the level of the left ventricle.
However, it did not rise to this height at once, but gradually, and
finally exhibited small oscillatory fluctuations.
This single vertical tube was displaced later on by a U-shaped tube, a further
reduction in its length being made possible by filling it with mercury, because this
element possesses a specific gravity 13.5 greater than that of water. Ludwig finally
equipped the distal limb of the mercury column of these manometers with a float
and slender vertical rod to which he attached a writing point. This arrangement
enabled him to record the excursions of the mercury upon the paper of a kymograph
(Fig. 149). In recent years use has also been made of various types of membrane-
manometers, in which the intravascular pressure is counter-balanced by the elastic
force of a rubber membrane. The displacements of this membrane can be accu-
rately recorded by permitting it to act
against a writing lever, or by permitting it to
reflect a beam of light from a delicate mirror
fastened to its surface.
For obvious reasons the direct method
can only be applied to arteries and veins
which are sufficiently large to allow the in-
troduction of a cannula. On the arterial
side, the pressure is measured most con-
veniently in the carotid and femoral arteries,
the former blood-vessel being used most
frequently, because it is more accessible and
in closer proximity to the center of the cir-
culatory system. In either case, it should
be remembered that we are not determining
the pressure in this particular vessel, but in
the one situated centrally to it. To illustrate,
the carotid artery leaves the aorta almost at
right angles and plays, therefore, the same
role as the free end of a T-tube, i.e., it per-
mits the pressure which is exerted in a radial
direction upon the internal surface of the wall
of the aorta to be propagated directly out-
ward into the manometer (Fig. 189). It
must be clear, therefore, that the pressure prevailing in the carotid artery itself can
only be ascertained if this vessel is connected with the recording instrument
either by means of a T-tube, or by means of a straight cannula inserted into one
of its branches. This purpose may be served by the arteria thyroidea, because
the lateral carotid pressure is propagated through this blood-vessel directly into
the manometer (Fig. 189, II). In this connection attention should also be called
to the fact that the distal stump of an artery is not necessarily without pressure,
because in most cases anastomoses are present which permit at least a slight
quantity of blood to enter this channel in an indirect way.
In order to ascertain the venous pressure, it is necessary to insert a T-tube,
the free end of which is connected either with a U-shaped manometer filled with
normal saline solution, or with a membrane manometer possessing the least possible
resistance. The oscillations of the column of saline solution may be registered
by placing a bell-shaped float and writing needle upon its distal limb. This modi-
fication in the method of registration is made necessary by the fact that the
La.vo't'tti
fiiorfa.
F I G . 1 8 9. — Diagram to Show
THAT A Manometer Connected with
THE Carotid Artery Measures the
Lateral Pressure in the Aorta.
364 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
pressure throughout the venous system is very low and cannot therefore support a
column of mercury of adequate height nor deviate a membrane possessing shght
elastic powers. Furthermore, the venous pressure cannot be measured by con-
necting the manometer with the peripheral or central end of the vein, because the
blocking of the distal stump of the vein would give rise to a venous stagnation which
would be indicative of the pressure prevailing in the corresponding arterial supply
tubes. Quite similarly, the use of the central stump would expose the manometer
to the pressure existing in the more central vein.
Having inserted a suitable cannula in the blood-vessel, the entire tubing
between it and the manometer is filled with a solution tending to prevent the
coagulation of the blood. A saturated solution of sodium carbonate or bicar-
bonate, a 5 per cent, solution of sodium citrate or a 25 per cent, solution of mag-
nesium sulphate may be used for this purpose. A device which often saves
much time is to connect the manometer with a reservoir containing one or the
other of these solutions, so that the connecting tubes may be flushed out when-
ever they become blocked by coagula. On the venous side, a 0.7 per cent, solu-
tion of sodium chlorid should be employed, because as the pressure encountered
in these channels is low, and may even fall below zero, a part of the fluid in the
connecting tube may be drawn into the circulation and, unless non-toxic, may
produce depressive effects. In some cases it may be necessary to render the
blood as a whole non-coagulable, which end may be accomplished by the injection
of a solution of peptone or of an extract of leeches (hirudin).
On removing the clamp previously placed upon the artery, the blood will
be seen to enter the connecting tube and to displace the column of mercury out-
ward until the weight of the latter exactly counterbalances the blood pressure.
As soon as an equilibrium between these two opposing forces has been established,
the mercury undergoes a series of rhythmic fluctuations, the smaller ones of which
are dependent upon the contractions of the heart and the larger ones upon the
respiratory movements. The former are known as the cardiac and the latter as
the respiratory variations in the arterial blood pressure. Both must be sharply
differentiated from oscillations of a similar kind which appear in the central veins
and are designated as the cardiac and respiratory variations in venous pressure.
Moreover, if the experimental conditions are especially favorable, a third type of
variation frequently appears in the arteries which is of much longer duration
than the others and is known as the Traube-Hering curve. The character and
cause of these changes will be considered more fully in a subsequent chapter.
It has been pointed out above that the mercury is quite unable to follow
quick changes in pressure with accuracy. On this account, a membrane manome-
ter should be used whenever it is desired to depict the character of the individual
■pulsations. A mercury manometer, on the other hand, should be employed when-
ever it is intended merely to obtain a general picture of the height of the pressure.
Special directions for the use of these instruments have been given previously
(page 293).
The Arterial Pressure in Different Animals and Arteries. — The
direct method has been applied to man in a few isolated cases, when
it became necessary in the course of operations to divide certain
peripheral blood-vessels. For the femoral and brachial arteries^
the average value of 120 mm. Hg has been found and for the tibial
the value of 80-90 mm. Hg. The pressures obtained under the most
favorable conditions in other animals have been compiled by Volkmann
and Nikolai as follows:
1 Faivre, Gazette m6d. de Paris, 1856, and Albert, Med. Jahrb., Wien, 1883.
BLOOD PRESSURE 365
Horse 180 mm. Hg
Calf. 160 mm. Hg
Sheep 160 mm. Hg
Dog 140 mm. Hg
Goat 130 mm. Hg
Cat 110 mm. Hg
Rabbit 100 mm. Hg
Guinea-pig 85 mm. Hg
As the fluctuations even among animals of the same species are very
considerable, it is not apparent that the size of the animal bears a
direct relationship to the pressure. It is also noted that the pressures
among animals of different species vary so widely that they overlap.
In spite of this divergency, however, there seems to be a definite tendency
on the part of animals of the same group to preserve a certain height
of blood pressure. The cold-blooded animals show much lower values
than the mammals. The following table may be of interest:
Cephalopods 25-80 mm. Hgi
Fishes (torpedo) 25 mm. Hg^
Amphibia:
Grassfrog 29-40 mm. Hg^
Bullfrog 22-26 mm. Hg*
Reptilia :
Crocodile 30-50 mm. HgS
Turtles 25-35 mm. Hg^
Concerning the arterial pressure it may be stated that it diminishes
gradually in the direction from the heart toward the periphery, but
the decrease is slight, because the pressure in the distalmost arteries
is only a few millimeters below that prevailing in the aorta. This fact
implies that the blood does not encounter a considerable resistance
during its journey to the arterioles. Volkmann, for example, found
the pressure in the carotid arteries of two calves to be 116.3 and 165.5
mm. Hg, respectively, while the pressure in the metatarsal arteries
amounted as yet to 89.3 and 146.0 mm. Hg. For the dog Fick^ gives the
values of 176 mm. Hg for the aorta and 132 mm. Hg for the tibial
artery. According to Burton-Opit z , ^ the difference in pressure between
the femoral and hepatic arteries of the dog amounts to 4.4 mm. Hg,
and between the former and the more distal arteria gastroduodenalis
to 10 mm. Hg. The fact that the original pressure is used up much
more rapidly in the distalmost branches of the arterial system is
indicated by the observations of v. Frey,^ who has furnished the fol-
lowing data:
1 Fuchs, Pfluger's Archiv, 60, 1895, 173.
2 Schonlein, Bull, scient. de la France, xxvi.
3 Hofmeister, Pfliiger's Archiv, 44, 1889.
"^ Burton-Opitz, Am. Jour, of Physiol., vii, 1902, 243.
5 Edwards, ibid., xxxiii, 1914, 229.
^ Festschr. zur Iten Sacularf. der Univ. Wiirzburg, i, 1882.
7 Pfluger's Archiv, cxlvi, 1912, 344.
8 Festschr. flir B. Schmidt, Leipzig, 1896.
366 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
Radial artery at wrist 150-160 mm. Hg
Radial artery at base of thumb 120-130 mm. Hg
Radial artery at last phalanx 100-110 mm. Hg
In this connection the following determinations of the mean blood
pressure in dogs, made by Dawson, ^ may be of interest:
Carotid, brachocephalic, superior mesenteric and renal
arteries 123 mm. Hg
Inferior mesenteric artery 119 mm. Hg
Iliac, femoral, saphenous and brachial arteries 118 mm. Hg
Arteries of the circle of Willis 104 mm. Hg
The Indirect Method of Recording the Arterial Blood Pressure.
The Method of Palpation. — The principle upon which the indirect
method is based is simple, and has really
r /^^ — ^^'^^'^^ been employed for centuries in palpating
^^'^ 7^ ^xS. ^^^ pulse. Two or three fingers are usually
used for this purpose, the artery being com-
W*'^'*^^ \l pressed with the central finger until the
naff I JtB 1 1 pulsations can no longer be felt with the
^'^*^==^^CI/^ lii ^ore distal one. The force required to
occlude the artery serves as the measure
of the pressure existing within it.
The indirect method consists in estab-
lishing a known outside pressure which ex-
^Sphygmo'^TSL^S!'' actly balances the pressure in the blood-
C, metal capsule and rubber vessel. The first mstrument of this type
pouch for occluding artery; M, was Constructed by Vierordt^ who attempted
tonometer for registration of ^^ measure the degree of pressure neces-
pressure which is necessary to , ,. ° ^ . , .
occlude the artery. sary to obliterate an artery by attaching
a pelotte to the receiving lever of a sphygmo-
graph. A distinct advance was made in 1876 by v. Basch^ who employed
a glass tube which was closed at one end by a rubber membrane and
was then filled with water. Its free end was joined with a mercury
manometer so that the pressure required to occlude the artery could
be accurately registered. In 1883, v. Basch advised the use of a metal
capsule (C) which was closed by a rubber membrane and equipped with
a metal spring and indicator {M). This principle was subsequently
made use of in the construction of the dynamometer of Hill and
Bernard^ and the sphygmometer of Oliver.^ At about this time the
experiments of Marey led to the invention of the plethysmograph, an
instrument which was made use of by him as well as by Hiirthle® and
Mosso^ for the compression of the artery.
1 Am. Jour, of Physiol., xv, 1905, 244.
2 Lehre vom Arterienpuls, 1855.
3 Zeitschr. flir klin. Med., ii, 1883, 79.
^ Jour, of Physiol., xxiii, 1898, 4.
5 Ibid., xxii, 1897, 51.
^ Deutsche med. Wochenschr., 1896.
7 Zentralbl. flir Physiol., x, 1896.
BLOOD PRESSURE
367
A very simple sphygmomanometer has been devised by Riva-Rocci.^ A
rubber pouch measuring 5 cm. in width and possessing a length sufficient to
encircle the arm, is connected with a mercury reservoir and a pressure bulb. This
rubber bag is protected upon its outside by a leather or canvas cuff which is
tightened until it fits the arm snugly. The arm is placed in an easy position at
the level of the heart, and consequently, no corrections need be made for the
hydrostatic effects. If the pouch is now inflated, the pressure in this system
rises until the tissues around the brachial artery are compressed in such a degree
that the lumen of this blood-vessel is obliterated. This moment is clearly marked
by the disappearance of the pulsations in the radial artery, while the pressure
necessary to accomplish this end is registered by the manometer of the mercury
reservoir. The best procedure to be followed is this : The cuff having been
properly adjusted, the fingers of the left hand are placed upon the radial artery at
Fig. 191. — Riva-Rocci's Sphygmomanometer. (From Janeway's "Clinical Study of
Blood-pressure," D. Appleton and Co., Publishers.)
the wrist, while the right hand is employed to inflate the rubber pouch. The
pressure is read at the very moment when the radial pulse disappears. In quite
the same way, the pressure is again noted when the pulse reappears during the
gradual deflation of the pouch. The principal involved in this procedure is
obvious. When the outside pressure just barely overcomes the intravascular
pressure, .as is indicated by the loss of the radial pulse, the former may correctly
be taken as a measure of the latter. Naturally, this procedure does not permit
of definite conclusions being drawn regarding the mean blood pressure, but indi-
cates solely the maximum or systolic blood pressure, i.e., the moment when the
peaks of the individual pulse waves are just capable of overcoming the outside
pressure.
1 Gaz. med. di. Torino, 1896.
368 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
The Method of Auscultation. — The moment of the disappearance
and reappearance of the pulse may also be determined by means of
auscultation, because, as Marey has noted, the constriction of an artery
gives rise to noises (bruit de souffle) which are heard best distally to
and in the immediate vicinity of the constriction. Thus, if a stetho-
scope is applied over the brachial artery below the border of the arm-
piece,^ the gradual deflation finally gives rise to a sharp blowing sound
which presently becomes fuller and then disappears altogether. The
first occurrence of this sound indicates the systolic height of the blood
pressure, while the moment at which the sound beco^mes muffled shortly
before its complete disappearance, corresponds to its diastolic value.
The mean pressure can only be obtained in an approximate way with
the help of these two extremes.
The Graphic Method. — The determination of the blood pressure
may also be attempted in accordance with the principle that the
arterial wall executes its greatest movements at a time when the
intravascular pressure is accurately balanced by the outside pressure.
This fact to which attention was first called by Marey, has been proven
experimentally by Mosso upon excised segments of arteries. The
idea is to oppose the intravascular pressure by an outside pressure
which, being equal to that within, permits the most perfect elastic
play of the arterial walls. Thus, if the hand is placed in a receptacle
filled with mercury, the pulse is felt either at the base of the thumb
or along the fingers. In accordance with von Frey,^ the pressure
prevailing in the blood-vessels of the hand may be obtained by deter-
mining in millimeters the depth to which it must be pushed into the
mercury in order to produce this subjective phenomenon. In a simi-
lar way, it is possible to register the arterial pressure upon the paper
of a kymograph by simply connecting a recording tambour with the
cuff of a sphygmomanometer or with the free end of its mercurial in-
dicator. During the complete compression of the brachial artery, the
pulsations so registered retain a small ampUtude, because they are
simply transmitted from the central end of this blood-vessel. . When
however, the outside pressure is lowered step by step, their size is
gradually increased up to the time when the diastoUc mean value of the
blood pressure has been reached. Subsequent to this point the con-
spicuousness of these oscillations is again diminished. In this way,
the moment may be accurately determined at which the outside or
extra vascular pressure precisely equals the intravascular pressure.
Quite similarly, if the pressure is gradually increased, the beginning
of the large oscillations indicates the diastolic minimum.
This procedure must be followed if measurements are undertaken
1 In accordance with Janowski, Miinchener med. Wochenschr, 1907, the aus-
cultation method was first employed by Karotkow in 1895. Also see: Strass-
burger, D. Archiv fiir klin. Med., 1907, 459, and Fellner, Verhandl., Kongr. fiir
inn. Med., 1907.
2 Festschrift fur B. Schmidt, Leipzig, 1896, 79.
I
BLOOD PRESSUBB
369
with the sphygmomanometers devised by Erlanger^ and Miinzer^ or
with the sphygmoscope of Bing,^ or the oscillometer of Widmer.* It
is true, however, that the greatest number of instruments of this kind
are modifications of the Riva-Rocci apparatus^ described previously.
The fundamental principle has remained the same in all cases and only
insignificant changes have been made. Thus, it has been shown by
direct measurements, that a narrow arm-piece gives somewhat lower
values, and hence, a much broader one, measuring 12 cm. in width, is
now most commonly employed. In addition, the original mercury-
FiG. 192. — Jaisteway's Sphygmomanometer.
A, folding U tube; B, arm cuff; C, pressure bulb; D and E, needle-valve for release
of pressure; F, cork for closing end of mercury tube.
reservoir has been displaced in several of them by a modern mercury
manometer to which a more convenient and patent form has been given
so that it can be carried from place to place without spilling the mer-
cury. An ordinary valved rubber bulb may be used for the inflation
and deflation of the cuff. By using the metal tonometer devised by
V. Basch, as a sample, certain instruments have recently been con-
1 Am. Jour, of Physiol., Proc. xxii, 1902, also ibid., x, 1904.
2 Miinchener med. Wochenschr., 1907, 1357.
3 Berliner klin. Wochenschr., 1907, 690.
* Vaquez, Compt. rend., Ixvi, and Paris medicale, 1911.
* Gartner, Wiener med. Wochenschr., xxxi, 1899, and Martin, Miinchener med.
Wochenschr., xxiv, 1903.
24
370 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
structed in which a metal spring ^ is employed instead of the mercury-
manometer. These so-called sphygmotonometers possess the advan-
tage of being convenient to handle, although they must be calibrated re-
peatedly to make sure that the tension of the spring has not changed.
The Factors Influencing the Arterial Pressure. — As far as the
influence of age is concerned, it has been well substantiated that the
arterial blood pressure increases constantly until the normal mean is
reached in adult life. In later years and old age, it again increases
owing to the fact that the elasticity of the vascular tissue diminishes
steadily at this time in consequence of retrogressive changes. These
facts are fully illustrated by the succeeding table in which values fur-
nished by Cook and Briggs,^ Shaw,^ McCurdy and Thayer* have
been included :
First few months 70-75 mm. Hg
1-2 years 80-90 mm. Hg
2-3 years 90-100 mm. Hg
3-10 years 95-115 mm. Hg
10-15 years 100-115 mm. Hg
15-20 years 105-128 mm. Hg
20-30 years 135 mm. Hg
30-40 years 140 mm. Hg
40-50 years; 142 mm. Hg
50-60 years 154 mm. Hg
60-70 years 180 mm. Hg
Janeway^ considers 150 mm. Hg as the upper limit in normal adults,
while a systolic pressure of 60-75 mm. Hg is generally regarded as
dangerously low, although a pressure of 30-40 mm. Hg is sometimes
observed during operations. The average normal systoUc pressure
amounts to 135-145 mm. Hg; women generally showing a somewhat
lower pressure than men. Persons with sedentary habits usually
exhibit a pressure between 120 and 125 mm. Hg. The diastohc pres-
sure most frequently retains a value about 35-40 mm. Hg below that
of the systolic.® If the pressure persists for longer periods of time
at 180-200 mm. Hg, and over, a condition of hypertension is said to
exist. Quite similarly, persistent low pressures indicate a state of
hypotension. Both conditions generally possess pathological causes.
The pressure is lowest during the first hours of sleep, and rises
gradually until the time of awakening, when it increases rather sud-
denly to a level somewhat higher than that retained before retiring.^
During the day the blood pressure shows considerable variations which
1 von Recklinghausen, Archiv fiir exp. Pathol., Iv, 1906, 375.
2 Johns Hopkins Univ. Report, xi, 1903, 451.
3 Albany Med. Jour., xxi, 1900, 88.
^ Am. Jour. Med. Sciences, cxxvii, 1904, 391.
6 Clm. Study of Blood Pressure, New York, 1904.
^ Hirschfelder, Diseases of the Heart and Aorta, Lippincott, Philadelphia, 1913,
and Faught, Blood Pressure, Saunders Co., 1916.
^ Brush and Fayerweather, Am. Jour, of Physiol., v, 1901, 199.
BLOOD PRESSURE 371
must be attributed to diverse external and internal influences. Fluc-
tuations of 50 to 60 mm. Hg are not uncommon. Meals possess an aug-
mentor effect, in spite of the fact that the portal blood-vessels receive
large quantities of blood during the periods of digestion. ^ Janeway's
charts show a rise of 5 mm. Hg in the systolic and a fall of 5 mm. Hg
in the diastolic pressure after the midday and evening meals. To
this augmentor effect, as well as to the sudden reflex vasoconstrictor
reaction, must be attributed the peculiar cerebral symptoms which
are frequently experienced after too hearty a meal. Apoplectic seiz-
ures are prone to occur under these circumstances, provided, of course,
that the arteries have been rendered brittle by calcareous infiltration.
Deep and forced breathing increases the pressure. It is decreased
during menstruation,^ but rises during pregnancy,^ especially during
its later stages, and shows a most decided increase during labor in
consequence of the pronounced sensory stimulations and musculo-
motor efforts. Baths at the temperature of the body have no marked
effect, but cold baths (30-35° C.) produce a rise in the systolic pressure.
Hot baths (40° C. and over) generally possess a similar effect on account
of the resulting increase in the frequency of the heart.* Water con-
taining carbon dioxid, acts augmentatively, but only if the cardiac
energy has not been diminished.
As far as the influence of muscular exercise is concerned, the more
recent determinations which have been made with the help of the in-
direct method, seem to fully bear out the results obtained in horses
and dogs at an earlier date by means of the direct method.^ Thus,
HilP has shown that on moving about, the pressure rises from 10 to
20 mm. above that shown when at rest or asleep. Furthermore, the
experiments of Edgecomb and Bain,^ Masing,^ Karrenstein,^Lowsley,^^
and others have demonstrated that the effect of muscular work depends
entirely upon its severity. In all forms of it, an initial rise results,
which is retained for a time if the muscular efforts have been slight,
or is displaced by a fall, if the exercise has been severe or of long
duration. A moderate fall in arterial pressure, however, is not an
uncommon symptom of moderate muscular work.
1 Gumprecht, Zeitschr. fiirklin. Med., xxxix, 1900; Jellinek, ibid., xxxix, 1900;
Somerfeld, Dissertation, Erlangen, 1901, and Janeway, Clin. Study of Blood
Pressure, New York, 1904.
2 Federn, Wien. klin. Wochenschr., xv, 1912.
^ Wiessner, Deutsch. Arch, fiir klin. Med., 1907, and O. Miiller, Kongr. fur
Inn. Med., 1902.
* Strasburger, Zeitschrift fiir klin. Med., liv, 1904, 373.
^ Zuntz and Hagemann, Deutsch. med. Wochenschr., 1892, and Kaufmann^
Archiv de physiol., ser. 51t. 4.
« Jour, of Physiol., xxii, 1898, Proc. 26.
7 Ibid., xxiv, 1899, 48.
8 Deutsch. Arch, fiir klin. Med., Ixxiv, 1902.
9 Zeitschr. fur klin. Med., i, 1903.
^° Am. Jour, of Physiol., xxvii, 1911, 446.
372 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
While ordinary changes in position^ do not affect the blood pres-
sure very materially, extreme changes always induce static effects
which the vascular system is at times unable to counteract. Thus, a
change from the recumbent to the standing position always leads to a
fall in blood pressure, if the tonus of the blood-vessels has been lessened
in any way. This condition may be general or local, and is especially
prone to involve the blood-vessels of the portal system. As these
channels are concerned with the digestion and absorption of foods,
they must absorb a large mass of blood, and hence, their static in-
fluence must be particularly potent at this time. The effects of vascu-
lar relaxation are counteracted in a large measure by a greater ven-
tricular discharge, because if a person assumes the erect position, the
heart beats more quickly, this increase being proportional to the fall
in pressure. If, however, the relaxation is pronounced, the heart is
quite unable to effect an adequate compensation and a fall in blood
pressure results. Concurrently, it may be concluded that a proper
tonicity of the blood-vessels suffices to retain the pressure at its normal
level without that the heart need increase its energy. In fact, a person
whose vascular system is tonically set, most frequently shows a slight
rise on assuming the erect position, because the heart nevertheless
tends to increase its frequency by at least a few beats.
These facts have been employed by Crampton^ in obtaining an index of coiv-
dition. A large number of determinations of the blood pressure in normal indi-
viduals have been compiled in such a way that their state of physical fitness may
be deduced directly from these figures. This is made possible by arranging these
values in series in accordance with the alterations in the height of the blood pres-
sure and the frequency of the heart which resulted when these persons changed
their position from the recumbent to the upright. In accordance with these deter-
minations, a person is said to be in a good physical condition if, on assuming the
erect position, his systolic pressure diminishes by no more than 12 nor increases by
more than 18 mm. Hg. Besides, this change must leave fhe diastolic pressure un-
changed, or must not increase it by more than 18 mm. Hg. Quite similarly, the
heart must at this time either retain its previous rate or increase its frequency by
no more than 40 beats. Greater variations than these are regarded as proving
that the vascular system is relaxed and that, therefore, the person is in a poor phys-
ical condition. While this test possesses a sound dynamical basis, the results ob-
tained should be accepted with great reserve and should not be applied with undue
strictness to all persons.
It should be mentioned that tests of physical fitness have also been devised
by Graupner,' and Katzenstein.* The former endeavored to test the functional
capacity of the heart by noting the influence of a measured amount of muscular
work upon the blood pressure and pulse rate, and the latter, by determining the
response of the heart to compression of both iliac arteries. Barach^ has sought to
determine the tonic condition of the circulatory system by multiplying the systolic
1 Shapiro, Med. Jahrb. der K. K. Gesellsch. d. Arzte, 1882; Erlanger and
Hooker, Johns Hopkins Hosp. Rep., xii, 1904, and Brocking, Zeitschr. fiir Exp.
Path., ix, 1907.
2 Med. News, 1905.
^ Berliner klin. Wochenschr., 1902.
4 Ibid., 1907.
^ Jour. Am. Med. Assoc, 1914.
BLOOD PRESSURE 373
and diastolic pressures by the pulse rate. When added to one another, the values
so obtained give the so-called S. D. R. index, for example:
Systolic pressure 120 mm. Hg X 72 = 8,640 mm. Hg
Diastolic pressure 70 mm. Hg X 72 = 5,040 mm. Hg
190 mm. Hg X 72 = 13,680 mm. Hg
By combining in this way the pressure with the cardiac frequency, it is possible
to obtain an estimate of the vascular energy for longer periods of time. The high-
est S. D. R. index which has been observed in normal persons is close to 20,000.
Thus, a person with a total energy index of 30,000 may be said to show a 50 per
cent, increase, and so on. The lower limit seems to lie at about the figure 12,000.
The efficiency test described by Barringer^ consists in determining the cardiac
rate and blood-pressure before and after a graded exercise which may be determined
in foot-pounds.
The Venous Blood Pressure. — It has been stated aoove that the
venous pressure may be determined in any vein of convenient size
and location by connecting it by means of a T-tube with a U-shaped
manometer containing normal saline solution. In this way, the lateral
pressure is obtained which prevails in this vein at the point of insertion
of the tube. By simultaneously registering the pressure in different
veins of the dog, Burton-Opitz^ has obtained the following average
values :
Saphenous vein (left) 7 . 42 mm. Hg
Femoral vein (left) 5. 39 mm. Hg
Femoral vein (right) 5. 42 mm. Hg
Facial vein (left) 5.12 mm. Hg
Brachial vein (right) 3 . 90 mm. Hg
Renal vein 10.9 mm. Hg
Mesenteric vein 14.7 mm. Hg
Splenic vein 10.1 mm. Hg
Portal vein 8.9 mm. Hg
External jugular vein (left) 0 . 52 mm. Hg
External jugular vein (right) — 0 . 08 mm. Hg
Superior cava (per. portion) — 1 . 38 mm. Hg
Superior cava (centr. portion) —2. 96 mm. Hg
Inferior cava at hep. vein 0 . 00 mm. Hg
This compilation shows that the pressure decreases gradually
from the periphery to the center at the rate of about 1 mm. Hg for
every 35 mm. of distance. The zero-line is reached in close proximity
to the chest. Centrally to this point, the pressure becomes negative
and eventually attains its lowest value in the auricular portion of the
heart, namely — 10 to — 15 mm. Hg. As the pressure in the peripheral
veins is only 10 to 15 mm. Hg, the total fall in the venous system
amounts to no more than 30 mm. Hg. It should also be remembered
that this fall is had only because the soft walls of the venous channels
are constantly exposed to the elastic pull of the lungs which becomes
greatest during inspiration. This can readily be proved, because
1 Arch, of Int. Med., March, 1916.
2 Am. Jour, of Physiol., ix, 1903; also Pfliiger's Archiv, cxxix, 1908.
374 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
if the chest is opened, the pressure in the central veins rises immediately
to above zero with a corresponding elevation of the pressure from here
outward. Hence, it may be concluded that this negative venous pres-
sure is dependent upon the elastic recoil of the lungs.
nder normal conditions, the area of negative venous pressure
begins at about the junction of the hepatic vein with the inferior
cava, and at the point where the external jugular vein passes deep
into the supraclavicular fossa. The so-called ''danger line" of the
Fig. 193. — Diagram to Pressure Throughout the Vascular System.
Z, abscissa or zero-line; P, curve of pressure (A) in arteries (C) in capillaries and (TO
in veins. The greatest fall in pressure occurs in the capillaries in which the resistance is
greatest.
surgeon corresponds to this line of zero pressure, because it has always
been thought that an injury to a vein centrally to this point, must
inevitably lead to an entrance of air into the vascular system and a
frothing of the blood by the cardiac valves. This danger, however,
is not so imminent as might be supposed, because the walls of the veins
yield easily and, as they are not firmly attached to the surrounding
tissues, collapse very readily, thereby preventing the ingress of air.
Moreover, while dangerous on account of the possible occurrence
of emboli, small quantities of air are fre-
quently gotten rid of by absorption.
The principle of the indirect method
of measuring venous blood pressure is
precisely the same as that made use of in
determining the arterial pressure. An
outside pressure which can be accurately
Fig. 194.— Small Rubber measured, is brought to bear upon a
Capsule Used for Obliteration £ • i • x-i 'j. j. i j.
OF Vein. Superficial vein until its central stump
becomes empty. As the venous pressure
is low, a water manometer is employed as the indicator in conjunc-
tion with an ordinary pressure bulb. In accordance with v. Reckling-
hausen,^ the obliteration of the vein is accomplished by means of a
small capsule of thin rubber (Fig. 194) which communicates with a
manometer and is held in place upon the skin by a flat box made of
glass or wood. Hooker^ employs a small glass chamber which is
fastened to the skin in the region of the vein by a film of collodion
solution.
• 1 Archiv fiir Exp. Path, und Pharm., Iv, 1906.
^ Am. Jour, of Physiol., Ixxiii, 1914, Proc. 27.
BLOOD PRESSURE 375
The compression of the vein can also be accomplished by means
of a spring manometer such as was first employed by von Frey,^ or
by means of a cuff connected with a water manometer. Frank and
Reh,2 for example, use two cuffs, one of which is applied to the fore-
arm and the other to the arm. The former is inflated so as to fit
snugly, but without exerting a pressure of more than 1 cm. H2O.
The arm-cuff is then inflated slowly until the pressure in the manometer
connected with the lower cuff, is suddenly seen to rise. This change
is taken to indicate an increase in the volume of the arm caused by the
obstruction to the venous return distally to the arm cuff. When this
obstruction first becomes evident, the pressure in the distal cuff must
equal the venous pressure. Obviously, these determinations must
either be made at the level of the heart or must be corrected for this
level, because the pressure in any vein varies with its position. Thus,
if the arm is allowed to hang pendant at the side, the pressure in the
Fig. 195. — Method of Measuring Venous Blood-pressure.
The rubber capsule is adjusted upon the vein and is covered with a glass plate or
small box glued to the surface with collodion. The capsule is connected with a ma-
nometer and pressure-bulb. (,v. Recklinghausen.)
veins of the hand is much greater than when it is elevated to a point
above the heart.
Gartner^ has advised the following procedure. If the arm is
slowly raised, the veins of the hand collapse as soon as a certain level
has been reached. If the distance between this level and that of the
heart at the junction of the fifth costal cartilage with the sternum is
now measured, we obtain the pressure supporting the blood at the
right auricle in centimeters of blood, or water, because 10 cm. of blood
equal 10.6 cm. of water. Moritz and Tabora"^ have called attention
to the fact that the venous pressure corresponds to the pressure neces-
sary to cause normal saline solution to enter the body. If the infusion
is made through the median vein of the arm when placed at the level
of the heart, the pressure in this vein must correspond to the height
of the column of saline solution still left in the buret at the end of the
injection. It is of interest to note that the values obtained with the
1 Deutsch. Archiv fiir klin. Med., Ixxiii, 1902.
^Zeitschr. fiir Exp. Path, und Therap., 1912; also see: A. A. Howell in Arch,
fiir int. med., ix, 1912.
3 Miinchener med. Wochenschr., Ixxlv, 1904.
* Deutsch. Archiv fiir klin. Med., xcviii, 1910.
376 THE MECHANICS OF THE CIKCULATION, HEMODYNAMICS
aid of these indirect methods closely agree with those given previously.
Thus, it has been found that the pressure in the small veins of the arm
and hand amounts to 100-200 cm. H2O.
The Capillary Blood Pressure. — Obviously, the pressure prevailing
in the capillaries cannot be measured by the direct method; in fact,
even the indirect procedures so far devised have given only approxi-
mate values. Thus, v. Kries^ has made use of a thin plate of glass
which he placed upon the skin and gradually weighted until the skin
underneath it became pale. This method is based upon the proba-
bility that the first indication of the paling of the surface corresponds
to the moment when the pressure in the capillaries is balanced by the
pressure without. The latter may be expressed in centimeters of
water by dividing the weight which has been placed upon the glass
slide by the size of the area under compression. Roy
and Graham-Brown 2 have attempted to determine the
moment of compression of the capillaries by exposing
them, while under microscopic observation, to a pres-
sure brought to bear upon them by means of elastic
capsules connected with a manometer.
When the arm was held at the level of the heart,
the pressure in the capillaries of the fingers amounted
to 24 mm. Hg. With the hand pendant at the side
of the body, the pressure rose to 62 mm. Hg. In the
capillaries of the ear, the pressure amounted to 20 mm.
F 196 — -^^ ^^^ ^^ those of the gums of a rabbit, to 33 mm.
Apparatus OF Hg. The determinations of von Recklinghausen^ have
VON Kries for given a value of 55 mm. Hg for the small arterioles
i^^ryTlo^oT- supplying the capillaries of the tips of the fingers.
PRESSURE. While the capillary pressure must vary in different
organs and tissues, it seems that its average value
must lie somewhere between 40 and 50 mm. Hg. To illustrate: If the
intraventricular pressure is 125 mm. Hg, it will be found that the
peripheral arterial pressure amounts to about 105 mm. Hg. About
3 or 4 mm. Hg of the initial driving force are lost between the heart
and the aorta and the remainder between this blood-vessel and the
arterioles. Distally to these, the original driving force is used up very
rapidly, the greatest reduction occurring in the capillaries proper.
This cannot cause surprise, because the resistance in these channels
is very great. As we have seen, the blood arrives in the distal veins
under a pressure of only about 10 to 15 mm. Hg and hence, almost
100 mm. Hg of the original pressure have been used up in forcing the
capillary passage. As the blood approaches the heart, the pressure
becomes less and less, amounting at the cardiac vestibule to only —5
to —10 mm. Hg. Naturally, these negative values which are de-
1 Verh. sachs. Gesellsch. der Wissensch., 1875.
2 Jour, of Physiol., ii, 1879, 323.
2 Archiv fiir Exp. Path, und Pharmak., Iv, 1907.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 377
pendent upon the elastic pull of the lungs upon the soft walls of the
central veins, serve as accessory means to augment and to conserve
the initial driving force of the heart.
CHAPTER XXXII
THE PULSATORY VARIATIONS IN BLOOD PRESSURE
A. THE CARDIAC VARIATIONS IN ARTERIAL PRESSURE
The Cause of the Arterial Pulse. — Fluctuations in pressure are
encountered in the arteries as well as in the veins; in fact, they are
also perceptible at times in the capillaries. They possess a twofold
origin, being caused either by the contractions of the heart, or by the
movements of respiration. If the former, they are designated as the
cardiac, and if the latter, as the respiratory variations in blood pressure.
Moreover, as each group of changes makes itself felt in the arteries
as well as in the veins, they are again subdivided into the cardiac varia-
tions in arterial and venous blood pressure, and into the respiratory
variations in arterial and venous pressure. The principal changes
due to the activity of the heart, are the so-called arterial pulse and the
physiological venous pulse.
Each ventricular systole adds a certain quantity of blood to that
already transferred into the arterial system by the preceding systoles.
The arterial pressure increases with each ventricular discharge above
that prevailing during the previous diastolic period. Furthermore,
owing to the elasticity of the arterial channels, each inrush of blood
causes a distention of their walls which is followed by a recoil as soon
as the influx has ceased. Obviously, this elastic play serves the pur-
pose of lessening the systolic strain upon the cardiac muscle as well as
that upon the walls of the blood-vessels, because if the heart were
forced to pump into a system of rigid tubes, its contractions would
necessarily become labored, owing to the fact that a certain amount of
blood would first have to be dislodged from the tubes before a new
amount could be accommodated therein. A condition of this kind
would occasion a periodic escape of venous blood to counterbalance
the quantity of arterial blood forced in, and this intermittent or re-
mittent flow would be characterized by very high systolic and very low
(iiastolic pressures.
Contrary to this result, the distensibility of the arterial walls
enables this system to accommodate the successive outputs of the heart
by simply enlarging its caliber. Moreover, this process insures the
least possible expenditure of energy and does not permit of the develop-
ment of disturbing fluctuations in pressure and flow. In addition,
the subsequent recoil of the arterial walls serves the purpose of con-
378 THE MECHANICS OF THE CIKCULATION, HEMODYNAMICS
tinuing the initial driving force of the heart even during the diastolic
period, so that the blood is forced to escape into the capillaries in a
perfectly steady stream and not remittently. Obviously, therefore,
the pressure in the arteries is increased during each systole of the heart,
and, as the ventricles are emptied rather quickly (0.3 sec), this rise
must develop with a certain abruptness. The diastolic decline, on the
other hand, is gradual, because the peripheral resistance is adjusted
in such a way that a very copious escape of arterial blood during
this period cannot result. By means of a proper adjustment of this
resistance, the arterial system is constantly kept in a condition of
overJ&lUng.
The aforesaid systolic-diastolic variation in the arterial pressure
forms the basis of the arterial pulse. Although primarily dependent
upon the activity of the heart, its place of origin is really in the root of
the aorta, whence the individual fluctuations in pressure are trans-
Fig. 197. — The Cardiac Variations in the Arterial Blood-pressure.
S, systolic pressure; D, diastolic pressure; M, average pressure. The systolic-
diastolic difiference constitutes the pulse-pressure. A, abscissa.
mitted throughout the arterial system in the form of successive waves.
Thus, it happens constantly that the central portion of this system is in
a state of maximum distention, while its more distal segments still
retain their diastolic caliber. A moment thereafter, however, these
conditions are reversed, the advancing wave causing the peripheral
portion to become distended, while the more central portions recoil
and bring their elastic power to bear upon the blood within them. The
pulse, therefore, is essentially a reproduction of the changes in pressure,
modified by the elastic qualities of the arterial wall.
Each systole of the heart generates a certain amount of energy
which is transferred in part to the arterial wall where it is stored as
potential energy, to be made use of subsequently during the diastolic
period of the organ. As the cardiac energy is transmitted at regular
intervals, this elastic recoil of the arteries must also occur at regular
intervals. It is betrayed externally by an alternate expansion and
shrinkage of the arteries, or ''pulse," which is most manifest near
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 379
the heart and gradually becomes less apparent in the direction of the
distal channels. In the capillaries, these pulse waves are usually not
in evidence, because the friction encountered in this particular division
of the vascular system is so great that the fluctuations in pressure are
completely neutralized. But, in the event of a capillary dilatation,
this resistance is usually diminished to such an extent that the individ-
ual pulsations are able to extend directly into the distalmost veins.
This phenomenon is often observed in glands during secretion, because
their activity necessitates a copious supply of blood and hence, an
injected state of their capillaries. In the submaxillary gland, this
vasodilatation may be produced by stimulation of the chorda tym-
pani nerve. The arterial pulse is then clearly visible in the small vein
draining this organ.
Fig. 198. — Sphygmogram from the Radial Artery, Dudgeon Sphygmograph.
D, the dicrotic wave; P, the predicrotic wave. {Howell.)
The Frequency of the Arterial Pulse. — It is evident that the number
of the pulse-waves must coincide precisely with the frequency of the
heart, because the cardiac output forms the basis of these oscillations.
For this reason, the palpation of the pulse in such arteries as the radial,
brachial, temporal, or carotid, is practised primarily for the purpose of
ascertaining the cardiac frequency. As this topic has been dealt with
at length in a preceding chapter, it need not be discussed further at
this time. Attention should, however, be called to one or two pomts
of clinical value.
Under certain abnormal conditions, it may happen that some of
the ventricular contractions do not develop a power sufficient to raise
the semilunar valve flaps, or, if they do, are quite unable to overcome
the general arterial pressure. In the first instance, the cardiac efforts
fail absolutely in producing pulse-waves, and in the second, in sus-
taining them for any considerable distance. This is generally true of
the so-called extrasystoles which, as the name indicates, are special
contractions interposed between the regular ones. As long as these
extra efforts of the ventricles do not interfere with the general rhythm
and output of the heart, no circulatory disturbances result. In further
illustration of this fact, that the frequency of the pulse does not always
indicate the rate of the heart, might be mentioned the condition of
heart-block, during which, as has been stated above, the auricular rate
is maintained, while the number of the ventricular contractions is
diminished. Thus, it may be gathered that the best policy is to bring
380 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
the arterial pulse into relation with the apex-beat, as well as with the
venous pulse. The latter is generally noted in the region of the cen-
tral end of the right external jugular vein and is, of course, indicative
of the rate of the auricles. In this way it is possible to detect imme-
diately any dissociation in the rhythm of the heart.
The Velocity of the Arterial Pulse. — The fact that the pulse
progresses as a wave,^ may readily be proved by the simultaneous
palpation of the carotid and radial arteries, because, as the former
blood-vessel lies closer to the hearty the characteristic systolic bump
will be noted sooner here than in the latter region. The interval,
however, is so brief that only a practised observer will be able to per-
ceive it. A more plastic way of demonstrating the wave-like character
of the pulse is furnished by the graphic method. Two receiving tam-
bours which in turn are connected with two recording tambours, are
placed upon an artery at different distances from the heart. Upon
being permitted to record in the same vertical line, it will be found
that the lever nearest the heart is always raised first, and naturally,
the difference in time between the upstrokes of the two levers is the
time which the pulse-wave requires in traversing the segment of
the artery situated between them. Having determined this distance,
it is a simple matter to calculate the velocity of this wave.
While it may be said that the rate of progression of the pulse is
fairly constant, its speed must differ somewhat from moment to
moment, because the conditions in the vascular system are subject
to frequent changes. This is especially true of the elastic coefficient
of the arterial wall. Thus, it may be inferred that its velocity in-
creases whenever the arterial pressure is raised and decreases whenever
the latter is diminished. ^ These differences may readily be demon-
strated by the repeated stimulation of the vagus nerve which procedure
is followed by a fall in pressure incurred by the diastolic tendency of the
heart. For very similar reasons the velocity of the pulse is also de-
creased during sleep and anesthesia. The difference may amount to
1 m. per second and more. Concurrently, it may be reasoned that a
lessening of the distensibility of the arteries must induce a greater
velocity of this wave. A condition of this kind arises, for example,
during arterio-sclerosis. Landois,^ Edgren,^ and others have found
values ranging between 6.5 and 9.0 m. in a second. The arteries used
for these determinations were the carotid and femoral or the carotid
and radial. It has also been noted that the velocity of the pulse is
somewhat greater in the blood-vessels of the arm than in those arising
from the descending aorta. It seems that 7 m. per second may be
regarded as a fair average value.
^ Discovered by Erasistratus, but denied by Galenus. It remained obscure
until the time of Haller. In 1850 E. H. Weber made the first attempts to deter-
mine its velocity.
2 Moens, Die Pulskurve, Leyden, 1878.
3 Lehre vom Arterienpuls, Berlin, 1872.
* Skand. Archiv fiir Physiol., i, 1889, 67.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 381
In this connection the student is cautioned against confounding
the velocity of the pulse- wave with the velocity of the blood-stream.
The latter is seldom greater than 0.5 m. in a second. Thus, a stone
thrown into a river produces ripples upon its surface which progress
in all directions with a speed which is not at all identical with that of
the flow of this body of water. This must be so, because the production
of a current necessitates the bodily onward movement of the different
particles of water in a-definite direction, while a ripple merely indicates
the passage of a wave incited by changes in the position of a relatively
small number of these particles. The wave, therefore, is enabled to
attain a much greater speed and to progress even against the stream.
While this phenomenon cannot be said to be identical with the arterial
pulse, the stone thrown into the river, really plays a part similar to
that of the ventricular discharge, in consequence of which those differ-
ences in pressure are established which give rise to the elastic excursions
of the arterial wall. A much better way of proving this point is to take
a fairly long piece of band-tubing which is connected at regular dis-
tances with a number of vertical glass tubes. If this tubing is now
filled with water by the rhythmic compression of a rubber .bulb, every
addition of water gives rise to a wave which may easily be traced
through this system, because it induces a successive oscillation of
the fluid in the different collaterals.
It is possible to ascertain the length of the pulse- wave by multi-
plying the velocity of transmission with the time required by the wave
to pass a certain point. The former value is 7 m. per second and the
latter 0.8 sec, because each pulse-wave occupies the time of a cardiac
cycle, i.e., it begins with the systolic discharge and ends immediately
before the succeeding one. The value so found is 5.6 m. It may there-
fore be concluded that each pulse wave arrives at the periphery of the
arterial system long before its completion at its point of origin in the
aorta.
The Registration of the Arterial Pulse. Sphygmography. — It has
previously been shown that the cardiac variations in arterial pres-
sure may be registered without difficulty by connecting the artery with
& mercury manometer. It is true, however, that the minute details
of these oscillations cannot be depicted in this manner, because the
mercury is altogether too sluggish to follow the variations in pressure
with accuracy. It is best, therefore, to employ a membrane manome-
ter or an optical manometer, such as have been described by Hlirthle
and O. Frank. When properly dampened, these instruments com-
bine a slight inertia with an exceptionally high speed of reaction.
The graphic method of investigating the pulse was first employed
by Vierordt^ in 1885, but the instrument which he devised for this
purpose is not well suited for this kind of work, owing to its relative
inelasticity. A much more sensitive instrument has been constructed
^Lehre vom Arterienpuls, Braunschweig, 1855.
382 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
by Marey/ to which the name of sphygmograph has been given.
Although variously modified in subsequent years, the principle in-
volved in its construction has not been changed.
A pellotte, attached to a steel spring, is placed upon the skin over the radial
artery in such a way that the pulsations of this blood-vessel are communicated
Fig. 199. — Schema Illustbating the Sphygmograph op Marey.
B, pelotte applied to blood-vessel; W, toothed wheel fitting into toothed rod; R,
the up and down movements of this rod give rise to a back and forth movement of the
wheel; to its axis is attached a writing lever (L) registering its excursions upon a
kymograph (K).
to it directly. But as the excursions executed by the arterial wall and over-
lying tissues are relatively small, it is necessary to magnify the movements of the
sphygmograph considerably by increasing the leverage of its writing lever. The
latter must be very light and a certain resistance must be imparted to it, otherwise
Fig.
Fig. 200. Fig.
200. — The Dudgeon Sphygmograph in Position.
201.
Fig. 201. — Diagram Illustrating the Action of Dudgeon's Sphygmograph.
(Howell.)
The lever of the Dudgeon sphygmograph : P, the button of the spring F, to be placed
upon the artery. The movement is transmitted to the lever, Fi, and thence to the
bent lever, F2, the movement of which is effected through the weight, g. The writing
point S, of this lever makes the record on the smoked surface, A.
its movements may be much exaggerated by inertia. In the instrument of
Czermak, ^ the place of the recording lever is taken by a mirror by means of which
a beam of light is reflected upon sensitive paper moved at an appropriate speed.
1 Jour, de la physiol., iii, 1860.
2 Sitzungsb. der Akad. der Wissensch., Wien, 1863.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 383
Dudgeon and Jaquet^ have modified this instrument by adding a time marker and
an arrangement by means of which a narrow plate of blackened glass is moved
past the recording needle. But as the length of this recording surface must
necessarily be Umited, it does not permit of the taking of long-continued records.
This disadvantage is not present in those instruments which consist of a receiving
and a recording tambour, the former being equipped with a button-like pro-
jection which is placed directly over the artery.^ As the recording drum of this
instrument may be adjusted to a kymograph at some distance from the artery,
it is possible to obtain long and uninterrupted records. The so-called angiometer
of Hiirthle has been devised to register the pulsations of blood-vessels when fully
exposed to the view. The vessel itself is held in a metal groove, while a pellotte is
placed upon its upper border. The latter is connected with a writing lever by
means of a slender rod.
Character of the Arterial Pulse Wave. Sphygmogram. — The curve
recorded by a sphygmograph is designated as a sphygmogram. It
A
Fig. 202. — The Chabacter of the Arterial Pulse.
AB, anacrotic limb; BC, catacrotic limb; B, apex; D, dicrotic wave; N, dicrotic
notch; E, predicrotic wave; F, postdi erotic waves.
gives information regarding (a) the frequency, (6) the rhythm,
(c) the amphtude, and {d) the dicrotism of the pulse. Each pulsation
begins with an ascent which is the counterpart of the rise in systoUc
pressure. Furthermore, as the ventricle discharges its contents rather
quickly, this upstroke must necessarily be steep. The curve attains
its greatest height at the point of greatest distention of the artery,
forming here the so-called apex. It then declines slowly until the
following systole of the heart again sends it abruptly upward. In
contradistinction to the almost vertical upstroke, the downstroke
slants considerably, because, being opposed by a high capillary re-
sistance, the recoil of the distended arteries cannot give rise to a per-
fectly free escape of blood into the capillaries and veins. Each wave
of the pulse, therefore, consists essentially of two phases, its ascending
portion being designated as the anacrotic limb, and its descending por-
tion as the catacrotic limb.
Keeping these facts clearly in mind, we are now in a position to
consider some of its minor details (Fig. 202). The anacrotic limb
1 Zeitschr. fiir Biologie, xxviii, 1891. A description of the sphygmograph of
Petter and Frank is given in this Journal, xlix, 1907, 70.
2 Brondgeest, Onderz, gedaan in het physiol. Lab. d. Utrecht. Derde Reeks,
U, 1873.
384 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
(A-B) is generally smooth; its steepness, however, varies with the
tension prevailing in the arteries. If the pressure is high, the ascent
must be slower, because it is then developed against a greater resist-
ance. A low pressure, on the other hand, favors a more rapid rise in
pressure and hence, also the production of a more vertical anacrotic
limb. It should also be remembered that if the resistance in the arterial
system is high, the upstroke frequently shows certain secondary waves
which indicate the occurrence of an elastic quivering. Conditions of
this kind are encountered in arteriosclerosis and stenosis of the semi-
lunar valves. These extra oscillations which are generally situated
near the apex of the curve, are known as anacrotic waves. In accord-
ance with the preceding statement, it may be assumed that they are
tension- waves, i.e., quick reflections from the periphery. This view
was first expressed by v. Kries, ^ who produced them in the radial artery
by raising the hand to such a level that the static effects permitted the
occurrence of reflections from the periphery before the summit of the
pulse-curve had been reached. Obviously, any condition which hin-
ders the quick emptying of the ventricles, must give sufficient time for
these reflections to develop. They are especially prone to occur in
aortic stenosis when the narrowing of the aortic orifice is associated
with a hypertrophy of the ventricular musculature.
The apex (B) of the normal pulse-wave possesses a rounded out-
line, while in the sphygmogram it is generally very pointed. This
discrepancy must be attributed to an instrumental error, namely, to
the ''fling" which is imparted to the lever and its connecting parts
whenever the artery is suddenly expanded. When especially conspicu-
ous it is called the "percussion-wave.'^
The catacrotic limb (B-C) exhibits several details which deserve
a more lengthy discussion. Its most constant characteristic is a
well-marked secondary rise which appears near the middle of the de-
scent and is known as the dicrotic wave (D) . Subsequent to this point
a number of smaller wavelets are usually observed which are desig-
nated as the postdicrotic waves (F). Immediately preceding the di-
crotic wave, a small oscillation is generally obtained which is called
the predicrotic wave (E). Between points E and F, the curve shows
a depression, known as the dicrotic notch (n).
While the dicrotic character of the pulse was recognized by pal-
pation long before the invention of the sphygmograph, its dicrotism
was first demonstrated in a plastic manner by Thelius in 1850.^ Some-
time later Marey^ obtained graphic records of it, while Landois*
proved its existence by pricking an artery with a needle and by permit-
ting the blood to spurt against the paper of a slowly revolving
kymograph. Records of this kind are called hematograms.
1 Studien zur Pulslehre, 1892.
^ Vierteljahrschr. fiir prakt. Heilkunde, xxi, 1850.
3 Jour, de la Physiol., iii, 1860.
* Pfluger's Archiv, ix, 1874.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 385
A pronounced dicrotism of the pulse usually indicates a low blood
pressure, because a low tension permits the systolic-diastolic differences
and other fluctuations in pressure to become extreme. Conditions
of this kind frequently develop in the course of many wasting diseases,
and especially during fevers, such as typhoid, when a low peripheral
resistance is associated with an, as yet, efficient pumping force of the
heart. Any factor, therefore, which induces sudden and extreme
variations in pressure, or favors the elastic resiliency of the arterial
wall must tend to augment the dicrotism. For this reason, it is
usually very conspicuous in young people, but not in adults and
older persons, because their arteries have been rendered more rigid by
calcareous infiltration.
Any discussion as to the cause of the dicrotic wave must first of all
take into Account that it may be a reflection traveling from the heart
outward, or that it may be a peripheral reflection passing inward. The
second possibility may be disposed of very quickly, because if it really
were a centripetal wave, it should be possible to obtain it apart from
the principal wave of the pulse. The latter has been proven to be of
central origin. Now, since the dicrotic elevation always keeps at a
definite distance from the apex of the primary wave, we are entirely
justified in concluding that it originates centrally and represents,
therefore, a centrifugal wave, traveling at the same velocity as the
principal one.
Having established the direction of the dicrotic wavelet, it now
becomes a relatively simple matter to detect its cause. As may
readily be surmised, the latter must be sought in the closure of the
semilunar valves. A thorough distention of the aorta having been
attained, its walls recoil immediately upon the completion of the ventric-
ular systole and place the blood within under continued pressure. The
blood then seeks to escape in the direction of least resistance, namely,
toward the capillaries as well as toward the heart. The centripetal
movement of the column of blood is at first greatly facilitated by the
negativity resulting in the root of the aorta in consequence of the
ventricular discharge, but is suddenly cut short by the approximation
of the aortic semilunar valve-flaps. Being thus suddenly thrown
against the closed semilunar valve, a reflection results which is con-
veyed toward the periphery in the form of a wavelet superimposed upon
the principal wave.
The dicrotic notch immediately preceding the dicrotic elevation,
seems to have its origin in the decrease in pressure resulting in the root
of the aorta at the beginning of ventricular diastole. As the aortic
walls recoil and force the blood against the closed semilunar valves,
a slight downward deviation of the latter results, because they are
no longer supported by the firmly contracted ventricular musculature.
This yielding of the '^semilunar floor," however, is very limited and
soon gives way to a rebound of the blood which in turn causes the
distention of the aorta described a moment ago as the dicrotic wave.
25
386 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
The predicrotic wave or waves appear to be exaggerations of the
recoil produced by the ''fling" of the writing lever, but, contrary
to the inertia which gives rise to the pointed apex, or percussion-wave,
these secondary elevations are not dependent upon the initial upward
throw of the lever, but upon its rebound as it again endeavors to as-
sume the resting position. These oscillations, however, are destroyed
very shortly by the negative variation appearing in the form of the
dicrotic notch. The postdicrotic wavelets have also been regarded
as inertia movements of the instrument. It is more than probable
that the dicrotic elevation suffers an exaggeration in the same way as
the primary wave and hence, the writing lever and its connecting parts
can assume their position of rest only after they have passed through
several adj usting oscillations. Another view is that they represent after-
vibrations of the column of blood following in the wake of the dicrotic
wave.
It should also be remembered that the tracings of the pulse taken
from different arteries, show certain differences regarding these minor
fluctuations. In explanation of this phenomenon it has been suggested
by Frank ^ that certain regions of the vascular system are so shaped that
they are capable of giving rise to special types of reflections which then
tend to modify the character of the principal pulse-wave. Thus, it
has been stated that the carotid pulse is influenced by waves reflected
from the circle of Willis, while the pulse in the descending aorta suffers
a slight modification in consequence of reflections from the bifurca-
tion of the iliac arteries. It is true, however, that many of these
secondary currents interfere with one another in such a way that they
become neutralized.
Pulse Pressure. — When referring to blood pressure, we usually
have its average value in mind. It has been pointed out above that
this value may be determined most accurately by ascertaining the
arithmetic mean of the systolic and diastolic pressures, as registered
by the direct method. It may also be determined by the indirect
method, but only approximately, because this estimate must be based
upon the diastolic pressure. The mean pressure follows the diastoUc
minimum pressure more closely than the systolic maximum and hence, a
greater importance is frequently attached to the former than to the
latter. But as a definite numerical relationship between these factors
does not exist, the average blood pressure is usually determined in a
rough way by adding one-third of the systolic-diastolic difference to
the diastolic pressure. It has also been estimated at 75 per cent, of the
systolic pressure.
The systolic-diastolic difference in blood pressure is generally desig-
nated as the pulse pressure. Thus, if a systolic value of 130 mm.
Hg is opposed by a diastolic value of 90 mm. Hg, the pulse pressure
equals 40 mm. Hg. Keeping this fact clearly in mind, the changes
which the pulse-pressure may undergo need not be considered in
1 Tigerstedt, Ergebn. der Physiol., viii, 1909.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 387
detail, because they are identical with those exhibited by the systolic
and diastolic pressures individually. It naay therefore be said that
it is subject to alterations in (a) the energy of the heart, (6) the
peripheral resistance, (c) the elasticity of the blood-vessels, and (d)
the quantity of the circulating blood.
The Clinical Significance of the Sphygmo^am. — The information
to be derived from a study of the sphygmogram is of slight clinical
value. No doubt, if properly adjusted, the sphygmograph may serve
as an accurate means for determining the frequency and rhythm of the
heart, although it does not permit us to draw definite conclusions re-
garding the dynamical conditions prevailing in the vascular system.
In the first place, the length of the individual pulse-waves, as well as
their general character, may be varied considerably by technical errors
committed in adjusting the instrument. Thus, it is often difficult to
apply it with that degree of pressure which is required to counter-
balance the systolic pressure. In the second place, it must be granted
that the excursions of the instrument depend in a large measure upon
the thickness of the tissues overlying the artery and upon the degree
of injection of the neighboring veins. It is best, therefore^ to regard
the sphygmograph merely as an aid to diagnosis and to draw no rigid
conclusions from its records. It is much easier, and also much safer,
to base your deductions upon the methods of inspection and palpation,
because by these means the frequency and regularity of the heart are
made evident in a much more direct manner. In addition, these
simple methods enable us to estimate the general character of the
pulse-wave, and hence, also the tension prevailing in the arterial sys-
tem and the efficiency of the entire circulatory mechanism. The fol-
lowing quaUtative differences are generally ascribed to the pulse:
(a) Frequens or Rams. — A pulse is characterized as quick if it surpasses the
normal maximum and as slow if it falls below the normal minimum. For men,
these limits lie respectively at 75 and 68 beats in a minute.
(6) Celer or Tardus. — Attention should first be called to the fact that these
terms do not refer to the frequency of the pulse, but solely to the speed with which
the individual waves are developed. Their rise and fall may be quicker or slower
than normal. Pulses of the first type indicate either a relaxed condition of the
vascular system, a quick escape of the arterial blood, or an undue brevity and slight
force of the ventricular contraction. An especially pronounced pulse of this kind
is present in aortic regurgitation, because the incompetency of this valve permits
of a quick escape of arterial blood into the heart. A tardy pulse is obtained
whenever the ventricular discharges encounter a high peripheral resistance.
(c) Magnus or Parvus. — These terms are used to describe the amplitude or
volume of the different pulse-waves. A third term, namely, pulsus inequalis, is
employed to show that the successive waves are unequal in their volume.
(d) Durus or Mollis. — These qualities of the pulse are independent of the
condition of the arterial wall and are indicative of the tension prevailing in the
arterial channels. If an undue force must be employed to compress the artery
sufficiently to cause the disappearance of the pulse, it is characterized as hard.
If it is readily obliterated, it is said to be soft.
(e) Intermittens or Deficiens. — Disturbances in the rhythm of the pulse
result either in consequence of weak contractions of the heart or in consequence of
388 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
an occasional intermittency. If the former, the pulse is characterized as inter-
mittent, and if the latter, as deficient. Clearly, the absence of the pulse in a
peripheral blood-vessel does not signify that it is also absent near the heart or that
the cardiac contractions have ceased altogether.
(/) Intercurrens, Alternans, and Bigeminus. — These types of pulses also indi-
cate a disturbance in the cardiac rhythm. If an occasional wave is forced in
between two regular ones, the pulse is said to be intercurrent. Its cause must
be sought in extra systoles. A true alternating pulse consists of rhythmic waves
of large and small amplitude, this abnormality being usually dependent upon a
degeneration of the myocardium. The prognosis, therefore, is grave. An en-
tirely different significance, however, must be attached to the pseudo-alternating
pulse and the pulsus bigeminus. As these types of pulses are dependent upon
extrasystoles, two waves must necessarily appear at the periphery whenever an
additional contraction results, but the wave produced by the extra contraction
is always smaller than the normal one. In the bigeminus variety the pulse-waves
appear in couplets, i.e., the normal and succeeding extra waves are separated from
the neighboring ones by a definite interval. In the pseudo-alternating pulse, on
the other hand, this separation is not clearly in evidence, because it is caused by
extra systoles of the premature type.
B. THE CARDIAC VARIATIONS IN VENOUS BLOOD PRESSURE
The Physiological Venous Pulse. — The venous entrances to the
heart are not guarded by valves; moreover, while the size of these
orifices is greatly lessened during systole in consequence of the con-
traction of the circular layer of muscle fibers, their complete closure
is not effected. For this reason it cannot surprise us to find that the
auricular pressure is propagated outward into the central veins, where
it influences the venous pressure as well as the flow. Thus, if a water-
manometer is connected with a central vein, the level of the water
immediately exhibits rhythmic fluctuations which occur synchronously
with the contractions of the heart. In addition to these oscillations
it also shows much larger wave-like variations which are dependent
upon the respiratory movements. The finer details of these waves
may be brought out more clearly by registering them with the help
«f a membrane manometer.
The cardiac variations in venous pressure are most manifest near-
the heart and gradually decrease in amplitude in the direction of the
peripheral veins. They are usually absent from the abdominal
portion of the inferior vena cava as well as from the distal end of the
external jugular vein, but their presence in' these channels depends
very largely upon the force of the heart beat and the tension prevailing
throughout the venous system. These changes in pressure give rise to
pulsations which are generally obtained from the external jugular vein
in close proximity to the aperture of the chest. Distally to this point
they are usually so slight that they cannot be properly registered.
Tracings of the venous pulse may also be obtained from the central
veins of animals after the chest has been opened. A receiving and a
recording tambour are commonly employed for this purpose. This
record is known as a phlebogram.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 389
The Speed and Character of the Physiological Venous Pulse. —In
agreement with the low tension prevailing in the venous system, the
physiological venous pulse does not attain a considerable velocity.
Morrow^ states that it is only 1-3 m. in a second. A study of its
general outline shows that it consists of three undulations (Fig. 203).
In accordance with Fredericq,^ the initial elevation (A) is caused by the
contraction of the auricle, the wave of high intra-auricular pressure
being propagated into the veins. The second positive wave (C)
is due to ventricular systole, because the auriculoventricular valves
are forced upward and thus encroach upon the space of the auricles.
The third rise (F) is dependent upon a reflection caused by the rapid
influx of venous blood into the passive auricles. If this explanation
is accepted, and it seems to be the most feasible one, the physiological
venous pulse is to be regarded as the counterpart of the curve of intra-
auricular pressure, the latter being propagated outward into the central
Fig. 203, — Diagrammatic Representation of the Physiol. Venous Pulse from the
Central End of the Ext. Jugular Vein.
A, a- wave; C, c-wave; V, ■y-wave.
venous charxnels through the incompetent caval and pulmonary
orifices. The a-wave is generally the largest, but if it should prove
difficult at any time to differentiate these summits from one another,
it is advisable to identify the c-wave first of all. This is a simple
matter, because it merely involves the determination by auscultation
or palpation of the onset of ventricular systole. For this reason, it is
always safest to record the venous pulse in conjunction with the arterial
pulse or the apex-beat.
In accordance with the view presented by Mackenzie,^ the changes
in intra-auricular pressure should not be regarded as the sole cause
of the venous pulse, because its real character is more directly deter-
mined by the pulsations occurring in the blood current of the neighbor-
ing carotid artery. If we follow the usual custom of designating
the three elevations of the venous pulse as the a, c and v waves, it
becomes evident that:
1. The a-wave is dependent upon the outward propagation of the principal
elevation of the intra-auricular pressure and is caused, therefore, by the contrac-
tion of the auricle.
2. The c-wave is not identical with the second rise in the intra-auricular pressure
caused by the systolic elevation of the auriculoventricular system, but is occa-
sioned by the transfer of the pulse from the neighboring carotid artery.
1 Pfliiger's Archiv, Ixxix, 1900, 442.
2 Centralbl. fiir Physiol., xxii, 1908.
^ Study of the Pulse, London, 1912; also see: Lev/is, Mechanism of the Heart
Beat, London, 1911.
390 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
3. The y-wave appears normally from 0.1 to 0.2 second after the commence-
ment of the a-wave and finds its origin in the pressure changes resulting from
ventricular systole.
In view of the fact that the c-wave appears in the external jugular
vein before the corresponding cardiac impulse has had sufficient time to
make itself felt in the carotid artery, it seems that this explanation of
Mackenzie cannot be correct. In this connection it should also be
remembered that a venous pulse is present in the pulmonary veins,
and that its cause is precisely the same as that producing these pulsa-
tions in the systemic veins. •
The Pathological Venous Pulse. — This phenomenon is most com-
monly associated with an incompetency of the tricuspid valve, but may
also appear in the pulmonary vein in consequence of mitral regurgita-
tion. It may be surmised that this regurgitation of the blood into the
auricle gives rise to a much larger c-wave than the normal upward
movement of the auriculoventricular
'^..'•>. septum could possibly produce. In
fact, a severe insufficiency often in-
creases the amplitude of this wave
so greatly that it completely over-
laps the a-wave. Under this condi-
tion, the phlebogram presents only
Fig. 204.— Diagrammatic Representa- one large initial rise which is followed
TioN OF THB Pai^. Venous Pui^e. ^y ^ ^^^^^^ ^^^^ previously desig-
In tricuspM^regurd^^^^^^^^ ^^^^ ^^ ^^^ ^_^^^^ j, ^^^, ^^
evident that the conspicuousness of
the pathological venous pulse must differ with the severity of the
valvular lesion, a severe regurgitation increasing the radius of these
pulsations so that they may be perceived even in the distalmost veins.
The venous engorgement always accompanying the regurgitation
eventually produces a hyperemic condition of different organs and
preeminently of the Uver. It is then possible to obtain these pulsa-
tions directly from this organ by applying a flat metal cup to the skin
overlying it, but naturally, the minute details of the individual waves
are difficult to record, because the intervening mass of tissue does not
readily transmit the rapid oscillations in pressure. A third type of
venous pulse is observed at times in the veins of glands, but only
when the latter are actively secreting. These pulsations are nothing
more than the arterial pulse propagated through the highly distended
capillaries of the gland.
C. THE RESPIRATORY VARIATIONS IN ARTERIAL AND VENOUS BLOOD
PRESSURE
The General Character of the Respiratory Variations. — Besides
the small cardiac oscillations, the blood pressure also exhibits fluctua-
tions of a much larger amplitude which occur synchronously with the
THE PULSATORY VARIATIONS IN BLOOD PRESSURE
391
respiratory movements. It is to be noted that inspiration produces a
fall in pressure in the veins and a rise in the arteries, whereas expiration
causes an increase in the venous and a fall in the arterial pressure (Fig.
205). These changes are generally associated with an alteration in the
cardiac rhythm, the heart beating more frequently during inspiration.
Moreover, these fluctuations do not begin precisely with the onset of
the respiratory movements, but somewhat later, the intervening period
being about 0.2 second in duration. It happens, therefore, that the
arterial rise is always continued for a brief period of time after the be-
ginning of the expiratory motion, while the fall is prolonged right into
the succeeding inspiratory phase.
The Cause of the Respiratory Variations. — After the first breath
has been taken, the lungs are held in a continuous state of hyperdisten-
tion. The elastic fibers contained in them are put on the stretch and
must therefore always attempt to recoil. This enables these organs to
exert an elastic pull upon the chest wall as well as upon the contents of
A?\
Fig. 205. — Diagrammatic Representation of tee Respiratory Variations in ARTERiAii
{AP) AND Venous Pressure (VP).
JE, inspiration; EJ, expiration. It is to be noted that the variations in pressure
lag behind the onset of the respiratory movement; this interval {JB) being especially
evident in the case of the arterial pressure.
the thoracic cavity, which is betrayed, on the one hand, by a nega-
tivity in the intrapleural pressure ( — 6 to —9 mm. Hg) and, on the
other, by the low degrees of pressure existing in the central venous
system (--5 to —15 mm. Hg). The blood-vessels situated outside
the thorax are exposed to positive pressures, and hence, it cannot
surprise us to find that the blood in the intrathoracic vessels is con-
stantly exposed to this aspiratbry force. But inasmuch as the ar-
teries are relatively resistant and unyielding, they are not so severely
affected as the veins.
It must be granted, therefore, that the negative pressure in^ the
thorax favors the venous return. Moreover, as the elastic pull upon
the venous trunks is greater during inspiration than during expiration,
the inspiratory movement must be the more effective of the two. For
this reason, it is only natural to assume that the venous pressure is
decreased during inspiration and increased during expiration. It
may be inferred that these changes in pressure influence the flow in
392 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
such a way that a greater quantity of blood is drawn into the central
venous channels during inspiration than during expiration. Conse-
quently, as the heart receives more blood during the former period, it
is in apposition to pump more blood into the arteries.^ This explains
the inspiratory rise in arterial pressure. This mechanical explanation
of the respiratory variations finds support in the following conditions:
(a) It has already been stated that the heart increases its frequency during
inspiration. This phenomenon may be explained in two ways. Thus, it may be
assumed that it is a reflex elicited within the heart in consequence of the influx
of a greater quantity of blood, or that it is due to accelerator impulses generated
by the cardiac center. The latter explanation has been submitted by Fredericq,
who has found that this acceleration takes place even after the mechanical in-
fluence of respiration upon the heart has been removed by opening the chest.
The fact that the division of the vagi nerves destroys the acceleration immediately
proves that this system is directly concerned with the production of this phe-
nomenon. It is also interesting to note that this acceleration is more marked in
persons whose nervous system is in a state of hyperirritability.
(6) The transfer of blood from the right into the left side of the heart is greatly
facilitated by inspiration, because this movement permits of a greater distention
of the pulmonary blood-vessels, thereby lessening the resistance in this circuit.
During expiration, on the other hand, the elastic pull upon these vessels is dimin-
ished and the resistance within them increased.
(c) The inspiratory descent of the diaphragm favors the venous return from
the abdominal organs, because it tends to increase the pressure in the abdominal
cavity and to lessen the resistance in the thorax. ^
(d) The fact that these changes may be rendered more conspicuous by in-
creasing the amplitude of the respiratory movements is another point in favor
of this explanation. Last of all, it should be taken into account that these varia-
tions are completely reversed during artificial respiration.^ This need not cause
surprise, because the artificial inflation of the lungs induces conditions practically
the reverse of those prevailing durin| normal respiration, when this organ is ex-
panded by a force resting upon its external surface. As the air is forced into the
pulmonary passage, the capillaries of the lungs are subjected to a certain pressure
which tends to increase the resistance within them. This implies that the venous
pressure is increased during the period of inflation, whereas the influx of blood is
diminished. The deflation of the lungs, on the other hand, relieves this com-
pression of the pulmonary capillaries and permits a more unhindered through-
flow in consequence of the diminution in the resistance.
As has been emphasized by Wiggers,* the respiratory variations in
blood pressure may be explained without difficulty upon the basis of
the circulatory changes in the lesser circuit just enumerated. Lewis,^
on the other hand, believes that the respiratory motions affect the
heart in a direct way, and that the effect upon the arterial blood
pressure varies with the type of respiration. Thus, diaphragmatic res-
piration is said to give an inspiratory rise and expiratory fall in ar-
terial pressure, while a pronounced costal movement induces an inspira-
tory fall and expiratory rise. This result, however, is easily explained
1 Burton-Opitz, Am. Jour, of Physiol, vii, 1902, 435.
2 Burton-Opitz, ibid., xxxv, 1914, 64.
3 Burton-Opitz, ibid., ix, 1903, 198.
* Ibid., xxxv, 1914.
6 Ibid., xvi, 1906.
THE PULSATORY VARIATIONS IN BLOOD PRESSURE 393
in another way, because Henderson^ has shown that the exposure of
the heart to a direct pressure of this kind hinders the normal filhng
power of this organ and hence, also the flow through the lungs. Cer-
tain discrepancies have also been found by Erlanger and Festerling,^
as well as by Snyder, ^ but as a more satisfactory explanation of this
phenomenon has not been submitted, it seems bjest to adhere to the
analysis previously given.
The Traube-Hering curves are rhythmic fluctuations in pressure,
each of which always embraces a number of respiratory variations.''
They are long, but do not attain a significant height. Their con-
FiG. 206. — Traube-Hering Curves.
The time is given in seconds. The smallest pulsations represent the cardiac varia-
tions, those of intermediate size the respiratory variations, and the large waves the
Traube-Hering variations.
spicuousness, however, may be increased by curarization, anemia of
the bulbar centers and asphyxia. They are commonly ascribed to
irradiations of impulses from the excited respiratory center to the
vasomotor center.
Waves of similar character are frequently observed in normal
animals and especially in those narcotized with morphin. They are
known as the Mayer curves and find their origin in a hyperirritable
condition of the vasomotor center. This hyperirritability arises in
consequence of bulbar anemia, an increased venosity of the blood,
irritations of the central nervous system and the administration of
certain drugs, such as digitalis and strophanthus.
^ Jour, of Physiol., xxxvii, 1908.
2 Jour, of Exp. Med., xv, 1912.
' Am. Jour, of Physiol., xxxvi, 1915.
* Traube, Zentralblatt fur die med. Wissensch., iii, 1865, 882.
394 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
CHAPTER XXXIII
THE BLOOD FLOW
The Volume of the Blood Stream. — If the arterial system were com-
posed of a number of rigid tubes, each ventricular output would be
forced through this system in the form of a uniform column which
would come to a standstill at some distance from the heart. But as the
vascular system is elastic, and is kept in a state of hyperfilling by an
appropriate peripheral resistance, the different ventricular discharges
must be retained temporarily near the outlet of the heart, their
retention being made possible by an enlargement of the main distribut-
ing tube, the aorta. The elastic recoil immediately following this
distention, then forces a portion of this blood into the more peripheral
segment and from here into the adjoining one, and so on until the periph-
ery has been reached. In this way, the conditions incited by the
ventricular discharge are repeated again and again and are thus
propagated throughout the arterial system. Moreover, as the blood-
bed of the aorta is larger than that of its branches put together,
this blood-vessel, and especially its ascending and transverse portions,
serve the purpose of an elastic reservoir from which all the peripheral
blood-vessels are supplied.
Soon after its emergence from the heart, th% blood enters the differ-
ent branches of the aortic system and is distributed to the various
tissues and organs in amounts commensurate with their activity. In
close proximity to the heart, the flow very nearly equals the ventricular
output, only that amount of blood having been removed from it which
is destined to nourish the cardiac musculature. Farther distally, how-
ever, the reduction becomes more apparent, because a considerable
quantity of blood is now diverted into the blood-vessels of the head
and anterior extremities. In endeavoring to obtain an idea regarding ]
the volume of the blood stream in any particular artery, it is not
sufficient to collect the blood escaping from the opened blood-vessel in
a graduated cylinder, because the removal of the peripheral resistance
seriously disturbs normal dynamical conditions. With a closed
vascular system, two procedures are practicable which may be desig-
nated respectively as the direct and the indirect.
The direct method consists in connecting the artery with an instrument known
as a current-measurer or stromuhr. The one described by Ludwig^ is composed
of two glass bulbs (A and B) which are placed upon a metal disc (P) and may be
rotated around a common vertical axis (Fig. 207). In this way, it is possible to
^ Stolnikow, Archiv fiir Anat. und Physiol., 1886. This instrument has been
modified by Tigerstedt, Skand. Archiv fiir Physiol., iii, 1891.
THE BLOOD FLOW
395
bring the bulbs successively into communication with the cannula inserted in
the central end of the artery (C). To begin with, one of the bulbs is filled
with normal saline solution and the other with oil. The latter is first turned
toward the inflow tube (C). On permitting the blood to flow into this instrument
by removing the clip temporarily placed upon the central end of the artery, the
oil is forced upward and through the con-
necting tube into the limb containing the
saline solution. When the latter has been
completely driven into the peripheral end
of the artery, the bulbs are quickly re-
versed so that the oil is again brought
into direct communication with the influx,
while the blood is forced into distant ar-
terial channels. In order to obtain the
volume of the blood stream it is necessary
to record the number of revolutions of
the stromuhr in conjunction with the
time. Thus, if the capacity of the bulb
is 5 c.c. and it has been filled 12 times in
the course of one minute, then 60 c.c. of
blood have passed this point of the artery
in the course of this period.
Much more serviceable instruments
for the calibration of the blood stream
have been devised by Hiirthle^ and Bur-
ton-Opitz.2 Both types of instruments
contain a piston which moves within a
cylinder and records its excursions upon
the paper of a kymograph. For this
reason, they are known as recording stro-
muhrs. The cylinder of the instrument
described by Burton-Opitz is adjusted
horizontally at the level of the blood-
vessel, while the resistance of the piston is
minimized by counterpoising (Fig. 208).
By means of a double U-shaped valve
with which the central and peripheral
segments of the blood-vessel are con-
nected, the blood may be diverted either
into the compartment to the left or to
the right of the piston. The piston is
thus forced to move successively from
left to right, and from right to left, its
movements being recorded upon the kymo-
graph by means of a lever and connecting
string. This instrument having been
properly calibrated, the quantity of blood
which has traversed it may be read off
directly from the paper. Naturally, the
insertion of the stromuhr necessitates a
temporary interruption of the blood flow
in this vessel, but unless unduly prolonged,
normal conditions are generally reestablished within a few moments after the re-
moval of the clips. As the instrument is filled with normal saline solution, and as
.1 Pfliiger's Archiv, xcvii, 1903, 193.
2 Ibid., cxxi, 1908, 150. Ishikawa and Starling have described a current
measurer of which a siphon forms the essential part.
Fig. 207. — Ludwig's Stromuhr.
a, Is filled with oil to tRe mark (c.c),
while b and the neck are filled with salt
solution or defibrinated blood; p, the
movable plate by means of which the
bulbs may be turned through 180 de-
grees; cc, for the cannulas inserted into
the artery; s, the thumb screw for turn-
ing the bulbs; h, the holder. When in
place the clamps on the arteries are re-
moved, blood flows through c into a,
driving out the oil arid forcing the salt
solution in b into the head end of the
artery through c'. When the blood en-
tering o reaches the mark, the bulbs are
turned through 180 degrees so that b lies
over c. The blood flows into b and
drives the oil back into a. When it just
fills this bulb, they are again rotated
through 180 degrees, and so on. (Howell.)
396 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
the blood entering it is always returned into the vascular system by way of its
distal cannula, the volume of the circulating blood must remain the same. All
in all, it seems fair to state that the objections which may be raised against the
use of this instrument (Starling) are in no way more valid than those raised
against the employment of manometers or physiological apparatus of a similar
kind.i
Bii
ii X'-.. /v^ iii ••/' .J
FiQ. 208. — Diagram of Recordino Stromuhr.
C, cylinder; K, piston; F, piston-rod; AR and AR, tubes for influx of blood; A»
double U-shaped valve connected with blood-vessel at B and B'; D\ and Di, positions
occupied by valve when blood is directed either into the left or right side of the cylinder;
Ro, Sf, H and St, apparatus required for registering the excursions of the piston upon
the paper of the kymograph.
An idea regarding the volume of the blood flow may be obtained from the
accompanying table which embraces the results of a series of experiments made
by Burton-Opitz^ and Tschuewsky.' The values here given are calculated for
a dog weighing about 15 kg. :
^ An optical stromuhr has been described by Hiirthle in Pfliiger's Archiv,
cxlvii, 1912, 509.
2 Pfliiger's Archiv, cxxix, 1909, 189, and Quart. Jour, of Exp. Physiol., vii,
1913, 57.
»Ibid.,xcvii, 1903, 214.
THE BLOOD FLOW
397
Carotid artery. . .
Femoral artery . . ,
Hepatic artery . . .
Thyroid artery . . .
Ext. jugular vein.
Renal vein
Mesenteric vein . .
Splenic vein
Portal vein
Femoral vein
in a second
cc. in a minute
2.53
150
0.87
52
2.39
143
0.37
22
2.40
144
1.64
98
2.74 '
164
0.95
57
4.56
273
0.85
51
The indirect method of measuring the blood flow embraces several different
procedures, namely, the calorimetric, plethysmographic, and the gas-analytical.
The calorimetric method devised by Stewart^ arrives at the quantity of blood
traversing a part, by measuring the amount of heat liberated by it in a certain
Fig. 209. — Calorimetric Method of Measuring Blood-flow in Hands. (From
Stewart's "A Manual of Physiology ," William Wood and Co., Publishers.)
period of time and by ascertaining the difference in the temperatures between
the inflowing and outflowing blood. This method is applicable to the human being.
Having established the basal temperature by immersing the hands or feet for some
time in water, the temperature of which is one or two degrees below that of the
arterial blood, they are rapidly transferred to a calorimeter filled with water of the
same temperature. As the parts are kept motionless, the heat given off by them
while in this compartment, must be derived chiefly from the blood passing through
them. The temperature of the arterial blood at the wrist was found to be lower
by 0.5° C. than that of the rectum, while the venous blood exhibited a temperature
* Cleveland Med. Jour., x, 1911, and Heart, iii, 1911.
398 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
only a fraction of a degree above that of the water in which the parts were immersed.
The flow is calculated in grammes per minute in accordance with the formula :
Q
H
1
M{T - T') S
Q being the quantity of blood, H the number of small calories given off in Af
minutes, T the temperature of the entering blood, T' the temperature of the out-
flowing blood, and S the specific heat of the blood. The volume of the hands or
Fig. 210. — Kidney Oncometer.
I, the kidney is placed into the oncometer consisting of two hemispherical parts,
connected with a recording tambour (T). II, the sides of this oncometer are lined with
rubber membrane, the space between the membrane and the metal wall being filled with
water of 37° C. The upper bag is connected with a recording tambour.
feet is measured by permitting them to displace an equal quantity of water from a
graduated receptacle. The bloodflow is expressed in grammes per 100 c.c. of
tissue per minute.
These tests upon the hands of normal individuals have given the average value
of 5.5 grammes of blood per 100 c.c. of hand- volume in a minute, but naturally,
this figure is subject to considerable variations, because the vascularity of a part
may be changed at any time either by influences brought to bear upon it directly, or,
Fig. 211. — Diagram of Schafbe's Air Plethysmograph (Spuenic Oncometer).
P, box for insertion of spleen; R, piston-recorder; L, writing lever.
in an indirect way, by reactions occurring in other regions of the body. In a robust
young man the average flow amounted to 12.8 grammes per 100 c.c. of hand per
minute for the right hand and to 12.3 grammes for the left. In the foot, the
flow per unit of volume of the part is smaller than in the hand. In the forearm the
flow is much less than in the hand (Hewlett).
The blood supply of an organ may also be determined in an approximate way
THE BLOOD FLOW
399
by the plethysmographic method.^ The part to be experimented upon is enclosed
in a rigid capsule, known as a plethysmograph, which is then connected with a
volume recorder or an ordinary tambour. The shape of this instrument, however,
must necessarily be changed to suit
the anatomical peculiarities of the
organ. We have so far been placed in
possession of plethysm ©graphs for the
kidney, spleen, heart, lung, liver, brain
and the anterior and posterior extremi-
ties. Special names have been given
to these; the one for the heart being
designated as a cardiometer, and the
one for the kidney as a kidney
oncometer, in contradistinction, for
example, to the splenic and hepatic
oncometers.
The principle of plethysmography
may be illustrated with the help of the
cranial cavity. If the skull is trephined, and the trephine-opening connected with
a recording drum, the variations in the volume of the brain coincident with the
various bodily activities, may be accurately followed upon the paper of a kymo-
graph. ^ This same procedure may be practised upon any other organ provided, of
t
Fig. 212. — Brodie's Recordek.
A, rubber pouch; R, is placed between
two plates A and B;the latter is equipped
with a writing lever.
FiQ. 213. — A Schematic Diagram of Mosso's Plethysmograph for the Arms
a, The glass cylinder for the arm, with rubber sleeve and two openings for filling
with warm water; s, the spiral spring supporting the test tube, t. The spring is so cali-
brated that the level of the liquid in the test tube above the arm lemains unchanged as
the tube is filled or emptied. The movements of the tube are recorded on a drum by
the writing point, p. (Howell.)
course, that its shape and position permit of its being enveloped by a rigid capsule.
Air transmission or fluid transmission may be employed, and the organ may be
1 For a full description, see : Francois-Frank, in Marey's Traveaux du Labora-
toire, 1876.
2 Suggested by Hallion and Comte, Arch, de Phys. norm, et pathoL, 1894.
400 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
exposed to the medium directly, as in Mosso's instrument, '^ or may first be
surrounded by an envelope of soft rubber (Fig. 210). The changes in volume which
the organ undergoes may be recorded by means of an ordinary U-shaped manom-
eter filled with water, or with the help of tambours of the type designed by Marey
and Hiirthle, and the piston-recorders constructed in accordance with the suggestions
of Roy, 2 Ellis, 3 Schafer,* Hiirthle,^ and Lombard.* A very convenient and prac-
tical recorder has been described by Brodie,^ the essential constituent of which is
a pair of bellows made of thinnest rubber and equipped with a delicate writing
lever. A plethysmograph, which is frequently made use of in the laboratory, is the
one designed for the reception of the hand and forearm (Figs. 213and214). Itcon-
sists of a cylindrical chamber of glass which is filled with warm water through two
openings in its upper wall. The space around the arm is made air-tight by a cuff of
Fig. 214. — Detailed Drawing of the Glass Plethysmograph with Rubber Glove to
Prevent Escape op Water,
2, The glove with its gauntlet reflected over the end of the glass cylinder; 1 and 3,
supporting pieces of stout rubber tubing; D and E, sections ol outer and inner rings of
hard rubber to fasten the reflected rubber tubing and reduce the opening for the arm.
(Hoxvell.)
rubber membrane which is adjusted in such a way that it does not compress the
blood-vessels of this locality. The small orifice in the far end of this cylinder is
connected with the recording instrument. This arrangement allows any change
in the volume of the arm to cause a corresponding displacement of the water which
in turn varies the level of the recording lever.
The uses to which this instrument may be put are very manifold. It has been
stated above that the cardiometer may be employed to determine the volume
of the output of the heart by obtaining the differences in the volume-curve of this
organ during systole and diastole. In a similar way the attempt has been made by
Brodie to measure the blood supply of the kidney by temporarily blocking its
venous return and recording the increase in volume occurring at this time. The
^ Diagnostik des Pulses, Leipzig, 1879.
2 Jour, of Physiol., iii, 1880, 203.
3 Ibid., vii, 1886, 309.
< Ibid., XX, 1896, 1.
fi Pfluger's Archiv, liii, 1893.
6 Am. Jour, of Physiol., iii, 1890.
' Jour, of Physiol., xxvii, 1902. A very simple method of registration has been
described by O. Miiller (Archiv fiir Anat. und Physiol., 1904, Suppl.).
THE BLOOD FLOW 401
supposition in determinations of this kind is that the venous drainage balances the
arterial influx and that an increase or decrease in the volume of an organ may be
taken as a measure of its vascularity. This inference may be a safe one to make
when dealing with passive and compact organs, but may lead to errors if the part
experimented upon is soft in texture and embraces varying amounts of active
tissue elements. The plethysmograph has also been employed for the registration
of those changes in the volume of parts which occur in consequence of the activity
of the heart or respiration, and also in consequence of different experimental
procedures. In all these cases it is assumed that the alterations in the volume
of a part are dependent upon displacements of fluid and are therefore directly
attributable to changes in its blood supply. When a study is made of the volume-
curve of the arm it will be seen to be made up of smaller and larger oscillations,
the first of which occur synchronously with the action of the heart, and the second,
with the respiralory motions. This means that the systolic discharge of the heart
increases the vascularity of this part momentarily and that a similar increase
takes place throughout inspiration. A most striking demonstration of these
Fig. 215. — Plethysmographic Curve of Forearm.
Showing the cardiac and respiratory variations in the volume of the arm. The
decided decrease in its volume observed here is due to mental activity; hence, to a
transfer of blood from the cutaneous circuits into that of the cerebrum. {Howell.)
changes may be had by observing the surface of the brain through a rather small
trephine opening which contains a small quantity of v/armed saline solution.
The level of the solution will be seen to rise with every systole and to fluctuate in
larger waves with every respiration.
When taken with a fairly sensitive apparatus., the general appearance of the
volume-curve of a part presents practically the same details as a tracing of the
blood pressure. It displays not only the cardiac and respiratory oscillations, but
also Traube-Hering waves and all those variations which are dependent upon more
lasting increases or decreases in the blood supply. In this way, for example, it has
been demonstrated by Mosso that the vascularity of the brain is diminished during
sleep, because the intracranial blood is transferred during this period into other
circuits of the body.
The chemical method which has been introduced by Bornstein^ is founded upon
the principle that the volume of blood passing through the lungs of a man may
be obtained by calculation from the quantity of nitrogen absorbed by the blood.
This value is derived from the tension difference of this gas in the alveolar air and
the blood. Zuntz and his co-workers, ^ as well as Krogh and Lindhard,^ employed
1 Pfliiger's Archiv, xxxii, 1900.
2 Zeitschr. fiir Balneologie, iv, 1912.
3 Skand. Archiv fiir Physiol., xxvii, 1912, 100.
26
402 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
nitrous Oxid instead of nitrogen . A similar procedure has been followed by Boothby ^
who has determined the minute-volume of the pulmonary blood stream of man dur-
ing rest and muscular exercise. These experiments have shown that the total blood
flow through the lungs amounts to more than 3 liters in a minute, and hence, about
60 c.c. of blood must be discharged by each systole of the heart. But this figure
may be varied somewhat by changes in posture, muscular work, and a more thor-
ough ventilation of the lungs and consumption of oxygen.
The Velocity of the Blood Flow. — We have seen that the main pur-
pose of the circulation is to supply the different colonies of cells with
nutritive material and to remove from them all those substances which
are of no further use to them. This interchange occurs in the capil-
laries, where the blood and the body-fluid are separated from one
another by only a very thin layer of cells. These tubules, therefore,
are of much greater metabolic value than the arteries and veins. The
latter merely play the part of supply channels.
The systemic and pulmonary circuits arise from single tubes, the
repeated division and subdivision of which eventually gives rise to an
intricate network of the finest pos-
sible tubules, the capillaries (Fig.
216). The gradual reunion of
these in turn leads to the forma-
tion of large collecting channels
which are finally united in a com-
mon reservoir, the auricles. It
should be remembered, however,
that the total cross- section of the
vascular system increases con-
j ^ ^ stantly in the direction of the capil-
Fio. 216.-Diagr1m to' Illustrate Varies, but diminishes again distally
THE Changes in the Cross-section of to these, and the more SO the closer
THE Vascular System. ^^ approach the heart. The
^' ^'''''''±^:VL^^^'^'''' ""' s^^llest blood-beds, therefore, are
found at the aorta and at the venae
cavae. The latter, however, is somewhat larger than the former.
Their peripheral ramifications put together represent a blood-bed
which is very much larger than that of either the arteries or veins.
As has just been stated, the blood-bed again decreases in size on the
other side of the capillaries, because while the sectional areas of the
different single veins increase constantly as they unite into larger
channels, their combined area becomes less. Consequently, the size
of the vascular system at the venae cavae is almost as small as that at
the aorta. It is also of interest to note that the blood-bed of the
aorta is somewhat larger than that of all the arteries combined, which
fact again tends to show that the aorta serves as the elastic reser-
voir of the circulatory system.
As far as the velocity of the blood flow is concerned, the preceding
statements must show immediately that the speed of flow is greatest
1 Am. Jour, of Physiol., xxxvii, 1915, 383.
THE BLOOD FLOW 403
in the arteries, least in the capillaries, and intermediate in the veins.
(Fig. 217). These changes in the flow, as we shall see later, are in no
way different from those displayed by water while traversing a tube
of varying diameter. Provided, therefore, that the quantity of the
circulating blood remains the same, its speed of flow must be inversely
proportional to the size of the blood-bed. It has been stated that the
cross-area of the capillaries is from 600 to 800 times larger than that
of the aorta. Thus, Tigerstedt estimates the capillary expanse of
man at 800 to 2200 sq. cm., while Nikolai, upon the basis of a ventricu-
lar output of 75 C.C., gives the value of 1500 sq. cm. It need not
surprise us, therefore, to find that a most profound reduction in the
speed of the blood flow results as soon as the capillaries have been
reached.
In the second place, the velocity of the flow in any tube is dependent
upon the friction to which the constituents of the fluid are exposed.
s
y" —
A ''*...
f
\ ..'••"
'•,
/
\ .•'
'••
/
7.
/ y
/
-^
^"^^^
/
•^
•
'\
/
_ •
»,
/
B.^- ^
':
• •'
Fig. 217. — Diagram to Illustrate the Relationship Between the Size of the
Blood-bed and the Velocity of the Flow.
B, cross-section; S, speed of flow in {A) arteries; C, capillaries and (F) veins; Z„
zero line.
Thus, we recognize two types of friction, namely the one produced by
the fluid in coming in contact with the wall of the tube and the one
produced by its molecular constituents when thrown against one
another. The former is called ''external" friction and the latter "in-
ternal" friction or viscosity. For this reason, the blood does not speed
onward as a uniform column, but is separated into layers, the outer-
most of which remains stationary, while the central one, forming the
core of the stream, moves ahead with the greatest possible speed. The
red corpuscles and heavier elements are thus forced into the central
stream, while the lateral zone is filled chiefly with plasma. Hence, in
attempting to determine the speed of the blood flow under the micro-
scope, we reaUy measure the rate of progression of the cellular elements
in the axial stream. If these could be removed, the speed of the
plasma-blood would thereby be much augmented. Obviously, there-
fore, the solids tend to retard the flow, because they heighten the in-
ternal and external frictions.
If these two factors are now united under the general term of
peripheral resistance, the further conclusion may be drawn that, every-
404 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
thing else remaining equal, the speed of flow must be least in that di-
vision of the circulatory system in which the greatest resistance is
encountered. It has previously been shown that the friction is greatest
in the capillaries, and hence, it may be gathered that these tubules
place the greatest resistance in the path of the circulating blood.
A few figures may suffice to illustrate this point. Some of the capil-
laries are so small that the red cells cannot enter them at all, while
those which possess a diameter of 5-7 ju, permit their passage only after
they have been compressed into a shape approaching the elliptical.
The larger capillaries, measuring 14/i and over in diameter, allow several
erythrocytes to pass side by side. The average length of these tubules
has been estimated by Tigerstedt at 0.02 cm. Moreover, if the
average cross-section of a capillary is 7.5)u^, a capillary area of 1500
sq. cm. would embrace two billion capillaries, placed side by side.
Ordinarily, of course, the capillaries recur at distances of less than
0.02 cm.
In the arterial channels, on the other hand, the blood encounters
only a relatively slight resistance, so that it is able to retain practically
the entire pressure developed by the heart until it arrives in the arteri-
oles. The blood rushes through these vessels , with a considerable
speed, but its function is in no way curtailed thereby, because a direct
interchange between it and the neighboring cells does not take place
until the capillaries proper have been reached. Here radically different
conditions are met with. Since the walls of these tubules consist of a
single layer of elongated and flattened cells which are only slightly
thickened in the regions of the nuclei, the tissues are brought into al-
most immediate relationship with the blood. The latter, moreover,
moves past these cells with the slowest possible speed. This is im-
portant, because it is essential that a sufficient time be allowed for the
interchange of material between the blood and the lymph bathing the
tissue-cells. In the veins, practically the same conditions prevail as
in the arteries. The nutritive interchanges having been completed
in the capillaries, the blood again rushes onward at a much greater
speed, without, however, at all equaling that of the arterial stream.
The Determination of the Velocity of the Blood flow. — As the
dynamical conditions in the different segments of the vascular system
differ considerably, it is quite impossible to employ the same method in
all cases. Volkmann (1850) has succeeded in obtaining approximate
values for the speed of the arterial flow in the following way: A U-
shaped glass tube of definite length and caliber is connected with the
artery in such a way that the blood may be made to pass either through
it or through a much shorter tube situated in the base of this instru-
ment (Fig. 218). To begin with, the tubes of this instrument which is
known as a hemodromometer, are filled with normal saline solution which
is then forced into the circulation by the entering blood. The length
of the U-tube being known, the speed of flow may be determined with-
THE BLOOD FLOW
405
out difficulty by simply noting the time when the blood enters and
leaves its orifices.
Instruments embodying the principle of PitoVs tubes have been
designed by Cybulski.^ Two tubes {d and d') which have been bent
at right angles, are inserted in the blood-vessel in such a way that the
orifice of one points in the direction of the bload stream and that of
the other against it (Fig. 219). The level of the saline solution with
which they have previously been filled will then rise in the latter and
^cS
I -^ I
u> or
m^^m^::^^
E\ C
© ®
Fig. 219.
Fig. 218.
Fig. 218. — Volkmann's Hemodromometer.
A and B, cannulas for connecting the central and distal ends of the blood-vessel with
this instrument. C, short cut through base of instrument; D, U-shaped tube of definite
length. The blood may be diverted into the latter at any moment by turning the valves
E and F.
Fig. 219. — Diagram to Show the Principle of the Cybulski Photo-hem otacho-
METER.
fall in the former. The push (d) and the pull (d') which the moving
blood exerts upon them must, of course, be directly proportional to
the speed of the flow. It need scarcely be mentioned that these varia-
tions in the levels of the Hquid {h and h') may be recorded either by
means of ordinary tambours connected with the ends of these tubes,
or by means of a beam of reflected light.
The hemotachometer, devised by Chauveau and Lortet,^ is another
instrument of this type. It consists of a T-tube made of metal, in
which a very delicate pendulum is suspended (Fig. 220). The short
arm of the latter projects into the blood stream, while its long arm
1 Pfiiiger's Archiv, xxxvii, 1885, 382.
2 jour^ de la Physiol., iii, 1860, 695.
406 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
rests upon a millimeter scale. As the blood strikes its lower end, it is
deflected in the direction of the current, its degree of deflection being
clearly marked upon the scale. Naturally, this apparatus is first
graduated with currents of water of known velocity. It can also be
made to register its deflection by simply attaching the long arm of the
pendulum to the membrane of a tambour.
The speed of the flow in the arteries and veins may also be de-
termined with the help of the stromuhr which, as has been stated above,
measures the quantity of blood traversing a
blood-vessel in a given period of time. This
calculation, however, also necessitates the de-
termination of the internal diameter of this
vessel. Burton-Opitz^ and Tschuewsky^ have
made use of the following simple procedure
in obtaining this value. Having ascertained
the external diameter by means of calipers,
the blood-vessel was gently compressed be-
tween two thin platelets of glass until it be-
came empty. The thickness of the platelets
and vessel wall was then subtracted from
the external diameter, and in addition also
the thickness of the platelets. The fact that
the speed in the arteries is astonishingly
great has been brought out by the experi-
ments of Volkmann, Dogiel and Chauveau.
The maximal speed in the carotid artery of the
dog is given as 500 mm. in a second during
systole and as 250 mm. during diastole. In
the horse, the speed varies between 520 mm.
and 150 mm. in a second, and naturally, these
systoHc-diastolic differences are most evident
in the arteries in the immediate vicinity of
the heart. In the smaller arteries the flow is
quite constant. The same holds true of the
capillary flow although it may be rendered
remittent at any time by producing a slight obstruction centrally to
the capillary area. Burton-Opitz and Tschuewsky have furnished
the following average values:
Carotid artery 241,0 mm. in a second
Femoral artery 234 . 4 mm. in a second
Hepatic artery 350. 0 mm. in a second
In general, therefore, it may be said that the velocity of the blood
flow in the peripheral arteries amounts to 250-300 mm. in a second.
It decreases somewhat in the smaller arteries, reaching its minimum
1 Am. Jour, of Physiol., vii, 1902, 435.
2 pfliiger's Archiv, xcvii, 1903, 286.
Fig. 220.— The Hemo-
DROMOGRAPH OF ChAUVEAU
AND LORTET.
B, blood-vessel. The
end of the pendulum (P)
is played against by the
blood, its deflection being
registered by the receiving
drum (T) which in turn is
connected with a recording
tambour (Jf^). The pendu-
lum is contained in a cannula
(M)..
THE BLOOD FLOW 407
value at the arteriocapillary junction. On the venous side, such
high values are not encountered under ordinary conditions. Thus, if
the accompanying determinations of Burton-Opitz^ are used as a
guide, it must be concluded that the speed of the venous blood is only
about one-fourth as great as that of the arterial, viz. :
Ext. jugular vein 80. 0 mm. in a second
Renal vein 63 . 0 mm. in a second
Mesenteric vein 83 . 6 mm. in a second
Femoral vein 61.6 mm. in a second
It is slowest in the vicinity of the capillaries and fastest in the central
veins; moreover, when the blood reaches the neighborhood of the
heart, it is brought under the influence of the right auricle and shows
alterations in flow similar to those encountered in the central arterial
trunks. Thus, it has been proved by Burton-Opitz^ that the influx
into the right auricle is not constant, but is diminished during the
periods of high intra-auricular pressure, z.e., during the systole
of the auricles and again during the systole of the ventricles. It
may be surmised that the heart influences the current in the pulmonary
veins in a very similar manner.
The capillaries, of course, are not accessible to any one of the
instruments described previously. In the frog, however, fairly
accurate results may be obtained by placing a translucent capillary
area, such as the web or mesentery, under the microscope in such a
way that a rather straight capillary comes to lie directly across the
divisions of an ocular micrometer. The time is then determined
when a certain erythrocyte enters and leaves this capillary. The
length of this tubule is ascertained later on by determining the mag-
nification, which requires a comparison of the ocular micrometer with
the stage micrometer. By this procedure Weber^ and Volkmann*
have found the velocity of the capillary blood stream to be 0.5 to 0.8
mm. in a second.
Vierordt^ has also described a method which is applicable to man
and depends upon the following entoptic observation. As the red
cells traverse the retinal blood-vessels they cast their shadows upon
the underlying rods and cones. The visual sensations set up by the
latter may be rendered clearly perceptible in an indirect manner by
fixedly gazing at a white surface placed at a distance of 11-16 cm.
in front of the eyes. Having first determined the speed of the pro-
jected shadows upon the screen, the speed of the red cells in the retinal
vessels may be ascertained in accordance with the proportion :
7 be
a :b = c:x:x = —
1 Pfluger's Archiv, cxxiv, 1908, 469.
2 Am. Jour, of Physiol., vii, 1902, 435.
3 Archiv fiir Anat. und Physiol., 1838, 450.
* Haemodynamik, 1850.
^ Archiv fiir physiol. Heilkunde, xv, 1856.
408 THE MECHANICS OF THE CIRSULATION, HEMODYNAMICS
in which a stands for the distance between the screen and the anterior
nodal point, h for the distance between the retina and the posterior
nodal point, and c for the distance traversed by the projected image.
Values between 0.6 and 0.9 mm. in a second have been found by this
method. If it is now remembered that the length of the true capil-
laries varies between 0.4 and 0.7 mm., the general conclusion may be
drawn that a red cell traverses a capillary of average length in about
1 second.
The Circulation Observed under the Microscope. — The study of
the blood flow was made possible at an early date by the discovery of
the microscope. To begin with, cold-blooded animals were employed,
partly because their tissues are more accessible and resistant, and
partly because their erythrocytes are much larger than those found
in warm-blooded animals. These observations may be arranged in the
following chronological order :
Malpighi (1686): Lung, mesentery, urinary bladder of the frog.
Leeuwenhoek (1689) : Tail of the tadpole and fish, wing of the bat.
Cowper (1704) : Mesentery of the rabbit.
Spallanzani (1773): Embryo of the chick.
Hueter (1879) : Mucous membra,ne of man.
Ewald (1896): Lung of the triton.
When a capillary area is subjected to a magnification of about 15
diameters, it will be seen that many of its tubules are extremely
small and do not permit the passage of anything more than the plasma
and occasional white cells. Others, again, possess a somewhat larger
caliber arid allow two or three red cells placed side by side to traverse
them. The most interesting picture, however, is presented in those
tubules which are just sufficiently large to permit the entrance of
single erythrocytes, so that it becomes possible to follow them as they
wend their way in single file through these circuitous passages. In
fact, in many cases these elements must be considerably elongated
before they can enter these tubules. They may be thrown across a
bifurcation and be rocked back and forth for some moments before they
manage to escape into one or the other of these branches. The latter
phenomenon, in particular, permits us to obtain a clear idea regarding
the elastic properties of these elements, as well as regarding the friction
and resistance which they must overcome in their journey through
these tubules.
In general, it may be said that the principal characteristics of the
capillary flow are its slowness and constancy. The arterial capillaries
and arterioles are much larger than the capillaries proper and are,
therefore, able to accommodate a much greater number of red cells.
Furthermore, as the speed of flow within them is much greater, it is
difficult to distinguish the individual cells. The venous capillaries
and venules show essentially the same characteristics, but as the flow
within them is not so rapid, the different red cells may be more easily
differentiated from one another. On the arterial side, the stream
THE BLOOD FLOW 409
presents a clear outer zone, measuring about 0.01 mm. in width and
containing only plasma and a few leukocytes, as well as a dark central
zone in which the red cells are massed. The platelets occupy the
peripheral layers of the stream. This arrangement is also evident
in the venules, but as the venous current is less rapid, the red cells
are more widely scattered and the marginal zone is not so clearly
defined. In the capillaries, very naturally, the distribu+ion of the
corpuscular elements cannot be dominated so much by ordinary
physical conditions, because these channels are so small that one or
two erythrocytes placed side by side fill them completely. Another
means of differentiating between the true capillaries and their supply
and collecting tubules is presented by the color of the blood. It is
darkest in the venules owing to the presence of greater amounts of car-
bon dioxid, and lightest in the capillaries, because the red cells are here
spread out in thin layers and single cells, as has been mentioned above,
are practically colorless. Still another means of differentiation is
furnished by the structural appearance of the different blood-vessels.
As the wall of a true capillary is composed of only a single row of
flattened cells, it cannot be made out very clearly. Keither is it
possible to focus a venule very sharply. The arterial capillaries, on
the other hand, are generally well defined. This is especially true of
the arterioles, owing to the deposition of smooth muscle cells within
their wall. Moreover, these tubules generally pursue a serpentine
course, whereas the venous tubules are rather straight.
The Circulation Time. — A droplet of blood leaving the left ven-
tricle may pursue many different courses. It may enter the coro-
nary circuit and return to its starting point within a very short time,
or it may pass through the portal organs, the posterior extremity, the
brain and other parts, in which cases a very much longer period of
time will be required before it can again reach the cardiac vestibule.
E. Heringi attempted to determine the time required to complete the
circuit of the vascular system by introducing a chemical substance
into the blood which could be easily recognized. He made use of
solutions of potassium ferrocyanid which were injected into the right
external jugular vein and were tested for in the blood withdrawn
from the corresponding vein on the opposite side. These samples were
arranged in series in accordance with the time of their withdrawal
and were permitted to clot, after which the serum was tested with
ferric chlorid. The results showed that the solution completed the
circuit through the heart and carotid arteries in from 20 to 30 seconds.
Vierordt^ made use of a more accurate method for determining the
length of the intervening period by permitting a series of receiving
cups to rotate at a uniform speed below the vein. Hermann employed
sodium ferrocyanid and permitted the blood to drop at regular inter-
vals upon paper moistened with ferric chlorid.
1 Zeitschr. fur Physiol., iii, 1829.
^ Erschein. und Gesetze der Stromgeschw. des Blutes, Frankfurt, 1858.
410 THE MECHANICS OF THE CIRCULATION, HEMODYNAMICS
The circulation time for this particular circuit is: 6.6 seconds in
the cat, 7.4 seconds in the rabbit, 16.3 seconds in the dog, and 28.8
seconds in the horse. For man the time for the completion of a cir-
cuit of medium length has been calculated at 23 seconds so that from
26 to 28 beats of the heart are required to effect this journey. In
other words, a droplet of blood traverses the circulatory system about
three times in every minute.
More recently, Stewart^ has devised a method which is based upon
changes in the electrical conductivity of the blood. The carotid
artery is connected with non-polarizable electrodes, the segment be-
tween them being inserted as a resistance in one arm of a Wheatstone's
bridge. As soon as a balance has been established so that the galvano-
meter remains at rest, a solution of sodium chlorid is injected into the
external jugular vein of the opposite side. This salt serves the purpose
of lessening the resistance of the blood to the electrical current. As
soon as this quality of blood arrives at the point designated, the balance
in the Wheatstone's bridge is lost and the galvanometric needle is
deflected. The time elapsing between the injection and the moment
of the deflection is determined by means of a stop-watch or an ordi-
nary chronographic appliance. Stewart^ has also employed solutions of
methylene-blue which were injected into the external jugular vein and
were rendered visible in the opposite carotid artery by means of
transillumination upon a white sheet of paper. With the help of the
first method, Stewart has also determined the time consumed by the
blood in its passage through various organs. In the case of the spleen
the average time is given as 10.95 seconds, and in the cases of the kidneys
and lungs as 13.3 and 8.4 seconds respectively. These figures show
first of all that a considerable part of the total circulation time of the
blood must be apportioned to the capillary networks of these organs
and secondly, that the time for the pulmonary circuit is relatively
short. In man it has been estimated at 12-15 seconds. A still
shorter time is required for the completion of the coronary circuit.
In this connection, brief mention might also be made of the fact that
the circulation time between the portal vein and the arteries amounts
to about 12 seconds, and the time between the femoral or renal veins
and the arteries to 16 and 13 seconds respectively.* These figures
have been obtained by measuring the interval between the injection
of adrenalin and the resultant rise in arterial blood pressure.
1 Jour, of Physiol., xv, 1894.
2 Manual of Physiol., London, 1896.
' Burton-Opitz, Am. Jour, of Physiol., xli, 1916, 91.
SECTION XI
THE NERVOUS REGULATION OF THE
BLOOD-VESSELS^
CHAPTER XXXIV
THE INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT
ORGANS
General Discussion. — The nervous control of
the vascular system is effected by two groups of
elements, one of which is concerned with the control
of the activity of the heart, and the other with that
of the caliber of the blood-vessels. The former, as
we have seen, are acceleratory and inhibitory in
their nature and are dominated by nervous ele-
ments situated in the medulla oblongata. The
latter, on the other hand, are apportioned to the
peripheral vascular system and regulate the size of
the blood-bed. For this reason they are designated
as vasomotor elements. The general arrangement
of this mechanism is the same as that controlling
the function of the heart. It consists of a central
mass of ganglion cells and of two sets of nerve fibers
which conduct either in an afferent or in an efferent
1 Vershuir (Diss. Groningen, 1766) observed that the me-
chanical excitation of the walls of such arteries as the caro-
tid and femoral, led to a marked constriction of their lumen.
Wedemeyer (Kreisl. des Blutes, Hanover, 1828) obtained
the same results with electrical stimulation. In 1831, E. H.
Weber (Archiv fiir Anat. und Physiol., 1847) explained the
phenomenon of flushing and paling upon the basis of varia-
tions in the resistance to the blood which are brought about
by the muscular contractions following nervous discharges.
Claude Bernard (Compt. rend., 1851) then called attention
to various vascular changes connected with the cutting of
the cervical sympathetic nerve, while Brown-Sequard (Phila-
delphia Med. Exam., Aug., 1852) ascertained that the excita-
tion of the proximal stump of this nerve led to a constriction
of the blood-vessels. Very similar results were obtained
by Waller (Compt. rend., 1853), but their publication was
deferred until 1853.
411
Fig. 221.— Re-
flex Circuit for
Vasomotor Actions.
R, receptors; A,
afferent path; VMC,
vasomotor center
which is intimately
connected with
other centers, for
example, the cardiac
(CC) and respiratory
centers (RC); E,
efferent path; B,
effector in blood-
vessel. Stimulation
between fl and VMC
gives rise to pressor
and depressor
effects, stimulation
between VMC and
B to vasoconstrictor
and vasodilator
effects.
412 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
direction. The former convey impulses from all parts of the body to
the center and the latter, from the cent-er to the blood-vessels (Fig.
221).. But as the lumen of the blood-vessels may be either decreased
or increased in size, the efferent or motor path must be composed of
two' types of fibers, namely, those which diminish and those which
enlarge it. The former are designated as vasoconstrictors and the
latter as vasodilators. In accordance with this functional division of
the fibers, it is possible to look upon the vasomotor center as being
composed of a vasoconstrictor and a vasodilator part.
As the afferent impulses arriving in the center are capable of
producing either a vasoconstriction or a vasodilatation, the fibers
conducting them are commonly designated as pressor and depressor
fibers. Thus, if an impulse is generated either in the center or along
the course of an efferent nerve, and produces a constriction of the
blood-vessels, the reaction is spoken of as a vasoconstrictor action.
Again, if the stimulation of the same constituents of the vasomotor arc
leads to a dilatation of a certain area of blood-vessels, the effect is said
to be vasodilator in its nature. But, if the stimulus arises in a re-
ceptor or along the course of an afferent nerve, the reaction is desig-
nated as pressor if constrictory, and as depressor, if dilatory in its
nature. The last two terms, therefore, signify that the vascular reac-
tions have been brought about reflexly.
The Location of the Vasomotor Center. — Nerve fibers, regulating
the caliber of the blood-vessels, may be contained in almost any
nerve, together with fibers possessing other functions. They may also
be grouped in such large numbers that they form individual nerve
strings of considerable size. But whether mixed with other fibers
or pursuing an independent course, they cannot be differentiated from
fibers possessing a different function excepting by physiologic means.
In other words, as nerve fibers bear no special points of difference in
their appearance, their function must be arrived at by subjecting them
to certain physiological procedures, such as mechanical and electrical
stimulation.
It is a well-known fact that the division of the spinal cord in the
cervical region gives rise to an extensive relaxation of the blood-
vessels and a fall in the general blood pressure, while the division of
the nervous system above the upper border of the meduUa remains
without effect. From this it may be inferred that the separation of
the peripheral nerve paths from the brain occasions a loss in the tonus
of the blood-vessels ordinarily imparted to them by ganglion cells situ-
ated between these two cuts. Repeated experimentation has finally
led to the localization of a colony of cells in the medulla oblongata
to which it has been possible to ascribe a vasoconstrictor activity.^
In accordance with the experiments of Dittmar,^ this center is bilateral
and lies about the middle of the fourth ventricle in the tegmental
^ Owsjannikow, Ber. d. sachs. Gesellsch. d. Wissensch., xxiii, 1871.
* Ber. der sachs. Akad der Wissensch., math. phys. Klasse, xxv, 1873.
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 413
region near the nucleus of the facial nerve and the superior olivary-
body. In the rabbit it possesses a length of 3 mm. and a breadth of
1-1.5 mm. A general, vasodilator center has not been definitely
located as yet, but it may be assumed to form either a part of the vaso-
constrictor center or to be situated in its immediate vicinity.
Secondary centers controlling the caliber ^of the blood-vessels
are supposed to exist at different levels of the cord, as well as in the
sympathetic system, but the evidence upon which this statement is
based is not very conclusive. Thus, it has been found that the
tonicity of the blood-vessels is retained in a measure even after they
have been separated from the central nervous system and that their
tonus frequently reappears very soon after the division of the cervical
segment of the spinal cord.
The. Activity of the Vasomotor Center. — Under normal conditions,
the activity of the vasomotor center is dependent upon an influx of
extraneous impulses. The sum total of these determines the tonicity
and the dynamic state of the vascular system. Its function may be
continued for some time after all these different afferent impulses
have been shut off, but naturally, a continued absence of these stimuli
always tends toward retrogression and functional uselessness. But,
besides these "external" impulses which are conducted to it by way of
many different centripetal nerves, the constituents of the vasomotor
center are also influenced by ''internal" stimuli, such as arise in
consequence of changes in its blood supply or variations in the gas
content of the blood.
Thus, if the carbon dioxid of the blood is increased, as can readily
be done in a curarized animal by discontinuing the artificial respiration,
the general blood pressure will be seen to rise gradually until it attains
a height much above normal. The pressure usually remains at this
level for a considerable period of time, but declines subsequently on
account of the increasing diastolic tendency of the heart. This rise
is occasioned by a general constriction of the blood-vessels which is
dependent upon the direct excitation of the vasoconstrictor center by
the carbon dioxid. Eventually, however, the contractions of the
heart lose their force, because the continuous supply of blood poor in
oxygen, reduces its strength so that it is no longer able to act against
the high peripheral resistance occasioned by the vasoconstriction.
The blood pressure then falls in proportion to the diminution in the
energy of the heart and obviously, this fall must result in spite of the
fact that the blood-vessels remain in the constricted condition. If
the dyspneic or asphyctic condition of the blood is now lessened by
again instituting artificial respiration, the heart usually regains its
vigor within a short time. This change is clearly betrayed by a rise
in the blood pressure. above normal. Presently, however, the relaxa-
tion of the blood-vessels following upon the restitution of the vigor of
the cardiac contractions permits the pressure to become normal again.
Should the dyspnea and asphyxia be continued, a narcotic and para-
414 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
lytic state eventually results which is characterized by a general vas-
cular depression and may lead to the death of the animal.
Very similar effects may be obtained by temporarily obstructing
the blood supply of the brain. In all experiments of this kind, how-
ever, it is advisable to deepen the narcosis by the administration of
curare, because in the non-curarized animal, the increased respiratory
movements, as well as the general muscular spasms which eventually
occur in the course of the asphyxia, must tend to raise the blood pres-
sure and to interfere with the effects of the vasoconstriction. It
need scarcely be emphasized that in the case of asphyxia, the constric-
tor agent may be either a lack of oxygen or a superfluity of carbon
dioxid.
The Distribution of the Vasomotor Fibers. — The axons derived
from the cells of the vasomotor center descend in the cord and termi-
nate at different levels in the anterior horn of the gray matter. From
here connections are made with the sympathetic system by way of the
rami viscerales, but naturally, as these bridges exist only in the tho-
racic and sacral regions of the cord, the vasomotor outpourings must
necessarily be restricted to these spinal segments. It has also been
found that the cerebrospinal and sympathetic systems are connected
with one another by way of several of the cranial nerves, and hence,
it is possible that some of the vasomotor fibers leave the central
nervous system by way of these channels. At all events, it must be
concluded that while the control of the blood-vessels is in last analysis
a function of the cerebrospinal system, it is eventually transferred
to the autonomic or sympathetic system.
After the spinal neurons have entered the sympathetic system their
impulses are conveyed to the more remote ganglia by secondary neu-
rons which in turn are connected with the blood-vessels of the thoracic,
abdominal and pelvic organs. The blood-vessels of the head are
reached by way of the ganglia of the thorax and the cervical sympa-
thetic which connects the latter with the superior cervical ganglion.
Obviously, therefore, the fibers conducting vasomotor impulses, are
typically autonomic and form such important paths as the greater
and minor splanchnic nerves, the nervi erigentes and the cervical
sympathetic. There are, however, many blood-vessels present in our
body which do not lie directly within the realm of sympathetic nerves,
but are innervated by cerebrospinal nerves. In this group belong
the blood-vessels of the anterior and posterior extremities. This
innervation is made possible by the fact that some of the fibers leave
the sympathetic system and enter the cerebrospinal nerves where they
intermingle with others pursuing a perfectly straight course from the
spinal gray matter to the periphery. These "recurrent" fibers form
the so-called gray rami viscerales.
To summarize: the vasomotor fibers passing out from the chief
center, attain the first sympathetic ganglia by way of the anterior
roots of the cord, and the white rami viscerales (Fig. 222). Two or
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 415
vmc
three neurons generally cover this entire distance. They form the
preganglionic path. Distally to these ganglia, the fibers constituting
the postganglionic path, either continue onward to different parts of
the sympathetic system, or reenter the spinal roots by way of the gray
rami communicantes where they intermingle with other efferent and
afferent fibers composing the different spinal nerves. In this way, even
the vasomotor mechanisms situated in the domain of the cerebrospinal
nerves, procure a sympathetic innervation
and are rendered, therefore, characteristic-
ally autonomic.
The Location of the Motor End-organ
or Effector. — It has been proved histologic-
ally that the walls of the central arteries
contain much connective tissue and only a
relatively small number of smooth muscle
cells. In the peripheral arteries, on the
other hand, the latter are much more
numerous and are arranged here in the
form of a massive circular (tunica media)
and a thin longitudinal layer (tunica ex-
terna). No muscle tissue is present in the
true capillaries, these tubules being com-
posed solely of flat, nucleated epithelial
cells similar to those found in the intima of
the arteries. In the veins, connective tissue
predominates, while the muscular units are
poorly developed and not organized. Thus,
it happens that some of the veins possess
no muscle cells at all, while others, and
especially those of the lower extremities,
are equipped with only a very thin circular
layer of these cells.
As the only effector present in the vas-
cular system is the smooth muscle cell, it
must be clear that vasomotor reactions
must be restricted to those channels which
are actually in possession of these elements, namely the arteries and
certain veins. To be sure, it has been stated by Mall^ that the portal
vein receives a vasoconstrictor supply through the greater splanchnic
nerves, but these results have been shown by Burton-Opitz^ to be
based upon unsatisfactory experimental evidence. Thompson,^ how-
ever, has found that the stimulation of the sciatic nerve in dogs
and cats produces a visible constriction of the veins of the posterior
Fig. 2 22. — Diagram to
Illustrate the Path Pursxjed
BY THE Vasomotor Fibers.
SC, spinal cord; PR, its
posterior root ; AR, its anterior
root; Sn, spinal nerve; 5, sym-
pathetic ganglion; B, blood-
vessel; preganglionic path in
red; VMC, vasomotor center
P (red) white ramus; postgan-
glionic path in blue; P^, di-
rectly to blood-vessel; P, re-
current fiber, reentering spinal
nerve by way of gray ramus.
lArchiv fiir Physiol., 1892, 409.
2 Am. Jour, of Physiol., xxxvi, 1915, 325.
Archly fur Physiol., 1893; also see: Bancroft, Am. Jour, of Physiol., i, 1898,
477.
416 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
extremities, but as this effect is inconstant and very localized, it may
have an indirect cause. Moreover, while Henderson^ has found that
strips of veins react toward solutions of adrenalin in the same man-
ner as segments of arteries, this evidence cannot be considered as a
direct proof of the existence of vasomotor elements in the veins.
On the whole, therefore, this question seems to have found a negative
solution.
As far as the capillaries are concerned, it has been shown by Strieker
and others^ that these tubules possess a certain degree of contractility,
but it appears that this reaction cannot acquire a definite dynamical
value. All living substance exhibits this property and hence, it can-
not be denied to the living cells of the capillaries. Stimuli brought to
bear upon them must result in a rearrangement of their contents
and a possible constriction of the lumen of the capillary. This re-
action, however, does not seem to be of central origin, but appears to
be elicited solely by local excitations. In this connection attention
should also be called to the fact that the capillary blood-bed may be
materially altered by variations in the tension of the surrounding
tissues. Thus, the lumen of these tubules may be compressed in
consequence of the contraction of the numerous smooth muscle cells
which are widely scattered through the skin. The relaxation of these
muscular elements, on the other hand, must tend to widen the capillary
blood-bed and to grant a more copious blood-supply to the cutaneous
parts. Reactions of this kind result in consequence of variations in
the temperature of the surrounding air as well as in consequence of
the immersion of the body in cold or warm water. The influence of
these muscular elements upon the injection of the cutaneous capil-
laries can scarcely be overestimated. It should be emphasized, how-
ever, that we are not dealing in this case with a true vasomotor
phenomenon, but solely with a direct mechanical action. At the
same time it must be granted that any influence causing a contrac-
tion of the cutaneous smooth muscle tissue, would be prone to
produce a vasoconstriction in addition. A reverse relationship, how-
ever, need not exist.
In view of the evidence here presented, it seems permissible to
conclude that true vasomotor actions are possible only in the arterial
system. Since the smooth muscle tissue is most massive in the arteri-
oles, it may be surmised that the most powerful effects of this kind are
obtained at the arteriocapillary junction. This segment of the arterial
system, therefore, gives lodgment to the gate or sluice through which
the blood must pass in order to reach the capillaries. Consequently,
the size of this orifice must determine the volume of the arterial escape
as well as the vascularity of the more distant capillary networks.
Excepting, therefore, certain local influences in the shape of the cuta-
neous smooth muscle cells, the caliber of the latter is determined
1 Am. Jour, of Physiol., xxiii, 1909, 345.
^ Steinach and Kahn, Pfliiger's Archiv, xlvii, 1903.
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 417
exclusively by the quantities of blood which are permitted to escape
through this gate.
The Nature of the Reaction. — Two views are held regarding the
manner in which vasomotor changes are brought about. Thus, it
may be assumed that the blood-vessels are constantly kept in a state of
tonicity and that vasoconstriction is had in consequence of an extra
discharge of impulses by the center, while vasodilatation is the result
of a loss of tonus which is immediately followed by a passive enlarge-
ment of the blood-vessels. For this reason, the former condition may
be regarded as an augmentor and the latter as an inhibitor phenome-
non. A condition comparable to this one exists in the heart, where
accelerator and inhibitor impulses are played against one another.
The second theory proposes that vasoconstriction and vasodilatation
are two distinct processes resulting in consequence of the activity of
two separate mechanisms.
If the first theory is accepted, the effector need not possess special
l^gtructural characteristics, because vasoconstriction could then be
[assigned to the contraction, and vasodilatation to the extreme relaxation
^of the circular musculature. But, if the second view is adhered to,
itwo distinct effectors would have to be present, namely, one for vaso-
[constriction and one for vasodilatation. Regarding the former, no
I difficulty need arise, because it could justly be ascribed to the con-
[traction of the circular layer of muscle cells. Less manifest is the
'vasodilator mechanism, because the only other available element is
the layer of. smooth muscle cells which is arranged longitudinally to
the lumen of the blood-vessel. In the absence of a structurally more
definite effector, we are practically forced to assume that these cells
accomplish the dilatation either alone, or through an interaction with
the circular coat.
It is quite impossible at the present time to decide with certainty
whether the first or the second theory is the correct one. The evi-
dence favoring the second view, namely, that the vasoconstrictor and
vasodilator reactions are effected by separate mechanisms, is as
follows :
(a) Certain nerves are in existence which possess solely a dilator function.
First among these is the chorda t3'-mpani, a branch of the facial nerve, which
embraces dilator fibers for the submaxillary and sublingual glands, as well as the
tympanic branch of the glossopharyngeal nerve which contains dilator fibers for the
posterior third of the tongue, the tonsils, pharynx, and parotid gland. In this
group should also be placed the cervical sympathetic nerve, by way of which the
dilators gain access to the mucous membrane of the lips, gums, palate and the skin
of the cheeks and nostrils. '^ Some direct evidence is also at hand to prove that the
abdominal sympathetic system contains nerves of this kind.^ It is also possible
to incite dilator effects in the domain of the nervi erigentes, by way of which the
erectile tissues of the reproductive organs are reached. It must be remembered,
however, that the tenseness of these organs is not caused by vasodilatation alone,
^ Dastre and Morat, Red. exper. sur le systeme nerv. vasomoteur, 1884.
2 Burton-Opitz, Pfltiger's Archiv, cxxiii, 1908, 553.
27
418 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
but also by an actual stagnation of the blood stream which results in consequence
of an obstruction to the venous return. The latter effect is made possible by the
contraction of circular cushions of muscular tissue which form sphincters at the
points of junction between the venules and the cavernous blood spaces.
(b) The dilator and constrictor reactions may be dissociated by chemical means.
Thus, it has been found by Dale ^ that ergotoxin possesses the property of paralyzing
the constrictor mechanism, so that the stimulation of any mixed vasomotor nerve
must give way in time to dilatation. It is also possible to produce vasomotor
effects solely with the aid of chemical agents so that we need not resort to the
electrical stimulation of a nerve. For example, adrenalin in very small doses
dilates the blood-vessels of the cutaneous circuits, while larger doses give rise
to a constriction. ^ In the same way, it has been found that proteoses cause a
dilatation, while chrysotoxin (ergot) stimulates the constrictor mechanism,
(c) The constrictor and dilator reactions may also be dissociated by changing
the temperature or by changing the frequency of the stimulation. Thus, Howell,
Budget and Leonard ^ have shown that the irritability of the dilator fibers of the
sciatic nerve may be destroyed sooner than that of the constrictors by simply
heating or cooling the nerve. If a quickly interrupted current of moderate strength
is applied to a nerve, the usual result is vasoconstriction. Bowditch and Warren,*
however, have found that infrequent electrical stimuli commonly give rise to a
dilatation instead of a constriction. In the case of the renal blood-vessels,
Bradford^ employed fifty induction shocks at intervals of one second. Very
similar results have been obtained with the greater splanchnic nerve, by Meltzer
and Auer,^ and Burton-Opitz.^ The infrequent excitation of the central end of this
nerve gave rise to reflex vasodilatation and a most pronounced fall in blood pressure.
It might also be mentioned that the degeneration following the division of the
sciatic nerve, affects the constrictor fibers first of all, so that vasodilator effects
may be obtained for some time after its constrictor power has been lost.
The Results of the Reaction. — In general, it holds true that the
division of a nerve containing vasomotor fibers is followed by a
relaxation of the blood-vessels innervated by it. The vascular area
so affected loses its tonic resistance and becomes engorged with blood
and distinctly warm to the touch. If this area is sufficiently large, these
changes must, of course, react upon the general circulation and produce
a fall in the general pressure, because a considerable quantity of the
systemic blood must find its way into these relaxed vessels. In many
cases these blood-vessels regain their tonus within a comparatively
brief period of time, provided, of course, that they are still in connec-
tion with ganglionic elements. The latter are capable of assuming the
function of those chief centers with which they were previously con-
nected. This is especially true of the blood-vessels situated in the
realm of the sympathetic system, because this system embraces
numerous local conglomerations of ganglion cells which are markedly
independent in their function from the cerebrospinal structures.
Most generally, the excitation of the distal end of a divided vaso-
1 Jour, of Physiol., xlvi, 1913, 291.
^ Hartman, Am. Jour, of Physiol., xxxviii, 1915, 438.
3 Jour, of Physiol., xvi, 1894, 298.
^ Ibid., vii, 1886, 416.
6 Ibid., x, 1889, 358.
6 Centralb. fur Physiol., 1916.
' Am. Jour, of Physiol., xlii, 1917, 498.
TNNEEVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 419
motor nerve with currents of medium strength and frequency gives
rise to a vasoconstriction in the part innervated by it. This result
may also be obtained by stimulation of the intact nerve, and naturally,
if a certain nerve is composed solely of dilator fibers, its excitation
must be followed by a dilatation. As an example of this kind might be
mentioned the chorda tympani which, as has been stated above,
consists of dilator fibers for the submaxillary and sublingual glands.
As far as the result of these constrictor reactions is concerned, it
must be evident that the diminution in the caliber of the arterial
terminals must reduce the arterial throughflow. This change is asso-
ciated with an increase in the arterial presure and a decrease in the
capillary and venous pressures. Conversely, a vasodilatation must
favor a greater escape of blood into the capillaries and occasion a fall
in the arterial and a rise in the capillary and venous pressures.
It has previously been emphasized that the vasomotor mechanism
is the chief factor concerned in the production of the peripheral re-
sistance, and that the latter in turn plays a most important part in the
)roduction of blood pressure. The other three factors are the energy
)f the heart, the total quantity of the blood, and the elasticity of the
blood-vessels. Consequently, the blood pressure must be entirely
dependent- upon the proper interaction of these four values. Thus, it
will be seen that the effects of a vasoconstriction may be greatly les-
sened by a reduction in the cardiac output, while a vasodilatation may
be quite offset by an augmentation of the action of the heart. This
compensatory phenomenon is indeed a very common one, because a
high blood pressure, resulting in the course of a general vasoconstric-
tion, is usually neutralized by a reduction in the cardiac output. But,
it may also happen that the other factors act in perfect unison with the
vasomotor mechanism and thus occasion an exaggeration of the vaso-
motor effect. For example, if a general vasoconstriction occurs syn-
chronously with a high cardiac rate, a rise in blood pressure must
result which must greatly exceed the rise produced by the vasocon-
striction alone.
Nothing further need be said regarding the pressor and depressor
reactions. Inasmuch as these effects are brought about reflexly
by impulses generated in different parts of the body, the vasomotor
center must be activated first before these impulses can be transferred
upon the efferent channels. One or the other of these effects may be
elicited either by stimulating the afferent nerve while intact, or by
dividing it and using its central end for the stimulation. Obviously,
if the distal end of a nerve of this kind is subjected to the excitation,
.the impulses here generated cannot reach the center at all and hence,
10 pressor or depressor effect can be evoked. As a typical example of
depressor nerve might be mentioned the depressor cordis, the stimu-
lation of which produces a general reflex vasodilatation and a most
[decided fall in blood pressure. Similar results may be obtained by
Ithe excitation of the splanchnic nerve, and especially if currents of
420 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
low strength and frequency are employed. In fact, pressor and de-
pressor fibers are contained in many nerves, such as the sciatic and the
vagus, but their presence can only be detected by the stimulation of
the central ends of these nerves and by the use of infrequent shocks of
low intensity.
Methods Used to Detect Vasomotor Action. — While it has been
possible to prove histologically that the walls of the blood-vessels
contain nervous structures, this fact in itself is not sufficient to show
that they are in possession of vasomotor elements. In other words,
the only definite proof of vasomotor activity is to be found in the oc-
currence of the reaction itself. We may resort to inspection, because
if all indirect factors, such as external pressure, have been ruled out,
the blanching of a part may justly be referred to a vasoconstriction
and its reddening to a vasodilatation. These alterations in the
vascularity are usually associated with changes in temperature, a vaso-
constriction occasioning a fall and a vasodilatation a rise in the tem-
perature of the part. Probably the most direct proof of vasomotor
activity may be obtained with the help of the recording stromuhr,
this instrument being inserted in the artery or vein of the part to be
experimented upon. As has been stated above, this instrument
registers the volume of the blood stream and may therefore be used
to see whether or no the flow is affected by the excitation of nerves and
other experimental procedures. A decrease in the arterial supply
would then betray a constrictor action, and an increase a dilator
effect. It is also permissible to detect these vasomotor changes by
making a simultaneous record of the pressure in the artery and vein
of the organ to be examined. A mercurial manometer and water
manometer are employed for this purpose. Clearly, a rise in the
arterial and a fall in the venous pressure would betray a vasoconstric-
tion, and a fall in the arterial and a rise in the venous pressure, a
vasodilatation. These changes are easily explained, because the
former reaction must increase and the latter decrease the resistance
to the arterial throughflow. The manometer is also used to detect
vasomotor effects of a more general kind. It is then connected with
one of the principal arteries, such as the carotid or femoral. A rise in
the general pressure may then be attributed to a constriction of an
extensive area of the circulatory system, and a fall in the general
pressure to a vasodilatation of rather wide extent. Lastly, it is pos-
sible to place the organ to be experimented upon in a plethy sinograph.
Under this condition a diminution in the volume of the organ would
point toward a vasoconstriction, and an increase in its volume toward
a vasodilatation. But naturally, if these procedures are practised,
care must be taken to exclude all indirect effects, such as may be pro-
duced by a mechanical obstruction to the blood flow. An occurrence of
this kind usually leads to a stagnation of the blood and an increase in
the volume of the organ which can scarcely be differentiated from a
true vasomotor effect.
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 421
SPECIAL VASOMOTOR REACTIONS
The Spinal Cord. — As the spinal cord is the chief highway by-
means of which the vasomotor center in the medulla stands in com-
munication with the constrictor and dilator mechanisms of the blood-
vessels, the destruction of this part must lead to a pronounced fall
in blood pressure. The tonic influences of the higher center are then
prevented from reaching the periphery, as are also those generated in
the minor centers of the cord itself. In other words, a general vascular
relaxation now results which may finally produce an almost complete
stoppage of the blood flow. The animal, so to speak, is bled into its
own highly relaxed vessels.
A fall in blood pressure may also be produced by dividing the cord
either in its cervical or in its thoracic region. In both cases the
blood-vessels innervated by those nervous elements which are situated
posteriorly to the cut, lose their tonus and relax. It is to be noted,
however, that this relaxation is not permanent, because the lower
spinal centers then develop a tonic power independent of that of the
rest of the cord. The blood-vessels gradually regain their former
caliber and enable the blood pressure to return to a value approaching
normal. From the foregoing data, it may also be inferred that the
excitation of the peripheral stump of the spinal cord must give rise to a
vasoconstriction and a rise in the general blood pressure, because the
constriction of the formerly relaxed blood-vessels leads to the trans-
fer of a large amount of previously stagnated blood into the general
circulatory system. The stimulation of the central stump of the
divided spinal cord with currents of ordinary strength sets up different
reflexes which usually result in a pressor reaction.
The Sciatic Nerve. — This nerve must be considered as the vaso-
motor highway of the posterior extremity. In accordance with the
preceding analysis, it may be gathered that its division occasions a
relaxation of the blood-vessels innervated by it, but a marked reduction
in the general blood pressure cannot result in consequence of this
procedure, because the extra quantity of blood which finds its way into
the circulatory channels of the leg, is not sufficiently large to affect
the dynamic conditions in the general circulation. The stimulation
of the distal stump of the divided sciatic nerve is usually followed by a
constriction of the peripheral blood-vessels, the superfluous amount of
blood being again driven into the general circuits of the body. But
this transfer remains as a rule without decisive effect upon the general
circulation for the reason just given. The result ordinarily obtained
upon excitation of its central end is a rise in blood pressure, but this
pressor effect may be changed into a depressor reaction by lessening the
frequency and intensity of the stimuH. The foregoing account is also
applicable to other spinal nerves, such as the brachial.
Our knowledge regarding the vasomotors of skeletal muscle tissue
is still very indefinite, owing to the difficulties experienced in differ-
422 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
entiating between the nervous effects and those caused by the contract-
ing muscle fibers. GaskelP states that the excitation of the distal end
of the motor nerve of the mylohyoid muscle gives rise to a dilatation
which persists even after the administration of curare. Besides, the
determinations of the blood supply of the gracilis muscle of dogs,
which have been undertaken by Burton-Opitz^ and Tschuewsky,^
have shown that the flow is greatly diminished during the period of
contraction of the muscle but much increased during its relaxation.
It need scarcely be emphasized that these changes may be chiefly
mechanical and must occur whenever the motor nerve of a muscle is
stimulated. This is shown by the fact that the tetanization of the
muscle reduces the blood flow almost to zero. We have no means of
differentiating between these mechanical effects and those of vasomotor
origin,: unless we should paralyze the motor plates by means of curare.
But again, inasmuch as this agent might also affect the vasomotor ter-
minals in muscle, it could not serve as a means to decide this question
one way or another. This uncertainty regarding the existence of
vasomotor nerves in muscle tissue, has not been lessened by the experi-
ments of Kaufmann,* who has ascertained that the blood flow through
the masseter muscle of the horse may be increased as much as five times
by permitting this animal to masticate normally. Instead of referring
this change to a stimulation of the nervous mechanism, we might
attribute it with equal justification to a mechanical widening of the
blood-vessels. This explanation might be adhered to in spite of the
fact that this action is associated with a fall in pressure in the artery
supplying this muscle, and an increase in pressure in the vein draining
it.
The Trigeminus Nerve. — This nerve embraces vasoconstrictor
fibers for the conjunctiva, the sclerotic coat and iris of the eye, as
well as for the mucous lining of the nose and gums. Its lingual branch
innervates the blood-vessels of the tongue. In the rabbit, the auricu-
laris magnus nerve, a branch of the third cervical, embraces vaso-
motor fibers for the ear.
The Cervical Sympathetic Nerve. — This nerve forms the connec-
tion between the inferior and superior cervical ganglia. During its
course along the neck, it lies in relation with the carotid artery and
the vagus nerve. In some animals, such as the rabbit, it pursues an
independent course, while in others it attaches itself to the vagal fibers
(cat) or becomes completely intermingled with them (dog). Distally
to the superior cervical ganglion, the individual fibers follow in the
path of the blood-vessels and finally attain such structures as the
cerebrum, the ear, submaxillary gland, larynx, thyroid body, and
the integument of the head.
1 Jour, of Physiol., i, 1878, 108.
2 Am. Jour, of Physiol., ix, 1902, 161.
3 pfliiger's Archiv, xcvii, 1903, 289!
4 Arch, de Physiol, et Path., 1892.
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 423
One of the most striking vasomotor reactions obtainable with the
aid of this nerve is the following: If the blood-vessels in the ear of a
rabbit are rendered more clearly perceptible by transillumination, it
can readily be observed that the division of this nerve occasions a very
decided vascular relaxation. Many blood-vessels which were previ-
ously quite invisible to the naked eye, are now sharply outUned, and
the ear on the operated side is distinctly warmer than the one on the
normal side. If the distal (cephalic) end of this nerve is stimulated, a
vasoconstriction soon results which betrays itself most unmistakably
by a diminution in the caliber of the central artery and its principal
branches. These vessels grow smaller and smaller until they can
Fig. 223. — The Vasomotor Reactions in the Ear of the Rabbit on Division
AND Stimulation op the Cervical Sympathetic Nerve.
A. Normal. B. After division of the cervical sympathetic nerve,
lation of the distal end of the divided cervical sympathetic nerve.
C. On stimu-
scarcely be made out. The veins remain visible for a much longer
time, but eventually collapse owing to the cessation of the arterial
influx. This ear now feels distinctly colder than the one on the normal
side. On discontinuing the stimulation, the arteries again relax until
they have attained their former caliber. These changes may be pro-
duced again and again, but naturally, only at intervals, to avoid fatigu-
ing this vasomotor mechanism.
The superior cervical ganglion also serves as the distributing center
of the sympathetic fibers to the sublingual and submaxillary glands.
These fibers follow in the course of the art. glandularis submaxillaris.
The aforesaid organs also receive a second nerve supply which is de-
rived from the bulbar autonomic system and appears peripherally in
the form of a small nerve known as the chorda tympani. The latter
leaves the system of the facial nerve and attaches itself at first to the
lingual nerve of the fifth system. When it reaches the region of Whar-
424 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
ton's duct, it turns abruptly and attains the aforesaid glands by way of
this duct. Under ordinary conditions of experimentation, these two
sets of fibers possess an antagonistic action upon the vascularity of
these glands, because the cerebral nerve or chorda tympani possesses
vasodilator and the sympathetic nerve vasoconstrictor qualities. The
former change is associated with a secretion of a large quantity of
very watery saliva, and the latter with a scanty production of a very
viscous and turbid saliva.^
These changes may be studied most advantageously in a dog or
large cat. The stimulation of the chorda is undertaken as a rule in the
triangle where this nerve leaves the lingual to attach itself to Wharton's
duct. The excitation of the sympathetic may be accomplished at
any point of its course along the neck, but as the vagal and sympathetic
fibers of the dog intermingle, it becomes necessary to apply in this case
the electrodes to the distal (cephalic) end of this nerve. .It should be
Fig. 224. — Schema Illustratikg the Nerve Supply of the Submaxillaey Gland.
SG, submaxillary gland; supplied by a small aitery from the carotid system (CA).
It is drained by a small vein which generallx enters the facial {FV) at its point of con-
fluence with the lingual vein (LV). The external (ESV) and internal (JSV) maxillary
veins invest the gland and unite to form the external jugular vein (EJV). The sympa-
thetic nerve supply is derived from the sup. cerv. ganglion (SCG). The chorda tympani
(CT) attaches itself to the lingual nerve LiV and then to Wharton's duct iW);S, lower
jaw.
remembered, however, that we are concerned at this time solely with
the aforesaid vascular reaction and not with any other effect whioh
this stimulation might produce. In the cat, it is possible to isolate
the sympathetic fibers from the vagus proper, because their line of
contact is clearly marked by a small blood-vessel. If the surface of
the submaxillary gland is now fully exposed to the view, it will be seen
that the stimulation of the chorda causes it to redden, while the excita-
tion of the (vago-) sympathetic causes it to pale. These changes
in the vascularity of this organ may also be made out manometrically,
or, as has been done by Burton-Opitz,^ by means of the stromuhr
inserted in the distal end of the external jugular vein. In the latter
case, however, all tributaFy veins must first be ligated in such a manner
that solely the blood from the submaxillary gland is enabled to enter
^ Heidenhain in Hermann's Handb. der Physiologie, v, 1883.
a Jour, of Physiol, xxx, 1903, 132.
INNERVATION OF THE BLOOD-VESSELS OF DIFFERENT ORGANS 425
this instrument. Quite naturally, the excitation of the chorda tym-
pani then gives rise to an augmentation of the venous pressure and
flow, because the resulting vasodilatation allows a greater quantity
of arterial blood to pass through this gland. The stimulation of the
sympathetic, on the other hand, then leads to a diminution in the
venous pressure and flow, because the vasoconstriction immediately
following, serves to place a greater resistance in the path of the
arterial blood.
The superior cervical ganglion is also connected by postganglionic
fibers with the blood-vessels of the brain. This fact has been demon-
strated by Jenson^ who has measured the venous return from this
organ with the aid of a stromuhr inserted in the external jugular vein.
Under this condition, the stimulation of the distal end of the cervical
sympathetic nerve invariably led to a diminution in the blood flow
through this vein. The fact, that the cerebral blood-vessels are equip-
ped with vasoconstrictor powers, has also been established by Wiggers,^
who measured the quantity of fluid perfused through the blood-
vessels of an excised brain before and during the administration
of adrenalin. Very similar reductions in the cerebral blood-supply
have also been incited by the direct stimulation of the internal carotid
artery at the point where it enters the skull. It is entirely probable
that the constrictor fibers follow this artery in their course to intra-
cranial parts. Less convincing are the results obtained with the help
of the plethysmograph, but several observers (Weber) claim to have
noted certain variations in the volume of the brain which could not
be explained in any other way than by assuming that this organ is
innervated by constrictor and dilator fibers.
The Greater Splanchnic Nerve. — This nerve embraces those fibers
of the thoracic outpouring of sympathetic fibers which are destined
to regulate the caliber of the blood-vessels of the abdominal organs,
inclusive of the kidneys, adrenal bodies, stomach, intestine, Hver,
pancreas and spleen. These organs, which are commonly called
the splanchnic organs, are not reached by them directly but only by.
way of several relay stations forming the so-called solar plexus. The
latter embraces the right and left suprarenal, and the mesenteric and
celiac ganglia. The connection between these and the organs just
enumerated, is effected by several postganglionic paths, such as the
renal, mesenteric, splenic, celiac and hepatic plexuses.
The point to be especially emphasized at this time is that these
nerves control the blood supply of extremely large and vascular struc-
tures and possess, therefore, an almost dominating influence upon the
distribution of the total quantity of the circulating blood. This
statement can be substantiated by the following simple experiment.
If the general blood pressure is recorded by means of a mercurial mano-
meter connected with the carotid artery, it will be seen that the di-
1 Pfliiger's Archiv., ciii, 1904, 195.
2 Am. Jour, of Physiol., xiv, 1905, and xxi, 1908.
426 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
vision of the right or left splanchnic nerve leads in the course of a
few moments to a marked diminution in the pressure. This effect
may be rendered even more conspicuous by dividing both nerves.
If the distal (abdominal) end of this nerve is now stimulated with a
current of moderate strength and duration, it will be noted that the
systemic blood pressure rises rather abruptly and remains high for
some time after the cessation of the stimulation. All vasomotor reac-
tions, however, develop slowly, for the reason that smooth muscle
cells do not contract so rapidly as the striped variety. Neither is
it possible to continue an experiment of this kind for any considerable
length of time, because it is eventually cut short by fatigue. It has
been mentioned above that the excitation of the central (thoracic)
Fig. 225. — Record of the Carotid Blood-pressure in Rabbit During Stimulation
OF the Left Greater Splanchnic Nerve.
end of this nerve with currents of low frequency and strength gives
rise to a general vasodilatation and fall in the systemic blood pressure.
In explaining this reaction it should be borne in mind that the di-
vision of the splanchnic nerve is soon followed by a relaxation of the
blood-vessels innervated by it. Consequently, a steadily increasing
quantity of blood must leave the systemic channels and become lodged
in those of the splanchnic organs. In some animals, this transfer
of blood may lead to circulatory disturbances which actually endanger
their life. At all events, the fall in general pressure resulting from the
engorgement of the splanchnic blood-vessels, eventually gives rise
to cerebral anemia and various symptoms, such as vertigo, mental
lethargy and muscular weakness. Conditions constantly arise in our
system which require extra amounts of blood to be transferred from
place to place and especially when the digestive organs are actively
engaged in reducing and absorbing the food. This means that they
must be supplied with larger quantities of blood which, on being with-
THE CIRCULATION THROUGH SPECIAL ORGANS 427
drawn from the systemic circuit, generally give rise to mental -and
bodily fatigue. These symptoms are also observed whenever the
tonicity of the splanchnic blood-vessels is lost in consequence of general
nervous debiHty, irritation of the intestines, and other conditions.
Concurrently, it may be gathered that the stimulation of the distal
end of the greater splanchnic nerve must occasion a transfer of blood
from the splanchnic area into the general circulation, because the
vasoconstriction resulting in consequence of this procedure, forces
a large quantity of blood out of these channels into the veins and the
general circuit and prevents at the same time a corresponding influx
of arterial blood. The systemic blood pressure, therefore, is rapidly
increased, but naturally, this augmentation cannot exceed physiolog-
ical limits, because while the arterial blood does not find free access to
the splanchnic organs, it is still in a position to leave the arterial chan-
nels by way of the carotid and femoral arteries.^ Thus, while the
stimulation of the splanchnic nerve lessens the flow through the organs
innervated by it,^ the circulatory conditions in the central venous
system remain practically unaltered.
The Depressor Nerve. — The function of this nerve has been de-
scribed in detail in one of the preceding chapters (page 329). It is
a sensory nerve and conducts impulses from the heart to the cardiac
and vasomotor centers. Its function is to produce a general reflex
vasodilatation, and therefore a fall in the systemic blood pressure. In
the nature of things, this effect can only be obtained by the stimulation
of either the intact nerve or of its central or cephalic stump. It has
been stated above that marked depressor effects may also be obtained
with the help of the thoracic sympathetic nerve and its branches.
CHAPTER XXXV
THE CIRCULATION THROUGH SPECIAL ORGANS
A. THE CORONARY CIRCULATION
In man the orifice of the right coronary artery is situated in the
anterior sinus of Valsalva, whence this blood-vessel passes forward
and follows the right auriculoventricular groove until it reaches the
interventricular groove. At this point it divides into two branches,
the smaller of which continues onward in the left auriculoventricular
groove, and the larger in the inferior interventricular groove. The
left coronary artery arises from the left fossa of Valsalva and, passing
backward, divides at the left auricular appendix into two branches,
1 Edwards, Am. Jour, of Physiol., xxxv, 1914, 15.
2 Burton-Opitz, Quart. Jour, of Exp. Physiol., iv, 1912, 83.
428 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
one of which descends along the anterior interventricular groove to
the apex of the heart, while the other follows the left auriculoventricu-
lar groove. From these superficial blood-vessels, forming what is
known as the extramural system, branches are given off which pene-
trate the substance of the heart and by repeated division give rise to
the so-called intramural system.
The cardiac veins follow in the course of the arteries, uniting
eventually in the coronary sinus which is about one inch in length
and occupies the inferior extremity of the left auriculoventricular
groove. It empties into the right auricle in front of the inferior caval
opening, its orifice being guarded by the valve of Thebesius.
In this connection it should be recalled that the hearts of those
lower forms, which are not in possession of an independent circulation,
obtain their nutritive material directly from the blood as it traverses
the cardiac chambers. Many of these organs also contain irregular
tubular passages which penetrate the musculature and thus enable
the blood to come into contact with even the most remote cells. A
similar arrangement is present in the mammalian heart. Numerous
openings, the so-called foramina of Thebesius, establish a communica-
tion with a system of tubules which ramify below the endocardial
membrane,^ but the nourishment which the mammalian heart is able to
derive from this source is not sufficient for its metabolic requirements. ^
That the activity of the mammalian heart is actually dependent
upon the coronary blood supply, may readily be gathered from the
fact that an isolated and quiescent organ may be made to beat again
by instituting an artificial circulation through its coronary circuit.
In fact, the frequency and force of the cardiac contractions invariably
go hand in hand with the pressure under which the perfusion is made.
Very similar results may be obtained at times with the heart of the cat.
Thus, if its aortic orifice is occluded, it ceases to beat almost imme-
diately, but may be made to contract again by filling its chambers
with defibrinated blood under a pressure of about 75 mm. Hg. This
procedure, however, is not so reliable as the perfusion through the
coronary artery. This fact, that it resumes its activity under these
circumstances, might also be explained upon the basis that the cat's
heart possesses a more extensive system of direct nutritive channels
than that of other mammals. The ligation of the coronary arteries
in the dog is followed almost immediately by a diminution in the
rate and force of the heart beat and eventually by a complete stoppage.
In fact, Parker has shown that the occlusion of one of its branches,
namely the circumflex artery, suffices to arrest the heart in about
80 per cent, of the animals.
While the superficial cardiac vessels are protected in a measure
by the visceral layer of the pericardium, as well as by connective
tissue and fat, the deeper branches are directly exposed to the power
1 Pratt, Am. Jour, of Physiol., i, 1898, 86.
2 Langendorff, Pfluger's Archiv, Ixi, 1895, 291.
THE CIRCULATION THROUGH SPECIAL ORGANS 429
of the musculature. It need not surprise us, therefore, to find that the
mechanical influences thus exerted upon the blood stream play an
important part in the flow through this system of vessels. In fact,
much uncertainty has always prevailed regarding the manner and the
time during which the coronary blood-vessels are filled. Brucke,^ for
example, has expressed the idea that the heart possesses a self -regula-
tory mechanism whereby the circulation through this organ is made to
differ in certain particulars from that through other parts of the body.
As the orifices of the coronary arteries are situated behind the flaps of
the aortic valve, the claim has been made that these openings are com-
pletely closed during each ventricular systole^ and that the heart ob-
tains its sapply of blood only during the diastolic period when these
valve flaps are in the position of closure. This mode of filling seemed
the more likely, because the relaxation of the cardiac muscle must exert
a favorable influence upon the influx of the aortic blood, while its
contraction must force the blood onward into the veins and right
auricle.
This view, however, has found no substantiation, because it has
been proved by Martin and S»edgwick,^ as well as by Porter,^ that the
pressure changes in the coronary arteries coincide very closely with
those occurring in the systemic circuit. Moreover, RebataP has
shown that the coronary blood flow suffers an acceleration at the
beginning of each systole, but ceases as soon as the musculature has
attained a state of maximal contraction. A second augmentation
in the flow is said to result during diastole which, however, soon suffers
a retardation in consequence of the gradual filling of the right auricle.
These data prove, on the one hand, that the coronary circuit remains
in free communication with the aorta even during the systole of the
heart and, on the other, that the contracting musculature exerts
a powerful pressure upon the intramural blood-vessels which greatly
favors their emptying. In further substantiation of this statement
it might be mentioned that if a piece of ventricle is made to beat
rhythmically by perfusing it with a nutritive fluid through its artery,
a jet of blood is forced from the distal venous orifice with every
contraction (Porter).
The question whether the coronary circuit is equipped with a
vasomotor mechanism has not been decided as yet, because any
attempt to solve this problem, either by measuring the blood flow
directly or by determining the changes in pressure, must be seriously
hampered by the mechanical action of the contracting musculature.
Neither is it possible to obtain more accurate data by stimulation of
the efferent nerves of the heart, because the vagal and sympathetic
1 Der "Verschluss der Kranzschlagadern durch die Aorten Klappen, Wien,
1855.
2 A statement generally attributed to Thebesius (1708).
3 Jour, of Physiol., iii, 1880, 165.
* Am. Jour, of Physiol., i, 1898, 71.
^ Dissertation, Paris, 1872.
430 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
fibers modify the rate and force of the heart in such a degree that
it becomes quite impossible to recognize pure vasomotor changes.
For this reason, much stress cannot be placed upon the experiments
of Parker^ and Maas^ who measured the outflow from the coronary
veins of isolated hearts of cats while these organs were being perfused
through their coronary arteries. Under these conditions, the excitation
of the vagus led to a diminution and the stimulation of the sympathetic
fibers to an increase in the flow. In accordance with the foregoing
statement, we are not justified in attributing the former effect to a
vasoconstriction and the latter to a vasodilatation.
For the same reason no definite conclusions can be drawn from
the observations of N. Martin,^ showing that the stimulation of the
vagus produces an enlargement of the smaller blood-vessels situated
in the surface layers of the heart and that a dilatation of these channels
results early during the state of asphyicia, when the general blood
pressure preserves as yet a perfectly normal value. Schafer,^ as well as
Wiggers,^ is of the opinion that the changes following the stimulation
of the cardiac nerves during perfusion may be explained more satis-
factorily by attributing them to other than vasomotor influences.
It has been reported, however, that the coronary vessels of the
quiescent heart constrict in response to adrenalin, and that this agent
increases the flow through this organ by modifying the character of
its contractions.
B. THE PULMONARY CIRCULATION^
The dynamical factors which are responsible for the flow of the blood
through the lesser circuit, present the same general characteristics as
those previously discussed in connection with the greater circuit. The
pressure in the pulmonary artery finds its origin in the activity of the
right ventricle. As the driving force developed by this chamber
is relatively sHght, it cannot surprise us to find that the entire pul-
monary circulation is carried on with the aid of a rather low pressure
and, hence, with a lesser expenditure of energy, than the systemic.
But this statement is not meant to imply that the pulmonary circula-
tion is less effective, but merely to suggest that the low pressures here
pre trailing, are made possible by the fact that the resistance in this
circuit is very slight. That this deduction is correct may be gathered
from the observation that the pulmonary arterioles possess a larger
caliber and are equipped with only a scanty amount of smooth muscle
tissue.
The blood-vessels of the lungs are constantly undergoing passive
1 Boston Med. and Surg. Jour., 1896.
2Pfluger's Archiv, Ixxiv, 1899, 281; also see: Dogiel and Archangelski, ibid.,
cxvi, 1907, 482.
3 Transact., Med. and Chir. Fac. of Maryland, 1891.
^ Arch, des sciences biol., xi, Suppl., 1899.
6 Am. Jour, of Physiol., xxiv, 1909, 391.
s Discovered by Servet and Columbo during the middle of the 16th century.
THE CIRCULATION THROUGH SPECIAL ORGANS 431
variations in their caliber in consequence of the respiratory movements
of the thorax. They are widened during normal inspiration and
compressed during expiration. This leads us to infer that the through
flow is greatest during the former phase, because the resistance is
least at this time. But if the lungs are distended artificially through
the trachea, these conditions are reversed, because -their inflation with
air produces a compression of their blood-vessels. The peripheral
resistance is increased during the inflation. Conversely, it may be con-
cluded that the deflation of these organs enables the vessels to acquire
their previous caliber. This change is associated with a diminution
in the peripheral resistance.^ As has previously been noted, these
rhythmic variations in the conditions inside the thorax play an
important part in the production of the respiratory oscillations in
blood pressure. Attention should also be called at this time to the
fact that the vascularity of the lungs is subject to the conditions pre-
vailing in the heart. Any momentary excess in the venous influx
must, of course, be accommodated by the distended pulmonary chan-
nels until the heart is again capable of propelling it. A hyperemia of a
more permanent kind, however, must result whenever the left ventricle
is unable to relieve the lungs of a normal quantity of blood. A con-
dition of the kind must arise during stenosis or regurgitation of the
mitral or aortic valves. The lesser circuit, therefore, is capable of
acting as a reservoir, the purpose of which is to equalize the flow
through the heart.
The measurements of the pressure and flow in the pulmonary
^artery meet with serious difficulties, because the insertion of a cannula
this blood-vessel or in any of its branches necessitates in many
Lnimals the opening of the pleurae and a temporary blocking of the
►ulmonary circulation. In rabbits, however, it is possible to gain
free access to the heart by simply dividing the sternum in the median
le.^ As the pleural sacs do not quite reach to this line, they need
lot be opened and artificial respiration need not be resorted to. Beut-
ner^ has given the following values which have not been materially
changed in more recent years:
Dog 28-31 mm. Hg
Cat 15-19 mm. Hg
Rabbit 9-17 mm. Hg
[These figures harmonize completely with the fact that the right ven-
tricle develops much lower pressures than the left, without, however,
causing the usual systolic-diastolic differences to disappear. But as
the latter show oscillations of only about 15 mm. Hg, as against 30-
40 mm. Hg in the systemic circuit, their range is rather limited. In
^ Tigerstedt, Ergebnisse der Physiol., ii, 2, 1903; also see: Burton-Opitz, Am.
Jour, of Physiol., xxxvi, 1914, 64.
2 Knoll, Sitzungsber., Ak., Wien, xcvii, 207, 1888.
3 Zeitschr. flir rat. Med., N. F., ii, Ser., 1882; also see: Bradford and Dean,
Proc. Royal Soc, London, 1889, and Schafer, Quart. Jour, of Exp. Physiol., xii,
1919, 133.
432 THE NERVOUS REGULATION OF THE BLOOD-VESSELS
general, therefore, it may be said that the pressure in the pulmonary
blood-vessels is retained at a more constant height, amounting to
about one-fifth of that generally obtained in such arteries as the car-
otid and femoral.
In this connection it should be remembered that the heart and
large vessels are not fully exposed to the atmospheric pressure, but to
the atmospheric pressure less the elastic pull or recoil of the lungs.
Furthermore, this force must be of greater consequence in the case of
the soft veins than in that of the more soUdly built arteries. With
the glottis opened, the respiratory surface of the lungs is, of course,
fully exposed to the atmospheric pressure. In the second place, it
should be remembered that the inspiratory movements increase this
negative pressure in the thorax and tend, therefore, to augment the
aspiratory action upon the central blood-vessels. This accounts for
the fact that the pulmonary vessels are more fully dilated during
inspiration and offer at this time a lesser resistance to the through
flow of the blood. 1
The velocity of the flow through the lungs is much greater than that
through the vessels of the systemic circuit. It has been found that
about one-fifth of the total circulation-time is used up in the passage
of the blood through this organ. Stewart,^ for example, has shown
that the average time required by the blood to complete its journey
from the right to the left side of the heart, amounts to 8.7 seconds in
a dog weighing about 12 kg. and to 10.4 seconds in a dog weighing
about 18 kg. If appUed to man, these figures indicate that the
circulation- time for the pulmonary circuit is about 15 seconds.
The existence of vasomotors in the lungs is still an open question,
because their recognition is made difficult by the fact that satisfactory
test conditions cannot easily be established. Whether the animal be
made to respire normally (rabbit) or artificially (dog), the constant
mechanical action of the lungs upon the blood-vessels must neces-
sarily tend to destroy any variations in the pressure and flow of a
true vasomotor kind. Furthermore, this difficulty cannot be overcome
by keeping the lungs distended with a constant current of air, nor is
it possible to improve the experimental conditions by perfusing the
quiescent organs with a nutritive fluid. In either case, the pulmonary
circulation cannot be considered as being carried on under conditions
at all comparable to normal.
The foregoing statement explains in a way the diversity of the
results obtained. Bradford and Dean,^ for example, have decided
in favor of the existence of pulmonary vasomotors, their conclusions
being based upon differential records of the blood pressm-e in the car-
otid and pulmonary arteries during stimulation of the third, fourth and
^ DeJager, Pfliiger's Archiv, xxvii-xxxix, 1879-1886.
2 Jour, of Physiol., xv, 1894, 1.
3 Ibid., xvi, 1894, 34.
THE CIRCULATION THROUGH SPECIAL ORGANS 433
fifth thoracic spinal nerves. Brodie and Dixon, ^ on the other hand,
deny their presence, and state that the excitation of the vagus or
sympathetic nerve does not cause a significant alteration in the rate
of perfusion through an isolated lung. Similar results have been ob-
tained by Burton-Opitz,^ who measured the blood flow in the pulmo-
nary artery with the aid of the stromuhr. The -use of adrenalin
has failed to decide this matter one way or another. In the hands of
the investigators just named, this agent has given negative results,
while Plumier^ has found that the flow through a perfused lung may be
diminished by adrenalin. A diminution in the flow is also said to
follow the stimulation of those sympathetic fibers which pass between
the first thoracic ganglion and the pulmonary plexus. It is conceded,
however, that the changes so obtained are slight and not absolutely
constant. This result serves as an argument against an active be-
havior of the pulmonary blood-vessels, because true vasomotor reac-
tions are always of an amplitude which makes the use of very delicate
means for their detection superfluous.
C. THE PORTAL AND RENAL CIRCULATIONS
The portal system embraces those abdominal organs which drain
their blood into the vena portse, a large venous tube formed by the
union of the vencB mesentericce and the vena gastroUenalis. Before this
channel enters the hilus of the liver it receives another vein of consider-
able size, namely the vena pancreatica. Centrally to the liver, the
blood is conducted into the inferior vena cava by the hepatic veins.
As the name indicates, the mesenteric veins return the blood from the
intestines, while the gastrolienalis collects it from the spleen and the
largest part (left) of the stomach. The remaining portions of this
organ, as well as the principal mass of the pancreas and the middle and
upper segments of the duodenum, are drained by the pancreatic vein. ^
The arterial supply of these organs is obtained first of all from the
celiac axis which divides into three branches, namely: (a) the hepatic
artery which supplies the framework of the liver, the body of the pan-
creas, and the adjacent portion of the duodenum, (h) the gastric artery
which ramifies upon the right expanse of the stomach, and (c) the
splenic artery which passes to the spleen, the cauda of the pancreas
and the neighboring left segment of the stomach. The intestine
receives its blood from the superior and inferior mesenteric arteries.
The organs just enumerated are innervated, on the one hand, by
the vagi nerves and, on the other, by the greater and lesser splanchnic
nerves. The former terminate in the region of thegastro-esophageal
1 Jour, of Physiol., xxx, 1904, 476.
2 Proc. Soc. of Exp. Med. and Biology, 1904.
^ Jour, de physiol. et de pathol. generale, vi, 1904.
^ This description appHes to the dog. More complete data may be obtained
)m EUenberger and Baum's Anatomie des Hundes, BerUn, 1891.
28
434 THE NEEVOUS REGULATION OF THE BLOOD-VESSELS
junction, where the united ventral vagus forms the plexus gastricus
anterior, and the dorsal vagus, the plexus gastricus posterior. Both
plexuses are intimately connected with one another by fibers and com-
municate with the abdominal gangha of the sympathetic system by
direct rami to the plexus suprarenalis. The plexus gastricus ventralis
also gives off fibers which pass along the lesser curvature of the stom-
ach and eventually ramify upon the pylorus where they unite with the
plexus hepaticus.
It is a well-known fact that the vagi nerves convey musculo-
motor and sensory impulses to and from the stomach and the other
organs of the abdomen. ^ They do not, however, seem to possess a
true vasomotor function. It should be mentioned at this time that
the excitation of the vagus frequently produces very decided reduc-
tions in the blood supply of the stomach and intestine, which are not
due to the inhibition of the heart nor to an active constriction of the
blood-vessels, but ^re dependent upon the peristaltic motion invariably
ehcited by the stimulation of this nerve. The influence of the inhib-
itor action of the vagus upon the heart and blood flow may be avoided
by simply stimulating this nerve at any point below this organ or
by administering an adequate amount of atropine to paralyze the
inhibitor mechanism. The perseverance of these vascular changes,
even after these precautionary measures have been taken, must
lead us to conclude that the contraction of the gastric and intestinal
walls lessens the size of the blood-bed and thus diminishes the blood
flow in a perfectly mechanical manner.
The vagi, however, form a most important afferent path by means
of which the organs of the abdomen are connected with the central
nervous system. They are concerned, therefore, with the production
of numerous reflex actions, such as (a) the inhibition of the heart ^ in
consequence of strokes upon the region of the stomach (plexus Solaris),
(6) the systemic vasomotor and cardiac disturbances occasioned by
chemical and mechanical irritation of the intestine, (c) the referred
symptoms accompanying inflammatory reactions in any part of the
abdominal cavity, and others.
Like the vagi, the splanchnic nerves are efferent and afferent in
their function. They form the connection between the thoracic and
abdominal ganglia of the sympathetic system. Beginning at the
ganglion stellatiim, a number of fibers pass downward along the spinal
column to be constantly augmented by fibers derived from the differ-
ent spinal nerves (Fig. 226). Opposite the thirteenth rib, this nerve,
which is known as the thoracic sympathetic, divides into the splanch-
nicus major and the sympatheticus abdominahs. The former pierces
the diaphragm and passes toward the adrenal body, where it ramifies
extensively, forming here the so-called plexus suprarenalis. The lat-
1 Burton-Opitz, Pfliiger's Archiv, cxxxv, 1910, 205.
^ As we are here concerned solely with reflexes upon the circulatory system,
the accompanying inhibition of the respiratory action is not considered at this time.
this problem with the help of Gad's pneumatograph^ which consists
of a square box with double walls, the space between them being filled
with water (Fig. 249). The cover of this air-chamber is fastened
with hinges on one side, but is freely movable along its other three
sides. If air is breathed from or into its central compartment, the
cover moves down or up, its excursions being registered upon the paper
of a slowly revolving kymograph.
Quantities of Air Respired. — A full grown man inspires and expires
about 500 c.c. of air with each respiratory act, the expiratory volume
being slightly larger on account of its expansion by heat. This is
called the tidal air. By the deepest possible inspiration an additional
quantity may be accommodated which amounts to at least 1600 c.c.
This is the complemental air. Quite similarly, the most forcible
expiration relieves the lungs of about 1600 c.c. of air in addition to
the 500 c.c. of tidal air. This amount is designated as the supple-
Fig. 249. — Gad's Pneumatograph.
mental air. It is to be noted, however, that even the most forcible
expiratory effort does not empty the lungs completely. A certain
quantity is always left behind, because the lungs do not collapse
even during forced expiration, but remain in a condition of partial
distention. This air, which cannot be expelled normally, is the residual
air. Its amount has been estimated at 1000 to 1200 c.c.^ Its func-
tion, obviously, is to prevent the alveolar walls from collapsing, because
in this eventuality very much greater muscular efforts would be re-
quired to subject these cells again to a normal degree of inspiratory dis-
tention. Furthermore, it must be evident that this partially expanded
condition of the lungs favors a free movement of the blood through the
pulmonary capillaries. In this connection brief reference should also
be made to the fact that the residual air cannot be removed in its
entirety even by opening the thorax and by permitting the lungs to
collapse. Neither can this end be attained by exerting a gentle
pressure upon the surfaces of the excised organ, because the walls
1 Archiv fiir Anat. und Physiol., 1879, 181. Modifications of this spirometer
have been constructed by Durig (Zentralbl. fiir Physiol., xvii, 1904, 258), Gutz-
mann (Mediz. Klinik, 1910), and Zwaardemaker (Archiv intern, de laryngologie,
1906).
2 Jacobson, Pfluger's Archiv, xliii, 1888, 236.
FREQUENCY AND CHARACTER OF RESPIRATORY MOVEMENTS 481
of the small bronchial tubules have come together before the in-
fundibula have been completely emptied. In this way a portion
of the residual air has been entrapped in the different air cells. This
constitutes the minimal air. It is possible to remove it, however by
chemical means ; for example, by displacing it with oxygen and carbon
dioxid and bringing it in contact with water. A lung so treated ceases
to float.
From the foregoing discussion it may readily be gathered that the
reserve amount of air which is contained in the lungs at the end of a
quiet expiration, following a quiet inspiration, amounts to about
2500 c.c. and consists of the residual and supplemental portions.
It is designated as the stationary air. The term vital or respiratory
capacity signifies the quantity of air which may be expelled from the
lungs by the most forcible expiration after the deepest possible in-
spiration. It includes the tidal, complemental and supplemental por-
tions and may, therefore, be estimated at 3700 to 4000 c.c. If to this
quantity is added the residual air, the lung capacity is obtained, which
in round numbers may be said to equal 5000 c.c. The term bronchial
capacity refers to the quantity of air which is accommodated in the
trachea and bronchi. It is generally estimated at 140 c.c. so that only
360 c.c. of the 500 c.c. of tidal air are actually forced into the deeper
passages of the lungs. ^ What bearing this fact possesses upon the
interchange of the gases will be seen later. While it is true that these
figures allow us to draw definite conclusions regarding the respiratory
power of an individual, no special clinical value can be attached to
them, because they may be materially increased by practice and are
subject to a number of conditions, such as posture, age, sex, race,
and occupation. Mountaineers, for example, possess a greater
respiratory capacity than the inhabitants of lowlands.
These data now permit us to compute the quantity of air respired
by an adult person during a given period of time. Assuming that the
respiratory frequency is 15 in a minute and that the tidal air amounts
to 500 c.c, then 7.5 liters are breathed in a minute, 450 liters in an
hour, and more than 10,000 liters in the course of a day. It is from
this enormous quantity of air that the oxygen requirement of our
tissues is satisfied.
Modified Respiratory Movements.— The rhythmical enlargement
of the thorax has as its object the ventilation of the lungs so that a
proper interchange of the gases may be had between the intrapulmonic
air and the blood. Under certain conditions, however, the respiratory-
current of air is employed during brief periods of time for other pur-
poses, this change generally necessitating a modification of either
the inspiratory or expiratory movement. Acts of this kind are speaking,
singing, coughing, sneezing, sighing, laughing, crying, sobbing, hic-
cough, yawning, and snoring; in fact, if other species of animals are
here taken into consideration, this list may be made to include a
1 Loewy, Pfliiger's Archiv, Iviii, 1894, 416.
31
482 RESPIRATION
great number of noises and sounds, such as barking, neighing, purring,
roaring, bellowing, bawling, whining, braying and growling.
Some of these reactions are voluntary in their nature, others involuntary;
furthermore, while some of them are undertaken in consequence of a definite
mental concept, others lack a central cause and are reflex in their character. In
many cases the latter do not possess a local cause, but are the result of irritations
in other parts of the body. Thus, coughing frequently arises from inflammatory
reactions in the intestines, stomach, liver, ovaries or uterus, while hiccough is
commonly associated with irritations in the stomach, liver or nerve centers. Being
reflex in their character, it is possible at times to inhibit these reactions by setting
up simultaneous afferent impulses. Sneezing, for example, may be prevented by
firmly pressing the finger upon the upper lip, while the act of yawning may be
inhibited by a sudden cutaneous stimulus.
As far as the respiratory movements are concerned, coughing may be defined
as an interrupted expiration, the interruption being due to the partial closure of the
glottis. But, in order that its purpose may be achieved, which, obviously, is the
dislodgment of the irritating body from the respiratory passage, it is necessary
to have an adequate supply of air on hand. For this reason, this action is commonly
preceded by an inspiration. The air is then ejected through the mouth, the glottis
being forced open by the abrupt compression of the intrapulmonic air iri consequence
of the contraction of the accessory muscles of expiration. Sneezing is accomplished
in practically the same manner. In this particular case, however, the expiratory
blast of air is forced through the nasal cavity, the glottis being widely opened,
while the cavity of the mouth is shut off from that of the pharynx by the approxi-
mation of the base of the tongue to the soft palate. This act is also initiated by a
deep inspiration. Sighing is a deep and prolonged inspiration. Brief, jerky
inspiratory efforts, made with the mouth closed, constitute the act of sniffing.
If the mouth and glottis are kept open, while the vocal cords are thrown into vibra-
tion by an expiratory blast which is repeatedly interrupted, the phenomenon of
laughing results. Crying is differentiated from laughing by the rhythm of the
movement and the position of the facial parts. Sobbing consists of a series of
spasmodic inspirations, with partially closed glottis, which are followed by a
prolonged expiration. Hiccough is produced by the spasmodic contraction of the
diaphragm, the inspiratory motion being suddenly arrested by the closure of the
glottis. In yawning a deep inspiration is taken with the mouth and glottis widely
open; the succeeding expiration is short. Snoring results if the relaxed uvula
and soft palate are thrown into vibration by the inflowing and outflowing air.
Artificial Respiration. — Conditions arise at times when it becomes
necessary to maintain an adequate ventilation of the lungs by arti-
ficial means. The methods then commonly practised may be divided
into two groups, namely, those devised to expand the lungs from with-
out, as in normal breathing, and those effecting their rhythmic in-
flation through the trachea by air held under pressure. Artificial
respiration is resorted to very frequently during laboratory experi-
ments in order to allow us to open the chest without actually destroying
the life of the animal. In other cases, it becomes imperative to venti-
late the lungs artificially until the cause of the respiratory stoppage
has been removed. For example, if an overdose of ether has been
given, the prompt employment of artificial respiration generally
serves to tide the animal over this period, because in most instances
the heart does not cease to act until sometime after the stoppage of
respiration. In fact, if this organ has already ceased to beat, it may
FREQUENCY AND CHARACTER OF RESPIRATORY MOVEMENTS 483
at times be reactivated by the prompt institution of artificial respira-
tion, massage of the abdominal viscera and central blood-vessels,
elevation of the posterior extremities, injections of adrenalin and other
measures.
In animal experimentation artificial respiration meets with prac-
tically no difficulties, although its use upon human beings must neces-
sarily remain restricted to the most favorable cases. Thus, it can-
not yield beneficial results if the respiratory abeyance possesses a per-
manent pathological cause. Still, it cannot be doubted that it deserves
a much wider application than is accorded it at the present time,
when it is employed, and not always in a very scientific and efiicient
manner, in cases of drowning, asphyxiation by poisonous gases, and
suspended animation from electrical shocks or pressure upon nerve
Fig. 250. — Shows the Position to be Adopted for Effecting Artificial Respiration
IN Cases of Drowning. (Schaefer.)
centers. Whatever the method employed, and whether in animals or
man, artificial respiration must always be practised in closest imitation
of the normal rate and depth of the respiratory movements. Too
vivid a ventilation is almost as injurious as a subnormal one. Before
the attempt is made to distend the lungs, the respiratory passage must
be cleared of all obstructions, such as mucus and water. The mouth
must be opened widely and the tongue drawn out so as to prevent its
tip from becoming lodged behind the fauces. All tight clothing must
be removed.
In imitating the normal expansion of the lungs, Sylvester proceeds
as follows: The patient is placed on his back, with the head and
shoulders supported upon a firm cushion somewhat above the level
of the feet. The operator places himself at the patient's head, grasps
the arms just above the elbows and draws them upward above the
head. Having kept them in this position for two seconds, they are then
pressed gently but firmly against the sides of the chest during an equal
period of time. Galliano retains the arms in Sylvester's position,
so that the thorax remains in the expanded condition continuously.
Her then presses at intervals of three seconds with the flat hands
484 RESPIEATION
against the sides of the thorax and epigastric region. This procedure
may also be followed if the patient is placed in the supine position with
his arms resting against the sides of his body. A method, which is
commonly employed in the resuscitation of animals is the following:
The body is raised free from the floor by the hind limbs. The mouth
is opened and the tongue pulled out synchronously with the compression
of the thorax which is effected by placing the flat hands from behind
upon the sides of the lower part of the chest. Schafer^ suggests that
the patient be placed in the prone posture, a heavy garment being
placed underneath his chest and epigastrium. The operator assumes
a kneeling position beside the legs of the patient and, bending forward,
rests his flat hands against the sides of the lower part of the thorax,
so that the tips of his thumbs come to lie close to the vertebral column.
By gradually permitting his weight to be supported by his arms, the
chest is pressed upon and air is forced out of the lungs. On releasing
this pressure, the parts return into their original positions and cause
the air to flow in.
The methods which purpose to distend the lungs with air held under
pressure, are most commonly employed in long-continued experiments
upon animals, but may also be used in resuscitating human beings.
Thus, the expansion of the lungs of the new-born may be frequently
facilitated by blowing air into these organs, the mouth of the operator
being placed against that of the infant. In the laboratory, it is cus-
tomary to expose the trachea of the animal and to insert in it a rectangu-
lar cannula which in turn is connected with a pair of bellows. In
experiments of longer duration it is advantageous to employ a power
pump which it is possible to regulate in such a way that a different
rate and amplitude of respiration may be obtained within a few mo-
ments. The deflation of the lungs may be greatly hastened by the
withdrawal of the air by slight suction. ^
This principle is made use of in the construction of the so-called
pulmotor or lungmotor,^ a small force-pump intended to be employed
upon human beings. It is worked by hand and possesses safeguards
in the form of adjustable valves. It may readily be surmised that the
method of inflation through the mouth cannot present any unusual
difficulties in unconscious persons, but is not easily executed when
consciousness has again been established, because the current of air
is then strongly opposed by the voluntary muscles in the region of
the glottis, and may in addition be counteracted by those of the thorax.
By endeavoring to overcome this resistance serious injury may be in-
flicted upon the lung tissue, but the conscious subject may overcome
these reflexes by remaining passive and by making inspiratory move-
ments in unison with the ingoing blast of air. Tracheotomy obviates
1 Jour, of the Amer. Med. Assoc, li, 1908, 801.
^ A most satisfactory respiration machine has been described by Hoy t, Jour,
of Physiol., xxvii, 1901, 48.
3 Henderson, Jour. Am. Med. Assoc, Ixvii, 1916, 1.
FREQUENCY AND CHARACTER OF RESPIRATORY MOVEMENTS 485
this difficulty in some measure, but this procedure cannot be resorted
to in human beings unless undertaken as a last means to save life.
The manual method of artificial respiration possesses the advan-
tage that it can be applied almost immediately. A delay of more
than ten minutes should never result, because it is practically impossi-
ble to restore life if this period of time is exceeded. Furthermore, it
is to be remembered that the body becomes entirely flaccid in the
Fig. 251. — Device to Illustrate the Influence of the Respiratory Movements
UPON THE Flow of the Blood through the Pulmonary Blood-vessels. (Hering.)
A, bell jar; B, rubber membrane closing it; V, soft rubber pouch to imitate the
pulm. blood-vessels; GH, arrangement for forcing water through V under a constant
pressure; j, manometer connected with "intrapleural space." On inspiration, pro-
duced by moving the rubber membrane downward, the intrapleural pressure is de-
creased. This gives rise to an aspiration which tends to pull the wall of V outward,
facihtating the flow from G to H.
course of ten or fifteen minutes,^ and that it is then practically impos-
sible to ventilate the lungs by means of pressure with the hands. Res-
piration not having been restored within this time, it is advisable
to resort to the method of inflation, but the apparatus should be placed
in the hands of a thoroughly experienced operator.
It is a well-known fact that the arterial blood pressure rises during
inspiration and falls during expiration, while the venous pressure rises
1 Liljestrand, Wollin and Nilsson, Skand. Archiv fiir Physiol., xxix, 1913, 198.
486 RESPIRATION
during the latter and falls during the former period. These changes,
which are commonly referred to as the respiratonj variations in blood
pressure, are reversed during inlBation. It is easily conceived that
the establishment of a positive pressure in the pulmonary pas-
sages, corresponding to the normal inspiratory motion, must tend to
compress the pulmonary capillaries, thereby producing a stagnation in
the venous channels and right side of the heart and a deficiency in
its left side and arterial outlets. Just the opposite effect is produced
during the period of deflation. Inasmuch as the pressure is now
removed from the alveolar walls, the pulmonary blood-bed must be
enlarged, allowing a greater quantity of blood to reach the arteries.
For this reason, we obtain an inspiratory fall in arterial pressure and
an expiratory rise, while, on the venous side, the pressure rises during
inflation and falls during deflation.
The methods of artificial respiration previously enumerated are
intended to effect either a rhythmic expansion or a rhythmic infla-
tion of the lungs. But it should not be forgotten that these organs
may also be retained in a distended condition by the procedure of
constant insufflation.^ A long rectangular piece of tubing is inserted
through the larynx until its free end comes to lie at the bifurcation
of the bronchi. A steady stream of air is then permitted to flow
through this tube until the thorax assumes a position of moderate
distention. Care must be exercised, however, that the outflow of
air along the sides of this tube be not hindered in any way, because
an excessive positive pressure gives rise to an immediate fall in arterial
pressure dependent upon a compression of the pulmonary capillaries.
CHAPTER XXXIX
THE CHEMISTRY OF RESPIRATION
The Character of the Inspired and Expired Air. — The gaseous
metabolism of the tissues consists, on the one hand, in a constant
acquisition of oxygen and, on the other, in an evolution of carbon
dioxid. This change from one into the other is not accomplished
in a direct way, but only with the help of several intermediate reactions
which together constitute the process of oxidation. Obviously,
the purpose of these reactions is the reduction of the carbon and
hydrogen of the food and the liberation of energy in its different forms.
The blood and lymph serve as the medium in which this assimilation
and dissimilation is effected, while the lungs enable these body
1 Meltzer, Jour. Am. Med. Assoc, Ivii, 1911, 521, also, Zentralbl. fiir Physiol.,
xxvi, 1912, 161.
THE CHEMISTRY OF RESPIRATION 487
fluids to exchange their gaseous constituents with the surrounding
air. Respiration, therefore, consists of two processes, namely, an
interchange between the outside air and the blood and an interchange
between the latter and the cellular components of the tissues. The
former process is known as external respiration and the latter, as in-
ternal respiration.
The fact that the general metabolism of an animal necessitates
an intake of oxygen and an outgo of carbon dioxid may readily be
gathered from a comparison of the chemical and physical character-
istics of inspired and expired air. Concerning the former, it should
chiefly be remembered that the inspired air contains more oxygen
and less carbon dioxid than the expired. The figures in volume per
cent, generally given arathe following:
N O CO2
Inspired air 79.00 20.96 0.04
Expired air 79.50 16.02 4. 10
4.94 4.06
Argon, krypton and neon are not included in this table, because
they have not been shown to possess a definite function.^ Besides,
it should be remembered that these figures are subject to slight
variations, because inasmuch as the composition of the inspiratory
air differs somewhat in different localities, the expiratory air must
present very similar fluctuations. In addition, the latter exhibits
certain minor changes which are caused by periodic variations in the
depth of the respiratory movements and intensity of the tissue metab-
olism. In general, however, it may be said that the air loses during
its sojourn in the lungs 4.94 volumes of oxygen and gains 4.34 volumes
of carbon dioxid. Its content in nitrogen remains practically the same.
These analyses also show that the volume of oxygen retained is
larger than the volume of carbon dioxid given off, which fact seems
to indicate that a fractional amount of the former gas is excreted as
water. In the second place, the constancy of the nitrogen proves that
it possesses no respiratory value other than that it serves as the medium
in which the diffusion of the other two gases is enacted. It is to be
noted, however, that the expired air generally contains a slight quantity
of cellular material which on analysis tends to heighten the percentage
amount of nitrogen. In round figures this increase is usually esti-
mated at 0.4 per cent. The expired air may also contain traces of
hydrogen and methane which in all probability find their origin in
fermentations in the intestines.
Regarding the physical characteristics of the respired air, it is noted
that the expired air is warmer than the inspired ; but naturally, its actual
temperature varies considerably, because the temperature of the in-
spired air fluctuates with the time of the year and the conditions under
which the animal is living. Besides, much depends upon the rapidity
1 Regnard and Schloessing, Compt. rend., cxxiv, 1897, 302.
488 RESPIRATION
and depth of the respiratory movements, the intensity of the metab-
oHsm, and other factors. Under ordinary conditions, however,
air of 20° C. is warmed to the temperature of the body, or nearly so,
while, at lower temperatures, the rise as such may be greater but does
not reach 37° C. At 6.3° C, for example, the inspired air is heated to
29.8° C. The greatest heat absorption takes place in the deeper
respiratory channels, while the difference in the temperature of the
outside air and that in the lower portion of the trachea amounts to
only a few degrees centigrade. It is evident, therefore, that this loss
of body-heat is effected very largely through the blood of the pulmonary
circuit and adjoining venous trunks. This fact is made use of in the
open air treatment of respiratory diseases for purposes of lowering
the body-temperature. Ordinarily, of course, the respiratory tract
of man does not play an important part in heat dissipation, but
some animals, and especially those possessing a thick covering of
hair, are almost wholly dependent upon this channel for the regula-
tion of their body-temperature.
In consequence of this absorption of heat, the intrapulmonic air
increases in volume and becomes nearly saturated with water, but
if the necessary corrections are made for the temperature and pressure
and if the aqueous vapor is driven off, its volume is slightly less than
that of the inspired air (Hso part). This loss is accounted for by the
fact that a small portion of the oxygen is not given off as carbon dioxid,
but is either united with the sulphur of the proteins or is used in the
oxidation of the hydrogen. In the latter case it reappears as water.
It will be seen, therefore, that the body loses a certain amount of its
heat in the form of bound heat, because a portion of it is set aside for
the purpose of warming the air in the pulmonary passages, and a
portion for the purpose of converting the water into the gaseous state.
This aqueous vapor in the expiratory air is of considerable physiological
importance, because at 37° C. its tension amounts to 50 mm. Hg.
Assuming, therefore, that dry air is being breathed at the ordinary
pressure of 760 mm. Hg, the tension in the deeper recesses of the lungs
would amount to only 760 — 50 = 710 mm. Hg. Thus, the lungs
serve not only as a means of regulating the body-temperatm-e, but
also as a means of adjusting the water content of the tissues. The
expired air is also prone to contain extraneous material, consisting
chiefly of fragments of the lining of the pulmonary passage.
The Interchange of the Gases Between the Tidal Air and the
Blood. — It has previously been shown that the quantity of air shifted
with each respiratory movement is relatively small, amounting on
an average to only 500 c.c. For this reason, it must be evident that
only the outer respiratory passage is ventilated with each respiration,
while the air in the infundibula remains stationary. Consequently,
the interchange of the gases between the outside air and the blood,
which is commonly designated as ''external" respiration, consists
in reality of two processes, namely (a) the shifting of the tidal air in
THE CHEMISTRY OF RESPIRATION 489
mass and (h) the atomic movement of the constituents of the air in the
deeper recesses of the lung. Thus, we have, on the one hand, an alter-
nate inward and outward movement of definite quantities of air and,
on the other, an atomic interchange of the gases between the tidal
air and the blood directly through the walls of the alveoli and capillaries.
The former is a movement of a definite mass of air as a whole and the
latter, a progression of the atoms of the gases in accordance with
their diffusion pressures and other properties.
The interchange of the gases between the tidal air and the blood
has been explained in a physical and in a chemical way. The former
explanation, which is commonly accepted to-day, is based upon the
ordinary physical laws of the diffusion of gases, while the latter neces-
sitates the assumption that the cells lining the alveoli possess a
definite vital activity, leading to a secretion of the gases through this
membrane.
The physical theory, first of all, recognizes the fact that the gases
in the minute air spaces and in the blood are separated from one
another by a permeable membrane formed by the lining cells of the
alveoli and capillaries. If it is now assumed that the partial pressures
of these gases are the same on the two sides of this membrane, an
equilibrium must exist which renders the diffusion equal in both direc-
tions. But in as much as the body makes constant use of the oxygen
and yields in turn carbon dioxid, the region on the inner side of this mem-
brane must give lodgment to relatively miich smaller amounts of oxygen
and much larger amounts of carbon dioxid than the outer region.
Consequently, the partial pressure of the oxygen in the blood must be
considerably below that in the alveoli and adjoining larger air passages,
while the tension of the carbon dioxid must be greater in the blood.
Obviously, therefore, the atoms of oxygen must progress from without
to within, while the molecules of carbon dioxid must flow from within to
without. Inasmuch as the body does not make use of the nitrogen,
this gas remains "stationary, " and serves mostly as the medium for the
diffusion of the other two gases. It should be remembered, however,
that the term "stationary" is only a relative one, because an actual
standstill of the atoms of nitrogen, or of any other gas, is not in accord
with our modern conception of the behavior of gases. Even when
resting, their atoms move about constantly, although they do not ad-
vance in large numbers in any one particular direction.
On further inquiry into the conditions prevailing in the intrapul-
monic spaces, it is found that the capacity of the bronchial tree is
only 140 c.c. and that the air contained therein possesses practically
the same composition as the atmospheric. Consequently, the partial
pressure of the oxygen in these spaces must amount to 152 mm. Hg
and that of the carbon dioxid to practically zero. Keeping these facts
firmly in mind, let us see how great a partial pressure these gases
exert in the alveoli and in the blood entering the lungs. These values
can only be ascertained by a chemical analysis of the air resident
490
KESPIRATION
in the alveoli themselves, because as the air from the deeper recesses
of the lungs moves outward, it intermingles with that contained in
the outer passages, and gives rise to a disproportional relationship of
the gases. For this reason, an analysis of ordinary expiratory air
cannot yield exact results. It is possible, however, to determine its
mean oxygen and carbon dioxid content
by collecting the last portions of the air
expelled by two forced expirations, one
of which follows a normal inspiration
T^ J I 'r~~il ^^^ ^^® other, an ordinary expiration
^T II 1 (Haldane).
Zuntz and Loewy have calculated
the composition of alveolar air by con-
trasting the capacity of the bronchial
tree with that of the alveoh. Thus, if
the volume of the expiratory air is
reckoned at 500 c.c, 140 c.c. of this
amount must be derived from the bron-
chial tree and 360 c.c. from the deeper
recesses of the lung. Furthermore, if
the expired air contains 4.38 per cent,
of carbon dioxid, the alveolar air must
embrace 4.38 -^ ^%5, or 6 per cent, of
this gas. Actual analyses upon human
beiQgs have not yielded absolutely con-
stant values, but show variations be-
tween 11 and 17 per cent, of an atmos-
phere for oxygen and between 3.7 and
6.2 per cent, of an atmosphere for carbon
dioxid. The average percentage of
oxygen, therefore, may be estimated at
14.5, that of carbon dioxid at 5.5, and
that of nitrogen at 80. Thus, it will be
seen that the oxygen tension in alveolar
air amounts to 109 mm. Hg and that of
carbon dioxid to 40 mm. Hg. If these
figures are now compared with those
given previously for the air in the bron-
chial tree (tidal air), it is evident that
the atoms of oxygen must flow from with-
out to within, and the molecules of car-
bon dioxid from within to without.
Fig. 252. — Diagram to Show
THE Principle of the Aerotono-
METER.
A, the tube containing a known
mixture of gases, O, CO2, N; C,
the outside jacket for maintain-
ing a constant body temperature.
When stopcock b is open the
blood trickles down the sides of A
and enters into diffusion relations
with the contained gases. After
equilibrium is reached the stop-
cock b is closed and a is opened.
By means of the mercury bulb the
gases can then be forced out of A
into a suitable receiver for analy-
sis. (Howell.)
In further analysis of this subject matter let us now ascertain whether this
relationship also prevails between the alveolar air and the blood. The determina-
tion of the tension of the gases in the blood presents several difficulties, because
it requires the bringing together of the latter with different gases possessing
known tensions, until one is found with which it is in equilibrium. This end is
THE CHEMISTRY OF RESPIRATION
491
usually accomplished in a perfectly direct way with the help of an instrument
known as an aerotonometer. The apparatus, devised by Pfliiger, consists of two
glass tubes which are placed in a receptacle containing water at 37° C.^ One of
these is filled with a gaseous mixture having a greater and the other with a gaseous
mixture having a lesser partial pressure than is expected to be found in the blood
under examination. Thus, if it is our intention to determine the tension of the
CO2 in venous blood, which may be estimated at about 4 per cent., one of these
tubes is filled with a mixture containing 3 per cent. CO2, and the other with a
mixture containing 5 per cent. CO2. On permitting the blood to run in a thin
Fig. 253. — A, Krogh's Microtonometeb. B, Upper Part of Microtonometer
Showing Capillary Tube into Which the Bubble is Returned for Measurement and
Analysis.
layer down the walls of these tubes, it yields CO 2 to one mixture and abstracts it
from the other. The proportion of CO2 found in the mixtures at the end of the
experiment, forms the basis of the calculation of the partial pressure of thq CO2
in the blood, because this value corresponds to the partial pressure which would
have to prevail in the tubes in order that the blood be able to traverse them
without suffering a change in its CO 2 content.
The aerotonometer of Bohr^ embodies the principle of the stromuhr and
permits the blood to reenter the blood-vessel after it has been temporarily diverted
into the gas chamber. On this account, these determinations may be continued
for a much longer period of time, allowing a thorough equilibrium to be established.
Krogh^ uses a small bubble of air which is brought into contact with a correspond-
1 Modified by Fredericq, Zentralbl. fiir Physiol., viii, 1894, 34.
2 Skand. Archiv fiir Physiol., ii, 1900, 236.
3 Ibid., XX, 1908, 279.
492
RESPIRATION
ingly small quantity of blood until an equilibrium has resulted, which in this
case requires a much shorter time than by any of the procedures mentioned pre-
viously. The apparatus itself consists of a tonometer and a tubular receptacle
for the analysis of the gas bubble. The latter is first played upon by a small jet
of blood led in by a narrow cannula, its size being then measured by drawing
it into a graduate. The absorption of carbon dioxid and oxygen is carried out
in the usual manner by using potash and pyrogallic acid.
Another method frequently employed for the determination of the tension of
the gases in the venous blood of the lungs requires the use of a pulmonary catheter, ^
which consists of two tubes, one being situated within the
other. The outer tube is somewhat shorter than the inner,
C^i7 and is closed by a rubber balloon which after the insertion
^.- i of the catheter in the bronchus, is inflated until it com-
pletely blocks the respiratory passage. Samples of air
are then withdrawn through the inner tube at intervals,
until the diffusion of the gases between the alveoli and the
blood has continued long enough to establish an equili-
brium. Haldane and Smith^ have estimated the oxygen
tension in the arterial blood in the following manner:
The subject is permitted to breathe known quantities of
carbon monoxid until the hemoglobin has combined with
as much of this gas as it will acquire. The percentage
amount of this gas in the hemoglobin is then ascertained
in a sample of blood taken either from the finger or from
the lobule of the ear. Eventually, when the absorption
of carbon monoxid has ceased, its tension in the aerated
blood of the lungs will be the same as that in the inspired
air. The latter value, as well as the extent to which the
hemoglobin has been saturated with carbon monoxid,
being known, the tension of the oxygen in the blood leaving
the lungs is also known.
While the values obtained with these methods
show considerable fluctuations, it may safely be
concluded that the tension of the gases in the
arterial blood closely coincides with that of the
corresponding gases in the alveolar air. To be
exact, the carbon dioxid of the alveoli is always
under a slightly lower pressure than that of the
blood, while the oxygen is under a slightly higher
pressure. In the latter case, the difference amounts
to 1^ per cent, of an atmosphere; moreover, it has
been shown by Krogh to persist even if the com-
position of the alveolar air is altered artificially.
That is to say, while any change in the tension of
the constituents of the alveolar air is immediately followed by a cor-
responding alteration in the tension of the gases in the blood, the
oxygen pressure is always greater in the alveoli than in the blood,
whereas the carbon dioxid tension is higher in the blood than in the
alveoli.
Much greater differences have been ascertained in the venous
1 Loewy and Schrotter, Zeitschr. fiir exp. Pathol, und Therapie, i, 1905, 197.
2 Jour, of Physiol, xxii, 1897, 231.
Fig. 254.— Dia-
gram Illustrating the
Diffusion of the
Gases Between the
Tidal Air and the
Blood.
T, trachea; TA,
tidal air; B, bronchi;
/, infundibulum ; C,
capillaries; O, oxygen
atoms; CO2, molecules
of carbon dioxid.
THE CHEMISTRY OF RESPIRATION
493
blood leaving the heart, in which the tension of the oxygen is 5.3 per
cent. = 37.6 mm. Hg and that of carbon dioxid 6 per cent. = 46 mm.
Hg. If these values are now contrasted with those previously given
for the alveolar air, it is evident that the difference in the tension of
the oxygen amounts to 109 — 37, or 72 mm. Hg, and that of the carbon
dioxid to 46 — 40, or 6 mm. Hg. Consequently, the difference in the
tension of the oxygen on the two sides of the limiting membrane is
much greater than that of the carbon dioxid ; in either case, however,
it must be clear that the atoms of oxygen flow into the blood and the
molecules of carbon dioxid into the alveoli.
Oxygen,
mm. Hg
Carbon dioxid,
mm. Hg
Atmospheric air
152
109
i
00
Alveolar air
40
Membrane
T
Venous blood
37
46
Under normal conditions the lining cells of the alveoli and cap-
illaries offer no hindrance to the passage of these gases, the difference in
their partial pressures being sufficient to cause them to move in these
directions. At times, however, the orderly flow of the gases may be
greatly impaired by infiltrations of the lining cells or by serous mate-
rial exuded into the alveolar spaces in consequence of inflammatory
processes (pneumonia). As may readily be gathered, this difficulty
can be overcome in a measure by increasing the driving force behind
the atoms of oxygen. With this point in view, pure oxygen is some-
times substituted for the atmospheric air, the intention being to in-
crease the partial pressure of this gas so that at least a part of it will
be driven into the system. Obviously, pure oxygen possesses a
partial pressure five times greater than that of the oxygen in atmos-
pheric air.
Under normal conditions, however, the diffusion of the gases in
the lungs is amply protected, owing to the enormous expanse of the
respiratory surface. Upon the basis of 700,000,000 alveoli, possessing
an average diameter of 0.2 mm., Zuntz^ has estimated that the 3000 c.c.
of stationary air are in relation with 900,000 sq. cm. or 90 sq. m. of
surface. 2 Thus, it will be seen that each square centimeter of alveolar
surface is required to supply only 0.0003 c.c. of carbon dioxid in a min-
ute, the total diffusion of this gas in this period of time being calculated
at 300 c.c, namely, at 500 c.c. of tidal air X 0.04 per cent. X 15
respirations. The fact that the diffusion pressure is more than
sufficient to furnish the required amount of oxygen, may be gathered
1 Hermann's Handb. der Physiol., iv, 90.
^ Aeby, Bronchialbaum der Sauget. und des Menschen, Leipzig, 1880, 90.
494 RESPIRATION
from the following calculation of Loewy.^ The average thickness of
the membrane separating the alveolar air from the blood, amounts to
0.004 mm. In accordance with the diffusion rate of carbon dioxid
and nitrous oxid through the lung of a frog, the mammalian lung must
yield under a difference of pressure of 35 mm. Hg about 67 c.c. of oxy-
gen for each square centimeter of alveolar wall. The total absorp-
tion, therefore, amounts to 6083 c.c, a value much in excess of the
actual oxygen requirements of our body in quiet breathing. The lat-
ter is only about 250-300 c.c. It must be evident, therefore, that the
difference in the partial pressure of the oxygen could safely be much
reduced, and that a considerable portion of the total respiratory sur-
face could be rendered functionally useless, before a serious disturbance
in the normal supply of this gas would result. In the same way, it has
been established that the tension of the carbon dioxid in the blood
could be materially decreased without causing a fatal reduction in its
flow into the alveoli; in fact, as the speed of diffusion of this gas through
a moist membrane is twenty-five times greater than that of oxygen,
a difference in pressure of only 0.3 mm. Hg would suffice to yield the
250 c.c. of CO2 normally expired per minute.
The chemical theory necessitates the assumption that the cells
forming the alveolar lining, actively participate in the transfer of
the gases. This end is accomplished with the help of inherent proc-
esses which are very similar to those occurring in the cells of the
secretory glands. Hence, we find here a condition analogous to that
existing in the walls of the air-bladder of the fishes. Inasmuch as the
contents of this organ consist at times of as much as 85 per cent, of
oxygen, the partial pressure of this gas must amount to 90 atmospheres,
while that of the oxygen in the surrounding water scarcely exceeds J^
of an atmosphere (Biot). It must be obvious, therefore, that the air-
bladder of these animals is filled by a specific secretory activity of the
lining cells which is controlled by a special nervous mechanism. ^
The first attempt to show that the interchange of the gases in the lungs is not
one of simple diffusion was made by Bohr^ in 1890, but these results, indicating
that the oxygen tension of the blood frequently exceeds that of the alveolar air,
have been seriously criticised by Krogh, as well as by Haldane and Douglass. It
seems that certain errors in the manipulation of the aerotonometer and accidental
variations in the temperature have rendered these early determinations valueless.
In 1907 Bohr endeavored to substantiate his early contentions regarding the
secretory activity of the lung by the following experiment : If one lung is permitted
to obtain pure air and the other air containing 8.8 per cent, by volume of CO2,
the latter continues to give off CO 2 in spite of the fact that the tension of the CO2
in the venous blood of the right side of the heart equals that of an atmosphere
containing only 5 per cent, of this gas by volume.
This entire subject has recently been reinvestigated by Krogh,** whose micro-
aerotonometric tests have shown that the pressure of the CO2 in the arterial
1 Handb. der Biochemie, iv, 1908.
2 Bohr, Jour, of Physiol., xv, 1893, 494.
3 Skand. Archiv fiir Physiol., ii, 1890, 231.
* Ibid., xxii, 1910, 274.
THE CHEMISTRY OF RESPIRATION 495
capillaries and in the alveolar air is equal, and that the oxygen tension of the
latter is always slightly above that of the blood. In addition, attention has been
called to the fact that the pulmonary epithelium lacks all the essential char-
acteristics of a secreting membrane. In the mammals, for example, this lining
is composed, on the one hand, of small granular cells which are located in the
interstitial spaces between the capillaries and, on the other, of extremely thin
non-nucleated cells which are situated directly in the capillary wall- Besides,
this epithelial covering seems to be entirely lacking in birds, so that the surfaces
of the capillaries lie in direct contact with the air. Peculiarly enough, these
animals possess a very intense metabolism and must therefore be in a position to
interchange the gases with the greatest possible ease. In this connection, atten-
tion should also be called to the fact that the function of the pulmonary epithelium
cannot be deduced by analogy from that of the limiting membrane of the swim-
bladder, because the cells composing the latter are augmented by other cells which
form the so-called ''red glands" and exhibit true secretory properties. This same
statement could not justly be made regarding the lining cells of the alveoli. As
another point against the secretory theory might be mentioned the fact that the
respiratory activity may be altered at any time by increasing or decreasing the
CO 2 content of the inspired air or of that of the blood traversing the respiratory
center. Obviously, the assertion might be made that if the lining cells of the alveoli
were actually in possession of a secretory power, they should be able to resist
outside influences of this kind and should be under the direct control of the nervous
system.
Douglass and Haldane'^ have recently attempted to solve this problem in an
indirect way by the use of carbon monoxid. It will be remembered that this gas
combines with the hemoglobin of the blood to form the more stable monoxid
hemoglobin. Thus, if blood is exposed to a mixture of O2 and CO, a certain
portion of each gas eventually unites with the hemoglobin, but inasmuch as the
latter possesses a much greater avidity for CO than for O2, a much larger amount
of CO enters into this combination. Assuming that the same conditions prevail
in the body during the inhalation of CO, these authors permitted an individual
to breathe a certain quantity of this gas until the blood became fully charged
with it. The percentage saturation of the Hb by the CO was then determined.
This value may justly be regarded as indicating the O2 content of the blood, be-
cause the amount of this gas which must be inhaled simultaneously with the CO
in order to produce the saturation just ascertained, is open to direct calculation.
These tests which were supplemented by inhalations of varying quantities of
oxygen, showed that the pressure of the oxygen in the arterial blood remains
below that of the air in the alveoli until the saturation of the hemoglobin with
carbon monoxid surpasses 30 per cent. Beginning at this point, the oxygen
tension decreases and is finally reversed. This observation led Haldane to con-
clude that the epithelial cells of the alveoli play an active part in the interchange
of the gases. Thus, it is stated that these Hning cells gather the oxygen under a
tension of 15 per cent, and force it to the other side of the membrane until its ten-
sion in the blood greatly exceeds that in the alveoli.
Several objections may be raised against these experiments which render the
conclusions derived from them practically worthless. In the first place, it should
be noted that Haldane has employed the colorimetric method of estimating the
degree of saturation of the Hb by the CO, a method which has not as yet been
proved to be absolutely reliable. Secondly, it cannot rightly be assumed that the
avidity of the O2 and Hb remains the same throughout the course of these experi-
ments, and that the conditions under which these gases unite are the same in vivo
as in vitro. For these reasons, as well as others, Haldane has modified his previous
contention somewhat, and now seems to believe that the interchange of the gases
is accomplished under normal conditions by ordinary diffusion. Under abnormal
1 Jour, of Physiol., xliv, 1912, 305.
496 RESPIRATION
conditions, however, when the oxygen tension in the alveolar air is very low, the
lining cells may acquire a secretory power.
The Interchange of the Gases Between the Blood and the Tissues.
The Absorption of Gases by Liquids. — If a gas is brought into contact
with water, a certain number of its molecules enter the latter and be-
come dissolved, the amount absorbed being dependent upon the nature
of the gas, the temperature and the pressure under which it exists.
Provided that these factors remain unchanged, an equilibrium is
eventually established, during which the water retains a definite
quantity of the gas. But this condition of saturation does not signify
that the gaseous molecules remain absolutely stationary, because
in accordance with the kinetic theory of matter, it is commonly believed
that the molecular constituents of any entity are in constant motion.
In many cases, they pursue a definite course and collide with one another
so that they are deflected from their paths. It should be emphasized,
however, that molecular motion does not consist in incessant collisions,
because the distances which molecules actually traverse without
striking one another are relatively great. Furthermore, it cannot
be denied that these mechanical interferences seriously impede the
general progress of the molecules. But, while some of them may be
momentarily brought to a standstill, others are forced onward with
a certain momentum which makes them exceed their average velocity.
In the outer layers of the water, large numbers of these molecules
strike the walls of the receptacle and rebound, while elsewhere many
of them escape into the overlying mass of gas only to reenter the water
later on. In the state of saturation just as many molecules leave the
water as enter it.
If the preceding experiment is now repeated with a mixture of
gases, it will be found that practically the same interchange takes place,
the absorption of each constituent being proportional to the pressure
exerted by it, i.e., to its partial pressure. Thus, if the pressure of one
of the gases is greater in the atmosphere than in the water, it will
pass into the water, and vice versa. Moreover, it is to be noted that
the flow of this particular gas is independent of that of any other of
the constituents of this mixture and may be increased or decreased by
simply altering its partial pressure in one of these regions.^
The absorption behaves toward changes in temperature in an
inverse manner. Furthermore, inasmuch as these changes are not
proportional to one another, it becomes necessary to determine the
absorption for every degree of change in temperature. Thus, it has
been found that the volume of oxygen absorbed by one volume of
water at 0° C. amounts to 0.0489 c.c, that of carbon dioxid to 1.713
c.c, and that of nitrogen to 0.0234 c.c. At 15° C. the volume of these
gases absorbed equals 0.0310 c.c, 1.0025 c.c. and 0.0168 c.c,
respectively. As a means for comparison we have the so-called coeffi-
iLaw of Henry, Philos. Transact., 1803.
THE CHEMISTRY OF RESPIRATION 497
cient of absorption, by which is meant the quantity of a gas physically
absorbed or dissolved in 1 c.c. of a liquid at 0° C. and under a pressure
of 760 mm. Hg.^ Essentially the same changes result if a watery
solution is brought into relation with a mixture of gases, provided, of
course, that no chemical attraction arises between the substances
dissolved therein and the gases. It need not surprise us, however,
to find that the absorption is less now and gradually decreases as the
concentration of the solution is increased.
If a comparison is made between the pressure and the weight of the
gas absorbed, i.e., its density or the number of molecules in a certain
volume, it will be found that at a constant temperature the weight
of the volume absorbed increases and decreases in direct proportion
to the increase and decrease in the pressure. To illustrate, the volume
of oxygen absorbed by one volume of water at 0° C. and under a pres-
sure of 760 mm. Hg amounts to 0.0489 c.c. If the pressure is now
doubled, the volume absorbed remains the same, but its weight is
doubled. Quite similarly, a lowering of the pressure below 760 mm.
Hg does not affect the volume of the gas absorbed, but solely dimin-
ishes its weight (Law of Dalton).
The absorption of the gases by blood or by blood-serum cannot be
determined, because oxygen and carbon dioxid form dissociable chem-
ical compounds. In fact, even nitrogen has been said by Bohr to
possess certain chemical avidities which do not permit it to conform
to the ordinary laws of the diffusion of the gases. This, however,
is a debatable question. At all events, the fact that the blood con-
tains the gases just mentioned in physical solution, as well as in a
chemically dissociable state, necessitates a brief discussion of the
combinations which they may enter.
The Extraction of the Gases from the Blood. — Supposing for the
moment that we are deahng with a gas held in ordinary physical solu-
tion , the following procedure should be followed. The liquid containing
the gas is placed in a cylinder and its upper surface is brought into
firm contact with a piston, the weight of which is accurately balanced
by a counterweight. If this entire apparatus is now placed into the
receiver of an air pump, from which the air may be gradually exhausted,
bubbles of gas will escape from the liquid and collect in a thin layer
between its surface and that of the piston. At this time, therefore, the
piston is being balanced by the pressure of the escaping gas and that
existing in the receiver of the air-pump. On increasing the pressure
in this compartment, a point will be reached at which the gaseous
molecules again begin to enter the liquid. Consequently, at this time
the impacts of those molecules which are just leaving the Hquid are
being counter-balanced, and hence, if the pressure which is required
to accomplish this end is noted, we are in possession of a means of
^Bunsen, Gasometr. Methoden, Braunschweig, 1877; Hempel, Gasanalyt.
Methoden, Braunschweig, 1900, and Berthelot, Traite pract. de I'analyse des gaz.,
Paris, 1906.
32
498
EESPIRATION
determining the pressure or tension of this gas in the liquid. Thus,
it will be seen that a gas can be extracted from a liquid by simply
bringing it into relation with an atmosphere in which its partial pres-
sure is slight. The procedure usually followed is to subject the liquid
Fig. 255. — Gas Pump fob Extracting the Gases of Blood. (Grehant.)
M and F, the mercury receivers; P, the windlass for raising and lowering Af ; m, a
three-way stopcock protected by a seal of mercury or water; C, a cup with mercury over
which the receiving eudiometer is placed to collect the gases; B, the bulb in which, after a
vacuum is made, the blood is introduced by the graduated syringe, S. By means of the
stopcock m the vacuum in F, caused by the fall of the mercury, can be placed in commu-
nication with B. After the gases have diffused over into F, M is raised, and when the
stopcock m is properly turned these gases are driven out through C into the receiving
tube. The operation is repeated until no more gas is given off from B. {Howell.)
in which the gas is dissolved, to the vacuum of an air-pump or to bring
it into relation with some other gas.
The gases of the blood, however, present certain peculiarities be-
cause they are not entirely in pure physical solution, but enter loose
chemical combinations; in fact, a part of the carbon dioxid forms a
stable compound, the dissociation of which necessitates the use of
THE CHEMISTRY OF RESPIRATION
499
chemical agents. The usual procedure then is to expose the blood at
body-temperature to as perfect a vacuum as can be obtained, but it
must have been defibrinated or must have been rendered non-coagu-
lable by the addition of an oxalate or citrate solution.
The Torricellian vacuum was first employed for the extraction of the gases of
the blood by Ludwig and Setschenow.i Air-pumps of simple construction have
been described by Pfliiger^ and Grehant^ (Fig. 255) and one of greater complexity
by Topler-Hagen. The latter has been modified by Zuntz and Barcroft.* It
consists of a Woulfe bottle (A) filled with mercury and a long capillary tube which
also contains mercury (Fig. 256). Bottle A is connected with the water supply
Fig. 256. — Baecroft's Modification op the Topleb Pump.
tube by two taps W. The vacuum (B) is shut off against the sulphuric acid cham-
ber (E) for drying the gases by a glassfloat (F). At F a condenser is interposed
through which a stream of cold water is kept flowing. The blood is led from the
cyhnder K into the receptacle G as soon as a vacuum has been established. This
end is accomplished by permitting water to flow through the tap W into the Woulfe
bottle A. The mercury is then forced into tube B, where its further progress
toward E is finally made impossible by the raising of the glass valve Y. Its
only exit now is through C into D. If the influx of water is now made to cease, and
the second tap W is opened, the mercury assumes its original position. If the air
is at this time prevented from entering at D, the valve Y drops downward and per-
1 Ber. der Akad. der Wissensch., Wien, 1859.
2 Unters. aus dem physiol. Institut zu Bonn, 1866.
3 Compt. rend., Ixxv, 1872.
* Ergebn. der Physiol., vii, 1908, 699.
500 RESPIRATION
mits the air from the receptacle G and the rest of this connecting tube to enter the
chamber B. This process is repeated until a high vacuum has finally been attained.
A measured quantity of blood is then allowed to flow from the graduated cylinder
K into the receptacle G which is surrounded by warm water to hasten the escape
of the gases. The blood boils in this vacuum, but is prevented from boiling away
by the condenser. The gases given off by it are then collected over the mercury.
It is also possible to determine the quantity of oxygen or carbon dioxid in a
chemical way without the use of the pump. Thus, the CO2 may be liberated by
adding diluted acids to the blood and by collecting it in potassium hydrate. ^
Schultze^ has described a simple volumetric method for the estimation of CO2
which Rielander has applied to the analysis of the CO2 in the blood. In recent
years Haldane^ has devised an apparatus which has been modified by Fr. Miiller.*
It is based upon the principle that the oxygen in hemoglobin may be ascertained in
a quantitative manner by adding a solution of potassium ferricyanid to laked blood.
The apparatus consists of a bottle which is connected with a receptacle containing
the solution just mentioned. It also communicates with two burets united below
by a connecting piece. The second buret is joined to a bottle which is used as a
thermobarometer. A tube leads from the T-cannula to a niveau receptacle filled
with slightly acidified water. To the central bottle are attached two glass bulbs
separated from one another, as well as from the bottle, by stop-cocks. The upper
bulb contains a dilute solution of ammonia and the lower, th^ blood to be ex-
amined.
A perfect constancy of the temperature having been attained, note is made of
the level of the water in the burets. If the blood and the solution of ammonia are
now permitted to flow into the central bottle, the former will be laked immediately.
Under repeated shaking the ferricyanid is then added to the blood after which the
level of the water in the burets is observed at intervals. Its maximal fall in the
buret nearest the generator indicates the volume of oxygen evolved. In these
determinations close attention must also be paid to the temperature as well as to
the barometric pressure.
Haldane and Barcroft^ have given to this apparatus a more convenient form
so that even very small quantities of blood may be examined (Fig. 257). Moreover,
Mosso and Marro^ have proved that this procedure may be made to include a
determination of the carbon dioxid content of the blood. Tartaric acid is em-
ployed for the liberation of this gas. The same apparatus may also be employed
as a differential indicator of these gases in two different samples of blood. ^
In the latter case the apparatus consists of two bottles of equal size (Fig. 257)
which are connected with a manometer (1.0 mm. bore) filled with oil of cloves of
known specific gravity. Into one of these receptacles are then poured 1 c.c. of blood
and 2 c.c. of ammonia, made by adding 4 c.c. of strong NH3 to a liter of water. The
blood having been thoroughly laked, the stoppers are anointed with vaselin and
their inside compartments filled with 0.2 c.c. of a saturated solution of potassium
ferricyanid. The apparatus is then placed in a water bath for about five minutes
with both stop-cocks open. At the end of this period the ferricyanid solution is
allowed to trickle into the laked blood under repeated shaking of the entire appara-
tus. It is then replaced in the water bath. The column of the oil of cloves at the
side of the blood is now brought to its original level by means of the screw clamp,
after which the difference in the levels on the two sides is noted. The volume of the
oxygen evolved equals x = ?/ ( — j in which y stands for the difference of level
1 F. Kraus, Archiv fur exp. Path., xxvi, 1890.
2 Zeitschr. ftir die landw. Vers, in Oesterreich, 1905.
8 Jour, of Physiol., xxii, 1898 and xxv, 1900.
* Pfiiiger's Archiv, ciii, 1904, 541.
6 Jour, of Physiol., xxviii, 1902, 232.
* Rend, della R. Acad, dei Lincei, xii, 1903.
^ Barcroft, Jour, of Physiol., xxxvii, 1908, 12.
THE CHEMISTRY OF RESPIRATION
501
and p for the height of the barometer. P may be taken as 10,000 mm., so that the
V
expression — may be made to serve as the constant (c) of the apparatus. Then
X = y X c.
Having determined the oxygen content of this sample of blood, its carbon
dioxid content may be ascertained by the same procedure with the aid of tartaric
acid. If it is desired to compare the gas content of two different samples of blood,
they are placed in these two adjoining receptacles, 1 c.c. of each under 1.5. c.c.
of weak ammonia. They are then immersed in the water bath until the level of
the oil remains constant. The blood is then laked in the usual way. If the same
quantity of oxyhemoglobin is present in these samples of blood, the level of the oil
in the two tubes remains the same ; while if unequal amounts are present, the more
decidedly venous blood will absorb more oxygen from its bottle than the other.
Consequently, the level of the oil must rise on this side, the difference in the
:m^'
Fig. 257. — Barcroft's Blood-gas Apparatus.
levels indicating the amount of oxygen taken up, and hence, also the content in
hemoglobin.
The quantities of oxygen and carbon dioxid vary greatly in different
samples of arterial and venous blood. Much depends upon the char-
acter of the blood-vessel, or rather, upon the intensity of the metabolism
of the tissue supplied by it. Still greater differences are encountered
if the blood of different animals is examined. Obviously, these
variations pursue a course parallel to the hemoglobin content, as well
as to the affinity which this body displays toward oxygen. It is the
general opinion that the percentage of oxygen is greater in carnivora
than in herbivora and birds, while the percentage of carbon dioxid
is smaller. The experiments of Pflliger and others have furnished
such values as are included in the following table:
502
EESPIRATION
100 C.C. OF ARTERIAL BLOOD CONTAIN:
CO2
Dog.
Horse.
Rabbit.
Average
Maximal
Minimal
Average
Maximal
Minimal
Average
Maximal
Minimal
22.6
25.4
18.7
14.0
16.6
9.2
13.2
14.6
10.7
34.3
42.6
23.9
1.8
3.3
1.2
49
55
39.0
34.0
36
31
2.1
2.3
1.7
A difference of 9 per cent, was frequently encountered, dependent
entirely upon the speed of the extraction of the gases; in fact, inas-
much as the oxidations continue for some time after the blood has
been removed, a greater yield of carbon dioxid is generally obtained
than would be, if these processes could be made to cease immediately.
But naturally, this oxidation is restricted to the formed elements of
the blood, for the very obvious reason that their metabolism does not
cease directly after their escape from the circulation.
The observations of Setschenow upon blood withdrawn directly
from the arteries of man have given 21.6 c.c. of oxygen, 40.3 c.c. of
carbon dioxid and 1.6 c.c. of nitrogen for each 100 c.c. of blood. Argon
is present in very insignificant amounts, its exact value being about
0.04 volume per cent. Traces of hydrogen and carbon monoxid may
also be present, the former being derived from the intestinal canal
and the latter from the air. Thus, it may be said, in a general way,
that 100 c.c. of arterial blood yield about 60 c.c. of a mixture of gases.
In the venous blood of the dog the oxygen varied between 5.5 and
16.6 c.c. and the carbon dioxid between 38.8 and 47.5 c.c. If the aver-
age values of these determinations, namely 11.9 c.c. and 44.3 c.c.
respectively, are now compared with the figures given above, the fol-
lowing averages are obtained for each 100 c.c. of blood at 0° C. and
under a pressure of 760 mm. Hg: •
Arterial blood 20 c.c. O2 40 c.c. CO2 1-2 c.c. N
Venous blood 8-12 c.c. O2 46^0 c.c. CO2 1-2 c.c. N
The Condition of Oxygen in the Blood. — The plasma of the blood
is a watery solution containing 9 per cent, of solids, whereas its formed
elements embrace 40 per cent, of soUds. At this time, attention
should again be called to the fact that the absorption of oxygen by the
blood is different from that of oxygen by water, because this gas enters
into a chemical combination with the hemoglobin of the red cells.
Normal blood, as we have just seen, contains about 20 volume per cent.
THE CHEMISTRY OF RESPIRATION 503
of this gas, while 100 c.c. of water under identical conditions are
capable of absorbing only 0.7 c.c. (0.7 volume per cent.). This fact,
that the oxygen is not simply absorbed by the blood, may also be
deduced from the observation that its quantity does not vary directly
with its partial pressure in the surrounding medium. It is a well-
known fact that blood exposed to the vacuum of an air-pump does not
discharge its oxygen until the pressure has been considerably reduced.
In most instances a diminution to about half an atmosphere is re-
quired before this gas begins to escape. This corresponds to a pressure
of oxygen of about 80 mm. Hg. At about 70 mm. Hg the dissociation
is intense, and becomes more and more rapid as the pressure declines
toward zero. Meanwhile, the blood changes its color from bright
red to purple. This behavior of the oxygen clearly proves that it is
not held in a simple physical condition, but enters into a dissociable
union with some constituent of the blood.
If the blood is now centrifugalized, it will be found that the plasma
is capable of absorbing only a very small amount of oxygen, while
by far the greatest quantity of this gas is held in the corpuscular
elements. Only 0.65 volume per cent, are obtainable from the plasma.
Another striking difference is the variability of the oxygen content
of the plasma in consequence of changes in the tension of this gas in
the surrounding medium. If the latter is increased, a greater quan-
tity of oxygen will be absorbed by it, and vice versa. Consequently,
plasma behaves like water; i.e., it follows the Henry-Dalton law of
pressures absolutely. The corpuscular elements, on the other hand,
do not show a direct relationship of this kind. To be sure, they also
take up a greater amount of oxygen when the partial pressure of this
gas is high, but a more copious absorption takes place when its tension
is low. As higher degrees of pressure are reached, the absorption
becomes less, relatively speaking.
This fact may be illustrated by subjecting defibrinated blood to different
tensions of oxygen. At the temperature of the body a pressure of 10 mm. led to
an absorption of 6 c.c. of oxygen, while 30 mm. of pressure sufficed for an absorp-
tion of more than 16 c.c. Consequently, these low tensions were sufficient to
produce a saturation of 80 per cent. ; moreover, while higher pressures gave rise to
a still greater absorption, the increase obtained with each additional rise in tem-
perature, became gradually less. Thus, with 40 mm. of pressure only 2 c.c. were
taken up in addition to those already absorbed, and at 50 mm. only 1 c.c. It
has also been ascertained that the degree of saturation of the corpuscles which it is
possible to achieve with pure oxygen, namely, with a partial pressure of 760 mm.
Hg, is only slightly greater than that obtainable with atmospheric air in which this
gas exerts a pressure of only about 150 mm. Whole blood, on the other hand,
takes up a somewhat greater amount of oxygen if exposed to it in its pure form,
but this oxygen cannot be held by the corpuscles, because they are quite unable to
acquire much more than may be chemically united with them. Consequently,
this extra amount must be held by them in a physical state and must eventually
overflow into the plasma. It need scarcely be mentioned that oxygen thus dis-
solved in the plasma, obeys the ordinary laws of diffusion, i.e., it escapes from the
blood as soon as its partial pressure in the surrounding medium is diminished and
long before its chemically combined portion is liberated. These facts indicate
504 RESPIRATION
that practically all the oxygen is held by the corpuscles in the form of an unstable
chemical compound.
It has been shown that the element which unites with the oxygen,
is the blood-pigment or hemoglobin of the red cells. This deduction
finds substantiation in the fact that oxygen is bound by crystalline
hemoglobin in quite the same way as by whole blood and in perfect
agreement with the law of the tension of the gases. Thus, if projected
upon an abscissa, the curve of absorption of oxygen by hemoglobin
forms a curved line, the convexity of which is turned upward. This
result proves that the absorption is greatest at low tensions and least
at high tensions, but the employment of hemoglobin, instead of whole
blood, introduces several factors which may render a direct comparison
of the results practically impossible. In the first place, it is difficult
to procure a solution of this pigment which can justly be compared
with samples of whole blood, and secondly, it is not always a simple
matter to exclude or to control the influence of the carbon dioxid up-
on the binding power of the hemoglobin. Thirdly, although oxygen
and hemoglobin form a dissociable compound, their dissociation ten-
sion may be varied by changes in temperature, as well as by the char-
acter of the salts present. Human blood corpuscles, for example, are
characterized by unusual amounts of potassium, whereas dog's cor-
puscles contain more sodium. The former salt is notably more effi-
cient in increasing the percentage of saturation of the hemoglobin than
the latter. In spite of these difficulties, however, the more recent
analyses have given a close quantitative agreement; for example, inas-
much as 1 g. of crystallized hemoglobin takes up about 1.3 c.c. of oxy-
gen, and inasmuch as whole blood absorbs about 20 volume per cent, of
this gas, the blood must contain about 15 per cent, of this pigment.
The correctness of this value has been established by analytical means;
moreover, the absorption of the oxygen may be ascertained directly
by determining the binding power of the iron of the blood. Inas-
much as this substance is normally held in measurable quantities
only in the hemoglobin, a direct comparison may be made between
the absorptive power of this pigment and its content in iron. It
seems, therefore, that the hemoglobin is present in amounts sufficient
to combine with practically all the oxygen ordinarily contained in the
blood.
It has also been found that the oxygen may be displaced from the
hemoglobin by equivalent amounts of carbon monoxid and nitrous
oxid, and furthermore, may be made to absorb carbon dioxid in greater
quantities than can be accounted for by the laws of solution. This
fact seems to suggest that the hemoglobin is also capable of entering
into a loose chemical combination with this gas, although it does not
permit its oxygen to be directly displaced by it. Conditions may
arise, therefore, which lead to a simultaneous saturation of the hemo-
globin by oxygen and carbon dioxid, thereby altering the oxygen-
carrying capacity of this pigment. As has been stated above, it is the
THE CHEMISTRY OF RESPIRATION 505
presence of this carbon dioxid which may seriously interfere with the
determination of the dissociation curve of hemoglobin and oxygen in
whole blood. Its action is similar to that of weak acids, such as lactic
acid, because the greater its tension, or the greater the acidity of the
blood, the greater is the dissociation of the oxygen. It possesses, there-
fore, a solvent action which, however, it does not unfold unless the
oxygen tension is markedly diminished. To illustrate, under a partial
pressure of the oxygen of 150 mm. Hg, the blood remains practically
saturated even if its carbon dioxid tension is varied within physio-
logical limits. If the oxygen pressure is now reduced to 20 mm. Hg and
the carbon dioxid pressure to 5 mm. Hg, the oxyhemoglobin content
of the blood is changed to 67.5 per cent. This value may be further
decreased by raising the carbon dioxid tension. This is a matter of
great importance to the body, because it facilitates the liberation of
oxygen in those parts of the body in which the tension of this gas is
low, i.e., in the tissues. By means of this peculiar action of the carbon
dioxid, the hemoglobin is relieved of all available oxygen, in fact, of
more than it would allow to be transferred to the cells under ordinary
conditions of oxygen diffusion.
The Condition of Carbon Dioxid in the Blood. — While the amount
of carbon dioxid absorbed by blood, is dependent upon its partial
pressure in the surrounding medium, a direct relationship between
these factors does not exist. In fact, the volume of this gas actually
acquired by a certain quantity of blood, is much greater than the
volume which could theoretically be allotted to it upon the basis of
its absorption coefficient. It is evident, therefore, that only a part of
the carbon dioxid is retained in a physical state,while another part
forms a dissociable chemical compound with some constituent of the
blood. Conditions, however, are not so simple as they are in the case of
oxygen, which gas unites with only one element of the blood, whereas
the carbon dioxid is bound to several, i.e., to the plasma as well as to
the corpuscles.
If the venous blood of the dog is exposed to .the vacuum of an air pump, from
45 to 50 c.c. of carbon dioxid may be extracted from each 100 c.c. of blood. It
has also been ascertained with the help of the aerotonometer that this gas is held
in the venous current under a pressure of about 40 mm. Hg, or 5-6 per cent, of an
atmosphere. This coexistence of a relatively high carbon dioxid content and
low degrees of pressure, immediately assumes a greater significance if these values
are compared with those obtained with pure solutions of this gas. Thus, if water
and carbon dioxid are shaken under a pressure of 760 mm. Hg and at the tem-
perature of the body, about 50 per cent, of the gas will be absorbed. Quite
similarly, if blood plasma is treated in this way, it will take up an almost equally
large amount of this gas, while whole blood assimilates almost 150 c.c. But
naturally, under normal conditions the blood is not exposed to a carbon dioxid
pressure of one atmosphere (760 mm. Hg), but only to a pressure of about 40
mm. Hg = 3^9 of an atmosphere. Hence, all the carbon dioxid, excepting 2.01
c.c. for every 100 c.c. of blood, must be held in chemical combination, and further-
more, if the volume of the corpuscles is reckoned at ^i of the total volume of the
blood, these bodies must contain 0.59 c.c. and the plasma 1.42 c.c. of this gas in a
506
RESPIRATION
physical condition. Thus, it will be seen that only a very small portion of the
carbon dioxid, namely, 5 per cent., behaves in accordance with the Henry-Dalton
law.
In endeavoring to locate that portion of the carbon dioxid which is held in a
condition of both loose and stable combination, it should first be noted that the
serum and plasma contain sodium salts with which this gas could doubtlessly
unite. These salts are sodium carbonate and dibasic sodium phosphate. It
has been shown, however, that the quantity of available alkali which is combined
in the blood in the form of carbonates or phosphates, is not sufficiently large to
bind the amount of carbon dioxid normally present. For this reason, it must be
concluded that at least a part of this gas is held in a dissociable condition by
certain organic substances.
If our attention is now directed to that portion of the carbon dioxid which is
united with the alkali of the blood, we are immediately confronted by the
difficulty that its quantity cannot be determined with accuracy and that even
that part of it which exists as bicarbonate, shows a most peculiar chemical be-
havior. Thus, defibrinated blood discharges all of its carbon dioxid with greatest
ease as soon as it is subjected to the vacuum pump, and even without the addition
of an acid to dissociate it from its bases. A bicarbonate solution, on the other
hand, possessing the concentration of the blood, liberates scarcely more than half
of its loosely bound carbon dioxid. If sodium bicarbonate is then added to whole
blood, all of its carbon dioxid can be obtained with the aid of the pump. To
these data should also be added the fact that the exposure of .plasma or serum
to the vacuum does not result in a complete liberation of the carbon dioxid. In
order to obtain it in its entirety, it is necessary to add an acid so that this so-called
"fixed carbon dioxid" may first be dissociated from its binder. While this point
has not been entirely cleared up as yet, it is doubtlessly true that the carbon
dioxid is contained chiefly in the plasma where it exists as sodium carbonate or
bicarbonate. A certain amount of it is also held in the corpuscles, in all probability
in combination with the sodium.
With reference to the organic combinations of carbon dioxid, it should first
be stated that the most conspicuous of these is the loose union which this gas is
capable of forming with the hemoglobin. At this time, however, reference is had
solely to the alkali free portion of this pigment, namely, to its globin molecule.
If the hemoglobin content amounts to 15 per cent., and the carbon dioxid tension
to 30 mm. Hg, each 100 c.c. of blood contain 8.1 c.c. of this gas in combination
with the hemoglobin. In addition, it has previously been shown that 0.59 c.c.
are present in the physical state, which makes in all 8.7 c.c. We know, however,
that the total absorption of carbon dioxid by the red corpuscles at a tension of 30
mm. Hg amounts to about 14 c.c, and hence, it must be concluded that the re-
maining 5 c.c. are united with other constituents of these bodies, in all probability
with the alkali as bicarbonate and in a small measure also with the lecithin. It
has also been shown that the carbon dioxid is capable of forming certain unstable
compounds with the proteins of the plasma. As a general summary it might be
well to give the table compiled by Loewy^ which is based upon the fact that under a
pressure of 30 mm. Hg each 100 c.c. of arterial blood yield 40 c.c. of carbon dioxid.
This total quantity is distributed as follows :
In plasma,
c.c.
In corpxiscles,
c.c.
In blood.
CO.
Physically absorbed
1.2
12.0
11.8
0.7
6.8
7.5
1.9
Held as sodium bicarbonate
18.8
Held in organic combinations
19.3
1 Handbuch der Biochemie, iv, 1908.
THE CHEMISTRY OF RESPIRATION 507
The Condition of Nitrogen in the Blood. — By far the greatest
amount of the nitrogen present in circulating blood, is held in solu-
tion and is therefore subject to the law of Henry. The same state-
ment may be made regarding blood kept outside the body, if it is
saturated with atmospheric air. It is true, however, that blood al-
ways absorbs a larger amount of nitrogen than is taken up by an equal
volume of air when subjected to the same conditions. This fact
tends to prove that a small portion of this gas is held in combination.
Moreover, the presence of this extra amount cannot be dependent
upon a special activity of certain tissues for the obvious reason that
blood experimented with outside the body, behaves in precisely the
same manner. The separate determinations of the nitrogen absorp-
tion of the plasma and corpuscles have shown that the nitrogen con-
tent of the former is proportional to the tension of this gas, whereas that
of the latter is not. Hence, it may be concluded that the corpuscles
are the element most directly concerned in this absorption. Besides,
it has been proved by Bohr^ that this union takes place solely in the
presence of oxygen and that the factor primarily responsible for it is
the hemoglobin. This investigator surmises that the nitrogen is held
here in the form of an unstable oxid, the functional significance of
which has not been established.
Internal or Tissue Respiration. — The freshly aerated blood tra-
versing the pulmonary veins, left side of the heart and systemic
arteries is in a state of almost complete saturation with oxygen which
is held here tmder a pressure of at least 100 mm. Hg. It has been
shown above that its saturation amounts to about 90 per cent., and
that this degree of saturation can be obtained with an oxygen tension
of little more than 30 mm. Hg. Thus, it will be noted that the oxygen-
carrying capacity of the blood is amply safeguarded, at least as far
as pressure is concerned. This is also shown by the fact that this
type of blood may be shaken with atmospheric air at the tempera^
ture of the body without absorbing more than about 2 volume per
cent, of oxygen in addition to that just stated. Venous blood, on
the other hand, requires 8 to 10 volume per cent, of oxygen for its
saturation.
The blood traversing the capillaries of the different tissues is
brought into diffusion relation with the cells through the intervention
of the lymph. It is a well-known fact that the cells acquire oxygen
constantly and give off carbon dioxid. It is evident, therefore, that
the oxygen tension is higher in the blood than in the tissues, whereas
that of the carbon dioxid is higher in the tissues than in the blood.
Thus, the physical conditions are such that the oxygen must flow from
the blood into the cells, while the carbon dioxid must pass from the
cells into the blood, as follows :
^ Compt. rend., cxxiv, 1897, 414.
508
RESPIRATION
Oxygen, mm. Hg
Carbon dioxid,
mm. Hg
Arterial blood
100
35
Capillary wall
t
Tissue
0
50-70
As far as the exchange of the oxygen is concerned, the conditions exist-
ing here are the same as those prevaiUng when the blood is subjected
to the vacuum of an air-pump. The neighboring tissues are always
greedy for oxygen, and abstract even the last traces of this gas from
the adjoining lymph. The latter in turn must replenish its oxygen
content by withdrawing a corresponding amount from the blood.
In this way, a descending scale of oxygen tensions is produced, begin-
ning with the red corpuscles and the plasma and lymph and terminating
in the interior of the cell. But while the speed of the capillary flow
is sufficiently slow to allow these interchanges between the blood and
the tissues to be completed with plenty of time to spare, the individual
red cells never tarry long enough at these cells to lose their entire
store of oxygen. Only if these corpuscles are prevented from recu-
perating their losses in the lungs can their oxygen store be depleted
further until, as occurs in asphyxia, the last traces of this gas have
been removed from them. It has been pointed out above ^ that the
evolution of the oxygen by the hemoglobin is greatly facilitated by carbon
dioxid, this effect being especially marked in conditions of low oxygen
tension.
CHAPTER XL
THE SEAT AND NATURE OF THE OXIDATIONS
The Oxidative Power of the Tissues. — It is commonly accepted
to-day that the seat of the oxidations is in the tissues and not in the
blood, as has been suggested by A. Schmidt^ and Pfliiger.^ Thus, we
are accustomed to compare the body to a steam engine and to speak of
the ''burning up" of foodstuffs in a manner indicative of the processes
taking place during an ordinary combustion. But while it seems to be
true that the reductions are confined in their entirety to the cells, the
fact must not be lost sight of that they are not always completed by
the same group of cells, i.e., while a certain colony of cells may incite
1 Barcroft, Respiratory Function of the Blood, 1914.
2 Arbeiten aus dem physiol. Inst, zu Leipzig, li, 1867, 99.
3 Pfltiger's Archiv, i, 1816, 98.
THE SEAT AND NATURE OF THE OXIDATIONS 509
the oxidation, some other tissue may be called upon to form the final
product.
The tissues possess a very pronounced avidity for oxygen. This
has been shown in a very convincing manner by Ehrlich. A saturated
solution of methylene-blue was injected into the venous bloodstream
of an animal. After an interval of ten minutes it was killed and its
organs fully exposed to the air. The tissues which exhibited at first
their natural color, soon assumed a decidedly blue color. It is evident,
therefore, that they are able to decompose the comparatively stable
methylene-blue into a colorless product, which on exposure to the air
is again oxidized into methylene-blue. It has also been noted that
hemoglobin-like bodies are present in the cytoplasm of the cells of the
worms, presumably for the purpose of effecting respiratory interchanges.
In addition, Lillie^ has found that the colored products of the oxida-
tions, such as may be obtained in the course of indophenol and similar
reactions, accumulate chiefly in the vicinity of the nuclei. Some
fight is also thrown upon this question by the fact that the tissues
contain large quantities of carbon dioxid and that this gas is present
in considerable amounts in the lymph occupying the peripheral
radicles of the lymphatic system. It might also be mentioned that
a frog may be kept alive even after its blood has been replaced by
physiological salt solution, by simply placing the animal in an atmos-
phere of pure oxygen. Inasmuch as the consumption of oxygen and
the production of carbon dioxid are had in this instance even in the
absence of the blood, these processes must actually be completed in
the tissues. The same result may be obtained with excised muscles,
in which case the production of carbon dioxid follows a course parallel
to the activity and general condition of this tissue.
In whatever form the energy of the body may be liberated, its
source lies in cellular combustions which in turn necessitate respiratory
interchanges. The nature of these microchemical and microphysical
processes is not clearly understood, nor has the chemist been able to
form a concise picture regarding the changes that occur during one of
the simplest possible combustions. On this account, it is quite
impossible to describe these processes in anything more than a very
general way. When the blood enters the tissues, it delivers not only a
definite amount of oxygen, but also certain amounts of nutritive mate-
rial in the form of proteins or amino acids, fats and sugars. These
substances are acted upon within the boundaries of the cells. Con-
sequently, the processes of life consist in an uninterrupted change in
energy which presents itself as a conversion of latent energy into work,
heat and electricity. It is to be noted, however, that animals are not
capable of sustaining themselves unless fully formed organic sub-
stances are placed at their disposal, and hence, the amount of energy
which they produce, is absolutely dependent upon their power of reduc-
ing these organic molecules. Plants, on the other hand, are able to
1 Am. Jour, of Physiol, vi, 1902, 15.
610 RESPIRATION
form these complex substances from inorganic material by permitting
carbon dioxid and water to act in the presence of sunlight. Obviously,
therefore, animal life depends upon the products of the higher plants,
for the reason that the latter contain energy-rich organic material.
While these general facts are incontestable, much uncertainty
still prevails regarding the nature of these reducing processes. In its
widest sense, the term oxidation is applied to any chemical reaction
which results in an increase of the positive or a decrease of the nega-
tive valencies of a compound. Whether or no oxygen or some other
agent is the cause of the reduction is not of deciding value. Thus, the
evolution of iodin during the action of ferric chlorid upon potassium
iodid is essentially an oxidation, as may be gathered from the fol-
lowing formula:
+ + +— - + - ++ — - +
Fe+36+K+ J = Fe+3&+K+J
This process has resulted in the passage of a positive charge of elec-
tricity from the ferric atom to the iodin atom, or the transfer of a negative
charge of electricity from the iodin ion to the ferric ion. It will be seen
that a substance which freely yields a negative charge. is a very active
reducing agent, while a substance which readily liberates a positive
charge is a powerful oxidizing agent. Upon this basis, oxygen may be
said to act as an oxidizing body, because it possesses the power of
removing a negative charge from other substances and of attaching
itself to them as an oxygen ion, or as electronegative oxygen.^
At this time, however, we are chiefly concerned with those proc-
esses which are consummated in the living tissues with the aid of oxygen.
These reductions belong to the class of the slow reactions, and are not
simple combustions, because the oxidations are generally initiated
by reductions participated in by various ferments, ^.e., the complex
molecules are first simplified by catalytic agents before they are actu-
ally oxidized. It should also be remembered that these oxidations may
result in many cases without any apparent stimulus, while in others the
substances must first be activated by some outside agent. Thus,
metallic sodium, phosphorus and certain organic bodies bind free oxy-
gen even at ordinary temperatures, while the rare metals, wood and coal
must first be exposed to a high temperature. The former process
takes place slowly and the latter with considerable speed. Quite simi-
larly, foodstuffs possess no tendency to take up atmospheric oxygen
under ordinary conditions but may be made to unite with this gas
by heating them. Their combustion may be incited immediately by
exposing them to the temperature of a flame, while at the temperature
of the body, the upper limit of which is near 40° C, their oxidation
is slow and gives rise to intermediary substances. For this reason,
they are classified as dysoxidizable substances.
^ Barcroft, Ergebn. der Physiol., viii, 1908, and Winterstein, Dissertation,
Jena. 1906.
THE SEAT AND NATURE OF THE OXIDATIONS 511
In the second place, it should be remembered that a substance
may be very closely allied to one of the known oxidizable bodies, and
still fail completely in being oxidized by the tissues. Thus, it has been
foimd that only four of the sixteen sugars, possessing the formula
C6H12O6, namely, glucose, fructose, galactose and mannose, are
acted upon by the cells, while the others cannot be utilized. In the
third place, a tissue may lose its power of reducing certain foodstuffs
completely, a condition met with in diabetes mellitus. Consequently,
the cell must possess a certain chemicophysical constitution which
becomes completely disarranged in the course of certain diseases
with the result that formerly assimilable substances are rendered non-
assimilable. It is evident, therefore, that the general arrangement of
the intracellular material constitutes the principal factor in the de-
termination of the manner in which the dysoxidizable foodstuffs
combine with the oxygen. On this account, there is imparted to the
oxidations a definite specificity and a limit is set to them in conformity
with the requirements of the different tissues. Consequently, the
magnitude of the oxidation is regulated by the tissue itself and not by
the amount of oxygen actually available. Thus, inhalations of pure
oxygen cannot augment the oxidations, because the tissues are already
acting at their fullest capacity. The oxygen which is required for
these processes may be furnished either in a free or bound state.
In the latter case, it is in combination with some of the nutritive sub-
stances. As bound oxygen must also be regarded the oxygen of water
which, on account of its wide distribution, must play a most important
part in biological oxidations. The latter are commonly designated
as hydrolytic oxidations.
As slow combustions are the rule in living matter, the energy which
is required to instigate these processes must be furnished by the sub-
stances to be oxidized. The latter, therefore, must possess the power
of activating the molecular oxygen, and hence, the real purpose of
respiration is to allow the mechanism of the activation of oxygen to
be set in motion. Unfortunately, however, the nature of this process
is not clearly understood, although several theories have been formu-
lated to serve as possible explanations.^
The theories regarding the activation of oxygen may be divided
into two groups, namely: those which assume that the oxygen is first
of all split into an active modification and those which hold that the
molecides of oxygen are used in their complete form. Among the
former may be mentioned :
1. The ozone-autozone theory of Schonbein and Clausius which assumes that
the inert oxygen appears in the form of two different and active modifications.
2. The ionization theory of van't Hoff which holds that the modifications of
the oxygen are not chemically different but only carry different electrical charges.
^ A more detailed account will be found in Oppenheimer's Handbuch der
Biochemie, Jena, 1913, or in Mathews, Physiol. Chemistry, New York, 1915. Also
see Engler and Weissberg, Krit. Studien liber die Vorg. der Autoxydation, Braun-
schweig, 1904.
512 RESPIRATION
3. The theory of Hoppe-Seyler denies these pecuUarities of the oxygen-fraction
and explains this reaction upon the basis of reductions in which nascent hydrogen
plays a part. It is said that reducing substances are formed by the hydrolytic
splitting of the foodstuffs in consequence of ferment activity. The atomic hydro-
gen acting upon the oxygen, forms water during which process some atomic oxygen
is left over which is used to oxidize the split products of the fermentation.
Traube, ^ on the other hand, advocates the view that the molecule of oxygen acts
in its entirety. He assumes, however, that the oxidizable substances are not
acted upon by free oxygen but only by the bound oxygen of the water. Thus, it
is stated that the molecule of water is first split into its components, oxygen and
hydrogen, and that the former is combined with the oxidizable body and the latter
with one whole molecule of oxygen to form hydroperoxid. This theory, however,
does not give satisfactory answer to the question of why the oxidizable substance
prefers bound oxygen to free oxygen and why the latter selects the hydrogen of the
molecule of water and not the oxidizable body. But, this theory possesses the
advantage of being more truly chemical, because it minimizes the atomic action of
oxygen and calls attention to the primary formation of hydroperoxid. Much
greater emphasis has been placed upon this process by Engler^ and Bach^ who be-
lieve that the oxygen-molecule 0 = 0 is incompletely split by the free energy
of the oxidizable one, so that — 0 — 0 — groups arise which combine with the
former under the formation of primary peroxid. Inasmuch as one-half of the
oxygen is contained in these peroxids in a loose and active state, it can be trans-
ferred without difficulty to other oxidizable substances.
Hydrolytic oxidations include first of all those processes which are
accomplished with the help of the peroxid-oxygen and secondly, those
which are carried on at the expense of the hydroxyls of water. But,
the separation of the latter necessitates the presence in the substance
of a relatively large amount of energy consisting in an affinity for the
hydroxyls. Substances of this kind are few in number and hence, it
generally happens that two substances take part in the hydrolysis, one
of which attracts the hydroxyl and the other the hydrogen. As an
example of this type of oxidation, Bach^ cites the splitting of water
by hjrpophoric acid or its salts in the presence of metallic palladium.
While the peroxid theory of combustion as such enables us to
explain many phenomena of life which would otherwise remain hidden
to us, several facts have been added to it in more recent years which
render it even more serviceable. Thus, it has been established that
the oxidations do not actually affect the substance of the cells and
cause its destruction, but merely take place in its presence under the
influence of specialized ferments. The latter, of course, are a product
of the cells and hence, we are dealing in this case with a chemical
process during which the organized cytoplasm does not suffer. As
an analogous reaction might be mentioned the conversion of sugar
into alcohol and carbon dioxid by the living yeast cell.
The biological oxidations are slow combustions, and as such must
be subject to the influence of catalytic agents. In the sense of Ostwald,
therefore, these processes are catalyses, i.e., true reactions, instigated
1 Chem. Berichte, xv, 1882, 659; xviii, 1885, 1877, and xviii, 1885, 1890.
2 Ibid., XXX, 1897, 1669.
3 Compt. rend., cxxiv, 1897, 951.
* Chem. Berichte, xlii, 1909, 4463.
THE SEAT AND NATURE OF THE OXIDATIONS 513
by an outside factor which does not enter into the formation of the
end-product. This view is strengthened considerably by the fact
that living substance contains three types of catalyzing agents in the
form of ferments, namely, oxidases, peroxidases and perhydridases.
Since these ferments possess a special function in so far as they com- '
plete the process of respiration, they may be classified as respiratory
ferments. As such they are comparable to the class of the "digestive''
ferments. Thus, a fat-splitting enzyme (lipase) and protein-splitting
enzymes (proteases) have been isolated from many tissues, and fer-
ments have also been found which act upon starch (amylase) sugar
(diastase) and glycogen (glycogenase). The fact that such catalyzing
agents exist in tissues is well illustrated by the phenomenon of auto-
lysis or self-digestion. If a tissue is removed from the body under
aseptic conditions and is kept warm and moist, it will finally be
digested. The same end-products are then formed as may be obtained
by boiling this tissue with acids.
In general, therefore, it may be said that the reductions in living
matter occur either in the presence or in the absence of free or bound
oxygen. At this time, however, we are chiefly concerned with those
of the first type, namely, with the respiratory reductions. In accord-
ance with the foregoing discussion it must now be evident that the
purpose of respiration is the burning up of the simplest constituents
of the body. This combustion is made possible by the respiratory
ferments which are produced by the cell and exert their action as
soon as the foodstuffs have been sufficiently simplified by the ferments
of the digestive type. The former, therefore, are organic catalyzing
agents which may be arranged in the following sequence:
1. Oxidases, produce their action with the help of free oxygen.
2. Peroxidases, hasten the formation and action of the peroxids, i.e., of those
easily oxidizable substances which take up molecular oxygen to form peroxids.
These organic peroxids produce the same effects as hydrogen peroxid, from which
atomic or active oxygen is removed as follows: H2O2 = HoO + O. At the
present time, however, no evidence is at hand to prove that hydrogen peroxid
is actually formed in the tissues, although it seems that it is produced in the green
leaves of plants in the course of their assimilation of carbon.
3. Perhydridase, hastens the reduction of the water-molecule by aldehyds.
*This ferment, therefore, regulates the hydrolytic cleavage and liberates the oxygen
of the water.
4. Catalase, changes hydroperoxid into molecular oxygen and water. This
substance is very prone to be formed in the course of these processes either in a
direct way or from peroxids. It would eventually destroy life. Consequently,
this ferment really serves as a protection to the cell, because it causes its removal.
The power of the cell to regulate the intensity of its oxidations is
dependent upon its faculty of producing ferments of the preceding
types. Secondly, it is also evident that the action of the cells is
specific, because several of these ferments affect the oxidation of only
particular substances. For this reason, special names have been
applied to them, such as xanthinoxidase, tyrosinase, etc. The former,
33
514 RESPIRATION
for example, accomplishes the oxidation of hypoxanthin and xanthin
to uric acid, while the latter regulates the oxidation of tyrosin. In
this connection, mention should also be made of the fact that oxidizing
ferments, or oxidases, are widely distributed through the vegetable
tissues. Thus, guaiaconic acid may be oxidized by the latter in the
presence of atmospheric oxygen, and peroxid of hydrogen is not needed
by them to color guaiacum blue. Quite similarly, many fungi contain
a ferment known as tyrosinase which, when added to solutions of
tyrosin in the presence of air, oxidizes the tyrosin into a brown pig-?
ment. The brown discolorations upon the cut surfaces of apples and
potatoes are attributed to the oxidation of a chromogen by the oxygen
of the air under the influence of an oxidase.
CHAPTER XLI
THE RESPIRATORY INTERCHANGE UNDER DIFFERENT
CONDITIONS
The Respiratory Quotient. — The quantity of air respired in a day
amounts to about 11,000 liters. In a man weighing 70 kg., this amount
of air is brought into relation with a diffusion surface measuring about
90 sq. m., so that 1 kg. of substance possesses a breathing surface of
1.28 sq. m. A person of this weight produces under ordinary condi-
tions about 250 c.c. of carbon dioxid for each kilogram of weight in
an hour, or 428 Uters in the course of a day. During absolute rest or
sleep the CO2 production is of course greatly diminished, amounting
to only 160 c.c. in an hour. Excessive muscular exercise, on the other
hand, increases it considerably, to possibly 1200 c.c. in an hour. Fur-
thermore, it may justly be assumed that the production of 85 c.c. of
carbon dioxid necessitates the absorption of 100 c.c. of oxygen. The
relation between the quantities of O absorbed and CO2 liberated dur-
ing a given period of time is designated as the respiratory quotient.^
Since the air during its sojourn in the lungs loses 4.78 volume per.
cent, of 0 and acquires 4.34 volume per cent, of CO2, the respiratory
quotient is: ~7p j^ = 0.901. This value, however, is subject to
fluctuations, because the amount of oxygen required to oxidize the
carbon seldom remains the same for long periods of time. It is under
the constant influence of such factors as : species, diet, age, temperature,
muscular activity and the composition of the inspired air.
The respiratory quotient of warm-blooded animals is larger (0.7 to 1.0) than
that of cold-blooded animals (0.65 to 0.75), because the latter consume less oxygen
for each kilo of body-weight than the former. The frog, for example, possesses
1 Zuntz, Hermann's Handb. der Physiol., iv, 90.
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 515
an oxygen requirement of only 0.07 per kilo of weight, which is from 6 to 18 times
smaller than that of different species of warm-blooded animals. When considered
in a relative way, it also holds true that the smaller animals display a more intense
respiratory interchange than the larger. This fact may readily be deduced from
the following compilation, containing the oxygen consumption for each kilo of
weight : in the horse 0.437, calf 0.48, sheep 0.499, ox 0.55, rabbit 0.92, and cat 1.00.
This rule may also be applied to animals of the same species, because the body-
surface of the smaller ones is more extensive in relation to their body-weight than
that of the larger. This implies that the loss of heat is proportionately much greater
in the smaller animals and must be compensated for by an increase in their metab-
olism. This in turn necessitates a greater consumption of O and production of
CO2. Thus, while an animal weighing 2.1 kg. gives off 1.02 g. of CO2 for each
kilogram of weight in an hour, one weighing 3.1 kg. yields only 1.96 g. in all.
The respiratory quotient is higher in herbivora (0.9 to 1.0) than in carnivora
(0.7 to 0.8) or omnivora (0.8 to 0.9). These differences find their cause in the
character of the food, because the formation of CO2 from carbohydrates, upon
which herbivora feed, requires the use of all the O for the reduction of the molecules,
while the H has already acquired an amount of 0 sufficient to satisfy it. During
the disintegration of the fats and proteids, on the other hand, a portion of the O
is employed for the oxidation of the H to form H2O. For this reason, the quotient
is lowered by a diet rich in proteid material, and heightened by vegetable foods.
It must approximate unity (1.0) as soon as a sufficient amount of carbohydrates
has been ingested. *For example, since 6 molecules of O oxidize 1 molecule of
grape sugar (C6H12O6 = 6CO2 + 6H2O), the quotient must be ^^ ^ = 1. In
the case of the fats which require a much greater number of molecules of O, the
quotient must, of course, become smaller. Olein, for example, needs 80 molecules
of O to reduce its molecules, as follows:
C3H5(Ci8H3302)3 = 57CO2 + 52H2O; hence, the quotient must be -^§^ =
• 0UU2
0.712.
Inasmuch as the proteins vary considerably in their composition and are not
oxidized in their entirety in the body, their quotient can only be arrived at by
calculation. Thus, it has been estimated that this value in the case of albumin
varies between 0.75 and 0.81, in accordance with the degree of disintegration of
the substance. During periods of starvation the quotient remains below normal,
because all the available carbohydrates have been utilized and the body subsists on
its own proteids and fats. The production of CO2 then falls off at a greater rate
than the consumption of O. In diabetic patients, whose consumption of carbo-
hydrates is at a minimum, the respiratory quotient is very low, namely, 0.6 to 0.7.
Hence, it will be seen that the respiratory quotient at any given moment is depend-
ent upon the nature of the substances undergoing oxidation. Atwater has fur-
nished the following table:
Starch 1.0
Cane sugar 1.0
Glucose 1.0
Animal fat 0 . 711
Protein 0 . 809
In hibernating animals the quotient becomes very small (0.25), because the
output of CO2 and the consumption of O are enormously reduced, but the former
in a greater measure than the latter. The CO2 output is also diminished during
slee-p and more so than the intake of O. The quotient, therefore, becomes smaller
than normal. Brief muscular exercise, on the other hand, increases it immediately,
because a considerable quantity of carbon dioxid is then washed out of the active
tissues. During longer periods of muscular activity the quotient remains prac-
tically the same, in spite of the fact that greater amounts of CO2 and O are worked
516 RESPIRATION
over. On a mixed diet, however, their relationship remains practically unaltered.
The ingestion of different foodstuffs changes matters considerably. Thus, the
quotient rises to 1, if the muscular work is performed exclusively at the expense
of the carbohydrate material. This is rarely the case, although muscular work
depends chiefly upon the carbohydrates, because these bodies are more immediately
available and may also be slowly replenished from the proteins. The fats may also
be drawn upon, but since there is no evidence at hand to show that these substances
are first converted into carbohydrates, it must be concluded that the muscles
are capable of utilizing them as such. Obviously, therefore, the respiratory quo-
tient serves as a rieliable index of the oxidations only if the determinations establish-
ing its value have been extended over a long period of time. Short experiments
may lead to absolutely erroneous results on account of the occurrence of accidental
variations, such as occasional muscular contractions and voluntary changes in the
depth of the respiratory movements. ^ Even the mere ingestion of food may
increase the gaseous exchange, because it augments the mechanical and secretory
activities of the alimentary canal. ^ None of these influences possess a permanent
metabolic value.
Sex and age influence the quotient through the general metabolism. In males
the average CO2 output is greater than in females, but this general difference
between the sexes is not in evidence if persons of the same body-weight are com-
pared. The influence of age manifests itself by the low value of the quotient in
children as compared with that of adults. Not only is the gaseous interchange in
proportion to the weight greater in the former, but more O is being absorbed by
them in comparison with the CO2 given off. Obviously, therefore, the child
possesses a more intense metabolism, presumably on account of the fact that its
surface in proportion to its weight is larger than that of the adult, thereby entailing
a greater loss of heat. Aside from this factor, age also influences the respiratory
interchange because the tissues gradually become less active. For the same reason,
the respiratory activity is greater in the robust than in the weak or sick.
Increases in the external temperature tend to heighten the gaseous interchange
and hence, to increase the quotient. In cold-blooded animals, in particular, the
CO2 output decreases as the temperature of the medium falls and increases as the
latter rises. In warm-blooded animals, on the other hand, cold within physiolog-
ical limits has a tendency to stimulate the consumption of O as well as the produc-
tion of CO2. Involuntary muscular tremors (shivering) increase the respiratory
activity, the oxygen intake as well as the CO2 output becoming greater. ^ When
the body temperature rises, as in fever, the respiratory quotient remains at first
practically the same, although the volumes of O absorbed and CO2 produced are
increased.
The rate and depth of the respiratory movements do not appreciably change the
relationship of the O and CO2, although, to begin with, the more ample ventilation
of the lungs tends to heighten the CO2 output. If the respiratory amplitude re-
mains the same while its rate is increased, the volume of air respired, as well as the
absolute quantity of CO2 discharged, is increased, but the amount of CO2 in com-
parison with the total volume of air becomes less. Very similar results are
obtained it the depth of respiration is increased while the frequency is permitted
to remain the same. Slow and deep respirations, of course, give rise to a greater
discharge of CO2.
The composition of the air may be changed considerably before the gaseous
interchange is markedly altered, because a variation in the partial pressure of the
two principal gases is generally compensated for by changes in the activity of the
body as well as in the gas content of the blood. This compensation, however, has
its limits, so that any extraordinary alteration in the partial pressures of the gases
^ Benedict and Cathcart, Muse, work, etc., Carnegie Institution of Washington,
1913.
2 Zuntz and Mehring, Pfliiger's Archiv, xxxii, 1883. 173.
3 Speck, Deutsch. Arch, fur klin. Med., xxxiii, 1889, 375.
TOU(
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 517
of the atmospheric air must finally lead to a serious disturbance of the normal
metabolism. The conditions to be dealt with at this time are a decreased and
increased supply of oxygen and an increased supply of carbon dioxid. In all these
cases we are concerned with changes in the volume per cent, of the gases.
A diminution in the partial pressure of the oxygen of the air must necessarily
induce a similar change in the pressure of this gas in the alveoli. But inasmuch as
the intensity of the pulmonary ventilation and the magnitude of the oxygen con-
sumption vary almost from moment to moment, a direct relationship cannot
exist between these factors, and hence, it is more correct to speak of the tension of
this gas in the alveoli than of that in the surrounding air. While the lower limit
of the former, which may be endured without danger to life, differs somewhat in
different persons, it may be adjudged at 30-35 mm. Hg. This value, of course,
holds true only under a normal atmospheric pressure and corresponds to an oxygen
content of the alveolar air of 4.5 per cent. Consequently, provided that 500 c.c.
of air are respired 17 times in a minute, an altitude of 5000 m. may be attained
before the oxygen tension in the alveoli reaches this low level. ^ Any difficulty
arising therefrom, may be remedied immediately by increasing the amplitude of
the respiratory movements. This change augments the alveolar tension and en-
ables the individual safely to ascend even to somewhat higher altitudes if he reduces
his muscular activity to a minimum. Paul Bert^ places the lower limit of the
oxygen pressure of the outside air at 50 mm. Hg, which corresponds to an oxygen
content of 6 to 7 per cent. At this time, the total atmospheric pressure amounts
to 250 mm. Hg. An animal which is exposed to still lower tensions develops symp-
toms of dyspnea and convulsions which generally terminate fatally. An oxygen
content of 12 per cent, is usually endured without changing the quality of the
respiratory movements, although the deficiency in oxygen may be quite apparent
from the bluish color of the face.
In explaining this phenomenon it is commonly believed that an alveolar tension
of the oxygen of about 30 mm. Hg causes the oxyhemoglobin to be dissociated
so rapidly that the blood is no longer in a position to aerate the tissues properly.
Hence, we are dealing here with a real deficiency in the oxygen supply which is
commonly designated as anoxemia. This explanation may also be expressed as
follows: We know that for physical reasons the system cannot absorb the oxygen
under a lower tension than the one just given. Consequently, the 350 c.c. of
oxygen which each kilogram of substance requires in an hour can only be obtained
with a differential pressure of 29 mm. Hg or more. If the pressure falls below this
value, the driving force behind the atoms of oxygen becomes so slight that they
cannot traverse the alveolar lining to enter the blood.
An increase in the partial pressure of the oxygen in the alveoli can be attained
either by the inhalation of a mixture of gases which is rich in oxygen, or by the
inhalation of pure oxygen under atmospheric pressure. But even if this gas is
supplied in a pure form, so that its pressure is increased five times, namely, from
152 mm. to 760 mm. Hg, no considerable variation in the consumption of oxygen
and the output of carbon dioxid results ; provided, of course, that the experiment is
not continued for an unusually long time. This fact tends to show that the oxida-
tions in our tissues cannot be affected in a favorable manner by this means so long
as physiological conditions prevail. It also proves that the atmospheric air
contains an amount of oxygen which is more than sufficient to satisfy our needs.
Any variation in our requirements is immediately adjusted by changing the respira-
tory rate and amplitude. But while ordinarily no advantage can be derived
from breathing pure oxygen, this procedure may prove beneficial in those diseases
which are associated with pulmonary infiltrations and a poor aeration of the tissues.
In accordance with the foregoing discussion, it must be clear that all we can hope to
accomphsh by this means is to increase the driving force behind the atoms of oxygen,
^Loewy, Respiration und Zirkulation bei Ander. des Sauerstoffgehalts der
Luft, Berlin, 1895.
2 La pression barometrique, Paris, 1878.
518 RESPIRATION
and to impart to them a greater penetrating power. In this way, at least a partial
aeration of the tissues may be retained for some time after the respiratory move-
ments have become inadequate, or after the alveolar spaces have become blocked
by exudated material (pneumonia). Especially beneficial results are obtained
in certain heart diseases, m which the supply of oxygen has become insufficient on
account of the impairment of the circulation. The oxygen seems to exert a stimu-
latmg influence upon the musculature of the heart m consequence of which its
contractions become more forceful.
If the oxygen is inhaled under a pressure of from 3 to 4 atmospheres, it acts as
a poison, death resulting in the course of a short time from respiratory depression,
loss of heat and a general intoxication. The same effect may be produced by the
continued inhalation of ordinary air under a pressure of from 15 to 20 atmospheres.
It has also been shown that the development of the eggs of insects is greatly re-
tarded if exposed to an oxygen pressure of less than one atmosphere. Fish are
killed when the oxygen content of the water is raised so that 100 c.c. contain more
than 10 volumes of dissolved oxygen. Quite similarly, it was found by Smith ^
that mice which had been exposed for several hours to an oxygen pressure of 2
atmospheres acquired a subnormal content in oxygen. These animals then exhib-
FiG. 258. — Effect of COa on Respiratory Movements of Rabbit. {Scott.)
During the first period indicated on the signal line the animal breathed 9.6 per cent.
CO2 in air, and during the second period 10 per cent. CO2 with 33 per cent, oxygen.
Time tracing = 2 seconds.
ited inflammatory changes of the lining cells of the alveoli, similar to those ob-
served in pneumonia. A longer exposure to this gas proved fatal in a few days.
Facts such as these unmistakably prove that the administration of oxygen is not
at all without danger.
A slight increase in the partial pressure of the carbon dioxid (to 5 per cent.) is
reacted against as a rule by an increase in the respiratory rate and amplitude
(hyperpnea), but the intensity of the oxidations is not materially changed. ^ In
those cases in which a greater output of carbon dioxid has actually been observed,
the change seems to be due to the greater activity of the muscles of respiration. If
the carbon dioxid in the inspired air is increased to 8 or 10 per cent., dyspnea results;
the output of carbon dioxid is diminished and later on also the intake of oxygen.
A further increase in the partial pressure of this gas to 15 per cent, leads to an
augmentation of these conditions until, at concentrations of from 30 to 40 per cent.,
a respiratory depression sets in which is soon followed by the death of the animal.
At first, therefore, the tendency is to increase the ventilation in the alveoli by
hyper efforts at respiration so as to maintain the tension of this gas in the blood.
This change is accompanied by a rise in blood pressure which is caused in part by
a greater cardiac output and in part by a constriction of the blood-vessels. Later
on, however, as the tension of the carbon dioxid is increased to 15 per cent., the
1 Jour, of Physiol., xxii, 1898, 307.
2 Speck, Menschl. Atmung., Leipzig, 1892.
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 519
dyspnea gradually becomes more evident until it eventually gives way to a respira-
tory and circulatory depression similar to that observed in deep narcosis (Fig. 259).
Changes in Barometric Pressure. — It is also feasible to change the
pressures of the gases by altering the barometric pressure. This can
be done either by compressing the air surrounding us, or by changing
our altitude. Thus, a deficiency in oxygen may be produced either
by placing an animal into a chamber in which the oxyger> tension is
low or by bringing it to a higher altitude. As is indicated in the suc-
ceeding table, the pressure decreases the more, the higher the altitude.
Fig. 259. — Record of the Carotid Blood-pressure During Dyspnea (Dog).
At L the tracheal tube was held shut until the blood-pressure began to drop.
Elevation above sea level,
m.
Barometric pressure,
mm. Hg
Per cent, of an
atmosphere
0
760
100
1000
670
88
2000
593
78
3000
524
69
4000
463
61
5000
410
54
6000
357
47
7000
320
42
Sojourns in rarefied air give rise to a complex of symptoms which
are grouped under the term of mountain sickness. A person affected
in this way suffers from headache, nausea, vertigo, hemorrhages and
a general mental and bodily apathy. It is true, however, that the
altitude at which these symptoms appear is not the same for all
individuals, because a process of adaptation is frequently brought into
play which allows the continuance of normal function even at higher
520 RESPIRATION
altitudes. Most generally, however, an elevation of about 4000 m,
suffices to produce definite discomforts and especially if the consump-
tion of oxygen has been markedly increased on account of the muscular
exertions incurred during climbing. At a height of 5000 m., at which
the pressure of the air is reduced to about one-half and the oxygen
tension to about 11 per cent, of an atmosphere, scarcely anybody
escapes the sensations of fatigue and respiratory oppression. Neither
is it possible to obviate these difficulties by ascending to these heights
in a balloon, because even in the absence of all unnecessary muscular
activity, the body is in need of more oxygen owing to an increased
action of the heart and a compensatory augmentation of the cellular
oxidations. More favorable conditions, however, may be estabhshed
during balloon ascensions, and hence, somewhat higher altitudes may
be attained in this way. Altitudes of 7000-8000 m. and over may be
reached by resorting to inhalations of pure oxygen, but even this arti-
ficial means does not afford an absolute protection against the develop-
ment of dangerous conditions. This is shown by the experiences
which Tissandier^ had while ascending in a balloon to a height of
8600 m. At an altitude of 7500 m. he and his two companions became
so weak that they could not make effective use of the oxygen bags.
All three persons finally lost consciousness but without having pre-
viously experienced a decided dyspnea. Tissandier was the only
survivor.
Henderson^ and his collaborators have produced acute effects of
oxygen deficiency at sea-level by breathing into an apparatus con-
sisting of a spirometer and a canister containing alkali. The exhaled
carbon dioxid is absorbed by the alkali, while the oxygen is gradu-
ally diminished by the continual rebreathing. The increase in the
frequency of the heart is slight at first, only about one to three beats,
but a marked acceleration sets in when the oxygen has fallen to be-
tween 13 and 9 per cent. (14,500 to 22,000 feet of altitude). In men
who do not tolerate low percentages of oxygen an increase of from
40 to 70 beats was not uncommon. The systolic blood pressure re-
mains about the same until the oxygen has been lowered to between
14 and 9 per cent., when it may rise 15 to 20 mm. Hg above normal.
The diastolic pressure remains fairly normal, but falls somewhat
after the oxygen has been reduced to 9.5 per cent, or less. The best
type of men may tolerate as low an oxygen content as 6 per cent.,
which corresponds to an altitude of close to 30,000 feet. The hemo-
globin showed a well defined increase in at least 25 per cent, of all
the men. No cardio- vascular lesions could be noted in men in
''optimum" condition; others, on the other hand, developed mur-
murs and hypertrophic conditions.
In accordance with Bert, it is generally held that the disturbances
just described, are due to a failure of the diffusion pressure which
1 La nature, 1875, 337.
2 Medical Studies in Aviation, Jour. Am. Med. Assoc, Ixxi, 1918.
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 521
quickly induces a lack of oxygen in the system, commonly called
anoxemia. This view has found experimental proof in the work of
Zuntz and others, who have shown that the oxygen tension in the alveoli
is diminished at high altitudes. Upon Monte Rosa, for example, the
different members of his party showed tensions of only 37-57 mm. Hg
and all suffered from mountain sickness. In this connection attention
should briefly be called to the fact that the number of the erythrocytes
increases at high altitudes, but clearly , Wen this change must eventually
fail in its purpose for the reason that the tension of this gas finally
reaches so low a level that it cannot enter in sufficiently large quan-
tities. The hemoglobin remains below its point of saturation. As a
result of this scarcity of oxygen, the heart muscle weakens and even-
tually fails to sustain the circulation. The nervous tissue is then
unable to effect a proper, coordination of the muscular movements.
Provided, however, that a certain limit has not been exceeded, these
symptoms disappear in the course of time and the individual finally
acquires a muscular force as great as that previously shown by him
upon the plains. This adaptation is dependent upon the production
of acid substances, especially lactic acid and carbon dioxid, which
exert a stimulating action upon the respiratory center and augment
the ventilation in the lungs.
Mosso^ has submitted a somewhat different explanation which is
based upon a diminution in the carbon dioxid tension of the blood,
constituting the condition of acapnia. The claim is made that
mountain sickness is associated with an excessive loss of carbon dioxid
in consequence of which the tissues themselves are impoverished. We
know, however, that acapnia may be present in individuals without
that the disorders just mentioned develop, and besides, this condition
may be absent during the most acute stage of mountain sickness.
It also happens at times that these symptoms appear sometime after
the individual has again reached the plains. These facts tend to show
that the real difficulty is more deeply seated and must be sought for
in a disorder of the tissue oxidations.
Higher barometric pressures are encountered in submarine work,
such as is required during the building of tunnels and caissons. It has
previously been mentioned that pressures of 5 to 6 atmospheres cannot
be endured for any length of time without serious consequences and
that a pressure of 15 atmospheres brings on convulsions and. death.
But, since a depth of 10 m. corresponds to an increase in pressure of
only 1 atmosphere, the human body will rarely be called upon to endure
a pressure of more than 2 or 3 atmospheres. In descending to this
depth it is imperative to proceed slowly, and to permit the system to
become adapted first to intermediate degrees of pressure before the
chamber of greatest pressure is entered. Quite similarly, it is abso-
lutely necessary to proceed slowly with the decompression, because
any abrupt cessation of the pressure is prone to produce a complex of
^ Der Mensch auf den Hochalpen, Leipzig, 1899.
522
RESPIRATION
symptoms which constitute the so-called caisson disease,^ or, as the work-
men call it, the ''bends. '* The muscles and j oints become painful and a
degree of dyspnea develops which leads to cyanosis, congestion,
vertigo and unconsciousness. In many cases certain groups of mus-
cles become paralyzed, giving rise to the condition commonly de-
scribed as "diver's palsy." These symptoms are attributed as a
rule to an evolution of nitrogen. Obviously, the absorption of this
gas by the tissues increases with the pressure, but if the pressure is
then suddenly released, the rapidly escaping bubbles of this inert gas
collect in large numbers in the capillaries and cause a blocking of the
blood-flow and a loss of function of the parts situated distally to the
obstruction. In fact, it is conceivable that the rapid evolution of this
gas may lead to an actual destruction of the soft nervous structures
and a loss of function of the structures innervated by them.
The Gaseous Composition of the Blood under Different Conditions.
Eupnea. — If the quantities of 0 and CO2 in the blood vary within
Fig. 260. — Stethogbaphic Record of the Respira-tory Movements.
E, eupnea; A, apnea produced by taking three or four deep breaths.
normal limits, the animal is said to be in the state of eupnea. The
respiratory movements exhibit during this period a normal amplitude
and frequency.
Apnea. — An animal may be placed in the condition of apnea
in two ways, namely, by increasing the frequency of its respiratory
movements or by permitting it to breathe pure oxygen. It is a matter
of common experience that the taking of two or three deep breaths in
rapid succession forces us to suspend our respiratory activity for a
short period of time (Fig. 260). Quite similarly, the quickly repeated
inflation of the lungs of a tracheotomized animal causes it to cease its
respiratory movements temporarily. The inhalation of pure oxygen
gives rise to the same effect. As far as the character of the respiratory
motions is concerned, apnea signifies a temporary cessation of these
movements. With reference to the condition of the blood, several
views have been advanced. Thus, it has been thought that this respira-
tory inhibition is dependent upon an overoxygenation of the blood,
1 Hill, Caisson Sickness, London, 1912.
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 523
this inhibition lasting until the extra amount of oxygen has again been
used up. Head,^ however, has shown that this effect may also be
obtained by inflating the lungs with pure hydrogen, although it is true
that the apneic cessation of respiration is then briefer in its duration
and may, in fact, be abolished altogether. Besides, it should be men-
tioned that the contention of Ewald, that in apnea the blood is actually
oversaturated with oxygen, has been disproved by Hoppe-Seyler.^
It seems, therefore, that some other factor, besides the oxygen, must
be responsible for this phenomenon. It has been suggested that the
repeated distention of the lungs acts as an excitaat to the receptors
of the vagi nerves, in consequence of which impulses are generated
which reflexly inhibit the inspiratory discharges from the respiratory
center.^ A more plausible explanation, however, is the one offered by
Mosso,^ which states that any excessive ventilation of the lungs induces
a scarcity of carbon dioxid (acapnia) which eventually leads to a con-
dition of subnormal stimulation of the respiratory center. The re-
spiratory actions then cease until the accumulation of carbon dioxid
in the blood has again been raised to normal. That this is so may be
gathered from the fact that augmentations of the respiratory move-
ments fail absolutely to produce the apneic standstill if the carbon
dioxid content of the inspired air is retained at 4.5 per cent. In order
to account for the different discrepancies just enumerated, it has been
suggested to recognize three types of apneas, namely:
Apnea vera, which is due to the lowering of the CO2 content,
Apnea vagi, which is caused by the stimulation of the inhibitor fibers of the
vagi nerves, and
Apnea spuria, which is dependent upon stimulations from other parts of the
body.
As an example of the first type might be mentioned the apnea fetalis,
i.e., the permanent inhibition of the respiratory activity of the young
while in the uterus. As an example of the second type may serve the
rather temporary inhibition following the distention of the lungs by
air or inert gases, and as an example of the third type, the cessation
of respiration exhibited by diving animals as soon as their nares or
beaks are brought in contact with water.
A very peculiar type of respiration is frequently observed during
such pathological states as arteriosclerosis, uremic coma, anemia,
increased intracranial pressure and lesions of the central nervous
system. The respiratory movements then occur in groups which are
separated from one another by apneic pauses. This condition of
periodic breathing is commonly designated as Cheyne-Stokes respira-
tion (Fig. 261). The periodicity of these movements, however, is not
the same in all cases; but whether only ten or forty of them appear
1 Jour, of Physiol., x, 1889, 1.
2 Zeitschrift fur physiol. Chemie, iii, 1879, 105.
' Miescher-Rtisch, Wiener Akad., Ixxxv, 1882, 101.
* Arch. ital. de biol., xl, 1903.
524 RESPIRATION
together, the, first respirations of each group always begin small and
gradually increase in amplitude until their maximum has been reached.
Subsequent to this point they again decrease slowly to complete stop-
page. The intervening respiratory standstills may last only a few
seconds or a longer time, say, 3(>-40 seconds. As Eyster^ has shown,
these variations in the respirations are accompanied by rhythmic
changes in the blood pressure, a rise occurring most generally toward
the end of the apneic phase, at which time the oxygen tension of
the alveolar air is, greatly diminished. The succeeding respirations,
therefore, would be incited by a lack in oxygen. Pembrey,^ on the
other hand, advocates the view that the apneic phase is caused by a
diminution in the carbon dioxid tension which leaves the respiratory
center temporarily without its normal stimulus. At all events, it is
possible to remove this condition for a time by the administration of
either oxygen or carbon dioxid. The former tends to heighten the
Fig. 261. — Tracing Showing the Cheyne-Stokes Form of Respiration. (Hill.)
irritability of the respiratory center, whereas the latter stimulates it
until it again discharges its impulses.
A similar type of respiration is frequently observed during sleep
and in meningitis, in which disease it constitutes an unfavorable
prognostic sign. It is known as Biotas respiration and consists of
rapid short breathing which is interrupted by pauses lasting from
several seconds to half a minute.
Hyperpnea. — This condition is characterized by a moderate in-
crease in the respiratory rate and amplitude. It is attributed as a
rule to a diminution of the oxygen and an increase of the carbon dioxid
occurring in the course of heightened muscular activity. Besides the
carbon dioxid, it is entirely probable that other fatigue substances are
present which act as powerful exciting agents of the respiratory center.
It is also possible to augment the respiratory activity in an indirect
manner by stimulating the receptors for touch, pain and temperature.
A reaction of this kind is usually experienced upon tactile impressions,
as well as upon the immersion of the body in water of 32° C. or in
water charged with carbonic acid gas. It can also be produced by
1 Jour, of Exp. Med., viii, 1906, 565.
2 Jour, of Path, and Bact., xii, 1908, 258.
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 525
exposing an animal to a high temperature or by heating its blood
directly as it traverses the carotid artery.^ These types of hyperpnea,
however, are not dependent upon the gaseous composition of the blood
and should, therefore, be classified as ordinary reflex reactions.
Dyspnea. — If prolonged, the condition of hyperpnea gradually
passes over into the condition of dyspnea, the essential characteristic
of which is labored breathing. Its cause lies either in a deficiency of
oxygen or in an excess of carbon dioxid; most generally, however,
these two factors act in unison. In accordance with this statement,
it must be evident that an animal may be rendered dyspneic in two
ways, viz., by interfering with its respiratory activity in a mechanical
way or by altering the composition of the inspired air. Among the
former occurrences might be mentioned the partial occlusion of the
respiratory passage by foreign bodies or by pressure from without.
In a chemical way, dyspnea may be produced either by lessening the
tension of the oxygen or by increasing the tension of the carbon dioxid.
The former is designated as O = dyspnea, and the latter as CO2 =
dyspnea. An animal may also be rendered dyspneic by permitting
it to breathe an indifferent gas, such as pure nitrogen or hydrogen.
Curiously enough, the dyspnea then ensuing cannot be prevented by
lessening the carbon dioxid tension of the blood, which would natu-
rally diminish the excitation of the respiratory center. It is also
possible to render an animal dyspneic by permitting it to inhale an
increased amount of carbon dioxid. In this case, the oxygen cannot
be the deciding factor, because the occurrence of this dyspnea cannot
be prevented by simultaneously raising the tension of this gas. De-
ficiencies in oxygen, which finally give rise to dyspnea, may be pro-
duced by bleeding, by the fixation of the hemoglobin by carbon mon-
oxid, by hemolysis of the red corpuscles, and by any impairment of
the cardiovascular system tending to lessen the vascularity of the
tissues.
While the general picture of dyspnea always remains the same,
certain differences may nevertheless be noted which allow us to differ-
entiate the 0 = dyspnea from the €62 = dyspnea. The former
usually runs a longer course and finally leads to marked motor disturb-
ances. The latter, on the other hand, immediately assumes a more
depressive and more narcotizing character. Moreover, during the
former the respirations are prone to be rather frequent and display a
forced inspiratory character, whereas during the latter they are slow
and of a pronounced expiratory type.
Asphyxia. — This condition represents the final state of dyspnea, a
state of functional exhaustion and collapse. It signifies that the
deprivation of oxygen has been completed. The powerful respiratory
movements ordinarily observed during the later stages of dyspnea,
^ Fick and Goldstein, Verhandl. math.-naturw. Ges., Wiirzburg, ii, 156. The
term polypnea has been applied to this form of hyperpnea by Richet, Compt.
rend., xcix, 1884, 279.
526 RESPIRATION
presently give way to infrequent convulsive efforts and these in turn
to slow and shallow respirations and finally to mere spasmodic twitches.
At this time, the pupils are markedly dilated, the reflexes are extinct,
the integument is cyanosed, and the extremities stiffened. The urine
and feces are voided generally before the heart has ceased to beat.
The blood pressure rises during the early stage of dyspnea, but falls
gradually as soon as the respiratory and cardiac depression has set in.
Inasmuch as the heart usually continues to beat for several minutes
after the cessation of respiration, it is still possible at this time to
resuscitate the animal.
Ventilation. — The problem of ventilation is essentially a physio-
logical one and has to do primarily with the chemical properties of the
respiratory air, and secondarily with its temperature and its content
in water vapor. Consequently, ventilation provides not only for a
continuous supply of pure air in place of that vitiated with the products
of metabolism, but also of air possessing a stimulating temperature and
a content in aqueous vaipor in keeping with the physiological require-
ments of the body. An undue emphasis, however, should not be placed
upon any one of these factors at the expense of the others.
Ventilation does not purpose to bring outdoor conditions indoors,
but simply to make indoor conditions fit for indoor life. As far as the
composition of the air is concerned, we know that an adult person in-
spires about 500 c.c. of air seventeen times in a minute and that his
output of CO2 at rest amounts to 17 liters, or to 0.68 cubic feet in an
hour. During gentle exertion this value rises to 0.9 and during actual
work to 1.8 cubic feet per hour. Assuming then that the normal
amount of CO2 is 0.03 per cent., the percentage of this gas in 1000
cubic feet (28,000 liters) of air will be increased to about 0.1 percent,
in the course of an hour. Obviously, therefore, the amount of fresh
air required per hour to keep the CO2 at 0.06 per cent., is 0.03 : 0.6 ::
100 : X or a; = 2000 cubic feet. If the normal amount of CO2 is reckoned
at 0.04 per cent., 3000 cubic feet must actually be provided for, but
naturally, this amount may be supplied in three lots of 1000 cubic
feet each. Furthermore, an allowance must be made for the weight
of the person, because a woman of 120 pounds exhales only 0.6 cubic
feet of CO2 in an hour and a child of 80 pounds only 0.4 cubic feet. It
is also essential to take account of the type of work to be performed by
these individuals.
In regard to O2, little need be said, because even in the worst ven-
tilated spaces the air seldom approaches a basis of 15 volumes per cent.,
at which respiration can still go on undisturbedly. Hence, we are
chiefly concerned at this time with the CO2 content of the respired air,
but its value should serve merely as a working unit to indicate the
degree of vitiation of the air, because even in the worst ventilated rooms
it is rarely present in amounts sufficient to exert a pernicious influence.
Ordinary increases are endured for some time without discomfort,
provided that the temperature and the humidity of the air remain
RESPIRATORY INTERCHANGE UNDER DIFFERENT CONDITIONS 527
low. Toward larger amounts of CO2, the system very readily reacts
by a greater respiratory rate and amplitude and other changes. Thus,
if it is said that the air of a room, in which more than 0.07 volume
per cent, of CO2 is present, feels distinctly close and uncomfortable.
This sensation should not be referred to a deficiency of O nor to a super-
fluity of CO2, but rather to its temperature, its humidity, and its con-
tent in volatile odorous substances and dust.
In poorly ventilated rooms the CO2 may reach 0.30 volume per
cent., and in crowded lecture halls 0.80 volume per cent., but the dis-
comfort experienced in places of this kind may be lessened consider-
ably either by lowering the temperature and the humidity of the air or
by fanning it. Even in rooms in which the CO2 content is 1.0 or 2.0
per cent., no discomforts are experienced so long as the aqueous vapor
and the temperature are kept low, but these facts are not cited to
minimize the importance of the composition of the air, but solely to
show that the other two factors play an important part. In a general
way, it may be stated that optimum conditions prevail when the tem-
perature of the room is between 65° and 68° C, and when the moisture
equals 50 to 75 per cent, relative humidity. The air itself should not
contain more than 0.06 per cent, of CO2 and should be as free as pos-
sible from bacteria, gaseous admixtures and dust. If it contains
more than this amount, artificial means should be resorted to to renew
it with a frequency which is to be determined by calculation from the
proportion of CO2 per volume of air.
It seems, therefore, that the injurious consequences of living in
poorly ventilated quarters are caused, at least to some extent, by the
physical qualities of the respired air, but precisely in what respect a
hot and humid atmosphere proves harmful, has not been fully deter-
mined. Hermanns 1 has found that the temperature of persons living
in very restricted quarters, rises considerably, and furthermore, the
results of the New York State Commission on Ventilation^ indicate
that a high temperature and high humidity give rise to an elevation
of the systolic and diastolic pressures, as well as to a diminution of the '
vascular tonus and a lowering of the resistance of the body against
bacterial infections. The general disinclination to exercise experienced
at this time, seems to have a deeply seated cause, because the muscles
themselves are incapable of performing a normal amount of work.
Lee and Scott^ have shown, that a loss of blood sugar results at this
time which under extreme conditions may equal 5 per cent, of normal.
1 Archiv fiir Hygiene, i, 1883, 1.
2 Lee, Science, N. S., xliv, 1916, 183.
s Am. Jour, of Physiol., xl, 1916, 486.
528
RESPIRATION
CHAPTER XLII
THE NERVOUS REGULATION OF RESPIRATION
The Respiratory Center and Its Nervous Connections. — The nerv-
ous mechanism concerned in respiration, consists of a center and
different efferent and afferent conducting paths. On the efferent side
the nerve paths always remain the same, because the same muscles
are constantly at work expanding the lung and producing related motor
effects. The impulses generated in the respiratory center, reach these
different effectors by way of their respective nerves, and hence, the
efferent half of the respiratory arc is formed by the different nerves
innervating the muscles ordinarily concerned in
respiration. On the afferent side, on the other
hand, conditions are not so simple, because the
character of the respiratory movements is subject
to variations in consequence of a very large number
of sensory impressions. Practically any one of
the receptors, internal as well as external, may be
the recipient of impressions which are eventually
relayed to the respiratory center, where they incite
an alteration in the rate and depth of the respira-
tions. In accordance with this brief preliminary
statement, it should be evident that the destruction
of the efferent paths must entail an immediate
arrest of the respiratory movements, because the
impulses generated by the respiratory center, are
then no longer able to reach the respiratory mus-
cles. An arrest of respiration must also follow the
destruction of the center itself, for the reason that
the stimuU upon which the contraction of these
muscles depends, then fail to materialize. Con-
trary to these results, the division of the afferent
path does not stop the respiratory movements,
because it does not destroy the rhythmic discharges from the center.
It is to be noted, however, that the movements are then wholly de-
pendent upon the automatic activity of the center and can no longer
be varied by afferent impulses arising in other parts of the body.
The Location of the Respiratory Center. — In accordance with the
experiments of Lorry, ^ Le Gallois^ and Flourens,^ the respiratory cen-
ter is situated in the medulla oblongata at the level of the apex of the
calamus scriptorius. More recent experiments by Volkmann and
• ^ M^moires pres. a I'acad. des Sciences, i, iii, 366.
2 Exper. sur la principe de la vie, Paris, 1812.
^ Rech. exp. sur la systeme nerveaux, Paris, 1824.
Fig. 262.— The
Nervous Regulation
OF Respiration.
C, respiratory
center is under the
control of afferent
impulses (A) from
different receptors
(R). On the efferent
side (E) it is in con-
nection with the dif-
ferent muscles of res-
piration (M).
THE NERVOUS REGULATION OF RESPIRATION 529
others have shown that it is possible to make a median incision through
this structure without destroying the respiratory movements. For this
reason, the center is said to be bilateral, each half being especially
concerned with the muscles situated on the corresponding side of the
thorax. In this connection brief reference should also be made to the
fact that injuries to the cerebral cortex (hemiplegia) most generally
leave the respiratory musculature unaffected. This is especially true
of the diaphragm and the intercostals. It seems, therefore, that these
muscles, besides being governed by lower centers, possess a bilat-
eral representation in the motor cortex of the cerebrum. Conse-
quently, the destruction of one motor area cannot possibly produce
a paralysis of the respiratory muscles, although it gives rise to a uni-
lateral paralysis of the other skeletal muscles.
It might also be stated that several authors have not felt incUned
to accept this rather sharp localization of Flourens. Gierke, ^ for ex-
ample, regards the tractus solitarius as an important part of this cen-
ter, while Mislawsky^ holds a similar view regarding a stretch of gray
matter in the vicinity of the hypoglossal nucleus. To be brief, it
seems that the respiratory center is not confined to a point-like zone
of bulbar gray matter, but occupies a more extensive area, inclusive of
its connections with other bulbar centers and the nuclei of important
cranial nerves. With Gad,^ it may be assumed that really the entire
formatio reticularis enters into the formation of the bilaterally coordi-
nated center of respiration.
A very general localization of this center may be effected in the
following way: A deeply anesthetized animal is connected with a
stethographic arrangement for recording the respiratory movements.
A section is then made transversely through the region of the pons.
Inasmuch as the respiratory motions continue after this cut has been
made, it is evident that the center is situated in the bulb or spinal
cord. A second cross-section is then made below the lower root of the
phrenic nerve, at about the level of the sixth cervical vertebra. Since
the respiratory movements do not cease even now, it is obvious that
the main center is situated above the level of the second cut, i.e., either
in the medulla or upper cervical cord. The latter point rday now be
decided by piercing the lower region of the bulb, when the respiratory
motions will cease immediately.
This result may also be obtained by dividing the spinal cord be-
tween the main center and the nuclei of the phrenic nerves situated
opposite the fourth and fifth cervical vertebrae. In this case, however,
the respiratory standstill is not caused by the destruction of the
centet, but solely on account of its separation from its principal motor
apparatus, consisting of the phrenic nuclei and phrenic nerves innervat-
ing the diaphragm. Inasmuch as this muscle is absolutely essential
1 Archiv ftir Anat. und Physiol., 1893, 583.
2 Zentralbl. fiir die med. Wissensch., 1885, 465.
3 Archiv fiir Anat. und Physiol., 1893, 75.
34
530 RESPIRATION
to respiration, its isolation and subsequent paralysis would make life
practically impossible. This is especially true of young animals.
For this reason, it has been advocated to regard the various nuclei of
the nerves innervating the different muscles of respiration, as secondary
or tributary centers to the main or medullary center of respiration.
It does, however, seem scarcely necessary or helpful to look at the
respiratory mechanism in this way, because in reality these different
nuclei form nothing more than mere stations upon the efferent path and
do not possess automatic power. The fact that the respiratory center
is situated in the medulla, may also be proved by injuring this structure
directly, as may be done by introducing a pointed instrument between
the adjoining dorsal borders of the atlas and axis. This constitutes
the act of pithing, a procedure which leads to an almost instantaneous
stoppage of respiration and a loss of the vascular tonus on account of
the destruction of the vasomotor center. The cardiac center is also
involved, although the heart itself continues to beat for a brief period
of time. Very similar conditions may be produced by sharply bending
the head upon the trunk, in which case the odontoid process of the axis
may lacerate the bulbar tissue.
The Cause of the Activity of the Respiratory Center. — The foregoing
discussion has shown that the respiratory motions are incited at regu-
lar intervals by impulses sent out by the center. The question which
now presents itself is this: Does this center possess the power of
discharging these rhythmic impulses in consequence of an inherent
property of its constituents, or does its activity depend upon afferent
impulses conveyed to it from other parts of the body? In brief, there-
fore, it would be necessary to ascertain whether the cells of the respira-
tory center possess an automatic power, such as is exhibited by the
components of the cardiac center, or whether they are activated solely
in a reflex way.
It must be conceded that the former view is the correct one, i.e.,
the rhythm is inherent in these nerve cells and is not generated in a
reflex manner. This conclusion is based upon the fact that the center
may be completely isolated from the rest of the bodj^ by the division
of its afferent connections without producing an absolute cessation of
the respiratory movements. An experiment of this kind necessitates
the division of the brain stem above the medulla and the severance of
the vagi and glossopharyngeal nerves. In addition, the spinal cord
must be cut across below the nuclei of the phrenic nerves,^ and must
also be rendered impermeable to sensory impulses by dividing the pos-
terior roots in its cervical portion. But even now the objection might
be raised that the center cannot be considered as being completely
isolated as long as it remains in connection with such efferent nerves
as the phrenics, the probabihty being that these nerves also conduct
in a centripetal direction. This contention has been disproved in
the following way. Having thoroughly curarized an animal in order
1 Loewy, Pfliiger's Archiv, xlii, 1889, 245.
THE NERVOUS REGULATION OF RESPIRATION 531
to paralyze its skeletal musculature,^ the phrenic nerves were cut and
their central ends connected with a galvanometer. It was found that
these nerves continued to conduct action currents in a centrifugal
direction, clearly indicating thereby a rhythmic activity on the part
of the respiratory center. The chemicophysical causes underlying this
automatism are wholly unknown, i.e., we have almost no conception
regarding the manner in which the metabolic activity of neuroplasm
can give rise to a nervous action of this kind.
When speaking of the respiratory center, we frequently lose sight
of the fact that this structure has to fulfill a double function, because
it activates not only the muscles of inspiration but also those of
expiration. To be sure, under normal conditions only the former are
brought into play, while the latter remain passive, but conditions may
arise at any time which make it imperative to increase the pulmo-
nary ventilation by an active participation of the expiratory muscles.
It may be assumed, therefore, that the respiratory center consists
in reality of two parts, namely, of an inspiratory and an expiratory.
It is conceivable that the function of this entire aggregation of nerve
cells is distributed in such a way that the control of the inspiratory
muscles is apportioned to some of them, while others are concerned
exclusively with the expiratory process. This view may be justified
by certain experimental evidence, in spite of the fact that the separate
existence of an expiratory center has not been proven. At all events,
it is evident that the activity of these cells does not conflict with the
function of those controlling the inspiratory mechanism; in fact, it is
really subordinated to that of the latter. Thus, active expiratory ef-
forts are invariably made when the venosity of the blood is increased,
the purpose of these being to aid the inspiratory mechanism in remedy-
ing this condition. In a volitional way, the expiratory mechanism is
brought into play during the acts of micturition, defecation, parturi-
tion, coughing and sneezing, and in all these instances the inspiratory
mechanism is made to conform absolutely to the expiratory. Such an
interaction gives rise to the so-called ''abdominal press," which plays
an important part in the expulsion of the feces and urine.
The Regulation of the Activity of the Respiratory Center. — Since
it has been shown that the power of automaticiiy is restricted to the
respiratory center, it should now be evident that the inspiratory
movements must cease whenever the muscles expanding the thorax
are separated from it. It will be seen, therefore, that the respiratory
mechanism differs somewhat from that controlling the activity of the
heart, because while the latter organ is also regulated by an automatic
center, it possesses the power of continuing its contractions even after it
has been separated from the central nervous system. Thus, unlike the
respiratory muscles, the heart is capable of developing an automaticity
of its own. Keeping these facts clearly in mind, the further statement
may now be made that the automaticity of the respiratory center may
^ Winterstein, Pfltiger's Archiv, cxxxviii, 1911, 159.
532 EESPIRATION
be varied at any time by conditions arising elsewhere in the body.
Moreover, these conditions may affect its activity in two ways, namely,
by means of the gaseous constituents of the blood as it passes by its
cellular components and secondly, by impulses conducted to it from
other parts of the body.
The chemical regulation of respiration has a nutritive basis, because
it is a well-known fact that an increased venosity of the blood supplying
the center immediately leads to an augmentation of the respiratory
movements. Conversely, a greater aeration of the blood gives rise to a
lessened respiratory frequency and amplitude. It is readily possible
to change a dyspneic type of breathing into an apneic type, and
vice versa. In either case, the question immediately arises, whether
the oxygen or the carbon dioxid is the stimulating agent. Thus, it
may readily be surmised that the respiratory movements may be
rendered dyspneic either by decreasing the amount of the oxygen
(Rosenthal), or by increasing the quantity of the carbon dioxid
(Traube) . The evidence, recently collected by Haldane and his pupils, ^
seems to show that neither one of these factors can be ruled out abso-
lutely. It is very obvious, however, that the center is especially sen-
sitive to changes in the carbon dioxid content of the blood ;2 in fact,
thS stimulating potency of this gas is so great that, under normal con-
ditions, the oxygen cannot play an important part in the regulation
of respiration. It is true, however, that these two conditions gener-
ally go hand in hand, because an increased production of carbon dioxid
necessitates a greater intake of oxygen.
In illustration of this statement, it might be mentioned that a
decided augmentation of the respiratory movements can only be
attained if the oxygen pressure of the alveolar air is reduced from its
normal value of 20 per cent, to about 13 per cent, of an atmosphere.
In fact, in many instances the subject of the experiment is absolutely
unaware of any scarcity of oxygen, although the color of his skin and
mucous surfaces clearly betrays a marked deficiency in oxyhemoglobin.
Unconsciousness frequently sets in before an augmentation in the
respiratory rate has been noticed. Consequently, the action of the
oxygen upon the center seems to consist merely in its preventing the
accumulation of the products of metabolism by quickly oxidizing them.
Whenever this gas is present in insufficient amounts, the cells soon
become overloaded with these waste products. This condition in-
creases their irritability so that the carbon dioxid finally acquires a
greater potency as a respiratory stimulant.^
Much more decisive results are obtained with carbon dioxid,
because an increase in the tension of this gas in the alveolar air of only
2 per cent, suffices to increase the pulmonary ventilation 50 per cent.
A rise of 3 per cent, increases it 126 per cent, and a rise of 6 per cent.
1 Jour, of Physiol., xviii, 1895, 442, and xxxii, 1905, 225.
2 Zuntz, Pfluger's Archiv, xcv, 1903, 192.
3 Haldane and Poulton, Jour, of Physiol., xxxvii, 1908, 390.
THE NERVOUS REGULATION OF RESPIRATION 533
757 per cent. Furthermore, it is a matter of common experience that
the breath can be held for only a brief period of time, obviously be-
cause- the tension of the carbon dioxid in the blood gradually attains
so great a stimulating power upon the respiratory center that it can
no longer be subdued by volitional efforts. A longer respiratory stand-
still may be effected either by taking several deep breaths beforehand
or by inhaling pure oxygen. These procedures are intended to remove
much of the superfluous carbon dioxid from the lungs and to supply
them with enough oxygen to postpone the excitatory influence of the
waste products. It is evident, therefore, that the respiratory center
is under the direct influence of the blood traversing it. As long as the
carbon dioxid tension of the latter remains normal, the respiratory
movements retain their eupneic character, while any increase in the
tension of this gas is immediately followed by hyperpneic and dyspneic
breathing. The tendency is to adjust the depth and frequency of the
respiratory movements in such a way that the pulmonary ventilation
is always kept the same. Any changes in the gas content of the
blood, whether brought about by internal or external causes, affect
the center directly and are immediately compensated for by increasing
or decreasing its automatic activity.
The reflex regulation of respiration is made possible by a multitude
of afferent impulses, which take their origin in different receptors.
Thus, it is a matter of common experience that the amplitude and
frequency of the respiratory motions may be varied not only by sudden
changes in the intensity of the light and unusual auditory impacts,
but also by sensations of smell, taste, touch, pain and temperature.
In addition, the automaticity of the respiratory center may be altered
by impulses conveyed to it from the psychic centers of the cerebrum.
The latter, therefore, must be classified in large part as volitional dis-
charges which reach this center by way of diverse transcortical paths.
To this class also belong the impulses arising in consequence of emo-
tional conditions.
A cold bath most generally produces a deepening and acceleration
of the respiratory movements, while the inhalation of irritating emina-
tions leads to an almost instantaneous respiratory standstill. Very
similar modifications follow the excitation of the receptors situated in
the realm of the splanchnic and sexual organs, but it would lead us
altogether too far to discuss these reactions in detail, and besides, their
analysis most generally presents no serious difficulty. A certain num-
ber of them, however, merit special consideration, because they origi-
nate along the pulmonary passage and influence respiration in a most
decisive manner. Reference is now had particularly to the acts of
sneezing and coughing, resulting in consequence of the excitation of
the lining membrane of the nasal, pharyngeal and laryngeal cavities.
In accordance with the innervation of these parts, it may be surmised
that these reflexes are effected principally with the help of the vagi
nerves, which contain afferent as well as efferent respiratory fibers.
534 EESPIRATION
Keeping these facts clearly in mind, it is now possible to assign a
definite cause to the taking of the first breath. In utero, the respira-
tory center of the fetus is not subjected to a stimulation by the carbon
dioxid, because its blood and tissues are constantly kept in an apneic
condition. Subsequent to the obliteration of the umbilical blood-
vessels, however, the carbon dioxid accumulates very rapidly and
finally incites the center to send out those impulses which give rise to
the first respiratory movement. This process is materially hastened
by mechanical and thermal stimuli, because the conditions which the
fetus meets with during and directly after the period of labor are
very different from those to which it has been subjected in utero. It
exchanges a practically indifferent medium heated to the temperature
of the body, with one much cooler and teeming with mechanical im-
pacts of all sorts.
The Innervation of the Upper Respiratory Passage. — With the
exception of a small patch of modified epithelium forming the so-called
olfactory area, all sensory impressions from the mucous membrane of
the nose are relegated to the system of the trigeminal nerve. In
accordance with the character of the stimulus, these afferent impulses
give rise either to an acceleration or a retardation of the respiratory
movements. In the latter case, respiration may be arrested with the
chest in either the inspiratory or expiratory position. It need scarcely
be mentioned that the impulses generated in the nasal cavity, are first
relayed to the respiratory center by way of the trigeminus and are
then conveyed to the different muscles of respiration. These stimuli
are usually followed by an active expiration, the blast of air being ex-
pelled through the nasal cavity, while the oral cavity is temporarily
shut off by the closure of the fauces. This constitutes the act of
sneezing, the purpose of which is to dislodge the irritating body from
the nose.
A similar reflex mechanism for safeguarding the respiratory passage
is situated in the pharynx. The lining of this cavity is innervated
in a sensory way by the glossopharyngeal nerves. Moderate excita-
tions occurring in the reahn of these nerves are immediately followed
by an inhibition of respiration and an active expiration, but in this
case the posterior nares are closed and the expiratory blast of air is
expelled through the oral cavity. This constitutes the act of coughing.
These impulses from the terminals of the glossopharyngeus are of
special value during the act of swallowing, because they lead to a
temporary arrest of the inspiratory movement and a closure of the
epiglottis so that the food cannot be aspirated into the laryngeal cavity.
The path pursued by these impulses is the same as that outlined pre-
viously, i.e,, they are first relayed to the nucleus of this nerve and to
the respiratory center, whence they are directed to the muscles of
respiration.
On passing into the cavity of the larynx another nerve is met with,
namely, the superior laryngeal branch of the vagus (Fig. 263). It is a
THE NERVOUS REGULATION OF RESPIRATION
535
.^^B^
matter of common experience that the entrance of a foreign body into
the larynx causes an immediate inhibition of inspiration and a forced
expiration, the air being ejected in this case through the mouth. It
need scarcely be repeated that the impulses generated in this region
of the respiratory passage, are first conducted through the nuclei of
the vagi nerves to the respiratory center,
whence the efferent discharges are di-
verted to the different muscles of respira-
tion. Obviously, the division of either
the right or left superior laryngeal nerve
must render the corresponding side
of the larynx insensitive to stimulation.
Furthermore, inasmuch as this nerve is
the only sensory nerve of this organ, the
division of both nerves must lead to a
complete paralysis of sensation. An
animal cannot long survive this proced-
ure, because the gradual accumulation
of foreign substances in the upper res-
piratory passage finally involves the lung
tissue and gives rise to an inflammatory
reaction which bears the essential char-
acteristics of pneumonia.
While discussing this subject, it might
be well to mention that the superior
laryngeal nerves are not entirely sensory
in their function, but also embrace a
number of efferent fibers which innervate
the cricothyroid muscles (Fig. 263).
Keeping these facts clearly in mind, it
will, therefore, be seen that the stimula-
tion of the intact superior laryngeal nerve
must produce impulses which (a) pursue
an afferent course and give rise to an in-
hibition of inspiration and a forced ex-
piration, and (6) pass in an efferent direc-
tion to cause a contraction of the corre-
sponding cricothyroid muscle. Accord-
ingly, the division of this nerve must in-
duce a loss of sensation on the side of
the injury, as well as a paralysis of the corresponding cricothyroid
muscle. The stimulation of the distal end of the divided nerve then
gives a contraction of the cricothyroid muscle, while the excitation
of its central end elicits those sensations which ordinarily produce an
inspiratory standstill and forced expiratory blasts of air.
The larynx also receives a second nerve supply by way of the
inferior laryngeal branches of the vagus (Fig. 263). Since these nerves
Fig. 263. — The Innekvation
or THE Labynx (Posterior View;
One Side).
B, base of tongue; E, epi-
glottis; A, arytenoid muscles;
CA, crico-arytenoid muscle; T,
trachea; V, vagus nerve; SL,
superior laryngeal nerve; J and
O, its inner and outer branches;
JL, inferior laryngeal nerve; Br,
vagal fibers innervating bron-
chial musculature.
536 EESPIRATION
are given off in the thorax and then return along the trachea to enter
the inferior aspect of this organ, they are generally designated as the
'' recurrent '' nerves. They are wholly motor in their function and
innervate all the laryngeal muscles with the exception of the crico-
thyroids. Obviously, therefore, the excitation of this nerve on
either the right or left side, must cause a contraction of the muscles in
the corresponding half of the larynx, with the exception of the one
just mentioned. Accordingly, the division of one or the other of these
nerves must lead to a unilateral motor paralysis of this organ, and the
division of both nerves, to a bilateral paralysis. Inasmuch as these
nerves conduct only in the direction from the center to the larynx
and are, therefore, efferent in their function, the excitation of their
distal ends must give rise to a contraction of all the laryngeal muscles,
with the exception of the cricothyroids. For the same reason, the
stimulation of their central ends cannot influence the respiratory
rate or amplitude.
The Function of the Vagus Nerve. — The preceding discussion
pertaining to the superior and inferior laryngeal branches of the vagus,
must lead us to suspect that the cervical portion of the main trunk of
this nerve embraces afferent as well as efferent respiratory fibers.
FiQ. 264, — Stethographic Record of the Respiratory Movements (Dog) After
Division of the Left (LV) and Right (RV) Vagi Nerves.
This assumption may be tested experimentally by simply dividing
one or both nerves above or below the points of origin of their superior
laryngeal branches. In either case, this procedure is followed almost
immediately by a reduction in the frequency and an increase in the
depth of the respiratory movements. The individual movements
become pronouncedly inspiratory in their character, and more so,
if both nerves have been divided. This change, however, does not
necessarily give rise to a dyspneic condition of the animal, because
the amount of air furnished by these slow and deep respirations,
is practically the same as that previously supplied by the more fre-
quent and shallow movements. It is true, however, that the division
of both vagi nerves renders the animal incapable of adjusting itself
to different conditions. Thus, if it is made to inhale air containing
a large percentage of carbon dioxid, it fails to compensate, owing to
its inability to increase its respiratory frequency. Working, therefore,
on so small a margin, its pulmonary ventilation soon becomes in-
adequate for the relief of the high carbon dioxid tension of the blood.
THE NERVOUS REGULATION OF RESPIRATION 537
In addition, the procedure of double vagotomy, as the division of
both vagi nerves is called, invariably leads to other conditions which
are absolutely incompatible with normal function.
Dogs are somewhat more resistant and frequently survive this
operation for many days, and in some instances even for an indefinite
period of time, whereas rabbits, sheep and horses succumb to it in the
course of a few days. In addition to the effects upon respiration
and the action of the heart, these animals also exhibit difficulties
in deglutition, digestion and assimilation. They lose weight constantly
until their lungs eventually consolidate in consequence of a pneumonic
affection. Whether, this infiltration of the pulmonary tissue is caused
by trophic influences or by the ingress of food and bacteria, owing
to the -functional uselessness of the epiglottis, has not been definitely
ascertained.
The division of these nerves should really be effected by the method
of freezing rather than by that of cutting, because by this means their
power of conduction may be destroyed without the usual initial
period of excitation.^ This accounts for the fact that the diminution
in the respiratory activity is commonly initiated by a hyperpneic type
of respiration. Furthermore, it should be remembered that these
alterations in the frequency and depth of the respiratory movements
manifest themselves only if both nerves are cut and that the division
of only one nerve generally produces little or no change. Aside from
the motor effects evoked with the aid of the inferior laryngeal nerve,
the stimulation of the distal end of the divided vagus leaves the general
character of the respiratory movements unchanged. It should be
noted, however, that this nerve also contains efferent fibers for the
musculature of the bronchi (Fig. 263). This has been shown by Roy
and Brown, 2 as well as by Einthoven,^ who have found that the excita-
tion of either vagus produces a constriction of the bronchi of both
lungs, while the division of either nerve eventually evokes a dilatation
of these tubes on the side of the section. It may readily be surmised
that these changes in the size of the bronchial passage must lead to
variations in the volume of the air contained therein. In this con-
nection it should also be mentioned that the recurrent attacks of
dyspnea, characterizing spasmodic asthma, are believed to be as-
sociated with spasms of the bronchial musculature. These are said
to find their origin in a neuritic condition of the vagus nerve.
The excitation of the central end of the divided vagus nerve with
a quickly interrupted current may be followed by either a slowing or a
quickening of the respiratory movements. The precise character of the
effect produced by this procedure depends upon the strength of the
stimulus and the irritabihty of the respiratory mechanisna.^ To
1 Gad, Archiv fur Anat. und Physiol., 1880, 9.
2 Jour, of Physiol., vi, 1885, 21.
3 Pfluger's Archiv, ci, 1892, 367.
4 Rosenthal, Archiv fiir Anat. und Physiol., 1881, 39.
r
538 KESPIRATION
begin with, however, it may be well to state that currents of moderate
strength invariably evoke a respiratory standstill in the inspiratory
position. This phenomenon is practically identical with that observed
upon stimulation of the intact superior laryngeal nerve, or of its
central end. Very weak stimuli are prone to develop expiratory
tendencies which are usually accompanied by an inhibition of the
inspiratory movements. With strong currents the results are per-
plexing, although it is quite evident that they consist essentially
in a respiratory cessation with the chest either in the inspiratory
or expiratory position. It need scarcely be mentioned that these
effects may also be evoked by the stimulation of the intact vagus.
The Self -regulation of Respiration. — The foregoing experimental
data show very clearly that the division of the vagi nerves prevents
certain stimuli from reaching the respiratory center which originate
along the pulmonary passage and ordinarily tend to increase the activity
of these ganglion cells. When no longer under the influence of these
afferent impulses, the center falls back upon its inherent automaticity,
which gives rise to regular but relatively infrequent impulses. In
the second place, it must be concluded that the vagus nerve em-
braces two kinds of afferent fibers, or rather, afferent fibers which are
capable of conducting two types of impulses. One of these inhibits
inspiration and the other expiration. Accordingly, it may be con-
jectured that the inhibition of the inspiratory muscles allows the
development of the expiratory process, while the inhibition of the
expiratory muscles favors the occurrence of inspiration.
In accordance with this exposition Hering and Brener^ have
formulated the hypothesis that the respiratory movements regulate
themselves; i.e., every expiration incites an inspiration and every
inspiration an expiration. The vagi, therefore, are regarded as form-
ing the most important link in a check-system which insures a proper
sequence and depth of the successive respiratory movements. This
leads to a much greater frequency of the respiratory movements than
could be obtained if the center alone were the controlling agent. The
latter, as has been shown above, possesses a slow rate of discharge.
When the lungs are expanded, a stimulus is set up in these organs
which travels over the inspiratory fibers of the vagus and eventually
stops this movement, permitting expiration to set in. Quite similarly,
the deflation of the lungs reflexly incites the subsequent inspiration.
Whether these intrapulmonic stimuli are chemical or mechanical
in their nature is a much debated question. It seems, however, that
the mechanical ones are the most important. They find their origin
in the alternate stretching of the vagal terminals which may be
imagined to invest the bronchial tubes in the manner of calipers.
It should be remembered, however, that the expiratory process is a
passive phenomenon and is not associated under ordinary conditions
with a contraction of the respiratory muscles, and hence, the inhibiting
1 Sitzungsb. der Wiener Akad. der Wissensch., cviii, 1868, 909.
THE NERVOUS REGULATION OF RESPIRATION
539
The first procedure
suddenly
is called
artif resp app.
fibers of inspiration would not be brought into play during quiet
respiration. An activation of the latter, however, would result
whenever forced expirations are required to effect a more thorough
alveolar ventilation. This mechanism, therefore, insures the perfect
regulation of the central discharges so that they develop at perfectly
precise intervals, but naturally, it is not concerned with the produc-
tion of the automaticity of the center.
This hypothesis may be tested in a simple way by
inflating or deflating the lungs,
positive ventilation and is invari-
ably followed by a relaxation of the
diaphragm and a long expiratory
pause, whereas the second, or nega-
tive ventilation, induces a contrac-
tion of this septum. Besides, the
existence of inspiratory and expira-
tory fibers in the vagus is also made
probable by the effects obtained on
stimulation of the intact vagus or
of its central end ; in fact, Grtitzner^
and Langendorf^ have proved that
the application of a constant current
to the vagus results in an inspiratory
arrest when descending, and in an
expiratory standstill when ascending.
In addition, it might be stated that
the collapse of the lungs invariably
gives rise to a nerve impulse which
ascends the vagus and may be regis-
tered by means of the string galvano-
meter. Head,^ moreover, has ascer-
tained that the collapse of either lung produces much more decided
inspiratory efforts than the division of both vagi nerves. This he
succeeded in showing in the following way : The left vagus of a rabbit
having been cut, the corresponding lung was inflated rhythmically
by means of a tube inserted in the left bronchus (Fig. 265). The
normal action of the right lung was then suddenly interrupted by
opening the right pleura. The resulting collapse of this organ incited
an immediate tonic contraction of the diaphragm which generally
lasted for some time, although the rhythmic inflation of the left organ
prevented the occurrence of dyspnea and asphyxia.
FiQ. 265. — Diagram to Illustrate
Head's Experiment on the Effect of
Collapse of the Lung.
R.c, respiratory center; r.v, l.v, right
and left vagi. (Starling,)
1 Pfliiger's Archiv, cvii, 1894, 98.
2 Ibid., cix, 1906, 201.
3 Jour, of Physiol., x, 1889, 1.
SECTION XIII
VOICE AND SPEECH
CHAPTER XLIII
THE GENERAL ARRANGEMENT OF THE PHONATING
ORGANS
The Lar3mx. — The production of noises and sounds by animals may
be accidental and intentional. Thus, the wings of an insect beating
the air at the rate of about 300 times in a second, produce a noise which
is merely a phenomenon accompanying muscular action, but animals
of this kind are also in possession of certain mechanisms by means
of which a simple communication between them is made possible.
The latter end they attain by the rubbing together of their hind-
legs or by the approximation of their mandibles. In amphibians,
the trachea opens anteriorly into the small laryngeal chamber which
is connected with the cavity of the mouth by a slit-like opening or
glottis. At one point, the mucous • membrane lining this chamber, is
folded into two transverse bands, the vocal cords, which are made to
vibrate by the expiratory blasts of air. In reptiles, the trachea is more
distinctly outlined and is expanded anteriorly to form the larynx with
its cartilaginous walls and transverse vibrating cords.
Curiously enough, the phonating mechanism of the higher animals
differs only slightly from that found in these forms. Its general
structural principle, as well as that of several of its minor parts, remains
the same. Contrary to this anatomical uniformity, the sounds of
these animals gradually attain a greater complexity until they acquire
the character of articulated sounds. Thus, vowels and consonants
may be distinguished in the notes of birds, which animals have in
general a much more extensive register than the mammals. Even-
tually, the sounds are joined into words and coordinated to give rise
to speech. In this regard, man is sharply differentiated from other
forms, because practically no other animal is capable of equaling
his register of sounds nor his faculty of sound coordination. This
difference, however, is not brought about by a relatively much greater
structural perfection of his motor apparatus, but rather by a more
exclusive development of the association area governing this faculty.
In the lower forms the production of sounds is largely a reflex phe-
nomenon. It becomes a complex coordinated act only in those species
which are in possession not only of association centers but also of a par-
ticular center, having to do solely with the control of the production
of sounds. At the present time, however, we are chiefly concerned
640
GENERAL ARRANGEMENT OF THE PHONATING ORGANS 541
with the motor organ, namely, with the larynx and its adjuncts as well
as with the nervous paths which connect this organ with the motor
area in the Rolandic area of the cerebral cortex. The function of the
psychic center for speech and the manner in which afferent impulses
are enabled to influence its action, will be discussed later on in connec-
tion with the function of the cerebrum and allied parts.
General Structure of the Larynx. — This organ consists of a
framework of cartilages held together by ligaments and acted upon
Fig. 266. Fig. 267.
Fig. 266. — Laryngeal Cartilages and Ligaments, Anterior Surface.
1, hyoid bone; 2, 2, 3, 3, greater and lesser cornua; 4, thyroid cartilage; 5, thyrohyoid
membrane; 6, thyrohyoid ligaments; 7, cartilaginous nodule; 8, cricoid cartilage; 9,
the cricothyroid membrane; 10, the cricothyroid ligaments. 11, trachea. (Sappey.)
Fig. 267. — Laryngeal Cartilages and Ligaments, Posterior Surface.
1, 1, thyroid cartilage; 2, cricoid cartilage; 3, 3, arytenoid cartilages; 3, 4, crico-
arytenoid articulations; 5, 5, cricothyroid articulations; 6, union of the cricoid cartilage
and of the trachea; 7, epiglottis; 8, ligament uniting it to the reentering angle of the
thyroid cartilage. (Sappey.)
by a system. of extrinsic and intrinsic muscles. The following carti-
lages enter into its formation:
Single cartilages Paired cartilages
Thyroid Arytenoid
Cricoid Cornicula laryngis
Epiglottis Cuneiform
But even in the case of the single cartilages, a certain tendency toward
bilateralism is unmistakable, because they are thickest and most
extensive at the sides of the larynx and are united in front by merely
a narrow bridge of connecting tissue. These cartilages are adjusted
upon the anterior extremity of the trachea in such a way that a rela-
tively large cavity is formed which is protected against the pharynx
by the epiglottis. Its pharyngeal aperture is triangular in shape,
its base being directed forward and its apex backward.
542
VOICE AND SPEECH
The larynx as a whole, as well as the trachea, is movable, because
it is suspended from the hyoid bone by the thyrohyoid muscles. This
bone in turn is affixed to the base of the skull and the maxillae
by a number of muscles, and is therefore also freely movable. The
upward movement of the larynx is counteracted by the sternothy-
rohyoid muscles which unite this organ with the sternum. The
larynx may be displaced for a dis-
tance of several centimeters, first
in consequence of the muscular
activity coincident with the act of
swallowing and secondly, in con-
sequence of the adjus^tment of the
laryngeal parts for purposes of
phonation. In the former case, the
larynx is also tilted forward, in-
suring a greater prominence of its
anterior border.
In longitudinal section the
laryngeal cavity exhibits the shape
of an hour-glass, the true vocal
cords forming the line of demarca-
tion between its upper and lower
recesses. Moreover, while the long
axis of its upper recess is directed
strongly backward, that of the lower
conforms more closely to the general
course of the trachea. The thyroid
cartilage forms the front and sides
of the upper part of the larynx.
It is composed of two nearly square
plates which are placed vertically
and are united in front by a bridge
which gives rise to a prominence,
known as the pomum Adami.
Posteriorly, they are rather widely
separated from one another, the in-
tervening space being filled by soft
tissues. The cricoid cartilage forms
a heavy ring which completely sur-
rounds the lower cavity of the
larynx. * It is narrow in front, but
broadens out posteriorly into a quadrate plate. The latter is narrowed
above into a pointed process. The arytenoid cartilages are two ir-
regular, triangular plates, the bases of which are placed transversely
upon the superior processes of the cricoid. The corniculce laryngis are
two small cone-shaped cartilages which are fastened to the upper pro-
FiG. 268. — ^Vertical Transverse
Section of the Larynx. (After Testut.)
1, posterior face of epiglottis, with 1',
its cushion; 2, aryteno-epiglottic fold; 3,
ventricular band, or false vocal cord; 4,
true vocal cord; 5, central fossa of
Merkel; 6, ventricle of larynx, with 6',
its ascending pouch; 7, anterior portion
of cricoid; 8, section of cricoid; 9, thy-
roid, cut surface; 10, thyrohyoid mem-
brane; 11, thyrohyoid muscle; 12,
aryteno-epiglottic muscle; 13, thyro-
arytenoid muscle, with 13', its inner
division, contained in the vocal cord; 14,
cricothyroid muscle; 15, subglottic por-
tion of larynx; 16, cavity of the trachea.
(American Text-book of Physiology.)
GENERAL ARRANGEMENT OF THE PHONATING ORGANS 543
jection of the arytenoids. The cuneiform cartilages are placed within
the aryteno-epiglottidean folds.
The Function of the Epiglottis. — The larynx is protected against
the digestive tract by a leaf -like plate of yellow elastic cartilage which
is attached below by a stalk to the thyroid cartilage. In the adult
it usually assumes a nearly vertical position, while in children it is
placed more slantingly. It has a double purpose, namely, to prevent
the ingress of food into the respiratory passage and to aid in the modi-
fication of the currents of air during respiration and phonation.
The closure of the pharyngolaryngeal opening, however, is not
effected solely by the epiglottis, because a rather efficient occlusion
of this orifice is also had when this structure is wanting or is imper-
fectly developed. Neither is it correct to assume that those muscle
fibers which arise upon the thyroid and are inserted upon the epiglottis
are sufficiently powerful to serve as sphincters.^ A third factor must
be taken into consideration, and that is the elevation and forward in-
clination of the entire larynx. This movement gives rise to an approxi-
mation with the hyoid bone so that the tongue, when drawn back- dur-
ing the act of swallowing, is in the best possible position to press the
epiglottis downward until it comes to lie across the laryngeal aperture.
At this very moment, the thyro-epiglottidean muscle fibers contract,
thereby tending to constrict this orifice. It is also held that the
epiglottis serves as a sort of sounding board against which the vibrat-
ing particles of air are forced. Thirdly, its partial closure upon the
forced expiratory blasts gives rise to the peculiar fragmented character
of the current of the air produced during the act of coughing. When
acting upon the inspiratory current of air, its partial closure gives rise
to such peculiar modifications as are noted during the act of hic-
coughing. The fact that the mucous lining of this structure is beset
with numerous taste-buds and glands does not possess a special
functional significance.
The True and False Vocal Cords. — When looked at from above, the
wide expanse of the laryngeal cavity is seen to be limited by two
membranous bands, the vocal cords, which extend transversely across
its lumen in a direction from before backward. The space between
these bands is known as the glottis. The size and shape of the latter
vary with the respiratory movements and phonation. During in-
spiration it becomes large and during expiration small. When the vocal
cords are widely separated, its width measures about 13.5 mm. in
men and 11.5 mm. in women. During phonation it usually assumes
the shape of a mere slit, designated as the chink of the glottis, or rima
glottidis.
The true vocal cords arise in front from the angle formed by the
alse of the thryoid cartilages, and, passing directly backward, are in-
serted upon the vocal processes of the arytenoid cartilages. They
^ Meltzer, The Closure of Glottis During Deglutition, Zentralbl. fiir Physiol.,
xxvi, 1912.
544 VOICE AND SPEECH
vary in length in men from 15-20 mm. (average 18.22 mm.) and in
women from 10-15 mm. (average 12.6 mm.). Their free edges are
thin and tilted slightly upward, while their outer margins are straight
and are everywhere adherent to the wall of the larynx. The yellow
elastic fibers composing their substance, are closely interwoven and
pursue in general a longitudinal course. Of functional importance is
also the fact that these bands are covered with thin, flat, stratified
epithelium, while the remaining extent of the larynx is lined with colum-
nar, ciliated epithelium. The effective stroke of these cilia is executed
toward the pharynx, i.e., in the same direction as that of the cilia
found in the trachea and bronchi.
The space above the vocal cords is known as the supraglottic
cavity. It is bounded above by the epiglottis. On each side of the
17
Fig. 269. — The Laryngoscopic Image in Easy Breathing. (Stoerk.)
1, Base of the tongue; 2, median glosso-epiglottic ligament; 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
cartilage; 16, cartilage of Santorini; 17, posterior wall of pharynx. (American Text-
book of Physiology.)
latter a fold of mucous membrane extends obliquely downward and
backward, forming the lateral boundary of the aperture of the larynx,
and covering the arytenoid cartilages. Besides these ary epiglottic
folds, the mucosa of the larynx also presents two transverse ridges,
one on each side, which are known as the false vocal cords. These
relatively narrow bands are situated a short distance above the true
vocal cords and are placed practically parallel to these, so that a long
slit-like space is left between them. The function of these bands is not
fully understood, but it has been assumed that they serve to protect
the true vocal cords against injury and excessive vibration. In the
second place, it is held that they serve as sphincters of the larynx,
their approximation tending to render the corresponding movement
GENERAL ARRANGEMENT OF THE PHONATING ORGANS 545
of the true vocal cords more effective. Special use is made of this
mechanism, in conjunction with the closure of the epiglottis, whenever
large amounts of air are to be temporarily retained in the lungs, or
when, as in running, the outflow of the expiratory air is to be retarded.
Thirdly, inasmuch as their mucous covering contains numerous mucous
and serous glands, it is also believed that they furnish the moisture
necessary to keep the vocal cords in a
proper condition for vibration. This secre-
tion is temporarily retained in the capillary
space between the true and false cords and
is in this way protected against evaporation.
In some of the lower animals, these spaces
which are called the ventricles of Morgagni,
are very commodious and are constructed
in such a way that they may serve as reso-
nating chambers. This peculiarity in their
general arrangement has led to the belief
that they tend to augment the vibration of
the true vocal cords.
The Tension of the True Vocal Cords.
— The thyroid and cricoid cartilages arti-
culate by means of a simple bilateral joint,
the axis of which is placed transversely.
Arising upon the anterolateral aspect of
the cricoid, a small conical muscle, known as
the cricothyroid, passes upward and back-
ward to be inserted upon the lower edge
of the alse of the thyroid (Fig. 270). Its
function is to diminish the height of the
space between the inferior border of the
thyroid and the upper border of the cricoid
cartilages. This end it attains by depress-
ing the former and raising the latter. The
result of this movement is made evident
immediately if it is noted that these car-
tilages are hinged posteriorly (R) and that
the arytenoids (A), which are situated
transversely upon the tips of the cricoid pro-
cesses, are thereby moved farther backward.
It will be remembered that the vocal cords
(VC) are attached to the anterior tips of
these cartilages and extend from here directly across the cavity to be
inserted upon the anterior wall of the larynx. Obviously, therefore,
since the approximation of the thyroid and cricoid cartilages increases
the distance between the vocal processes of the arytenoids and the
anterior wall of the larynx, these bands must be put on the stretch.
Thus, it is evident that the aforesaid muscle serves as the tensor of
35
Fig. 270. — Lateral View
OF Larynx to Illustrate the
Action of the Cricothyroid
Muscle.
H, hyoid bone; M, thyro-
hyoid membranes; PA, po-
mum Adami; T, thyroid carti-
lage; C, cricoid cartilage; Tr,
trachea; CT, cricothyroid
muscle; P, vertical plate of
cricoid with (A) arytenoid
cartilages placed transversely
upon its articulating processes;
VC, vocal cords; R, imaginary
center of rotation of cricoid.
When cricothyroid muscle con-
tracts, T and C are brought
closer together, while A is
forced away from PA.
546 VOICE AND SPEECH
the vocal cords, and that the mechanism just described is the one
ordinarily made use of in raising the pitch of the sounds. The ap-
proximation of these cartilages may be felt by placing the finger in
the notch below the pomum Adami while sounds of different pitch
are produced. In the human larynx, the vocal cords are penetrated
by a few muscle fibers which take their origin upon the arytenoid
cartilages and eventually reach the anterior wall of the larynx.
Their contraction is said to render the vocal cords more tense and
hence, this muscle, which is known as the tensor vocalis, is com-
monly regarded as an aid to the cricothyroid. Grlitzner,^ on the
other hand, believes that its contraction renders these bands more
flabby and forms, therefore, a typical detentioner. NageP adheres
to the first view and states that these muscle fibers antagonize the
lateral displacement of the edges of the vocal cords, thereby retain-
ing them more fully in the path of the expiratory currents of air.
The Approximation of the Vocal Cords. — As has been stated above,
the musculature of the larynx is arranged in a manner to form a sphinc-
ter for the upper end of the respiratory passage, the closure of which
is really effected at three different levels, namely, at the epiglottis, at
the false vocal cords and at the true vocal cords. The first two actions
having been discussed, we are now in a position to analyze the third,
namely, the adduction and abduction of the vocal cords.
The arytenoid cartilages are two triangular platelets which are
placed transversely upon the tips of the cricoid processes. They
attain their greatest width posteriorly, while their tapering extremities
or vocal processes, are directed forward to serve as points of attach-
ment for the vocal cords. Furthermore, while their anterior processes
are freely movable in a transverse direction, their basal portions are
relatively fixed, because they form articulations with the vertical
plates of the cricoid cartilages. The latter, as has been shown by
Stieda and Will,^ are prolonged upward into two small cylindrical
projections, the convex surfaces of which are turned upward to fit
into corresponding concavities upon the under surfaces of the aryte-
noid cartilages. These joints are adjusted in such a way that the out-
ward movement or abduction of the vocal processes necessitates a slight
elevation of these cartilages, while their inward movement, or adduction,
permits them to reassume their former low level. By inference, it
may then be concluded that the adduction of the arytenoid processes
brings the vocal cords closer together, while their abduction separates
them more widely. Consequently, the glottis assumes a mere slit-
like outline during the former rnovement and a typical V-shaped
outline during the latter. It should also be observed that the approxi-
mation of the vocal cords is greatly facilitated by an inward movement
1 Ergebn. der Physiol., i, 1902, 466.
2 Handb. der Physiol., iv, 1909, 702.
3 Dissertation, Konigsberg, 1895.
GENERAL ARRANGEMENT OF THE PHONATING ORGANS 547
of the arytenoid cartilages as a whole, which brings their posterior
extremities closer together.-
The muscles involved in this process belong to the intrinsic group
of the laryngeal musculature, and present the following individual
actions:
(a) The posterior crico-arytenoid muscle arises from the posterior surface of the
quadrate plate of the cricoid cartilage on either side of the median line and passes
obliquely upward and outward to be inserted upon the external angle of the
muscular process of the arytenoid cartilage (Fig. 271, 1). Its chief action is to
rotate the vocal process of the corresponding arytenoid upward and outward so
that the glottis is widened. This muscle, therefore, abducts the vocal cords.
(6) The lateral crico-arytenoid muscle takes its origin upon the upper border of
the cricoid cartilage and, passing upward and backward, is inserted upon the
forepart of the muscular process of the arytenoid (Fig. 271, 2). Its contraction
gives rise to an inward and downward movement of the vocal process, insuring
thereby an adduction of the vocal cords chiefly at their posterior ends.
B
Fig. 271. — Diagram Illustrating the Abduction and Adduction of the Vocal Cords.
A, adduction; 1, point of insertion of the post, crico-arytenoid muscle; G, glottis; B,
adduction; 2, points of insertion of the lat. crico-arytenoid and thyro-arytenoid muscles;
3, point of insertion of the arytenoid muscles. The dot indicates the position of the
center of rotation of the arytenoid cartilages.
(c) The thyro-arytenoid muscle extends between the inner surface of the thyroid
cartilage, post-external to the median line, and the anterior margin and external
angle of the arytenoid. Its inner fibers lie in close relation to the vocal cords and
are frequently designated as the musculus vocalis? When contracting, this muscle
rotates the corresponding arytenoid cartilage around its vertical axis, drawing the
vocal process forward and inward. It acts, therefore, as an aid to the lateral
crico-arytenoid muscle in causing the adduction of the vocal cords.
(d) The arytenoid muscle extends from side to side, joining the two arytenoid
cartilages. It consists of two groups of fibers, one of which is directed horizontally
across the median line and the other obliquely (Fig. 271, 3). The ends of the
former are fastened to the outer margins of the arytenoids on each side, while the
latter unite the outer angle of one with the apex of the other. Obviously,
these fibers have to do with the approximation of the posterior ends of the ary-
tenoid cartilages, lessening the length of the rima glottidis.
The Innervation of the Larynx. — The nerve supply of the larynx
is derived from the systems of the right and left vagi nerves. The
548 VOICE AND SPEECH
particular branches which govern the function of this organ are the
superior and inferior laryngeal nerves (Fig. 263). In general it may.
be said that their innervation is unilateral in character, but a slight
median overlapping, especially with regard to the sensory fibers, is
not uncommon. It has been shown above that the superior branches
are motor as well as sensory in their function, while the inferior or
recurrent branches are wholly motor. The motor qualities of the
former are restricted to their rami externi which supply the crico-
thyroid muscles. These muscles, as we have just seen, govern the
vertical approximation of the thyroid and cricoid cartilages and deter-
mine, therefore, the tension of the vocal cords. Consequently, it may
be stated that the inferior branches control all the muscles of the larynx
with the exception of the cricothyroids.
Keeping these facts clearly in mind, it must be evident that the
stimulation of the intact superior laryngeal nerve, or of the distal
end of the divided nerve, leads to an approachment of the thyroid and
cricoid cartilages and an increased tension of the vocal cords. The
glottis is slightly narrowed by this action, owing to the fact that the
arytenoid cartilages are not sufficiently resistant to withstand the pull
exerted by the vocal cords. The cricothyroid muscle as such, however,
does not serve as an adductor of the vocal cords. As has been stated
in one of the preceding paragraphs, the sensory qualities of this nerve
may be ascertained by the stimulation of the intact nerve or of its
central end. With currents of moderate strength, this procedure
evokes a respiratory standstill and forced expiratory blasts.
Certain evidence has been presented to show that the inferior
laryngeal nerve of the apes also conducts in an afferent direction. This
is also true of the corresponding nerve in the dog and cat, but only
under special conditions. In view of this uncertainty, it seems best
to regard this nerve essentially as a motor path for those impulses
which give rise to the different sphincter actions of the larynx, and
especially to that occurring at the level of the vocal cords. Attention
should also be called to the fact that the vagus innervates extensive
segments of the pharynx and esophagus and is thus placed in a position
to correlate the action of the laryngeal musculature with that of the
muscles used during the process of deglutition.^
In accordance with these statements, it may be concluded that
the division of either inferior laryngeal nerve must lead to a paralysis
of the muscles on the corresponding side of the larynx, excepting, of
course, the cricothyroid muscle. Quite similarly, the division of
both nerves must result in a bilateral paralysis, the aforesaid muscles
being excepted. In young animals, this procedure is usually followed
by serious symptoms, death from asphyxia resulting in the course
of a few days. But, while it is true that the vocal cords assume an
extreme median position in consequence of the paralysis of the aryte-
noid muscles, this condition cannot be regarded as the sole cause of
1 Schultz and Dorendorf, Archiv fiir Laryngologie, xv, 1904.
PHONATION 549
death. Account must also be taken of the fact that the accompanying
paralysis of the esophageal musculature leads to an accumulation of
food and fluids which eventually find their way into the respiratory
channel. Consequently, the division of the inferior laryngeal nerves
paralyzes that mechanism by means of which the lungs are ordinarily
protected against foreign bodies and injurious emanations. Suffo-
cation or pneumonic conditions are the usual outcome of this defect.
Very similar results m^y be obtained by the division of the superior
laryngeal nerves, because this procedure blocks those afferent impulses
which normally evoke the act of coughing, thereby dislodging the
foreign material from the larynx.
By selecting the highway of the vagus, these sensory impulses
eventually reach the nucleus of this nerve in the medulla, whence they
are relayed to other centers and finally to the motor area in the cere-
bral cortex. Those movements of the larynx which are associated
with respiration, are automatically controlled by a center situated in
the medulla and closely alhed to the respiratory center.^ Motor
points for the laryngeal muscles have been isolated by Krause^ in
the gyrus praefrontalis. It will be pointed out later on during the
discussions upon cerebral localization, that these motor points are
under the control of a psychic center for phonation and speech, which
is situated in part in the left inferior frontal convolution.
CHAPTER XLIV
PHONATION
In order to be able to produce a sound, it is necessary to be in
possession of a vibrating body the constituents of which may be set into
an alternating motion by some external force. In the higher animals,
the chief vibrating bodies are the vocal cords, while the power to make
them oscillate is most commonly suppHed by an expiratory blast of air
which may be softened or intensified by muscular activity. Moreover,
since these expiratory blasts are directed not only against the vocal
cords but also against other mucous folds and membranous septa,
noises and sounds of practically all descriptions may be obtained.
It is true, however, that those sounds which are ordinarily coordinated
into speech, are chiefly dependent upon the vibration of the vocal
cords, while the parts above and below them serve merely to modify
the primary sound. In this regard man possesses a decided advantage,
because the different parts of the human larynx are more delicately
adjusted and are under the direct control of an intricate system of motor
1 Grossman, Zentralbl. fiir Physiol., iii, 1889.
2 Archiv fiir Anat. und Physiol., 1884.
550
VOICE AND SPEECH
and sensory centers. Thus, the production of coordinate vocal sounds
is really a distinguishing characteristic of man; no other animal can
at all equal his power of phonation.^ Some seemingly authentic
cases, however, are on record which show that speech of a very crude
and hmited type may also be acquired by other mammals, and (^uite
aside from the *' talking horse" and "talking dog," it seems that the
monkeys and apes have a limited register of words, conveying different
meanings.
The Examination of the Lar3mx in Reflected Light. ^ — In animals
the play of the laryngeal parts may be studied without much difficulty
by direct inspection. A transverse incision having been made between
the hyoid bone and the upper edge of the thyroid cartilage, the larynx
is raised upward and tilted sufficiently to allow an unobstructed view
Lamp
Larynx.
Fig. 272. — Diaqrajh of Laryngoscope. {From Stewart's "A Manual of Physiology,"
William Wood and Co., Publishers.)
of the supraglottic cavity and especially of its floor formed by the
vocal cords. Killian^ has devised a method of transillumination
by means of which the larynx may be projected in magnified form
upon a screen. The human larynx may be inspected with the help of a
small plane mirror which is mounted upon a handle and is placed ob-
liquely against the uvula. A beam of light is then reflected upon it
from a head mirror (Fig. 272). The observer looking through a small
central opening in the latter, obtains an image of the parts below, but
those normally situated in front, appear in the picture to be located
behind, and vice versa.
The white glistening vocal cords are sharply outUned against the
red mucous Uning of the rest of the laryngeal wall (Fig. 268). During
^ Mott: The brain and the voice in speech and song, New York, 1910, and
Aikin, The voice, an introduction to practical phonology, London, 1910.
2 First successfully undertaken in 1854 by M. Garcia, a teacher of singing.
In 1857 Tiirck employed this method upon his patients in Vienna.
3 Miinchener klin. Wochenschr., No. 6, 1893.
PRONATION 551
quiet respiration, the glottis is moderately large, becoming smaller
on expiration. Moreover, by forced inspiratory efforts, the size of
this communication may be increased in such a measure that the upper
rings of the trachea, and even the bifurcation of the bronchi, are brought
intg view. Movements of the vocal cords also result in consequence
of various accessory respiratory efforts, such as are made necessary
during the acts of coughing, sneezing, and hiccoughing.
The production of sounds requires not only a varying approximation
of the vocal cords, but also a very precise adjustment of their tenseness.
The former effect which, as has been pointed out above, is based
upon the rotation of the arytenoid cartilages around their vertical
axes, seems to constitute a more accurate mechanism than the latter
which is largely dependent upon the backward movement of these
cartilages in consequence of the contraction of the cricothyroid
muscles.
The different laryngeal parts having been properly set, the air
stored in the lungs is forced outward through the narrow glottis,
thereby imparting a vibratory motion to
the vocal bands. In order to overcome
the resistance interposed at this level, it
has been found that the air-pressure in the
trachea necessary to cause a sound of ordi-
nary pitch and loudness, must be raised
to between 140 and 240 mm. of water.
Loud sounds require a pressure of as much
as 950 mm. of water. It should also be
remembered that the vibrations are not ,, ^^«- 2 7 3 .-Position of
,.,,.,, , 11, 1 Vocal Cords on Uttering a
restricted to the vocal cords, but are also high Note. (Landois.)
transferred to the air contained in the outer
respiratory passage as well as to that filling the trachea and bronchi.
Thus, we speak of a chest voice and a falsetto voice. Chest sounds
always impart a fremitus to the wall of the thorax which may be
perceived by placing the hands over the lower air-passage, from which
the resonance is obtained. Falsetto sounds derive their resonance
principally from the pharyngeal, oral and nasal cavities. In general,
therefore, it may be said that the vocal mechanism embraces: (1)
the motive expiratory blast of air, (2) the larynx which gives rise
to the fundamental sound, (3) the thorax, pharynx, mouth and nose
which modify the primary sound and give color to it, and (4) the
organs employed in articulating the sounds.
The Characteristics of Sounds. — The action of the vocal cords
may be imitated in a crude way by placing a short tube of a diameter
of about 2 cm. against the palmar surfaces of two adjoining fingers.
By blowing into the free end of this tube a sound will be produced
in consequence of the vibrations of the folds of skin along the two fingers.
A similar purpose is served by the so-called artificial larynx which
consists of a piece of tubing, one end of which is partially closed by
552 VOICE AND SPEECH
two bands of animal membrane. Appliances of this kind, however,
do not give a correct picture of the action of the vocal cords, because
the vibratory parts of these models consist of closely approximated
biUpped membranes which oscillate toward one another. Never-
theless, they serve the useful purpose of demonstrating that the vocal
sounds, in agreement with the sounds produced by any musical in-
strument, differ from one another in loudness, pitch and quahty.
The loudness or intensity of a sound is determined by two factors,
namely, the volume and force of the expiratory blast of air and the
amplitude of the vibrations of the vocal bands in either direction from
their position of rest or equihbrium. These vibrations, moreover, are
greatly reinforced by the sympathetic oscillation of the walls of the
chest and head parts.
The pitch of a sound depends upon the number of vibrations oc-
curring in a unit of time. Obviously, therefore, it is determined first
of all by the character of the vibrating body, i.e., by the length,
thickness and general elastic qualities of the vocal cords. Secondly,
it is dependent upon the degree of tension to which these bands are
subjected, the highest sounds being emitted when they are tightly
stretched beside a narrow glottis. As a rule, the outline of the latter
remains elliptical as long as the vibrations do not exceed 240 to the
second. Between 240 and 512 vibrations, on the other hand, the vocal
bands are gradually brought closer together until they eventually en-
velop merely the narrowest possible sht. In fact, the production of
very high notes requires an almost absolute approximation of these
bands so that only short segments of them are allowed to vibrate. At
this time, the vocal aperture or rima vocalis is restricted to a small oval
opening situated directly behind the anterior wall of the thyroid
cartilage.
The foregoing very general reference to the structural pecuharities
of the vocal cords may serve as an explanation for the differences
in the pitch and quality of the voice in men and women. Since the
vocal bands of children are relatively short, the pitch of their voice
must be high. At puberty, however, the larynx develops very rapidly
in both sexes, a fact which readily accounts for the rather sudden
drop in the pitch of the voice occurring at this time. Moreover,
owing to the fact that the cords attain a greater length in men, this
*' breaking^' of the voice is especially pronounced in them. In most
instances, the voice of women acquires at this time merely a fuller
and richer character. If the development of distinct sex character-
istics is prevented by castration or by disturbances in the function
of the internal secretory organs, the larynx fails to undergo these
changes and the voice retains its peculiar high pitch and immature
quality.
The quality of the sounds depends upon the character of the vibra-
tions. Like in any musical instrument, the vibrations of the vocal
cords are of the composite type, i.e., they are made up of fundamental
PRONATION 553
and secondary oscillations. In the first instance, the cords as a whole
swing to and fro, while in the second, only short segments of them
are made to vibrate. In this way, the fundamental tone is constantly
combined with secondary partial tones or overtones. Besides, the
laryngeal sounds are qualified by the resonance of the chambers
situated above and below, and especially by the oral and nasal cavities.
The Peculiarities of Vocal Sounds. — The musical sounds which
we are capable of producing, do not shade evenly into one another
from the lowest to the highest, but appear in groups, i.e., a number of
them always possess a quality which is often sharply differentiated
from that of the neighboring group. We speak, therefore, of vocal
registers, but it must be remembered that the "breaks" between
these may be rendered less conspicuous by training. It is commonly
stated to-day that the range of the voice embraces two registers, namely,
the chest voice and the falsetto. Some authors also recognize a third,
or middle register, and some even a fourth. As may be surmised,
these differences depend upon modifications in the use of the resonating
parts. The chest-register is the lowest and is produced by a pro-
nounced vibration or fremitus of the wall of the thorax. It is richer
in overtones, and requires somewhat smaller quantities of air, because
the vocal bands are more closely approximated than they are during the
production of the falsetto or head-notes. Inasmuch as the latter
depend principally upon the resonance of the cavities of the head,
their production requires a copious supply of air which is made to
escape through the anterior part of the rima glottidis, while the posterior
portion of the glottic space remains closed.
A fundamental difference between the voice used in talking and
that employed in singing, does not exist. During singing, however,
certain qualities of the sounds are intensified chiefly by rendering
the path of the sound-waves perfectly free so that they are enabled to
attain sonority and a greater penetrating power. This is especially
true of the vowels, the fundamental note of which is always protected
as much as possible against admixtures or formants. Moreover, in
singing, the individual notes are not maintained for so long a time as
in talking.
Under ordinary conditions the range of the singing voice extends
over two octaves, but it can be considerably increased by training so
that it finally embraces 3 or 33^^ octaves. ^ In whispering the vibra-
tions of the vocal cords are displaced by friction sounds produced
along the laryngeal and buccal pharyngeal walls. The vocal bands
are rather relaxed at this time, while the glottis is made to assume an
intermediate size.
Speech is articulated voice. The voice sounds are modified by the
resonance of the different chambers and are combined with noises
^ Gutzmann, Stimmbildung und Stimmpflege, Wiesbaden, 1906; also Roudet,
Elements de phonetique g^nerale, Paris, 1911.
554 VOICE AND SPEECH
produced outside the larynx. Thus, we obtain vowels or sonants
and consonants. The former are dependent upon the vibrating quali-
ties of the vocal cords and are, therefore, musical sounds, while the
latter are noises caused by irregular oscillations of the mouth parts.
One of these extralaryngeal constrictions, against which the ex-
piratory current of air is forced, is formed by the hps, another by
the teeth and the tongue and still another, by the soft palate and the
tongue.
While the fundamental character of the vowels is determined by the
vibration of the vocal cords, a special quahty is imparted to them by
the varied resonance of the oral cavity. Such factors as the size and
shape of this cavity, the position of the tongue and the shape of the
soft palate play a part in their formation. Their influence is chiefly
directed toward the reinforcement of certain overtones. This
view which is essentially the one advocated by Helmholtz,^ has been
modified somewhat by Hermann, ^ who claims that the mouth does not
act as a mere resonator, but actually gives rise to secondary musical
notes which need not be harmonics of the laryngeal sound.
As has just been stated, the consonants are produced by the various
constrictor adjustments of the mouth-parts, i.e.j by ^' positions of articu-
lation. " In accordance with the seat of the obstruction, these sounds
are classified as labials, dentals, gutturals and nasals. Every one of
them may be characterized as soft and hard, the former designation
being appHed to them if they are formed during phonation and the
latter if the vocal cords do not take part in their production. The
sound D, for example, is a soft dental sound, because the simultaneous
vibration of the vocal cords gives it quality, while the sound T is hard,
because it is a pure dental sound and is not accompanied by phonation.
Griitzner has divided the consonants into semivowels, explosive and
friction sounds. Among the first may be mentioned the sounds m, n,
ng, I and r. Thus, if sounded in part through the nose, as "reso-
nants, " as in him, hen, or being, they assume the character of vowels,
because they are produced by the vibration of the vocal cords, while
the air is forced out largely through the nasal cavity imparting to them
a peculiar nasal resonance. But if employed as real consonants, as
in make or no, they acquire the characteristics of explosive sounds.
Typical explosives are the sounds p and v (labials), t and d (linguo-
palatals or dentals) and k and g (gutturals). They are said to be
formed with or without voice, because the production of some of them
necessitates a vibration of the cords, for example, the sounds b, d and
g. Friction sounds or frictionals, are produced by the passage of the
expiratory air across the edges of constricted areas, which are thereby
thrown into vibration. In this way, there are produced at the labio-
dental communication the sounds of/, v, and w; the first of which does.
1 Lehre von den Tonempfindungen, Braunschweig, 1877.
2 pfliiger's Archiv, xlvii, 1890, 44.
PRONATION 555
not require voice, while the other two do. As lingual f rictional may be
classified such sounds as s, th, shy ch, z and j, the production of the last
two necessitating phonation. The vibrative r is produced entirely
with the tongue, while h finds its origin at the pharyngeal entrance.
In the latter case the mouth-parts assume the position ordinarily re-
quired to utter the vowel following the h, as in hear or hoiose.
PART V
THE CENTRAL NERVOUS SYSTEM
SECTION XIV
THE FUNCTIONAL SIGNIFICANCE OF THE NERVOUS
SYSTEM
CHAPTER XLV
THE STRUCTURAL ARRANGEMENT OF THE NERVOUS
SYSTEM
The Subdivisions of the Nervous System. — Topographically the
nervous system presents itself as a central mass, consisting of the cere-
brum, cerebellum, basal ganglia, medulla and spinal cord, and a
peripheral complex, formed by the cranial, spinal and sympathetic
nerves. The latter, of course, also embraces a multitude of ganglia
as well as different ramifications in the form of plexuses and end-plates.
For structural and functional reasons the nervous system is commonly
divided into a cerebrospinal system and a sympathetic or autonomic
system. The former embraces the cerebrum, cerebellum, basal
ganglia, medulla, spinal cord, and the cranial and spinal nerves, while
the latter includes the different sympathetic and parasympathetic
ganglia throughout the body and the nerves connecting these ganglia
with the cerebrospinal system. This division is based upon:
(o) Anatomical grounds, in that the gross arrangement of the sympathetic sys-
tem is very different from that of the cerebrospinal, consisting as we shall see later,
of a chain of ganglia, which begins above with the superior and inferior cervical,
and the superior, middle and inferior thoracic, and ends below with the solar,
and the pelvic ganglia. In many places the fibers emerging from these stations,
ramify very extensively, and form complex networks, or plexuses.
(6) Histological grounds, in that the sympathetic nerve fibers are non-medul-
lated and connect with cells-bodies possessing a very characteristic shape.
(c) Chemical grounds, in that the mass of the sympathetic neurones seems to
be made up of neuroplasm which is somewhat different from that constituting the
cerebrospinal neurones.
(d) Functional grounds, in that the life processes regulated by the sympathetic
system remain for the most part subconscious. For this reason, sympathetic
reactions are very largely non-volitional and reflex in their nature.
557
558
SIGNIFICANCE OF THE NERVOUS SYSTEM
The Structural Unit of the Nervous System. — In conformity with
other tissues, nervous tissue is composed of two types of cells which
may be characterized as true and accessory. The former are called
neurons and constitute the functional element of this tissue, while the
latter are used for the supporting framework composed of ependyma
and neuroglia or glia cells. It is true, however, that these cells are
indispensable to one another, i.e., one cannot in all probability exist
without the other, but looked
at in a general way, it is the
neuron which attracts our atten-
tion most, because it is more
directly concerned with nervous
processes. In the terminology
of Waldeyer,^ the neuron or
nerve-cell is the histological unit
of the nervous system, and as
such includes the cell-body as well
as its protoplasmic processes,
namely, the dendrites, axis
cylinder, arborizations and col-
laterals. Looked at in this way,
the nervous system consists of
enormous numbers of neurons^
supported by glia cells and en-
veloped here* and there by pro-
tective membranes, such as the
dura mater, arachnoid and pia
mater. This constitutes the
''neuron concept" of the nervous
system. We shall see later on
that the structural independence
thus granted to the neuron, is
associated with an unmistakable
physiological distinctiveness.
The External Characteristics
of the Neuron. — Neurons are
cells modified to suit a particular
purpose, namely, that of generat-
FiQ.274. — Normal Anterior Horn Cell Show- ing and conducting nerve im-
(Warrington.) pulses. They are in reality
neuroplasmic fibers possessing
an accumulation of cytoplasm
at one point of their course in which are embedded a nucleus and
nucleolus. In this regard they present the essential details of a cell,
^ Deutsche med. Wochenschr., xvii, 1891, 1244.
2 Kolliker objects to this term upon philological grounds without, however,
furnishing a more correct or convenient concept.
mo THE NissL Granules.
a, The Axon.
ARRANGEMENT OF THE NERVOUS SYSTEM
559
because they consist of cytoplasm and nuclear material. It stands to
reason, however, that their general configuration must be subject to
marked variations, because the physiological processes for which they
are destined, necessitate an absolute structural adaptation to the
conditions existing in different parts of the body. Thus we find that
while nerve-cells always present the characteristics of an elongated
conductor, they are frequently so highly modified that it becomes
difficult to recognize their true nature. Their structural wealth has
been brought out more especially in recent years as a result of more
advanced methods in fixing and staining J
It is now commonly believed that neurons are developed from
single embryonic cells which are called neuroblasts (Fig. 275). These
precursors are compact neuroplasmic
masses, possessing a round or oval
shape and containing a well-defined
nucleus somewhere near the center
of their cytoplasm. In the course
of time, these apolar cells become
pear-shaped and finally send out a
process which renders them unipolar
and eventually multipolar in char-
acter. This theory of His has been
modified in more recent years^ by
making allowance for the fact that
certain fiber paths seem to be de-
veloped directly from the neuro-
blasts, i.e.y the latter may lose their
cellular character entirely and be
converted solely into axons. Thus,
a number of neuroblasts may be
joined together in such a way that
a conducting path is produced which
is then united with other neuroblasts which have given rise to cell-
bodies.
As has been stated above, the mature neurons present such a wealth of struc-
ture that it is impossible to classify them satisfactorily. Many of them, however,
present a very characteristic appearance, enabling us to recognize them immedi-
ately. Cells of this type are the large pyramidal cells of the motor area of the
cerebral cortex, the bipolar cells of the sensory ganglia, the fan-shaped cells of
Purkinje of the cerebellum, and others. At all events, any attempt at classifica-
tion must take cognizance of the shape and size of the cell-body and of the number,
size, and manner of branching of the processes — axis cylinder and dendrites alike.
The shape and size of the cell-body vary considerably. In the cerebral cortex,
^ Among the investigators who have greatly enhanced our knowledge in this
regard, might be mentioned Ehrlich (Deutsche med. Wochenschr., xii, 1886, 49),
Apathy (Proc. Intern. Zool. Congress, Cambridge, 1898), Golgi (Arch, fisiol., iv,
1897), Nissl (Die Neuronenlehre, etc., Jena, 1903), and Ramon Y. Cajal (Hist, de
Systeme Nerveux, Paris, 1909).
2 Baglioni, Zur Analyse der Refiexfunktion, Wiesbaden, 1906.
Fig. 275.- — Growing Neueoblasts.
A, Silver method of Cajal; B, Golgi's
method. (Cajal.)
560
SIGNIFICANCE OF THE NERVOUS SYSTEM
for example, we find enormous numbers of small and large pyramidal cells, while
those constituting the spinal ganglia, are spherical, and those forming the ventral
horn of the gray matter of the cord, rather square irregular. Very typical flask-
shaped cells are found in the cerebellum. Many of these cell-bodies are visible
to the naked eye, for example, those of the cells of Purkinje (Fig. 276) and those
situated in the anterior horns of the gray matter of the cord (150ju). Others,
again, are extremely small, measuring only from 4-9/z in diameter.
The large pyramidal cells in the cerebral cortex (Fig. 277) measure from 20-30ju
and the small ones from 10-12^i in diameter. Among the smallest are those com-
posing the olfactory bulb, and those forming parts of the cerebellum. Neither are
we in a position to give definite measurements regarding the length of the neuron
as a whole, because the distances which the different nerve paths must cover, vary
Fig. 276. — Puhkinje Cell fbom Human Cerebellum.
Golgi's method of staining. (Stohr.)
very greatly. It is said, however, that they may attain a length of 1.0 m., bridging
the distance between the motor area of the cerebrum and the lumbar region of the
spinal cord, or the distance between the latter and the effectors in the foot. On
the afferent side, they do not attain so great a length, because the sensory paths
are usually beset with a greater number of relay stations. It is also of interest
to note that the volume of the axons of these cells greatly exceeds that of the
cell-bodies. In large motor cells, for example, the axis cylinder plus its enveloping
sheath, possesses a volume 1500 times greater than that of the cell-body. Golgi^
recognizes three types of cells, namely:
Type 1. — The dendrites are short and ramify in close proximity to the cell-body.
Broad and thick at their origin, they gradually become thinner as they divide in an
1 Boll. d. Societa Med. Chir. di Pavia, 1898-1899.
ARRANGEMENT OF THE NERVOUS SYSTEM 561
antler-like manner into their finest terminals. One of the dendrites generally
reaches farther into the surrounding tissue than the others. These cells possess
a single long axon and serve, therefore, the purpose of conveying impulses over a
long distance. In most instances, the axon finally leaves the central system and
becomes a nerve fiber, terminating eventually in an end-organ. Its collaterals
also break up in arborizations. Cells of this kind are the motor neurons, found in
Fig. 277, — A, B, C, and D, Pyramidal Cells from the Motor Area of Man.
a, b, Spaces which are filled with tigroid bodies; c, pigment; e, nuclei of glia tissue;
/, base of a dendrite; g, h, basal portion of axons. (CajaZ.)
the cortex of the cerebrum, the anterior horn cells of the spinal cord, and the cells
of Purkinje of the cerebellum. Cells of this kind we are prone to picture to our-
selves when describing a neuron.
Type 2. — This cell bears the same characteristics as that of the first type, but
its axon is short. These neurons, therefore, must serve the purpose of conveying
36
662
SIGNIFICANCE OF THE NERVOUS SYSTEM
impulses from place to place within the realm of a single center. For this reason,
they generally remain confined to the central nervous system and serve chiefly
as intermediate conductors. This deduction seems the more correct, because their
axon usually splits into several branches within the gray matter, thus tending to
associate its different areas. The first and second types of Golgi cells are, of course,
multipolar in character.
Type 3. — This cell is typically represented by the neurons forming the ganglia
upon the posterior root of the spinal cord and the ganglia occurring in the course
of the sensory branches of the cranial nerves. In lower forms (fish) and also
in the mammalian embryo, the cells of the spinal root ganglion possess two processes
which leave at opposite poles of the cell-body, and are, therefore, bipolar. In the
adult mammal, however, a union has been effected between them so that they now
arise as one (Fig. 278). The process passes away from the cell-body but soon di-
FiG. 278. — Unipolar Cells of the Gasserlan Ganglion.
At a is shown the glomerulus formation of the axon. (CajcU.)
vides into two, one of which extends into the posterior realm of the cord and the
other outward to the corresponding receptors. This peculiar distribution gives
rise to a unipolar cell with a T-shaped process, the branches of which become
meduUated and serve as long conducting fibers. It is questionable whether the
impulses conveyed inward from the distant receptor, must first of all enter the
cell-body proper before they can be transferred to the central branch. In fact,
one of the points regarding the fibrillar theory to be discussed later, is that the
cell-body is not necessary for conduction. It may be removed without disturbing
the passage of these afferent impulses, and hence, it must be concluded that the
dendrite-like distal branch is in direct functional relation with the axon-like
central branch.
ARRANGEMENT OF THE NERVOUS SYSTEM 563
The Internal Characteristics of the Neuron. ^ — The maturing of
the nerve-cell necessitates several changes. First, we have the
estabhshment of the polarity of the cell, i.e., the neuroblast sends
out an axon, which is soon followed by the formation of dendrites.
In some cases, these processes then become medullated or are en-
veloped solely b}^ neurolemma; or both. While these alterations in
'" i:
f
Ai
Fig. 279. — Cell from the Anterior Horn of the Spinal Cord of a Rabbit,
Showing Nissl's Bodies.
Ax, Axon; D, dendrite; K, nucleus; N, nucleolus. (Klopsch.)
the configuration of the neuron are being completed, the cytoplasm
of the cell-body becomes more highly differentiated, presenting finally
the following details:
(1) A well marked nucleus and nucleolus surrounded by a relatively thick layer
of cytoplasm; (2) flake-like masses of a complex protein substance chemically
^ Nerve-cells were first recognized by Ehrenberg, in 1833, in the spinal ganglia
of the frog. In 1838, Remak established the fact that nerve fibers are prolongations
of the cell-bodies. This observation was made upon the sympathetic fibers of
mvertebrates. It was found to hold true in mammals by Helmholtz and Hanover
(1842). In 1863 the observations of Deiters were published which showed that
the cells of the central nervous system possess two kinds of processes, namely,
protoplasmic prolongations and a real fiber process. Gerlach (1871), Golgi (1873)
and Ramon Y. Cajal (1888), furnished additional data regarding the structure
of the neuron.
564
SIGNIFICANCE OF THE NERVOUS SYSTEM
allied to chromatin which are scattered through the cytoplasm and also extend
into the larger dendrites but not into the axon. They are generally designated
as Nissl's granules or tigroid bodies; (3) strands of denser protoplasm which
traverse the cytoplasm in all directions making connections between the different
processes of the neuron. They do not invade the nuclear substance. These
so-called fibrillae are said to be continuous with the fibril] se composing the axis-
cylinder, and are regarded as the specific conducting element of the neuron.
To be sure, these characteristics are not shown by all nerve-cells,
because some of them possess very small amounts of cytoplasm;
while others appear to be composed solely of nuclear material. NissP
^5^^ '
t-'^%li:Jk.i
<^
fl
©
:*• ^^
0 \
Fig. 280. — Normal Nerve Cell from the Lobus Electricus of the Torpedo. {Garten.)
who has made an exact study of the structural details of the different
nerve-cells, divides them into:
1. Somachrome Cells. — The cytoplasm surrounding the nucleus, exhibits a dis-
tinct structure, showing thereby that it possesses a decided functional importance.
By far the largest number of nerve cells belong to this group. They may be sub-
divided further in accordance with the staining qualities of their cytoplasm. ^
2. Cytochrome Cells. — Their cell-bodies are poorly developed, so that they
seem to be composed of naked nuclei. Cells of this kind are present in the sub-
stantia gelatinosa of Rolando and in the granular layer of the cerebellum and olfac-
tory lobe.
1 AUg. Zeitschr. fur Psychiatric, liv, 1897, 101.
2 Barker- The Nervous System, New York, 1899, 121.
ARRANGEMENT OF THE NERVOUS SYSTEM 565
CHAPTER XLVI
THE FUNCTIONAL ARRANGEMENT OF THE NERVOUS
SYSTEM
The Neuron Doctrine. — While the histological individuaHty of the
neuron has been founded upon the work of many investigators, it was
left to Waldeyer^ to correlate the facts in such a way that clearness
was finally brought into the chaos of nervous elements and their func-
tion (1891). In accordance with the views of this investigator, the
neurons are to be regarded as the building stones of the nervous sys-
tem, and hence, must be dealt with as independent cellular units.
This implies that the nervous system is built up of individual neurons
which retain a definite structural relationship to one another. They
are connected with one another by means of their processes, but this
connection is had only by contact and not by confluence.
We have noted that the neuron possesses an embryological dis-
tinctiveness in the form of the neuroblast. To this must now be
added its specific histological and anatomical appearance and thirdly,
also a definite functional independence. The sum total of their
individual actions gives rise to the complex of nervous processes as
we observe them in the higher animals. This extension of the neuron
doctrine to function followed very naturally upon the establishment
of the fact that neurons are structural entities. Physiologically, the
neuron concept tends to place emphasis uppn the cytoplasm and nu-
clear constituents of the cell-body rather than upon the conducting
paths, so that the former must really be considered as the directing
element of the whole.
The Fibrillar Hypothesis. — Contrary to Waldeyer and his followers,
it is held by Nissl,^ Bethe,^ Apathy,^ Schenck,^ and Pfliiger^ that
the nervous system is made up of conducting strands of neuroplasm
which are directly continuous with one another. The element which is
thus brought into prominence, consists of the neurofibrils which, as
we have just seen, permeate the cytoplasm of the cell-body and go
to form the dendritic and axon processes of the neuron. In accord-
ance with this view, the structural and functional unit of the nervous
system is formed by the neurofibril. Here and there a number of
these fibrils may pursue a common course and form such structures
^ Deutsche med. Wochenschr., 1891. Also see: v. Leuhossek, Derfeinere Bau
des Nervensystemes, etc., Berlin, 1895; and Verworn, Das Neuron in Anat*
und Physiol., Jena, 1900 and Med. Khnik, 1908.
* Die Neuronenlehre und ihre Anhanger, Jena, 1903.
^ Allg. Anat. und Physiol, d. Nervensystemes, Leipzig, 1903.
* Mitt, der Zool. Station zu Neapel, xii, 1897.
"Wiirzburger Abhandl, ii, 1902.
^ Pfliiger's Archiv, cxii, 1906.
566
SIGNIFICANCE OF THE NERVOUS SYSTEM
as the axons, but naturally, without becoming confluent or losing
their functional independence. In other places, they cross and give
rise to by-stations upon the general conducting path which is amplified
by the deposition of cytoplasm and nuclear material. Very clearly,
however, the fibrillar concept lays emphasis upon the conducting
element and attaches little importance to the cell-body.
Fio. 281. Fig. 282.
Fig. 281. — Cell from the Anterior Horn of the Spinal Cord of Man, Showing
Neurofibrils.
ax, Axon; lil, spaces occupied by tigroid material; x, fibrillar connections between
neighboring dendrites. (Bethe.)
Fig. 282. — Schematic Representation of the Neurofibrillar Connections in a
Pyramidal Cell of the Cerebral Cortex. (Cajal.)
The fibrillar hypothesis is based upon structural and functional
evidence. Thus, it was found that the large ganglion cells frequently
display an intricate network such as is shown in Fig. 282. This net-
work was assumed to represent an intracellular ramification of fibrillse.
Bethe, moreover, has shown that in young animals the degenerating
peripheral ends of nerve fibers may regenerate without first having
1
I
AREANGEMENT OF THE NERVOUS SYSTEM 567
become connected with their cell-bodies. It has also been proved by
this investigator that the cell-body is not essential to conduction.
This has been demonstrated in Carcinus msenas in which the nerve
of the second antenna is composed of centrifugal and centripetal
fibers and connects with a ganglion the cell-bodies of which are situated
somewhat apart from the fiber network or neuropil. On removing
the former, it was found that the antenna regained its former tonus
very rapidly and that its stimulation gave rise to reflex actions. Ob-
viously, in this case conduction is had even in the absence of the
cell-bodies by means of the fibrillar network or neuropil. Steinach^
has shown that this condition may be duplicated by causing the cell-
bodies of the dorsal root ganglion to degenerate or by removing this
ganglion in its entirety. Curiously enough, the sensory impulses
continue to pour into the spinal cord even in the absence of this gan-
glion, and hence, it may be inferred that they reach the central end of
the posterior root without being required to make station at this point.
Arguments in Favor of the Neuron Doctrine. — Regarded in a very
general way, it may be said that nervous processes are of two kinds:
namely, generative or central and conductile or peripheral. The
former include the automatic production of impulses and psychic
activities such as volition, thought, perception, and others. The
latter, on the other hand, merely represent the phenomena of conduc-
tion accompanying the passage of an impulse through an axon. In
perfect harmony with this functional division, the nervous system
presents itself as gray matter and white matter; the former constituting
the central nuclei and centers of function, and the latter the paths of
conduction by means of which these complexes of ganglion cells are con-
nected either with one another or with peripheral effectors and recep-
tors. Physiologically, it is quite impossible to attribute the genera-
tion of impulses to the conducting element of the neuron, the fibrillse.
In other words, creative processes can only be referred to the constitu-
ents of the gray matter, the cell-bodies. Thus, the different phenom-
ena of consciousness, the automatic activity of the centers, and other
processes, can only be produced by the cellular units of the gray matter
and not by the fibers alone, and hence, the liberation of nervous
energy is distinctly a duty of the cells.
A similar conclusion must be drawn from the time relationship
between impulses traversing nerve fibers and impulses passing through
nuclei and centers. It is a well-established fact that their journey
through nerve fibers requires a much shorter time than their passage
through centers. The deduction to be derived from this is that the
ganglion cells possess a specific activity which directly affects the
nature of the impulse.
Looked at from the standpoint of embryology, the fibrillar concept
fails to establish a structural unit, because the axis cylinders of the
nerve fibers do not arise from outgrowths of the cell-bodies, but from
1 Pfliiger's Archiv, cxxv, 1908, 239.
568 SIGNIFICANCE OF THE NERVOUS SYSTEM
individual local cells which eventually coalesce to form the conducting
path. In accordance with the neuron concept, the different neuro-
blasts finally elongate and form their own axons. These changes may
be traced without difficulty in neurons which are made to grow out-
side the body in a medium of lymph.
The histological evidence favors the neuron doctrine in a very
decisive manner. In the first place, it has. been proved that the
'^ neurofibrillar" network found in the immediate vicinity of ganglion
cells (Bethe), is not composed of fibrillse at all, but constitutes an intri-
cate system of lymphatic channels set aside for the nutrition of the
cell-body. In this connection, reference should also be made to the
fact that complexes of ganglion cells are always well supplied with
blood-vessels and lymphatics, while nerve fibers are not (Kollicker).
In addition, it should be mentioned that some ganglion cells are in
possession of an internal system of capillaries. A condition of this
kind exists in the cells of the medulla of Lophius picatorius. Further-
more, the cytoplasm of some nerve cells contains a hemoglobin-like
pigment, a fact which suggests an intense metabolism.^
The neuron doctrine also receives support from certain data
pertaining to the metabolism of the nerve cell. Thus, it has been
found by Langendorff^ that the gray matter readily assumes an acid
reaction upon activity and also becomes acid after death. In analogy
with the changes occurring in active muscle, it has been assumed that
this acidity is due to the production of lactic acid. It has also been
stated by Mosso^ that increased mental activity is associated with a
rise in the temperature of the brain. Reference should also be made
at this time to the fact that a nerve fiber atrophies when separated
from its cell-body, and that ganglion cells display very obvious histo-
logical changes during growth or when fatigued. Since a more de-
tailed account of these trophic changes will be given in a subsequent
paragraph, attention need only be called at this time to the fact that,
unlike the cell-bodies, the nerve fibers cannot be fatigued under ordi-
nary conditions and do not betray an intense metabolism. This fact
implies that the refractory period of the nerve fiber is shorter than
that of the nerve cell. Naturally, the only deduction to be derived
from these data is that the ganglion cells are the more active nervous
units and that they serve as the generator or supply house of nerve
impulses.
Fatigue of Nerve Cells. — The development of the neuroblast into
its mature form manifests itself by a deposition of additional cellular
material, an increase in the number of its processes, an acquisition of
enveloping membranes and a formation of pigment granules within
;the cytoplasm.* During their mature state, the neurons become
1 Fritsch, Archiv fiir mikr. Anatomie, xxvii, 1886, 13; Holmgren, Anat. Hefte,
XV, 1899, and Pewsner-Neufeld, Anat. Anzeiger, xxiii, 1903.
2 Zentralbl. der med. Wissensch., 1886.
3 Die Temperatur des Gehirnes, 1894.
* Vas, Arch, fur mikr. Anatomie, 1892.
AERANGEMENT OF THE NERVOUS SYSTEM
569
subject to structural variations in consequence of changes in the bodily-
activities. In old age, certain retrogressive alterations appear which
present themselves in the main as a reversal of the processes observed
during the growth of the cell. The cytoplasm decreases in volume,
the nucleus becomes smaller, the pigment increases and the different
processes decrease in number and mass. In fact, in some cases vacu-
oles develop which finally lead to the complete disappearance of the
cell.
A most interesting picture is presented by nerve cells which have
been fatigued. Hodge, ^ Mann^ and Lugaro^ state that a normal
neuron, when stimulated, first increases in size, because its metabolism
is augmented thereby. Excessive activity, however, diminishes the
amount of its cytoplasm as well as that of its nucleus until the chro-
FiG. 283. — Spinal Ganglion Cells from English Sparrows, to Show the Daily
Variation in the Appearance of the Cells Caused by Normal Activity.
A, Appearance of cells at the end of an active day ; 5, appearance of cells in the morn-
ing after a night's rest. The cytoplasm is filled with clear, lenticular masses, which are
much more evident in the rested cells than in those fatigued. {Hodge.)
matic substance has been used up in its entirety. The NissFs
granules gradually lose their conspicuousness and finally disappear
altogether. If long continued, the exhaustion of the reserve supply
of energy-yielding material manifests itself in a vacuolization of the
cytoplasm and a degree of disintegration from which the cell cannot
recover. But if the fatigue is not carried beyond a certain normal
limit, the chromophil substance is replenished in time. Very similar
changes have been observed in the ganglion cells of birds after long
continued flight, for example, in the anterior horn cells of the sparrow
and in the antennary lobes of bees at the end of an active day. These
1 Jour, of Morphology, vii, 1892, 95.
2 Jour, of Anat. and Physiol., xxix, 1894. 100.
^Lo sperim. giornale medico. Biol., F2, 1895.
570
SIGNIFICANCE OF THE NERVOUS SYSTEM
changes belong in the same category as those following the separa-
tion of the cell-bodies- from their axons, when the central stump and
adjoining cell-bodies undergo retrogressive degenerative alterations.
We then obtain a turgescence of the cells which is superseded by
atrophic changes and chromatolysis.
The fact that the gray substance of the centers has a dej&nite meta-
bolic requirement, is also shown by the grave symptoms which follow
almost immediately upon the occlusion of the carotid arteries or upon
obstructions to arteries which supply individual centers of the cere-
brum. A functional uselessness of those ganglion cells then results
which are situated distally to the block. This uselessness is evinced
either by a loss of motion or sensa-
tion, or both. A similar condition
/ 1 1 \ ' J \ may be set up very quickly in rabbits
iIrA ' c\ by compressing the abdominal aorta
^ •^ '' ^ (Stenson's experiment). The anemia
of the spinal centers resulting from
this obstruction, soon leads to a pa-
ralysis of the posterior extremities and,
peculiarly enough, the motor paraly-
sis precedes the loss of sensation (anes-
thesia). This dissociation suggests a
difference in the resistance of different
nervous elements to anemia.
Verworn^ states that the fatigue
of nerve cells may be brought about
in two ways, namely, by causing an
accumulation of the waste-products or
by exhausting the reserve nutritive
material of the cell. The former in-
duces fatigue and the latter, the more
serious condition of exhaustion. The
experiments which are directly con-
cerned with the metabolism of nerve
centers, consisted in perfusing the
central nervous system through the aorta with defibrinated blood and
saline solution containing varying amounts of oxygen. Thus, if the
blood of a frog poisoned with strychnin, was slowly displaced by saline
solution free from oxygen, the muscular spasms gradually became less
violent and finally disappeared altogether. The subsequent perfusion
with thoroughly aerated defibrinated blood, however, soon caused
these spasms to reappear with renewed intensity. The same results
were obtained with saline solution fully charged with oxygen, while
blood serum free from oxygen, prevented the recurrence of the spasms.
This observation proves very conclusively that the recuperation is not
dependent upon the organic substances, but rather upon the oxygen;
1 Arch, ftir Anat. und Physiol., 1900, 385.
Fig. 284. — Two Motor Cells
FROM THE Lumbar Cord of a Dog.
A, From rested, and B, from
fatigued dog; showing the diminu-
tion in the size of the cell, the changes
in the size and shape of the nucleus
and the chromatolysis. (After
Mann.)
ARRANGEMENT OF THE NERVOUS SYSTEM 571
moreover, subsequent experiments have shown that the activity of
the ganghon cells varies directly with the quantity of oxygen supplied
to them. Hence, their power of oxidation can no longer be doubted.
It has been established that prolonged muscular exercise gives
rise to fatigue substances, consisting of carbon dioxid, lactic acid and
monopotassium phosphate.^ In analogy with this observation, Dol-
ley^ recognizes a ''fatigue of depression *' throughout the body, which
results in consequence of the production of toxic substances, and a
"fatigue of excitation" which follows the excessive consumption of
nervous material. Thus, it is a common experience that excessive
muscular fatigue reduces our mental efficiency, while conversely,
mental fatigue weakens our muscular power and other bodily functions.
It is argued further that the highly organized centers are more suscep-
tible to fatigue than the ordinary reflex centers, because mental work
produces symptoms of fatigue with much greater ease than muscular
exercise. This is especially true of young children who ''go stale"
very quickly unless their mental training is properly balanced by rest
and play. But while we may feel justified in assuming that ganglion
cells give rise to fatigue substances, we have not succeeded as yet in
isolating these bodies, the only possible exception being carbon dioxid.
Winterstein^ has shown that the administration of this gas produces
an exhaustion of the nerve cells within a very short time.
The Refractory Period of the Nerve Cell. — It will be recalled that
cardiac muscle is impervious to stimuli during systole but gradually
becomes more irritable as the end of the diastolic period is reached.^
Systole is the period during which the contractile substance is used up,
and diastole the period during which it is again acquired. This
type of protoplasm, therefore, is not in a condition to receive stimuli
so long as those internal reactions are being promulgated which give
rise to its contraction. It again becomes receptive during its recuper-
ative period, i.e., during the diastole and pause. In a similar way, it
is held that nerve tissue undergoes cataboUc and anabolic changes,
and hence, a sufficient time must always be allowed to elapse between
two successive stimuli, otherwise the material will not be at hand with
which to produce the subsequent reaction. Thus, if the successive
stimuli are sent into nerve tissue with an increasing rapidity, a point
will eventually be reached when no reaction can result. The stimuli
then become ineffective, because not enough time has been allowed
for the renewal of that material which has been used up during the
1 The formation of the so-called muscle toxins has been denied by Lee (Proc.
Soc. Exp. Med. and Biology, 1917).
2 Intern. Monatsschrift fiir Anat. und Physiol., xxxi, 1914, 35.
3 Zeitschr. fiir allg. Physiol., vi, 1906, 315.
* Discovered by Marey, (Compt. rend., 1891) and applied to nerve tissue by
Broca and Richet (Compt. rend., 1897). These investigators found that the
cortical cells are unirritable for some time after the cessation of the muscular
spasms, such as occur in chorea and epilepsy.
572 SIGNIFICANCE OF THE NERVOUS SYSTEM
preceding period of activity. This interval during which the irrita-
biUty is at low ebb, constitutes the refractory period.
In the case of nerve fibers, the period of refraction is extremely
brief, in spite of the fact that they undergo metabolic changes. It
amounts to only 0.002-0.006 sec. Their extremely rapid power of
recuperation is dependent upon their great affinity for oxygen. It is
possible, however, to render this period more evident by lessening the
amount of the available oxygen which can be done most easily by sur-
rounding the nerve fiber with some inert gas or narcotizing agent. ^
Cell-bodies behave very similarly, but as their metabolic requirements
are much greater than those of the nerve fibers, their refractory period
is also more clearly marked. Thus, it has been found that a refrac-
tory period of 0.006 sec. for the nerve fibers of the frog corresponds to
a refractory- period of 0.1 sec. for the ganglion cells of the same animal.
This time may be varied by altering the irritability of the cell, either by
lessening the amount of the available oxygen or by narcosis.
As the cell-bodies of different groups of neurons are destined to
perform different functions, it may be conjectured that their anabolic
requirements are subject to considerable variations. Hence, although
their refractory period is much longer than that of the nerve fiber, the
value of 0.1 see. must vary somewhat in accordance with the type
of cell under consideration. It has also been suggested that the
refractory period acts as a check upon those impulses which ganglion
cells discharge automatically. It is a well-known fact that the dif-
ferent motor organs, such as muscle tissue and glandular tissue, are
constantly kept in a condition of tonus in consequence of an outpouring
of subminimal impulses by their respective centers. These impulses
are said to be generated at the rate of about 10 in a second. Obvi-
ously, as the refractory period amounts to 0.1 sec, they could not
be repeated at shorter intervals. Nor could they recur at longer
intervals, because the excessive rise in irritability would eventually
cause them to be discharged irrespective of any stimulation. It is
believed that some ganglion cells discharge their impulses even more
rapidly than 10 in a second, namely, 40-100 in a second, but a mere
difference in rate does not destroy the principle involved in this
process of self -regulation, because the refractory period must neces-
sarily become the shorter, the greater the rate of discharge. At no
time, however, could it equal the refractory period of nerve fibers.
Summation of Stimuli in Nerve Cells. — The phenomenon of sum-
mation is well illustrated by the summation of the contractions of
skeletal muscle. If a number of stimuli of the same intensity are
passed into muscle tissue at brief intervals, the resulting contractions
are added to one another until the total reaction displays a very much
greater amplitude than that of the single contractions. A strength of
stimulus may also be employed which does not give rise to a reaction,
while two or three stimuli of this intensity applied in rapid succession,
1 Frohlich, Zeitschr. fur allg. Physiol, iii, 1904, 148.
ARRANGEMENT OF THE NERVOUS SYSTEM 573
produce a reaction. This phenomenon constitutes the summation of
subminimal stimuli. It should be remembered, however, that we are
not dealing in this case with a storage or ordinary addition of individual
stimuli, but with a state of increased sensitiveness of the living sub-
stance. In other words, the first stimulus, although subminimal
in character, gives rise to certain changes in the cell which render
it more susceptible to the succeeding stimulus. This is really a general
experience, because certain reactions may be elicited with much greater
promptness by a succession of moderate stimuli than by a single
stimulus of great intensity. This is especially true of the stimulation
of the cerebral cortex and other complexes of nerve cells mediating
reflex actions.
Setschenow^ has proved that nerve fibers and ganglion cells behave
very differently toward stimuli. Thus, it is conceded that the state
of excitation in nerve fibers does not outlast the stimulus for any con-
siderable length of time, while nerve cells retain a state of greater
irritability even after slight stimuli and show, therefore, a greater
responsiveness to succeeding stimuli. We make use of this fact in a
practical way in eliciting reactions in the realm of the sympathetic
system and in testing the different reflexes for purposes of diagnosis.
Thus, a number of light taps upon the patellar ligament often result
in a positive reaction when a single strong one does not. It has also
been observed that long-continued pressure is at times more effective
than a single mechanical stimulus of much greater intensity. The
same is true of the stimuli elicited by stroking the surface of the body
(tickling) and of the light, sound and chemical impacts imparted
respectively to our retinse, organs of Corti, taste-buds and olfactory
cells.
Facilitation or "Bahnung." — Most closely allied to this phenom-
enon is the so-called stair-case contraction or *'Treppe" of striated
and cardiac muscle tissue. It will be remembered that if these tissues
are rendered more sensitive either by exposing them to subminimal
stimuli or by the administration of fatigue substances, their contrac-
tions gradually increase and remain large until this state of hyper-
susceptibility has been terminated. It should be noticed, therefore,
that the '^Treppe" is not caused by an increased intensity of stimula-
tion but by an augmentation of the contractile power of the muscle
substance. A similar change takes place in nerve tissue when made to
perform the same task a number of times in succession. An impulse
which is made to pass through a certain set of neurons a great many
times, gradually breaks down the resistance in this path so that the
latter becomes more particularly adapted to it. This ''Bahnung"
is largely a matter of the cell-bodies, ^ because, as we have just seen,
the resistance in the centers is infinitely greater than that met with
^ tlber die elektr. Reizung der sens. Riickenmarksnerven des Frosches, Graz,
1868; also: Biedermann, Pfliiger's Archiv, Ixxx, 1900, 451.
2 Exner, Pfliiger's Archiv, xxviii, 1882, 487.
574 SIGNIFICANCE OF THE NERVOUS SYSTEM
along the fiber path. The repetition of impulses, therefore, leads to
the formation of open paths, and herein hes the cause of facihtation
which in turn gives rise to the formation of habits constituting the
neural basis of memory.
Inhibition. — It must be clear that afferent impulses can produce
their characteristic reactions only if the neurons over which they
pass, do not simultaneously conduct other impulses. Stated differ-
ently, the primary impulse must have a perfectly clear path before it,
otherwise a conflict will arise between them which must finally lead
to the obUteration of one or the other of these impulses. Only the
more effective of them will succeed in eliciting a reaction. It is com-
monly believed that this inhibition and elimination of impulses occurs
in the centers and not in the fiber paths, because the function of the
central cells consumes time and energy so that they cannot do more
than attend to a single activity.
Inhibitory phenomena are explained in two ways, namely, by as-
suming a paralysis of the assimilative^ or a paralysis of the dissimila-
tive processes. In accordance with the latter hypothesis, which seems
to be the more acceptable, all nervous processes are considered as
excitations of dissimilative changes and hence, inhibitions must
result whenever this dissimilation following upon the reception of an
impulse, is stopped. Clearly, therefore, the chief factor in inhibition
seems to be an attenuation of the refractory condition of the nerve
cell towards secondary impulses. ^
CHAPTER XLVII
THE FUNCTIONAL UNIT OF THE NERVOUS SYSTEM
The Reflex Concept. — In the same manner as the complex masses
of nervous tissue may be reduced to a single unit, designated as the
neuron, so may all nervous actions be reduced to a simple action,
known as a reflex. In the same way as the neuron forms the build-
ing stone of the nervous system, so does the reflex constitute the func-
tional basis of all nervous processes. To be sure, there are many
organisms in existence which are not in possession of a nervous system
nor even of nervous elements, but which nevertheless react in a manner
that, relatively speaking, cannot be said to be inferior to the power
of reaction of the higher forms. But as these forms are absolutely
devoid of nervous tissue, their actions cannot be said to be reflex in
iGaskell, Jour, of Physiol., vii, 1885; also: Meltzer, New York Med. Jour.,
1899.
2 Verworn, Archiv fiir Physiol., Suppl., 1900, and Zeitschr. fiir allg. Physiol.,
vi, 1907.
THE FUNCTIONAL UNIT OF THE NERVOUS SYSTEM 575
their nature. If an ameba retracts its pseudopodia or if a rhizopod
sends out its protoplasmic filaments into the surrounding medium,
stimulations of some sort must have taken place directly preceding
these responses. But as these excitations have resulted in living
substance which is free from nervous elements, the reactions, although
just as complex as many of those exhibited by the higher animals, can
only be said to be reflex-like in their character.
The other group of organisms, embracing those possessing nervous
elements, shows a gradually increasing complexity in the arrangement
of its nervous units and also a steadily increasing complexity in its
reactions. The simplest of these are designated as reflexes and the
most complex, as associated actions or voluntary reactions. The divid-
ing line between these processes lies in volition. Thus, we may use
the term reaction in a very general way as designating any response
to a stimulus, but, more correctly speaking, it should be restricted
to that response which is accomplished with the aid of the will. A
reaction, therefore, is a volitional action, while a reflex is an action
which is not influenced by volition. To summarize, the different
actions shown by animals may be divided into reflex-like actions,
reflexes and complex reactions. The first of these are had solely with
the aid of ordinary protoplasm, while the last two necessitate the pres-
ence of that differentiated type of living substance which we call
neuroplasm. Furthermore, as long as an action of the latter kind is
not influenced by the will, it remains a reflex, but becomes a complex
reaction immediately upon the entrance of volition.
The Reflex Circuit. — It need scarcely be emphasized that the pres-
ent discussion must be restricted very largely to the analysis of the
nervous activities of the higher forms and hence, reflex-like actions
must be left for later consideration. The phenomena of hfe have been
divided into spontaneous manifestations and manifestations of stimu-
lation. Strictly speaking, however, this classification is incorrect,
because life consists in a reaction of living substance to outside in-
fluences. Hence, stimulations are always present and a state of abso-
lute spontaneity cannot arise. Stimuli are constantly brought to
bear upon organisms and it is their destiny to react toward them in
accordance with their structural and functional equipment. Moreover,
if we define a stimulus as any extraordinary alteration in the conditions
which nature has imposed upon us, we must immediately be struck
by the enormous diversity of influences to which we may be subjected.
Animals, very naturally, react toward these changes in harmony
with the development of their nervous system. The lower forms being
constructed along much simpler lines, are essentially reflex animals,
for the reason that their psychic activities are lacking and their actions
cannot, therefore, be dominated by the will. The higher animals,
on the other hand, are reaction-animals, because their psychic life
absolutely controls their simple reflex functions.
A reflex is a response to a stimulus executed without the interven-
576
SIGNIFICANCE OF THE NERVOUS SYSTEM
tion of the will. This definition implies that the impulse generated
in the sense-organ, must be conveyed to a center before it can be
transferred to the corresponding motor end-organ (Fig. 285). In
its simplest form, therefore, the nervous circuit which is necessary
for the mediation of a reflex, must consist of two neurons, one of which
serves the purpose of conveying the impulse from the sense-organ {R)
to the center, and the other, from the center (C) to the motor organ
(Er). The first neuron forms the sensory path {A) and the second,
the motor path (E) of this reflex arc or circuit. The terms afferent and
centripetal are frequently applied to the ingoing path and the terms
efferent and centrifugal to the outgoing path. Furthermore, the sen-
FiG. 285. Fig. 286.
Fig. 285. — Diagram Illustrating the Construction of the Reflex Circuit,
R, Receptor; A, sensory path; C, center; E, motor path; Er, effector.
Fig. 286. — Diagram Illustrating the Construction of the Reaction Circuit
(Volitional Response).
R, Receptor; A, primary sensory path; C, reflex center; A', secondary sensory
path; V, higher center; E', primary motor path; E, secondary motor path, Er, effector.
sory side of the reflex arc is often designated as the analyzer, while the
sensory end-organ is called the receptor and the motor end-organ the
effector. Stated in detail, therefore, a reflex circuit is composed of a
receptor, a sensory path, a center, a motor path and an effector.
The circuit required for a volitional reaction, differs from the reflex
circuit only in the number of neurons which are necessary to convey
the impulse into the cerebrum where the psychic faculties (volition)
are situated. The impulse is first conveyed from the receptor to the
lower (reflex) center and from here by a secondary afferent neuron
to the higher center involving volition. Upon its being transferred
to the efferent side of the reaction arc, the impulse first attains the
lower center and later on the effector.
The Rudimentary Nervous System is a Reflex System. — The neuron,
as has been emphasized above, is the structural unit of the nervous
THE FUNCTIONAL UNIT OF THE NERVOUS SYSTEM 577
system. Physiologically, however, the neuron attains its greatest
importance only when several of them are joined to form reflex circuits,
because only then do we obtain the structural basis for the reflex act
which constitutes the functional unit of the nervous system. Obviously,
if an electric shock is passed directly into muscle tissue, it reacts by
giving a contraction. The same result may be obtained by stimulat-
ing the nerve innervating this muscle. In either case, it is to be
noted that this action does not constitute a reflex, because it is accom-
plished in a direct manner and not through the intervention of a num-
ber of neurons arranged in proper series. In order that the aforesaid
muscular contraction may become a true reflex response, it is neces-
sary to bring the stimulus to bear upon some afferent nerve, whence
the impulse is transferred to the motor nerve of this muscle.
Clearly, the cells constituting the tissues and organs of the higher
forms, behave in the same manner as unicellular organisms. They
possess irritability, conductivity and contractility and hence, give
rise to motor effects whenever stimulated. If a vorticella is touched,
an excitation results which is conducted to the myoids situated in its
stalk. A contraction follows which causes the bell-shaped upper
portion of this organism to be retracted from the seat of the stimula-
tion. In a similar way, an electrical shock applied to a muscle,
gives rise to a wave of excitation which finally leads to general changes
within its myoplasm. The function of the nervous system, there-
fore, is not to impart these elementary properties to organisms, be-
cause all living substance is irritable, conductile and contractile.
Its real object is to insure a functional correlation between the different
cellular units of the body, so that the latter are enabled to react to
changes in the environment as one single coordinated whole. It is
also true that nervous tissue is peculiarly suited to bring this coopera-
tion about, because the neuroplasm of which it is composed, possesses
the properties of irritability and conductivity in an even greater
measure than ordinary living substance.
A general survey of the animal kingdom shows that the forms be-
low the coelenterata do not possess definite nervous structures.
Their life processes, as far as we know at the present time, are not
correlated by cells other than those forming their tissues. In the
coelenterata, however, certain cells are found which are particularly
sensitive and appear to be set aside for the singular purpose of receiving
stimuli from without and of transferring the resulting impulses to
other colonies of cells. We find these units in the external strata of
the body, i.e., in the epiblast (Fig. 287,A). Their internal poles are
drawn out into slender processes which eventually invade the deeper
layers (Fig. 287, B and C). Here they are brought into contact with
secondary nervous elements which finally connect with the underlying
muscle tissue (Fig. 287,1)). An arrangement of this kind, representing
really the lowest type of nervous system, is found in the jelly-fish.
The sensory cells which are situated in among the external lining cells
37
578
SIGNIFICANCE OF THE NERVOUS SYSTEM
of the umbrella, lie in relation with a more. deeply placed network of
fibers in which a number of nerve cells are embedded. Fibers extend
from here to the reactive tissue in the innermost layers of the umbrella,
tentacles and manubrium. It appears, therefore, that these organisms
are already in possession of complete reflex circuits, each of which is
composed of a receptor, a sensory path, an intervening neuron
forming the center, and an efferent path with its effector. In fact,
this differentiation of the nervous elements seems to have progressed
quite far, because the sensory cells show certain individual differences
which lead us to suspect that some of them are set aside for the recep-
tion of mechanical impacts and rays of hght, while others seem to be
concerned with the position of the organism in space (static sense).
A
OjO 0 o
c
0 • 0 o o
B
1
■"l—
0 0
V
D
0 0
•
0 io
1 1
\.
Fig. 287. — Dla.gram Illustrating the Evolution of the Nervous System.
A, Ordinary living cells; B, processes are sent out by some of them which (C) con-
nect with similar processes of more deeply placed nerve cells; D, the latter in turn form
connections with the muscle cells, thereby completing the path between the sensory cell
and the effector.
It is, of course, quite probable that a more rudimentary arrangement
than this will in time be discovered in other forms; so far, however,
the one described is the most elementary with which we are acquainted.
The Evolution of the Reflex System into a Reaction System. — While
a segmental arrangement of the tissues and organs is quite apparent
even in the highest animals, this condition may be studied most
advantageously in such forms as the vermes and crustacese. The
term segmentahsm really signifies that the bodies of these animals
are made up of a number of smaller units which are capable of leading
an independent existence. This is made possible by the fact that each
segment is equipped with a digestive, excretory, circulatory and nervous
system, so that a structural dissociation may be effected between
them without destroying or seriously impairing their life processes.
As far as the nervous system is concerned, we find that the different
segments (Fig. 288) contain a centrally placed ganghon (G) from which
THE FUNCTIONAL UNIT OF THE NERVOUS SYSTEM
579
fibers extend in all directions to the different tissues of the segment.
A stimulus applied to its surface (S) , is soon followed by movements or
some other motor response (E) , and hence, we must conclude that the
nervous material allotted to each segment, is arranged in the form
of reflex arcs, the centers of which are situated in the ganglion. While
a high degree of independency is thus assured to each segment, it must
be admitted that the Hfe of the entire animal requires in addition a
proper correlation between its different
parts. The functions of its segments must
be subordinated to the requirements of the
whole. This end is accompHshed by in-
termediary neurons (A) which unite the
successive ganglia with one another. These
association fibers are placed longitudinally
to the long axis of the animal and form in
this way a conducting channel akin to the
spinal cord of the higher forms. It is also
to be noted that the head ganglia are es-
pecially well developed and exercise a con-
trolUng influence over the other ganglia.
Eventually these central complexes also
become the recipients of impulses from cer-
tain sense-organs, such as the eyes, and the
receptors for chemical and vibratory im-
pacts. This is of importance, because the
movements and general behavior of the
animal naturally demand a proper correla-
tion of all these different sensory impres-
sions. It should be emphasized, however,
that those animals which are equipped
with a nervous system of this kind, are not
capable of forming associations. They are,
therefore, true reflex animals for the reason
that they are not in possession of those
complexes of neurons which give rise to
psychic activities (cerebrum).
Fig. 288. — Diagrammatic
Representation of the Ner-
vous System of a Segmental
Animal.
G\ G^ and G^ Ganglia in
three successive segments.
S\ S^ and -S^, and E\ E^ and
E^, the receptors and effectors
of those segments forming the
end stations of typical reflex
circuits; A, association paths
uniting the reflex centers of
the successive segments.
By way of illustration, let us devote a few
moments to a consideration of the nervous system
of the crayfish (Fig. 289). It consists of thirteen
ganglia, six of which are allotted to the abdomen, six to the thorax and one to the
head region. As the most anterior of these lies in close relation with the esophagus,
it is usually called the supra -esophageal or supramaxillary ganglion (A ) . The fibers
emitted by every one of these ganglia, are distributed to the muscles and the sense-
organs of the integument. They are brought into relation with those of the opposite
side by intermediate neurons. Connections are also made with the neighboring
ganglia by means of commissural fibers. Each ganglion, therefore, is partially
divided into two lobes and this bilateralism is also apparent in the path connecting
them. The first thoracic or subesophageal ganglion (C) is more highly developed
than the others, because it forms the link between the chain of posterior ganglia
580
SIGNIFICANCE OF THE NERVOUS SYSTEM
and the supra-esophageal ganglion. It appears to be made up of several and sends
out two commissures {B) which encircle the esophagus and eventually unite with
the large supra-es.ophageal ganglion. Besides, it gives origin to ten pairs of nerves
which innervate the mandibles, the maxillae, and the maxillipedes with their
branchial appendages. A still greater differentiation is pre-
sented by the head ganglion which consists of three pairs of
nodular enlargements, namely, the protocerebron, the deutero-
cerebron and the tritocerebron. The optic nerves (O) enter the
foremost of these, while the middle ones receive fibers from the
integument, antennae and organ of hearing (R). The posterior
nodules give origin to the nerves innervating the large external
antennae (D).
An arrangement of this kind constitutes a typical reflex stem,
around which, in the higher forms, the association or reaction
system is developed. The greatest change is effected anteriorly
in the region of the head ganglia, because these bodies are destined
to become the recipients of the impulses from the chief sense
organs. Eventually, many of these impulses are not permitted
to pass directly upon efferent channels, but are first conducted
into certain complexes of nerve cells in which they are asso-
ciated. In this way, each sensory reflex area is finally invested
by a sphere of association, the nervous products of which give
rise to the psychic life of the animal. This development of the
different association centers takes place gradually. The first to
make its appearance is the center for smell, because smell is the
most primitive sense and many animals, such as the amphibia
and reptilia, depend upon it almost exclusively. It need
scarcely be emphasized that the development of these associa-
tion spheres increases the complexity of the nervous system
very pronouncedly, because the primitive reflex stem is now
materially augmented by the addition of the brain. Quite aside
from this structural and functional complexity of the nervous
system of the higher animal, it should be noted especially that
its reflex life is completely subordinated to the activities of
the association centers situated in. the more recently formed
cerebral hemispheres.
><
^<^
4 k
111
Fig. 289.—
Diagrammatic
Re presentation
OF THE Nervous
System of the
Crayfish.
A, Supraeso-
phageal gang-
lion; B, commis-
sure; C, subeso-
phageal ganglion ;
D, first abdom-
inal ganglion;
O, optic nerve ;
R, middle nerve;
P, antennary
nerve; S, stoma-
togastric nerve.
The Joining of the Reflex Circuits. — The struc-
ture of the most elementary reflex arc has been fully
considered in one of the preceding paragraphs. It con-
sists of a receptor, an afferent path, a center, an
efferent path and an effector. Moreover, it is to be
noted that, in the lowest forms, these reflex circuits
are few in number and retain a marked independency
of one another. In the higher animals, on the other
hand, they increase greatly in number and become
closely linked by intermediary neurons which thus es-
tablish a close functional relationship between them.
The simple reflex arc (Fig. 290) may be compounded
first of all into a reflex chain consisting of several arcs
{B). The impulse producing the primary reflex response is thus en-
abled to spread and to incite other responses until the so-called chain
reflex is obtained. Another way in which these reflex arcs may be
arranged is illustrated by Fig. 290, C. Here two effectors are connected .
THE FUNCTIONAL UNIT OF THE NERVOUS SYSTEM
581
with a single receptor, the efferent paths originating from a common
center. These effectors may or may not act in unison; i.e. they may
be alhed or antagonistic in their function. If the former case, the re-
action simply becomes more diversified and complex, but continues to
present a perfectly co-ordinated character. An antagonistic behavior
on their part, however, must lead to a disconcerted reaction which,
in most cases, can only be prevented by inhibiting the action of one of
the effectors. Conversely, two receptors may be associated with only
one effector (Z)). If stimulated simultaneously, the impulses arising
in these receptors, will have a tendency to interfere with one another
until the more effective of the two finally succeeds in gaining the com-
mon path to the effector. It may also happen that these impulses, if
C
^
1 1
1%
K
^
£ E
sf
E
^ i^
^
y
\
^ V
D
y
Fig. 290.-
RE R R R
-Diagram Illustrating the Joining of Reflex Circuits.
R, Receptor; C, center; E, effector.
simultaneously elicited, reinforce one another so that the response
becomes much greater than it would have been if only one of them had
been received. Reflex arcs may also be combined into the form
represented by Fig. 290, E. We observe here that the successive
circuits are brought into close relation with one another by connecting
paths, so that the stimulus applied to one of them may skip either to the
same or to neighboring effectors, or both. In this way, much more
complicated reflexes may be elicited which, although for the most part
allied, may at times assume an antagonistic character.
It will be pointed out in a subsequent paragraph that the spinal
cord, in combination with the spinal nerves and those apportioned to
the sympathetic system, is especially well adapted for reflex action.
In fact, as the cord really consists of a large number of reflex centers
582 SIGNIFICANCE OF THE NERVOUS SYSTEM
and their connecting paths, it is commonly regarded as one of the
chief realms of reflex action. This statement, however, is not meant
to convey the idea that the cerebrum and other complexes of the
nervous system are composed exclusively of reaction circuits, and are
devoid of reflex circuits. Such an assumption could easily be proved
to be incorrect, because many of the most common reflexes invade the
cerebrum and neighboring parts. For example, if the intensity of the
light is increased, the pupil is constricted, or if the cornea is touched,
the eyelids are closed. Similarly, we react to sound impressions quite
frequently by movements of the head, and to visual impressions by a
hyperproduction of saliva and gastric juice. In all these instances, as
well as in many others that might still be mentioned, at least a section
of the reflex circuit is situated in the realm of the cerebrum and parts
immediately adjoining. Nevertheless, these actions are thoroughly
reflex in their nature. As additional proof it might be mentioned
that a group of reflexes, known as the association reflexes, actually
necessitate the formation of distinct sensory concepts, otherwise
the motor response invariably fails to develop. This is true, for
example, of the act of yawning elicited by observing somebody else
yawning, and of the flow of saliva and gastric juice following the sight
of attractive food. In all these cases, voUtion does not play a part and
hence, it must be concluded that reflex circuits may be found in all
parts of the nervous system and even in the domain of the cerebrum,
where they are brought into relation with the processes of conscious-
ness. It is to be noted, however, that the impulses conveyed by them
do not lose their reflex character unless dominated flnally by volition.
Whenever this change takes place, the reflex becomes an associated
act or a voUtional reaction.
The conditions found in the lower forms are most closely simulated
in the sympathetic system, because this system consists of a series of
ganglia which are connected with one another by closely interwoven
nerve flbers. While these gangha are generally situated in the im-
mediate vicinity of the structures innervated by them, they may also
be placed directly within their substance. If we direct our attention
for a moment to the stomach and intestine, we find that these organs
may be made to contract and to secrete even outside the body, pro-
vided that they are kept under proper conditions of moisture and
temperature. They are thus proved to possess a remarkable independ-
ency of function which is made possible by the fact that they are
amply equipped with reflex circuits which in all probabiHty are con-
tained in the plexuses of Meissner and Auerbach. But even if these
organs are left in situ, it is not difficult to divide the bridges connecting
them with the cerebrospinal system. In this way, volition may be
absolutely excluded from them as well as from all other sympathetic
organs. Since their functions are not seriously disturbed thereby, it
must be concluded that they are typically reflex in their nature.
Very similar conditions are met with in the spinal cord, the reflex
KEFLEX ACTION 583
nature of which may be more clearly portrayed by severing the con-
nections between it and the brain. This end may be attained
by a section made either above or below the medulla oblongata. It
will be shown later on that an animal of this kind retains all those
functions which are ordinarily accomplished with the aid of the cord.
These responses, however, need not remain confined to a particular
segment of this structure, but may also involve higher or lower spinal
centers without losing their reflex character. The reactions of a
''spinal cord animaP' must necessarily be non-volitional.
When referring to reflex circuits and actions we are accustomed
to associate them immediately with the spinal cord. The preceding
discussion, however, must have made it clear that they are not ex-
clusively confined to this structure, but may involve almost any part
of the nervous system. It seems that the spinal cord is referred to
most frequently in this connection, because it is a relatively simple
matter to isolate it and to stimulate its nerves. Moreover, the spinal
reflexes are perfectly conscript actions and pursue easily recognizable
paths.
CHAPTER XL VIII
REFLEX ACTION^
The Different Types of EfEectors and Receptors. — If we adhere to
the general definition that a reflex is a non-volitional motor response
to a sensory impulse, the very diverse and complex character of these
reactions must immediately become evident. On the efferent side,
of course, conditions are relatively simple, because the effectors consist
of only two structural units, namely, the muscle cell and the gland
1 The term sympathy or consensus was applied by the ancients to almost all
phenomena of life. In 1649, however, Descartes separated from these general
reactions all those which did not produce an impression in consciousness and were
not subjected to the will. He applied to this class of reactions the term reflex,
because in analogy to the reflection of light, the sensory impression seemed to be
returned in the form of a motor effect. Subsequent to this time, Willis (1664),
Astrue (1743), and Unzer (1771) have described various reflexes such as the acts of
coughing, sneezing, the closure of the eyelids, the ejaculation of the semen, and
others. Their idea, however, seemed to be that these reactions can be brought
about with the help of the nerve trunks and do not require a center. Whytt
(1751) then proved that this conception is incorrect, because in the frog the
destruction of the spinal cord immediately destroys the reflex actions ordinarily
elicited with the help of this part of the nervous system. He also described the
reflex secretion of the tears and of saliva, and recognized the fact that the latter
may also be obtained by psychic stimulation; in other words, he recognized the
association reflex. The modern conception of reflex action is based upon the work
of M. HaU (1832-33) and Joh. MuUer (1833-34).
584 SIGNIFICANCE OF THE NERVOUS SYSTEM
cell. The former gives rise to motion and the latter to secretion.
It must be remembered, however, that the muscle cell presents itself
in three forms, giving rise respectively to the striated, non-striated
and cardiac tissue, and furthermore, that especially the second type
of muscle cell is a constituent of a most perplexing array of structures.
Thus, we find it in the iris, cihary body, stomach, intestines, blood-
vessels, ureter, bladder, sexual organs, skin, etc. In all these cases
it responds to stimuh by contracting, but the effect produced thereby
differs greatly in accordance with the general arrangement of the tissue
in which it is embedded. Clearly, the movement shown by the iris,
is different in character from that of the contracting stomach or blad-
der. The same is true of the gland cell. While representing only
one type of effector, this cell appears in various forms as a unit of the
multitude of the glandular structures present in our body. Its stimu-
lation, therefore, must give rise to secretions of very different appear-
ance and composition. Thus, while it is customary to illustrate reflex
action with the help of motion, and especially with that type of it which
is caused by striated muscle, it should not be forgotten that the body
is also in a position to give a multitude of secretory responses.
The conditions met with on the afferent side of the reflex circuit,
betray a much greater diversity of structure and function. The
layman commonly states that there are five sense organs present in
our body, namely the eyes, ears, nose, tongue and skin. We shall
find, however, that these five so-called external senses are augmented
by about twenty others which are chiefly concerned with the impres-
sions brought to bear upon internal parts. It appears, therefore, that
the two effector units, the muscle and the gland cell, are opposed by
more than twenty receptors, every one of which presents very special
structural characteristics. Motion or secretion are thus given in
answer to sensory impressions received from a relatively great number
of diversified receptors.^
The Reflex Animal. — In studying reflex action, it is customary to
make use of a frog, the brain of which has been removed or destroyed
by the process of pithing. Obviously, this procedure destroys the
"psychic'"' life of this animal and renders its actions absolutely non-
volitional. An animal of this kind, therefore, is incapable of ex-
periencing pain or of receiving any other sensation in consciousness.
In the absence of the cerebrum, an afferent impulse must necessarily
remain a simple reflex sensation. The removal of the cerebral hemi-
spheres, therefore, serves the purpose of converting the frog into a
simple reflex animal.
The reflexes commonly studied subsequent to this procedure, are
those occurring in the domain of the spinal cord, i.e., the so-called
spinal reflexes. The frog is suspended from a hook passed through
its lower maxilla. The sole of the foot is then stimulated either by
1 A further discussion regarding the structure of receptors will be found upon
page 729.
I
REFLEX ACTION 585
applying the electrodes lightly to its surface or by pinching the skin
with a pair of forceps. If more convenient, the foot may be immersed
in a weak solution of acetic acid. In either case, the stimulus pres-
ently gives rise to a contraction of the muscles of the corresponding
leg which results in its withdrawal from the seat of the stimulation.
If electrical stimuli are employed, the student should sharply dif-
ferentiate between the direct effect of the current as evinced by a
twisting of the toes, and the reflex effect, consisting in a more general
muscular action and the actual withdrawal of the leg. It should also
be observed that the stimulus is applied in this case to the tactile
receptors of the skin and that the response consists in a seemingly
purposeful movement. This reaction is similar to the one occurring
in us whenever our integument is suddenly stimulated, say, in a me-
chanical way. The subsequent contraction of the musculature
necessary to perform the protective movements corresponding to
this stimulus, is non-volitional, i.e., the response is had without that
its character can be changed by the will. In many cases, of course,
we obtain a perfect sensory concept of this act, but the sensorium is
activated in this instance after the completion of the primary act
and cannot, therefore, influence the latter in any way. But if this
cutaneous stimulus is first received in consciousness and is there
subjected to volition, the resulting response ceases to be a reflex and
becomes a complex reaction.
Reflex Time. Reflex Fatigue. — The time elapsing between
the moment of the application of the stimulus and the beginning of the
response, is known as the reflex time. As is easily observed in the re-
flex frog, this factor varies with the strength of the stimulus and
•the irritability of the nervous system. It has been stated above that
a series of slight stimuli are more effective than one strong one, and
that the best results are obtained if the receptor itself is stimulated
and not the afferent path leading from it. Thus, if a tetanic current
of very moderate strength is applied to the sole of the foot of the reflex
frog, a perfectly definite muscular response is evoked, consisting in a
seemingly purposive removal of the foot from the seat of stimulation.
There is, of course, no intent present, because this result "is wholly
dependent upon the general structural arrangement of the leg. If
the intensity of the stimulus is now increased, the response follows with
the same mechanical precision, but at a somewhat earlier moment.
In other words, the reflex time is inversely proportional to the strength
of the stimulus. It is also possible to vary the reflex time by altering
the receptive power or irritability of the nervous system. Depressive
agents, such as the narcotics, lengthen it, while stimulants, such as
strychnin, oxygen, warmth, etc., shorten it.
We are thus justified in applying to reflex action such characteriza-
tions as ''subminimal reflex stimulus," meaning thereby the stimulus
which just fails to elicit a reflex response, or ''reflex threshold," indi-
cating thereby the stimulus which is just becoming effective. It
586 SIGNIFICANCE OF THE NERVOUS SYSTEM
is also evident that the repeated elicitation of a certain reflex is very
prone to lengthen the reflex time and to lessen its conspicuousness,
because the structures participating in this reaction become fatigued.
We are thus forced to recognize the condition of *' reflex fatigue," and
to admit that reflexes also possess a definite '^ refractory period."
This implies that they cannot be elicited at shorter intervals than are
required for the anaboHc changes in the different elements of the reflex
circuit.
In all these cases, the cell-body, rather than the conducting paths,
seems to be the deciding factor. It is to be noted, however, that the
reflex time includes several elements, namely, the time of conduction
of the impulse through the afferent and efferent paths, its passage
through the center and lastly, the latent period of the motor organ.
Helmholtz^ has shown that the transfer of the impulses through the
gray matter of the spinal cord consumes twelve times as long a time
as their passage through the peripheral conducting channels. The
total reflex time may thus be regarded as being composed of the
''rough" and ''reduced" reflex phases. The former includes the
time elapsing between the moment of stimulation of the receptor
and the onset of the response, and the latter, the time consumed
by the processes occurring in the center, i.e., the total time less the
time of conduction over the afferent and efferent paths and the length
of the latent period of the motor organ. Exner,^ for example, states
that the closure of the eyelids upon stimulation of the cornea (corneal
reflex) occupies 0.0578-0.0662 second. As the conduction requires
in this case, 0.0107 second, the central transfer must consume 0.0471-
0.0555 second. Listing and Vintschgau^ estimate the time of the
reaction of the iris to varying intensities of light (light reflex) at 0.3-0.4
second. The reactions accomplished with the aid of smooth muscle,
are much slower, a fact which is in keeping with the lesser irritability of
this tissue as well as of the nervous elements innervating it. This
is especially true of the sympathetic system.
Spreading or Crossing of Reflexes. — If the stimulus applied to the
foot of a reflex frog, is of slight intensity, the leg is withdrawn in a
gradual and easy manner, while if the stimulus is severe, the leg is
jerked up, and besides, the muscular contractions do not remain
confined to this limb, but spread to the muscles on the opposite side
and possibly also to those of the trunk and forelegs. This result indi-
cates that the primary afferent impulse has been transferred to other
reflex circuits, or better, that the primary reflex has led to an activa-
tion of those reflex circuits which are in functional relation with the one
involved flrst. In order to allow this spreading to take place, certain
intermediary neurons must be present, the purpose of which is to
^ Prot. der Akad. d. Wissensch., Berlin, 1845; also Fano, Arch. ital. de biol.,
xxxix, 1903, 85.
2 Pfltiger's Archiv, viii, 1874, 526.
3 Ibid., xxvi, 1881, 324.
KEFLEX ACTION
587
conduct the impulses up or down in the spinal cord. This arrange-
ment is clearly indicated in Figs. 291, 292
and 293. The first two illustrate the conduc-
tion paths required for a simple reflex in which
a single posterior extremity is involved. In
I II
Fig. 291. Fig. 292.
Fig. 291. — Schema to Illustrate Simple Reflex Conduction in the Spinal Cord.
A, The sensory impulse is immediately transferred to the motor path E.
Fig. 292. — Schema to Show Simple Reflex Conduction in the Spinal Cord.
A, The sensory impulse is transferred in the anterior horn to the motor neuron E.
this case, the impulse arriving by way of the
mediately transferred to the motor neuron in
the anterior horn of the gray matter, and
from here to the corresponding effector.
Figure 293 shows how intermediary neurons
enable the impulse to attain higher or lower
levels of the spinal cord, where connections
are formed with the motor cells and effectors
situated at a more remote distance from the
primary circuit. The spreading of a reflex to
adjoining arcs may be demonstrated in various
ways. If the leg of a frog to which a stimulus
has been applied, is firmly held in place so
that the motor effects cannot fully develop
on this side, the primary action eventually
spreads to the muscles of the opposite limb as
well as those of the trunk and forelimbs. It
is also possible to elicit this phenomenon by
stimulating the central end of the divided
sciatic nerve of one side. As this section ren-
ders the muscles of the same side functionally
useless, the afferent impulses generated at the
seat of the stimulation, find their way into
the motor paths of the opposite leg as well
as into those of the trunk and forelimbs.
In general, it may be said that reflexes may
sensory neuron, is im-
FiG. 293. — Schema to
Illustrate Reflex
Spreading in the Spinal
Cord.
A, The sensory impulse
is transferred to an inter-
mediary neuron j which
conveys it to higher and
lower motor paths E.
be made to spread (a)
588 SIGNIFICANCE OF THE NERVOUS SYSTEM
by increasing the intensity of the stimulus, and (6) by heightening the
irritabihty of the nervous structures. The latter effect may be evoked
by any agent possessing a stimulating action upon the nervous system,
such as a weak solution of the sulphate of strychnin. If this drug is
injected under the skin covering the dorsal aspect of the frog, its grad-
ual absorption finally leads to an increased susceptibility to stimuli
which is clearly betrayed by the extensive and intense muscular spasms
resulting in consequence of even the slightest possible tactile or elec-
trical stimulus. The mere touch of the plate upon which the strych-
ninized frog has been placed or a current of air blown across the surface
of its body, now suffices to throw every muscle into a state of prolonged
contraction. The explanation usually given for this effect is that the
strychnin lessens the resistance to conduction. It is said to accomplish
this, end by increasing the continuity in the synapses, i.e., it is sup-
posed to bring the axon and dendritic terminals into closer relationship
so that the impulses are enabled to spread more readily from neuron to
neuron.
Inhibition of Reflexes. — This phenomenon consists in a lessening
and final abolition of the motor response following the application
of a stimulus. It is commonly believed that this depression is brought
about by a blocking of the reflexes in their respective centers. The
impulses which accomplish this end are derived from different sources,
namely, (a) from the faculty of volition in the cerebral hemispheres,
(6) from higher reflex centers situated in the midbrain and hindbrain,
(c) from peripheral nerves, and (d) from a lessening of the irritability
of the nervous system as a whole.
Cerebral Inhibition. — It is a matter of common experience that reflexes may be
suppressed by volitional efforts. While, under ordinary conditions, a touch upon
the cornea gives rise to a quick closure of the eyelids, special efforts may be made
to overcome this stimulus. In a similar manner, we may counteract the stimulus
which ordinarily gives rise to the act of coughing or sneezing. It seems, however,
that this cerebral inhibition necessitates two conditions, namely, that the excita-
tion be of moderate intensity, and that the reflex which we endeavor to suppress,
be in functional relation with volition. It must be evident that a strong excitation
must eventually overcome even very powerful counter efforts and furthermore, as
a large number of our reactions are not under the guidance of the will at any time,
it must be clear that volitional efforts cannot be brought to bear upon them.
This exception applies especially to the motor end-organs consisting of smooth
muscle tissue and situated in the domain of the sympathetic system. Thus, we
are quite unable to inhibit vasomotor and pilomotor reactions or to vary the size
of our pupils in antagonism to the stimulations received from the retinae. This
exception is also apparent in the case of several striated muscles, because we are
unable to influence the ci*emasteric reflex and to counteract the contraction of the
muse, bulbocavernosus.
The inhibitory power of the cerebral cortex upon reflex action is well illustrated
by the changes in the "croaking reflex" of the frog occurring in consequence of the
removal of the hemispheres. Under normal conditions, this act necessitates a
certain psychic activity. ^ It is dependent upon certain elementary associations
^ Goltz, Beitrag zur Lehre von den Funktionen der Nervenzentren des Frosches,
Berhn, 1863.
REFLEX ACTION 589
and is executed volitionally. The removal of the cerebrum converts this previously
complex reaction into a pure reflex, as may be gathered from the fact that the
decerebrated frog produces this sound at any time in consequence of such cuta-
neous stimulations as the stroking of the skin of the dorsum or the application of a
gentle pressure to the sides of the abdomen. Moreover, this reflex may be repeated
almost any number of times until reflex-fatigue causes it to cease. Another ex-
periment illustrating cerebral inhibition of reflexes, is the following: When the
female frog deposits its* eggs, the male endeavors as a rule to aid its mate by
firmly clasping her abdomen with his fore limbs. This reaction on the part of the
male may be converted into a reflex by removing the cerebrum, as is evinced by the
fact that the decerebrated male rtiay be made to clasp objects of any kind by sim-
ply bringing them in contact with the ventral aspect of his thorax. In fact, it is
possible to produce this reflex even in the absence of all parts excepting the thorax
,and the two forelimbs. In the higher animals, the removal of the cerebrum
distinctly shortens the time of the spinal reflexes and leads to the appearance of
certain reflexes which under normal conditions are scarcely perceptible. Such
acts as licking, scratching, growling, etc., then assume a clear reflex character,
because the influence of volition has been permanently removed from them.
Inhibition by the Midbrain. — It has been assumed that reflex action is regulated
by a higher center which, in accordance with Setschenow,i is located in the mid-,
brain, i.e., in the optic lobes of such animals as the amphibia and reptilia. This
conclusion is based upon the observation that the removal of this part of the
nervous system shortens the time of the spinal reflexes and renders them more
vivid. The opposite effect may be produced by stimulating these bodies while
eliciting any one of the spinal reflexes. The evidence, however, seems to be against
the existence of specific inhibitory centers for reflex action. Instead, it is generally
assumed that the optic lobes (corpora quadrigemina) and other bodies, are
enabled to unfold this faculty in consequence of their connection with the chief
conducting channels passing to and from the cerebral hemispheres. In the lower
vertebrates, they are of even greater importance, because they give origin to the
optic nerves. It is only natural to suppose that the sensory impressions derived
from this source must tend to hinder simple reflex action even in the absence of
special inhibitory centers. It seems, therefore, that this form of inhibition may be
most easily explained upon the basis of a central interference of different afferent
impulses with one another.
Inhibition by Other Afferent Impulses. — It is a well recognized fact that reflexes
may be inhibited by simultaneous afferent impulses. The act of sneezing may be
suppressed by exerting a gentle pressure upon the upper lip or by rubbing the nose.
Quite similarly, a mechanical stimulus to the skin may be rendered abortive by a
second stimulus applied elsewhere to the integument. Thus, it may easily be
shown that the reflex caused by stimulating the sole of the frog's foot, may be com-
pletely inhibited by the simultaneous excitation of the central end of the opposite
sciatic nerve. In the absence of distinct inhibitory reflex centers and nerves, these
results can only be explained upon the basis of an interference of impulses, result-
ing, as has been more fully discussed above, in the ganglion cells of the reflex cir-
cuit involved in this particular act. In consequence of the refraction of the cell,
one of these impulses is rendered ineffective.
Strong and continued stimulation of sensory nerves eventually leads to a
depression and complete abolition of almost all reflexes. This condition is known
as "shock," and if the immediate cause of this depression is located in the realm
of the spinal cord, as spinal shock.
Shock.^ — A person in shock is usually found in a state of complete muscular
^ Physiol. Studien iiber die Hemmungsmechanismen, etc., Berlin, 1863. Meltzer,
The r61e of inhibition in normal and pathological phenomena of life, Med. Record,
1902.
2 Short, Lancet, 1914, and Wiggers, Am. Jour. Med. Sciences, clii, 1917, 666.
590 SIGNIFICANCE OF THE NERVOUS SYSTEM
relaxation and if movements are made, they are feeble and irregular. The
face is pale and drawn, the pupils dilated, sweating is often profuse, the reflexes are
slight, consciousness is usually present but there is a diminished sensibility and
mental activity. The respirations are feeble, irregular and sighing. The pulse is
small, frequent and dicrotic, owing to the low blood pressure. The skin is cold and
the temperature subnormal. The theories which have been brought forth in ex-
planation of this phenomenon, may be grouped as follows :
(a) Exhaustion of the vasomotor mechanism by a depression of the activities
of the center. This theory is not satisfactory because while shock commonly in-
duces a fall in blood pressure, the vasomotor center is not exhausted and the blood-
vessels may be constricted ; moreover, the heart is not seriously affected, although
its output is small.
(b) Acapnia, or deficiency in CO2, removes a most important stimulus from
different nerve centers. The breathing becomes shallow and occasional, the blood-
pressure falls and the heart beats more quickly. The objections to this theory are
many, chief among which is that shock should then be prevented by artificially
supplying CO 2, which is not the case.
((f) Oligemia, or too little blood, acts by reducing the blood pressure, but allows
the cardiac and vasomotor centers to continue their activities. Gravity shock may
be classified under this heading, because it is caused by a stagnation of blood in the
splanchnic blood-vessels and consequent inadequate filling of the heart. Thus,
when a rabbit with a large pendulous abdomen is held vertically with the head up
for any length of time, it frequently passes into the condition of shock and may die
within 20 to 30 minutes.
{d) Exhaustion of adrenin, brought about by an initial outpouring of excessive
amounts of adrenin in consequence of sensory stimulation. This finally leads
to its exhaustion.
(e) Inhibition of the activity of the nuclei of the spinal cord and midbrain.^
When such an inhibition takes place, the function of the cord is greatly diminished.
Consequently, its constituent nuclei cease sending out those impulses which main-
tain the tonus of the muscles. The blood pressure falls. Even the respiratory
center shares in the paralysis. Eventually a venous engorgement is obtained
which makes a proper filling of the heart and arterial channels impossible. Spinal
shock, however, possesses a rather local character, because it affects only those
parts of the body which lie below the seat of the spinal lesion. Under this heading
may be classified the so-called nervous shock or shell shock, as well as the shock
accompanying overdoses of anesthetics. In the latter case, however, the reflexes
reappear after the discontinuance of the narcosis, while in surgical shock they do
not.
Inhibition in Consequence of the Lessening of the Irritability of the Nervous
System. — This condition results during sleep and narcosis. The reflexes which are
abolished first, are the abdominal, cremasteric and patellar, while those from the
sole of the foot and from the nasal mucosa are more resistant. The reflexes which
disappear last are the corneal and retinal. For this reason, sleep and narcosis
may be employed as a means to determine whether or no an action is a true reflex,
because if it persists during these states of cerebral depression, it must be non-
volitional. In infants and children this weakening of the reflexes is less evident
than in adults. It need scarcely be mentioned that the intensity of the reflexes
may be made to serve as an index of the depth of the narcosis. The reactions
usually employed for this purpose are the corneal and pupillar (light) reflexes, the
danger line being reached when a mechanical impact upon the cornea very nearly
fails to elicit a contraction of the muse, orbicularis palpebrarum and when imme-
diately thereafter the pupils become constricted. A weakening and final inhibition
of the reflexes also results in coma and depressions of the nervous system resulting
iPike, Am. Jour, of Physiol., xxx, 1912, 436, and Porter and Muhlberg, ibid.,
iv, 1900, 334.
REFLEX ACTION 591
from cerebral concussion and the absorption of toxic agents, such as picrotoxin,
morphin, quinin, potassium bromid, and others.
Acceleration and Conditioning of Reflexes. — Certain conditions
may arise at times which will tend to augment reflex action in such
a degree that it becomes difficult to differentiate these responses from
those previously described under the heading of spreading of impulses.
The causes to which this acceleration may be assigned are twofold.
Thus, it may be caused either by an increase in the strength of the
stimulus or by a heightened irritability of the nervous tissue. If an
irritant is applied to the nasal mucosa of a strength just sufficient to
incite merely a slight tendency to sneeze, this primary stimulus may be
reinforced by the act of sniffing. Clearly, as this augmentation is de-
pendent upon volition, it must be attained with the help of the cere-
brum. We are also in a position to strengthen those reflexes which
ordinarily result in consequence of cutaneous impressions, either by
the appH cation of cold water or by stimuli involving the optic or
auditory mechanism. In a similar manner, the corneal reflex may be
accelerated by gently blowing a current of air across the surface of the
conjunctiva. On the whole, however, it must be conceded that reflex
acceleration cannot be effected so easily as reflex inhibition.
By far the largest number of reflexes are not conditioned. A
particular kind of stimulus gives rise to a particular reaction with
almost mechanical exactitude. This is true of coughing, sneezing,
yawning and other acts with which we are familiar. It is possible,
however, to subject these reflexes to other influences so that they
assume an elaborated or conditional character. ^ Thus, we are able to
incite a flow of saliva quite readily by the introduction of a drop of
dilute acetic acid into the mouth of the subject. If this stimulation
is repeated a number of times at intervals and if this stimulation is
accompanied by a visual impression, such as may be effected by a
receptacle fllled with colored water, the primary stimulus may be
dispensed with in time, because the retinal stimulus alone will then
suffice to produce the aforesaid result. While many of our reflexes
may be conditioned in one way or another, it is true that this cannot
be done without the help of perception. In other words, the condi-
tioned reflexes require training or education. This conversion of a
simple reflex into an association reflex, however, does not necessitate
the participation of volition; in fact, it precludes this modification
for the reason that the reflex would then lose its primitive character
and become a reaction.
Classification of Reflexes. — In accordance with their qualitative
peculiarities, reflexes are divided into:
(a) Sim-pie reflexes, in which a single muscle or glandular unit is involved. As
an example of this kind of response might be mentioned the corneal reflex. The
afferent arc is formed by the nervi ciliares trigemini and the efferent arc by the
1 Pawlow, Livre jubil. du Prof. C. L. Richet, 1912.
592 SIGNIFICANCE OF THE NERVOUS SYSTEM
orbicular branches of the facial nerve. The effector is the muse, orbicularis
palpebrarum.
(6) Complex reflexes, in which several muscles or secretory units are affected, but
the response remains perfectly co-ordinated, in spite of the fact that the effector
is now more diversified. As an example of this kind of response might be men-
tioned the patellar reflex. The stimulus is applied to the patellar ligament whence
the impulse is transferred to the sciatic center by way of the afferent fibers of this
nerve. It attains the muscles upon the anterior aspect of the thigh by way of
the efferent fibers of the same nerve (ant. crural nerve).
(c) Spreading reflexes, in which a large number of motor organs are involved.
Thus, a certain stimulus may lead to the contraction of many muscles far removed
from one another. Their action, however, remains co-ordinated.
(d) Antagonistic reflexes are made possible by the so-called reciprocal innerva-
tion, first described by Sherrington. ^ It frequently happens that the reflex activa-
tion of a certain muscle causes at the same time a lessening of the tonus of the cor-
responding antagonistic muscle. In a similar way, the relaxation of a previously
contracted muscle very frequently incites a contraction of the relaxed antagonistic
muscle. This phenomenon is most clearly displayed by the flexors and extensors
of the arms and legs, and also by the constrictors and dilators of the iris and other
reciprocating effectors. It seems, however, that this reciprocity is not dependent
upon a paired arrangement of the peripheral nerves, but upon a peculiar adjustment
of the motor centers governing the action of these antagonistic muscles. ^ Appar-
ently, their connection is such that the excitation of one motor cell causes the
activity of the other to be inhibited.
(e) Tonic and Spastic Reflexes. — The reaction following a certain stimulus is
usually prolonged, and lasts much longer than the stimulus. In many cases, in
fact, it assumes so continuous a character that it may be characterized as a true
reflex spasm. Experimentally, this peculiarity may be imparted to reflexes very
easily by the administration of small doses of strychnin or morphin. It is also a
frequent symptom of certain pathologic conditions tending to augment the ir-
ritability of the nervous system. A not uncommon reflex of this type is the condi-
tion known as blepharospasm, a tonic spasm of the eyelids.
(/) Periodic and Clonic Reflexes. — In many instances a stimulus may cause a
certain response to be repeated a number of times at regular intervals. This is
true of the acts of sneezing, coughing, hiccoughing, swallowing, the clattering of
the teeth, and trembling. The cremasteric reflex also consists of an often repeated
raising and lowering of the testicle. The same is true of the scratching reflex, and
of those which may be elicited in decerebrated cats and dogs by tickling the lateral
aspect of the abdomen. In many cases, these reactions recur at very brief intervals
and assume a prolonged or clonic character. Of especial clinical importance is the
ankle clonus, a periodic reflex which may be set up by suddenly flexing the foot
and stretching the tendo Achillis. In certain nervous diseases even the patellar
reflex may assume a clonic character.
(g) Alternating reflexes are commonly produced by an alternating activity of
antagonistic groups of muscles. Instead of one reaction, a number of them are
obtained in orderly sequence. The rocking back and forth of the head upon the
trunk may be cited as an example of this type of reflex. In decerebrated animals
certain stimuli produce at times an alternate flexion and extension (kicking) of the
two posterior extremities.
{h) Association or Perception Reflexes. — It has previously been stated that the
differential sign between a reflex and a reaction is volition. Attention has also
been called to the fact that a relatively small number of reflexes necessitate an im-
pression in consciousness, otherwise, they cannot fully develop. These actions
which skirt the realm of volition without being actually influenced by it, are desig-
1 The Integrative Action of the Nerve System, Liverpool, 1906.
2 Ewald, Pfluger's Archiv, xciv, 1903, 46
REFLEX ACTION
593
nated as perception or association reflexes. Thus, the flow of saliva or gastric
juice may be eUcited upon gaining a visual or olfactory concept of well-cooked food.
Quite similarly, the yawning reflex may be evoked in us in consequence of a visual
impression of some one else already engaged in this act ; or we may receive stimuli
tending to produce micturition at the sight or sound of running water. To this
group also belongs the act of vomiting at the sight of foul food, as well as the so-
called idiomotor movements. The latter consist in involuntary movements
executed by us in imitation of the position of other people. Thus, we may follow
the movements of a football player and find ourselves eventually in a state of
muscular contraction without actually realizing how we got into it.
38
SECTION XV
THE FUNCTION OF THE SPINAL CORD
CHAPTER XLIX
THE SPINAL CORD AS A REFLEX CENTER— ITS POWER OF
AUT03VEATICITY
Localization of the Spinal Reflex Centers. — While it is true that
the -segmentaHsm so clearly betrayed by the lower forms, is also in
evidence in the mammals, it must be admitted that it has lost much
of its original conspicuousness on account of the development of the
long conducting system and of those central complexes of. neurons
which give rise to psychic and other singular activities. In endeavor-
ing to compare the conditions found in a typical segmental or reflex
animal, such as the crayfish, with those existing in man, it may be
advantageous to begin this discussion with a general survey of the
structural and functional arrangement of the spinal paths in the
intermediate groups of animals formed by the reptilia and amphibia.
We have previously noted that a stimulus applied to the foot of a
decerebrated frog, eventually induces muscular contractions which
lead to a retraction of the leg from the seat of the stimulation (Tiirck's
method). If the spinal cord is now thoroughly destroyed with the
aid of a thin wire, it will be found that subsequent to this time the
stimulus remains absolutely ineffective. This result proves that
the destruction of the spinal cord has produced in this case a break
in the circuit of this particular reflex. Secondly, as the receptor and
effector, as well as the afferent and efferent paths, have not been in-
terfered with in this instance, the aforesaid procedure must have led
to a destruction of the center necessary for this reflex. Thirdly,
inasmuch as all other reflexes occurring in the realm of the spinal
cord, have also been abolished, the deduction may justly be made
that this part of the nervous system contains the centers for a large
number of reflex circuits and may, therefore, be regarded as an impor-
tant seat of reflex action.
We have thus established one of the two most important functions
of the spinal cord, the other being its power of conduction by means
of which the actions of peripheral parts are correlated with those of the
cerebrum and allied structures. It is probably not necessary to remind
the student of the fact that the destruction of this part of the nervous
system does not abolish all reflex action. Only those reflexes are
594
THE SPINAL CORD AS A REFLEX CENTER
595
destroyed by this procedure which are normally mediated by the
spinal cord. Thus, the large number of sympathetic responses
continue even in the absence of the cord and the same holds true of
those accomplished with the help of the cranial nerves, provided, of
course, that the region of the medulla oblongata has been left intact.
In the frog, the spinal cord extends backward as far as the ninth
vertebra, namely, to the prominence upon the dorsal aspect of its
body. The tenth vertebra, or urostyle, continues onward from here
and forms the dorsal wall of the long extended ab-
domen and pelvis. By cutting transversely across
the cord, beginning at the level of the first vetebra,
it is possible to show that the reflexes from the
hind limbs are not abolished until the level of the
cartilage between the sixth and seventh vertebrae
has been reached. Any section distally to this
point of the cord destroys the aforesaid reflexes
immediately. The conclusion must, therefore, be
made that the reflex center for the hind limbs is
situated opposite to the seventh and eighth verte-
brae (Fig. 294). It is generally designated as the
''sciatic center," because the paths which connect
it with the periphery are collected on each side in
one bundle, known as the sciatic nerve. The latter
arises by three roots and it can be shown by stimu-
lation with weak electrical currents that these
radicles possess a somewhat different function, be-
cause they innervate different groups of muscles
and thus give rise to several specific movements
of the leg. With the aid of very delicate electrodes,
it can also be proved that a similar localization of
function is present in the sciatic center itself.
This method of dividing the spinal cord at
different levels has also proved that the centers for
the muscles of the abdomen are situated anteriorly
to the sciatic center and that the center for the fore
limbs is located anteriorly to these. Several reflex
and automatic centers are also found in the me-
dulla oblongata, namely, those controlling the car-
diac, respiratory and vasomotor activities. It is evident, therefore,
that the spinal cord of the frog and allied animals contains a series of
centers for simple reflex action and that a segmentalism exists in
these animals which closely approaches that found in the vermes and
crustacese.
Spinal Reflexes in the Mammals. — If the attempt is made to
pursue similar methods of localization in the mammals, we are
immediately confronted by several difficulties, one of which is
the much greater susceptibility and sensitiveness of the nervous
Fig. 294.— Dia-
gram TO SHOW THE
Position of the Re-
flex Centers in the
Spinal Cord of the
Frog.
BC and BN,
Brachial center and
nerve; A, center for
the parts of the
trunk; SC and SN ,
sciatic center and
nerve. The num-
bers indicate the
different vertebrae.
596 THE FUNCTION OF THE SPINAL CORD
system of these animals to operative interferences. The profound
general reactions following these operations, are commonly centered in
the phenomenon of shock and the development of a hypersensitiveness
which frequently overshadows the primary effect. But while it must
be granted that the spinal cord of the higher animals does not exhibit
quite so decided a segmentalism as that of the reptiles, amphibia and
fish, it nevertheless evinces a decided tendency at locaUzation of func-
tion. Sherrington, 1 for example, has shown that the decapitated cat
reacts to stimulations of the skin either by scratching movements or
by flexion and extension of the legs. In fact, it is easily noted that a
decerebrated animal, or one in which merely a part of the cerebral
cortex has been removed, exhibits an even greater number of reflexes
than a normal animal. Quite similarly, the division of the spinal
cord at a point posterior to the nuclei of the phrenic nerves does not
materially affect the reflexes from the posterior extremities. The
patellar and other deep reflexes are not destroyed thereby.
Besides these centers which are solely concerned with reactions
of skeletal muscle, it has been proved that the spinal cord also con-
tains centers for several reflex acts of different character, as follows:
(a) Dilatation of the pupil. This center lies opposite the 1.-3. thoracic ver-
tebrae. The motor fibers leave by the anterior roots and enter the upper thoracic
nerves and the cervical sympathetic, terminating finally in the ganglion cervicale
superior.
(6) The center for defecation, or centrum anospinale, is situated opposite
the fifth lumbar vertebra (dog). The afferent path is formed by the plexus
hemorrhoidalis and the efferent path by the nervus hypogastricus.
(c) The center for micturition, or centrum vesicospinale, is situated in the
lumbar or sacral segment of the spinal cord. The nervi hypogastrici and erigentes
constitute the efferent path.
(d) The centers for the erection of the male and female generative organs are
situated in the lumbar portion of the cord. The arteria profunda penis is inner-
vated by the vasomotor fibers of the 1.-3. sacral nerves, while the 3. and 4. sacral
nerves activate the muse, ischiocavernosus and transversus perinei profundus.
{e) The center for ejaculation is also placed in the lumbar segment of the
cord.
(f) The center for the contraction of the uterus is located in the lumbar seg-
ment of the cord.
{g) The centers in the bulbar enlargement of the cord, i.e., in the medulla
oblongata, regulate the activity of the heart, the respiratory movements, the cali-
ber of the blood-vessels, deglutition, reversed deglutition or vomiting, heat dissi-
pation, and other functions.
In view of this rather well marked segmentalism, it cannot be
denied that the spinal cord of the higher animals possesses a functional
arrangement very similar to that present in the lower forms. It is an
important seat of reflex action. But, inasmuch as the cerebrum gradu-
ally gains a more complete control over these simple functions,
the spinal centers lose their independency of action. This is especially
true of man, because, somewhat contrary to the results obtained in the
dog, cat and rabbit, the complete division of the spinal cord is followed
^ Jour, of Physiol., xxxviii, 1909, 375.
THE SPINAL CORD AS A REFLEX CENTER 597
in this case by an abolition of the reflexes and a general loss of irrita-
bility of the nervous structures situated posterior to the cut.^ A
partial division of the cord, however, is often recovered from without
permanent loss of function.
In this connection, brief reference should also be made to the ex-
periments of Goltz,^ purposing to arrive at a definite conclusion re-
garding the function of the spinal cord by the method of total or partial
extirpation. In the mammals, the former procedure is not feasible,
for the reason that the phrenic nerves take their origin from its cervical
portion. Any interference with the phrenic nuclei would cause a
stoppage of the respiratory movements. Goltz, therefore, removed the
cord merely as far as its upper thoracic segment, special care being
taken to protect these animals against an undue loss of heat and other
injurious influences. Those surviving the operation, showed a com-
plete motor paralysis which eventually gave way to an atrophic condi-
tion of these parts. They also exhibited a complete sensory anesthesia,
and although their vasomotor and other autonomic functions remained
depressed for some time after the operation, the vascular tonus re-
appeared in a large measure. In addition it was noted that the
ordinary pelvic reflexes again assumed their original qualities. These
results indicate very clearly that the sympathetic system is relatively
independent of the spinal cord and other parts of the central nervous
system, because the digestive, secretory, circulatory and. excretory
organs eventually regained their functions after the destruction of the
cord. Various other symptoms, however, such as a gradual lowering
of the body temperature and a very decided loss of adaptation of the
parts formerly innervated by the destroyed portion of the cord, sug-
gested that the animal was no longer able to influence its autonomic
organs and to correlate their functions with those of other structures.
The Automatic Activity of the Spinal Cord. — Having established
the fact that the spinal cord is an important seat of reflex action, it
should be noted that several of the centers situated within the domain
of the cord and bulb, are automatically active. Admittedly, an auto-
matic action finds its origin neither in volition nor in sensory impres-
sions of the ordinary intermittent type. Its cause must rather be
sought in an '4nner'' stimulus which arises in consequence of constant
and specific stimulations and renders the center self -inducing. The
question of whether the centers of the spinal cord possess automatic
qualities, must be answered in the positive and especially if the medulla
oblongata is taken to be a part of this structure. Thus, it is a well
known fact that the cardiac, respiratory and vasomotor centers are
composed of cellular elements which generate impulses rhythmically
in consequence of inherent stimuh. While it is entirely probable that
the centers situated in the more posterior segments of the cord
possess a much slighter automatic power than those just mentioned,
it must nevertheless be admitted that they generate impulses at regular
1 Collier, Brain, 1904, 38.
2 Pfluger's Archiv, Ixviii, 1896, 362.
598 THE FUNCTION OF THE SPINAL CORD
intervals. Moreover, as these impulses are intended merely to produce
a tonic setting of the peripheral musculature, the aforesaid spinal
centers may be said to be tonically automatic, in contradistinction
to the bulbar centers, which may be considered as being rhythmically
automatic.
It must be admitted, therefore, that the ganglion cells composing
these centers are in a state of constant tonic activity. This implies
that they produce ''subthreshold" impulses at regular intervals
which tend to retain the effector in a condition of functional alertness
ready at any time to yield maximal effects. Conversely, it may be
concluded that the loss of these impulses must diminish the tonus
of the effector and induce atrophic changes. You will have noticed
that the legs of a decerebrated frog, suspended from a hook, assume a
definite position of flexion, because the muscles are still in connection
with the motor cells of the cord. If one of the sciatic nerves is now
cut, the muscles on the side of the lesion immediately relax and allow
the leg as a whole to assume a more dependent position. In view of
the fact that these changes cannot be observed in a reflex frog after the
skin has been removed or after the posterior roots of the spinal cord
have been divided, it has been assumed that the tonic automaticity of
the spinal ganglion cells is due to a constant influx of subminimal
sensory impulses from the cutaneous receptors. In other words, it
is assumed that the ''inner stimulus" imparted to the motor cells of
the cord, finds its origin in sensory impulses of such slight intensity
that they cannot incite muscular contraction. Hence, the tonus
of a muscle is really a subminimal reflex phenomenon. The inherent
or inner stimulus upon which the automatic power of a nerve cell
depends, may thus be referred to subminimal sensory stimuli.
Superficial, Deep, and Organic Reflexes. — In man, the spinal
cord aids in the production of a number of reflexes which possess a
very distinctive character and may on this account be employed for
purposes of diagnosis. Among the superficial or skin reflexes may be
mentioned the:
(a) Cremasteric Reflex. — This reaction is elicited best by gently rubbing across
the inner aspect of the thigh. It consists in a raising of the scrotal sac and testicle
in consequence of the contraction of the muse, cremaster.
(6) Scrotal Reflex. — It presents itself as a contraction of the tunica dartos in
consequence of an excitation applied to the skin of the scrotum.
(c) Sternal and Abdominal Reflexes. — These reactions may be evoked by rapidly
drawing the blunt end of a rod-like instrument across the external surface of the
chest or abdominal wall. It consists in a contraction of the neighboring muscles.
(d) Scapular Reflex. — It results in consequence of excitations of the skin in
the vicinity of the spinal column. The muse, rhomboidei contract.
(e) Pharyngeal Reflex. — The touching of the posterior wall of the pharynx
incites a contraction of the muscles lining this passage.
(/) Mammillary Reflex. — The stimulation of the integument in the vicinity of the
nipple is followed by an erection of the papilla.
(g) Gluteal Reflex. — The muse, gluteus maximus contracts in consequence of
stimuli applied to the skin covering the buttocks.
THE SPINAL CORD AS A REFLEX CENTER 599
(h) Plantar Refiex. — It consists in a flexion of the toes in consequence of tactile
stimulation of the sole of the foot. In certain affections of the pyramidal tracts
of the cord, this stimulation elicits an extension of the great toe, instead of a flexion.
This constitutes the so-called Babinski phenomenon.
(i) Bulbocavernosus Reflex. — This muscle may be made to react to stimuli
applied to the glans penis.
(j) Reflexes from the mucosa may be elicited by stimulation of different mucous
surfaces.
(k) Winking Reflex. — The eyelids are closed if a stimulus is applied either
to the cornea, conjunctival membrane or skin covering the eyelids.
(Z) Reflexes from the Facial Muscles. — These responses are obtained by stimu-
lating the skin in vicinity of these muscles.
Among the so-called deep reflexes, i.e., reflexes which are elicited by stimula-
tions of the tendons, ligaments and periosteum, may be mentioned the :
(a) Patellar Reflex or Knee-jerk.^ — A sHght stroke upon the ligamentum patellae
produces a contraction of the muse, quadriceps femoris, involving especially the
muse, vastus medialis and vastus intermedins. The best results are obtained if
the muscle is first put under a slight tension which end can readily be attained by
crossing the knees or by sitting upon a chair or table and permitting the leg to
hang free across its edge.
(b) Achillis Jerk. — If the foot is placed in the position of dorsiflexion, a tap
upon the tendo calcaneus (Achillis) evokes a contraction of the muse, gastrocne-
mius and plantar flexion of the foot. The so-called ankle clonus is obtained if
the foot is quickly flexed so that the tendo Achillis and muse, gastrocnemius are
suddenly stretched. In certain nervous disorders this reaction acquires a periodic
character.
(c) Wrist Jerk. — This reflex is obtained by tapping the tendons of the muscles
of the forearm. Similar effects are yielded by the muse, gracilis, semitendinosus,
triceps and biceps.
{d) Jaw Jerk. — The jaws are closed if the lower jaw is tapped when in the
half -open position.
(e) Periosteal Reflexes. — The muse, supinator longus and biceps contract if the
head of the radius is tapped upon.
(/) Tensor Tympani Reflex. — The muse, tensor tympani contracts as a result of
sound impacts of high pitch. The ear drum is in this way rendered more tense.
The organic or visceral reflexes have been enumerated in part above. They
include those pertaining to micturition, defecation and the sexual activities. They
are executed chiefly with the help of smooth muscle and glandular tissue, while
the superficial and deep reflexes are largely concerned with striated muscle.
The Nature of the Patellar Reflex. — While the question whether
or no the knee-jerk is a true refliex, has been decided in favor of the
first view, this decision has not been reached without considerable
discussion. To begin with, it was thought that it could not be a
true reflex, because the time interposed between the stroke upon the
patella and the contraction of the muse, quadriceps, is altogether
too short to permit of the passage of the impulse through the spinal
cord. This view was based upon the early calculations of the speed
of the nerve impulse which, in accordance with Helmholtz, amounts
to 33 m. in a second in warm-blooded animals. It was believed,
therefore, that the sensory impulse does not enter the spinal center
at all, but is transferred to the muscle by way of a peripheral collateral.
If this conception were correct, the patellar reflex should really be
^ Discovered by Erb, Archiv ftir Psychiatric, v. 1875; and Westphal, ibid., 1875.
600 THE FUNCTION OF THE SPINAL CORD
regarded as a pseudo or axone reflex, i.e., as one which is had without
the intervention of the cell-body or center. In other words, the im-
pulse set up in the receptor, passes no farther than the next collateral,
where it finds a direct course to the effector. This explanation,
as has just been stated, was intended to bring the extremely brief time
of the patellar reflex into relation with the speed of the nerve impulse,
as determined by the older methods. Applegarth, for example, has
stated that the patellar reflex time is 0.014-0.02 sec. (dog), while
Waller and Gotch found it to be 0.008-0.005 sec. (rabbit). Later on,
however, it has been shown by means of the string galvanometer,
that the speed of the nerve impulse in warm-blooded animals may
amount to more than 100 m. in a second. In addition, Snyder^ and
Hoffmann^ have ascertained that the patellar reflex time lies somewhere
between 0.0113 and 0.024 sec. These figures, therefore, prove very
conclusively that the patellar reflex must involve the spinal center;
at least, the time allowed for it is sufficient to complete the entire
circuit from the ligament to the cord and back again to the muscle.
The objection has also been raised that the contraction of the
muse, quadriceps is a simple twitch and not a tetanus, as is usually
the case when muscles are activated reflexly. Much has also been
made of the fact that the aforesaid muscle reacts best when subjected
to a slight tension. It has been found, however, that not all muscular
responses are tetanic in their character. Sherrington,^ for example,
has called attention to the fact that the so-called ''extensor thrust"
which may be obtained in animals by suddenly pressing upon the
plantar surface of the hind foot, consists of simple contractions of the
extensor muscles of the hind leg. Lastly, it has been proved that
any injury to the lumbar segment of the spinal cord destroys the
patellar reflex and that its abolition may also be effected by dividing
either the posterior or the anterior roots of the cord. Obviously,
therefore, the production of the patellar reflex necessitates not only
an intact spinal center but also intact centripetal and centrifugal
paths. Its reflex nature, therefore, seems to be thoroughly established.
A similar controversy has led to the establishment of the fact that the
Achillis jerk is a true reflex.
Reinforcement of Reflexes.^ — In testing the different reflexes, it
soon becomes apparent that the subject must remain in a state of perfect
inattention, otherwise the response will be less intense, or may, in
fact, be entirely abolished. In other words, if the attention of the
subject is directed to the procedure of eliciting the reflex, the usual
result is its inhibition by the cerebral centers. In this way, a diagnosis
of abolition of reflexes may be made which in reality is nothing more
than a normal phenomenon. This diflftculty may be easily overcome
1 Am. Jour, of Physiol., xxvi, 1910, 474.
2 Archiv fiir Physiol., 1910, 223.
3 Jour, of Physiol., xxxviii, 1909, 375.
^ First observed by Jendrassik in 1883.
THE SPINAL CORD AS A REFLEX CENTER 601
if the subject is asked to engage in some mental process while the
stimulus is brought to bear upon his integument or tendons. The
reflexes may also be augmented by asking the subject to make a voh-
tional muscular effort at the time the blow is struck. This requires a
certain mental concept and it is conceivable that the activation of the
cerebrum temporarily abohshes its inhibitory power, and thus dimin-
ishes the resistance along the different reflex circuits. Under ordinary
conditions, the patellar reflex may be heightened very materially by
simultaneously contracting bhe muscles of the hands or by endeavoring
to pull the interlocked fingers apart. But, while we are able in this
way to intensify a feeble j erk, no effect can be produced after the reflex
has been aboUshed by disease.
This phenomenon which is usually described as reinforcement of
reflexes,^ also permits of a second explanation. It is commonly
recognized that the functional activity of one part of the nervous
system also influences the irritability of others. Thus, it may rightly be
assumed that the activation of the cerebrum, accompanying such
actions as the interlocking of the hands or fingers, renders this organ
more irritable. The motor impulses thus generated in its cortical
area, escape through the descending columns of the cord, where they
skip to neighboring columns and nuclei and give rise to a general
activity of these nervous elements. In other words, the constituents
of the spinal reflex circuits are sensitized by an overflow of the cerebral
impulses. It is quite impossible at this time to decide definitely
which of these two theories is the more correct. Obviously, the first
more closely agrees with the common phenomenon of inhibition of
reflexes by the cerebral centers, while, the second introduces a rather
new factor in the form of an activation of certain parts of the nervous
system which he at some distance from the seat of the primary process.
It should also be noted that the reinforcement does not develop
if the interval of time between the simultaneous effort and the excita-
tion is too long. Thus, it has been shown by Bowditch and Warren ^
that the knee-jerk suffers its greatest augmentation if the blow upon
the tendon precedes the reinforcing action by less than 0.6 to 0.9
sec. A greater interval will tend to minimize the reinforcement until
it eventually gives way to an inhibition. This diminution of the reflex
in consequence of a premature simultaneous eft^ort is designated as
negative reinforcement.
Abolition and Exaggeration of the Reflexes. — With few exceptions,
reflexes may be regarded as a safe index of the relative state of irrita-
bility of the nervous system, provided, of course, that the method of
stimulation is free from error. But even a perfectly normal body
undergoes diurnal and seasonal changes which reflect their influences
upon reflexes. Thus, we find that they are weakened during sleep and
other states of mental rest ; in fact, some of them are abolished entirely
^ Mitchell and Lewis, Am. Jour, of the Med. Sciences, xlii, 1886, 363.
2 Jour, of Physiol., ii, 1890, 25.
602 THE FUNCTION OF THE SPINAL CORD
during these periods. Conditions of mental excitement and general
neurasthenia, on the other hand, increase them very markedly.
While one or the other of the reflexes enumerated previously may
be absent in a perfectly healthy person, their general abolition sug-
gests in most cases a pathological lesion of some kind. This defect
may be restricted to a particular reflex circuit or may involve more
extensive areas of the nervous system. In the first instance, the break
must have occurred at some point of the reflex arc which now fails to
respond even on reinforcement, while, in the second instance, a more
general or central depression of the nervous system must have re-
sulted. In illustration of the first condition might be mentioned the
loss of a particular superficial or deep reflex of the spinal cord in con-
sequence of acute anterior poliomyelitis which infection destroys
the motor cells in the anterior horn of the gray matter. Reference
might -also be made to tabes dorsalis in which affection the posterior
root terminals in the cord are destroyed, thereby causing a break in the
central distribution of the analyzer. Among the general depressions
of the nervous system producing diminution or abolition of the spinal
and other reflexes, might be mentioned increases in intracranial pres-
sure, such as result in hydrocephalus or in consequence of cerebral
tumors. They are also abolished for a time in comas and epileptic
seizures and certain febrile reactions, such as pneumonia.
Reflexes are said to be exaggerated when the slightest possible
stimulus elicits an unusually brisk motor response. This is a common
phenomenon in simple neurasthenia and hysteria and other conditions
in which the irritability of the nervous system has been increased in
consequence of the absorption of various poisons, such as the products
of intestinal fermentation, strychnin, caffein, thebein, and others. In
many cases the reflexes are then augmented into clonic contractions
which are maintained until the tension upon the tendon is again re-
leased. Clearly, therefore, the presence of a true clonus^ implies that
the reflex arcs are in a state of hyperirritability. In this connection,
brief reference should also be made to the fact that the exaggera-
tion of the spinal reflexes constitutes a cardinal sign in chronic affec-
tions involving the motor neurons of the cerebrum. In general, it
may be said that a ''high'' (cerebral) lesion leads to an exaggeration
and a ''low" (spinal) lesion to an abolition of the reflexes. It cannot
surprise us, therefore, that an affection of the motor areas and pyramidal
tracts is generally associated with clonic contractions. As typical
examples of this condition might be mentioned hemiplegia from organic
brain disease, or paraplegia due to myelitis. Incomplete transections
of the cord, as often result in fractures of the spine, produce exagger-
ated reflexes, while complete transections are usually followed by a
loss of the deep reflexes.
These differences may be explained in the same way as the phe-
^ Spurious clonic reflexes are obtained at times in hysterical conditions. They
are usually irregular and poorly sustained.
THE SPINAL CORD AS A CONDUCTING PATH 603
nomenon of reinforcement of reflexes. Thus, we may assume that a
''high'' lesion tends to remove the central inhibition and to cause a
''Bahnung" of the reflex circuits, or, that a ''high" lesion gives rise to
an increase in the irritability of central parts which in turn induces
a similar condition in other divisions of the nervous system. In
brief, we may explain this phenomenon either upon the basis of removal
of cerebral inhibition or upon the basis of an overflow of irritability
from this organ. At all events, the facilitation of the spinal reflexes
in consequence of central lesions, finally throws the paralyzed muscles
into a state of continued contraction or contracture, their spastic
rigidity eventually leading to contortions of the extremities. But
a paralysis of the muscles is also present in "low" lesions, because
these organs then lose the volitional and tonic impulses from the spinal
centers. In the latter case, however, the muscles remain in a perfectly
flaccid condition and finally undergo atrophic changes from disuse.
These differences in the intensity of the reflexes and in the behavior
of the muscles are usually so typical that they may be employed in
ascertaining the exact location of the lesion.
CHAPTER L
THE SPINAL CORD AS A CONDUCTING PATH— ITS
TROPHIC FUNCTION
The General Structiire of the Spinal Cord. — We have previously
noted that the spinal cord in the invertebrates consists of a series
of ganglia which severally regulate the activities of those segments
of the body to which they have been apportioned. In further develop-
ment of this simple reflex system, the different ganglia have been con-
nected with one another and with the head-ganglion by means of a
system of afferent and efferent fibers which pursue a course parallel
to the longitudinal axis of the body. This primitive segmental
arrangement is also in evidence in the vertebrates, with this modifica-
tion, however, that the reflex functions no longer exhibit a strictly
local character but are now more closely correlated and subordinated
to the activities of the higher centers. This change necessitates first
of all the development of a system of conducting paths which connect
the different spinal centers with one another, and fuse them into a har-
monious whole. In the second place, it necessitates the formation
of certain conducting paths which connect these simple centers with
those situated in the brain. In this way, two types of conducting chan-
nels have been formed, namely, the short and the long. The former
represents the more primitive reflex system over which eventually the
604
THE FUNCTION OF THE SPINAL CORD
long reaction system has been constructed. For this reason, it may be
stated that reflex action is a more primitive function than the type of
conduction seen in the higher animals. But, while the spinal cord of
the latter has lost much of its simple reflex character, it cannot be
denied that it still displays it in a clearly recognizable manner. Thus,
we have seen that this structure contains a series of centers for super-
ficial, deep and organic reflexes, and that the location of these centers
roughly corresponds to the seats of these
actions, i.e., they are arranged in accord-
ance with a definite segmental pattern.
In addition, the succeeding discussion will
show that this segmentalism and dissocia-
tion of function has also entered into the
construction of the conducting paths.
295. — The Membranes of the
Spinal Cord.
1. Dura mater. 2. Arachnoid.
3. Posterior root of spinal nerve.
4. Anterior root of spinal nerve. 5.
Ligamentum dentatum. 6. Linea
splendens. {After Ellis.)
Fig. 296.- — Transverse Section
through the region of the fourth
Cervical Vertebra.
F, Body of vertebra; B, verte-
bral blood-vessels; N, spinal nerve;
RC, ramus communicans; S, spinal
ganglion; A, subarachnoidal space
investing spinal cord.
The spinal cord of man appears as a cylindrical structure which extends into
the vertebral canal for a distance of 40-45 cm., i.e., to the level of the second or
third lumbar vertebra. Beyond this point it continues as a narrow thread, called
the filum terminale. It measures 12 mm. in diameter and weighs 42 grams.
From it arise thirty-one pairs of nerves, in serial order so that each pair corre-
sponds to a vertebra and innervates symmetrical areas upon the two sides of the
body. The spinal nerves are mixed nerves, i.e., they consist of afferent and efferent
fibers connecting central parts with their respective receptors and effectors. It is
to be noted, however, that they do not arise as such directly from the cord, but
originate as two compact bundles, one of which lies in close relation with the an-
terior and the other with the posterior aspect of this structure. The former
constitute the anterior (ventral) root and are efferent in their nature, while
the latter form the posterior (dorsal) root and conduct only in an afferent direction.
These two groups of fibers are joined in the intervertebral foramina, their point
of union being roughly marked by a ganglion composed of the cell-bodies belonging
to the sensory fibers of the posterior root. The nerves which are distributed to
THE SPINAL CORD AS A CONDUCTING PATH
605
the arms and legs arise from the lower cervical and lower lumbar regions respec-
tively. It is for this reason that these particular segments of the cord are some-
what broader than the others, and present an elliptical outline, whereas the dorsal
region is almost circular.
In cross-section the spinal cord is found to be composed of a central mass of
gray matter which is surrounded on all sides by a shell of white matter. The
former appears on each side in the form of a crescent, the convex surface of which
is turned inward and is joined with the one in the opposite half of the cord by a
transverse band or commissure. The entire mass of gray matter roughly exhibits
the shape of the letter H, and is divided on each side into an anterior or ventral
and a posterior or dorsal horn, the intervening substance being known as the
intermediate gray matter. The anterior horn is short and bulky, while the
posterior horn is narrow and slender, extending to fhe surface of the cord where it
Dorsal median septum
Septum
Dorsal lateral groove
Dorsal nerve root
Substantia gelatinosa
Root-fibers entering
gray matter
Processus reticularis
Central canal
Nucleus from which \i
motor fibers for mus-
cles of upper limb arise
Ventral white commis-
Ventral nerve root
Ventral median fissure
Fig. 297. — Cross-section through the Human Spinal Cord at the Level, of the
Fifth Cervical Nerve, Stained by the Method of Weigert-Pal, which Colors the
White Matter Dark and Leaves the Gray Matter Uncolored. {From Cunning-
ham's Anatomy.)
is invested by the substantia gelatinosa. The latter is known as the caput cornu
posterioris. In the lower cervical and thoracic regions, the intermediate gray
matter becomes unusually prominent and forms here the so-called lateral horn.
The center of the commissure uniting the right and left halves of the gray matter,
is occupied by a canal (0.5-1.0 mm. in diameter) which extends throughout the
entire length of the cord, and eventually communicates with the lymphatic spaces
of the brain. This is the remains of the primitive neural canal of the embryo.
It is surrounded by substantia gelatinosa and its walls are lined with cylindrical
epithelium. It is j&lled with liquor spinalis, a lymphatic fluid of the same char-
acter as the liquor contained in the cerebral spaces.
The white matter of the spinal cord is made up of different bundles of sensory
and motor fibers which are arranged in such a way that they fill in the different
spaces externally to the gray matter. They are medullated, but possess no
neurolemma and run within tubes formed by the supporting neuroglia tissue. In-
asmuch as the entire mass of the spinal cord is divided into two halves by the ante-
rior and posterior median fissures, the white matter of each side presents itself in
606 THE FUNCTION OF THE SPINAL CORD
three columns or funiculi, namely: (a) one situated between the anterior furrow
and the anterior horn of the gray matter, (6) one neighboring upon the lateral
surface of the gray matter and (c) one located between the posterior fissure and
the posterior horn of the gray matter. We shall see later on that the anterior,
lateral and posterior funiculi are in turn made up of several tracts or fasciculi
which are anatomically and functionally distinct from one another. It is also to
be noticed that the median fissures do not extend directly to the commissure of
the gray matter, but permit bridges of white matter to intervene. These are the
so-called anterior and posterior commissures. The fissures themselves contain
a process of the pia mater which invests the external surface of the cord, and,
together with the arachnoid and dura mater, forms a protective envelope for this
structure.
The Functional Basis of the Gray Matter. — The gray matter
consists of the supporting neuroglia in which are imbedded numerous
cell-bodies and the beginning portions of their processes. The former
appears as a felt-like network of fibers with scattered nuclei. Around
the central canal and in the vicinity of the entrajice of the posterior
root, these reticular spider-shaped
cells are especially small and nu-
merous, forming here the so-called
substantia gelatinosa of Rolando.
The nerve cells of the spinal cord
are very numerous and exhibit a
variety of shapes and sizes. It
should also be noted that they oc-
cupy definite areas of the gray
matter and extend as distinct colo-
FiG. 298.— A Neuroglia-cell. Isolated nies for some distance up and down
IN 33 Per Cent. Alcohol. (Quain.) in the cord. In the anterior horn,
where they are especially promi-
nent, they are arranged in three groups. The median group is situ-
ated near the middle Une and its axons may be traced across to the
other side through the anterior commissure of the white matter. The
anterior group consists of large multipolar cells, the axons of which
pass outward in the anterior roots of the cord and are distributed
eventually to the different effectors of the spinal system. Some of
these cells, as we shall see later, send their axons into neighboring
sympathetic gangUa and thus form the efferent bridges between the
cerebrospinal and sympathetic systems. The aforesaid cells are es-
pecially numerous in the cervical and lumbar segments of the cord
which, as we have seen above, innervate the anterior and posterior
extremities. The posterior group of cells is present in those regions
of the cord in which the lateral horn is well developed. A very promi-
nent column of cells also extends through the dorsal and inner area
of the cord near the base of the posterior root. These cells begin at
the level of the seventh or eighth cervical nerve and reach downward
as far as the second or third lumbar nerve. They are most conspicuous
in the thoracic region, their large bodies being elongated in the longi-
THE SPINAL CORD AS A CONDUCTING PATH 607
tudinal axis of the cord. Their axons tend obhquely outward into
the so-called direct cerebellar tract of the lateral white matter. Some
of these processes also pass into the fasciculi next to the posterior
median fissure. Posterior to this group of cells, constituting the
so-called Clarke's vesicular column, we find a few ceils distributed
in an irregular manner through the posterior horn. The cells of the
sensory fibers forming the posterior roots, are, of course, situated
outside the cord, in the spinal ganglia.
When considered from the standpoint of gross and minute anatomy,
the white matter of the spinal cord presents itself as three funiculi
which in turn are divided into several fascicuh. The physiologist,
however, is more directly concerned with the function of these col-
lections of nerve fibers and hence, his unit is the tract, i.e., bundles
of fibers possessing an identical action. But as several of these
tracts have clearly defined anatomical boundaries, these terms are
frequently used interchangingly. As far as the cells of the gray
matter are concerned, is is important to determine the tracts to which
Fig. 299. — Spinal Ganglion op an Embryo Duck; Composed of Diaxonic Nerve-cells.
{van Gehuchten.)
these cells are functionally related. Upon this basis we may divide
them into two main groups, namely, local and general. As the former
are intended to establish a close relationship between the cells situated
in different parts of the gray matter and at different levels of the cord,
they are associative (tautomeric) or commissural (heteromeric) in
their nature. In this class should be placed the cells of Clarke's
column, because they are tributary elements to the direct cerebellar
and posterior tracts. The same is true of the cells of the median
group, because they send their axons across the middle line to the
opposite gray matter and thus become commissural in their nature.
Another type of associative cell is the cell of Golgi which is found
chiefly in the posterior horn. Its axon does not pass far away from
the cell-body, but ramifies extensively to establish connections with
neighboring cells at any level of the cord.
The group of the general cells is made up of those cells which are
concerned with bringing the cord into relation with the higher centers
as well as with the peripheral end-organs. Chief among these
are the large ganglion cells in the anterior horn, measuring 57
608 THE FUNCTION OF THE SPINAL CORD
to 135iu. They are efferent in their nature and innervate the skeletal
musculature. Second in importance are the somewhat smaller cells
of the lateral horn, the axons of which leave the cord by way of the
anterior roots but finally separate to enter the sympathetic ganglia.
In this way, the white ramus communicans is formed, constituting
one of the efferent bridges between the cerebrospinal and sympathetic
systems. As has been stated above, the afferent cells of the cord are
contained in the spinal ganglia which are situated upon the different
posterior roots. Other afferent cells of the projection system form the
nucleus gracilis and cuneatus, the end-stations of the posterior fasciculi.
Fig. 300. — Spinai< Ganglion-cells showing Transition from Bipolar to Unipolar
Condition. (Holmgren.)
The Functional Basis of the White Matter — The characteristic
appearance of the gray matter and white matter is dependent upon
certain structural differences. The former is composed principally
of cell-bodies and the dendrites and axons in their immediate vicinity,
while the latter consists chiefly of axons enveloped in their medullary
sheaths, in other words, of nerve fibers. It is evident that the white
matter decreases constantly in the direction toward the tip of the cord,
because the number of fibers still retained at its lumbar level is much
smaller than that near the medulla. Fibers leave this structure all
the time to reach peripheral parts, and fibers enter it continuously to
attain the higher centers. This does not imply, however, that there
is an absolute proportion between these fibers and the total area of the
white matter at different levels of the cord, because a large number of
them do not pass all the way through, but form merely local reflex
connections. In addition, it should be noted that the relative amounts
of gray and white matter vary at different levels of the cord, thereby
enabling us to determine with accuracy from what particular area any
given section has been taken. Sections from its lumbar region are
characterized by a copious amount of gray matter, while those from
its cervical portion are relatively poor in this substance. Besides, as
especially large numbers of fibers arise in its cervical and lumbar seg-
ments at the points of origin of the plexuses of the arms and legs, the
total cross-area of the cord must be markedly increased at these levels.
The posterior roots serve as points of entrance for about half a
million fibers and we may assume that an equal number leaves by
way of the anterior roots. The afferent impulses which are in this
THE SPINAL CORD AS A CONDUCTING PATH
609
way poured into the central nervous system are of different kinds and
may either remain within the domain of the cord or may be conveyed
onward to higher centers. The same holds true of the efferent im-
pulses. While some of them arise in the brain and neighboring parts,
some also originate in the motor cells of
the cord itself Obviously, therefore, the
conduction system of the cord is arranged
in the form of a long or projection system
and a short or reflex system. The latter
is the more primitive, and hence, we find
that it occupies a position next to the
gray matter, while the projection paths
correlating peripheral parts with the
brain, form the external shell of the
spinal white matter.
The axons of the nerve cells uniting
these widely separated portions of the
nervous system, are of different lengths.
It is said that the motor neurons in
the anterior horn of the spinal gray
matter reach all the way to the periphery
and attain a length of 1 .0 m. The same
holds true of the motor cells of the cere-
bral cortex, the axons of which terminate
low down in the cord. In many cases,
however, two or three neurons are re-
quired to cover a distance of only a few
centimeters. In adult life, the axons of
the spinal white matter are surrounded
by medullary sheaths but not by neuro-
lemma. They differ, therefore, in this
regard from ordinary nerve fibers. They
are of different size and give off small
collaterals which connect with the gray
matter at different levels of the cord.
Externally, they are invested by a tube
formed by neuroglia tissue.
The Methods Used for the Localiza-
tion of Spinal Conduction. — We have
previously seen that the white matter of
the cord is arranged as anatomically dis-
tinct bundles. The question may now
be asked whether these morphological
units also represent physiological entities. In other words, can it be
proven that the different fasciculi possess a different origin and desti-
nation so that their direction of conduction assumes a specific char-
acter? While the investigations pertaining to this topic cannot be
Fig. 301. — Sections thkough
DiFFEEENT REGIONS OF THE SpINAL
Cord.
A, At the level of the sixth cer-
vical nerve; B, at the mid-dorsal
legion; C, at the center of the
lumbar enlargement; D, at the up-
per part of the conus medullaris.
1. Posterior roots. 2. Anterior
roots. 3. Posterior fissure. 4.
Anterior fissure. 5. Central canal.
(After Schwalbe.)
610
THE FUNCTION OF THE SPINAL CORD
regarded as at all complete, the material already at hand suffices to
show that the spinal cord contains definite tracts which in the main
correspond with the anatomical grouping previously discussed. The
methods employed to trace the course of these different neiu-on sys-
tems are as follows:^
(a) Morphological. — Different procedures] of staining have been made use of
in order to differentiate the cell-bodies and their processes more clearly from the
surrounding tissue. The impregnation procedures of Weigert and Golgi consist
in hardening the preparation in chromate or bichromate and subjecting it subse-
quently to a solution of silver nitrate or mercuric chlorid. The silver or mercuric
chromate precipitates are not diffuse, but are restricted to certain parts of the
neuron and may be bleached sufficiently to allow the tracing of the processes in
Fig. 302. — Schema of the Tracts in the Spinal Cord, (KolUker.)
g, Fasciculus gracilis; b, fasciculus cuneatus; pc, fasciculus cerebrospinalis lateralis;
pd, fasciculus cerebrospinalis anterior; /, fasciculus cerebellospinalis; gr, fasciculus
anterolateralis superficialis.
rather thick sections. Ehrlich has advocated the intravitam staining with methy-
lene-blue.
The method of differential staining is frequently employed as a means of
recognizing medullated and non-medullated nerve fibers. It has been pointed out
by Flechsig that the newly-formed axons are non-medullated, but acquire a sheath
when developed sufficiently to become functional. Now, as the different parts of
the nervous system attain their full development in a definite sequence, it cannot
surprise us to find that the myelination of the various fiber groups takes place
successively and at certain intervals from one another. Moreover, as the projec-
tion system is the most recent acquisition of the nervous system, we are justified in
assuming that the pyramidal tracts, connecting the cerebrum with the cord, re-
^ Galenus compared the spinal cord to a stream which distributes nervous energy
to all parts of the body. Oribasius describes the effects following sections of the
cord. These are also discussed in the writings of Hippocrates.
THE SPINAL CORD AS A CONDUCTING PATH 611
ceive their medullary coverings last of all. In this assumption we are correct,
because the myelination of these fibers is not completed until the first month after
birth. Next in order follow those fibers which connect the cerebellum with the
spinal cord. These also belong to the long system. Following the same course
of reasoning, it may be assumed that the fibers composing the more primitive
system, which regulates the reflex life of the animal, acquire their medullary sheaths
long before the others. In this assumption we are also correct, because the fibers
connecting the centers in the spinal cord with the sensory and motor organs at the
periphery, are myelinated first. From here the myelination progresses to those
intraspinal fibers which connect the different segments of the cord. In the human
embryo, this process is practically completed at the time of birth.
The third morphological method consists in tracing the course of degenerating
nerve fibers. ^ It has been pointed out above, that a nerve fiber, when separated
from its cell-body, is eventually converted into a band-fiber. This process neces-
sitates the conversion of the phosphorized fat of the myelin into fat which is
absorbed and displaced by fibrous tissue. In studying the distribution of the
spinal fibers, it is possible to divide the cord in places and to trace the degenerating
fibers by the method of staining. The sections are hardened in a bibhromate
solution and are then placed in a mixture of osmic acid and bichromate. Normal
myelin remains unstained, while its fatty derivative assumes a black color. Ob-
viously, the degeneration of a tract above the section implies that the trophic
centers (cell-bodies) of these fibers are situated below the lesion and that the de-
generation is ascending in its character. Quite similarly, a degeneration below the
cut signifies that the cell-bodies are located above the lesion and that the degenera-
tion is descending in its nature. This method has been employed by Waller in
his determination of the function of the roots of the cord.
It should also be remembered that the localization of the cell-bodies of a given
tract of fibers does not always necessitate a repeated transection of the cord at
different levels, but may also be effected by means of staining the suspected cells.
It has been pointed out above that the degeneration following upon the separation
of a nerve fiber from its cell-body, does not remain confined to the peripheral stump
of the cut fiber, but also involves its central end and corresponding cell-body.
This central degeneration which is known as retrogressive degeneration, finds its
cause in a trophic disturbance of the cell-body in consequence of the inactivity
forced upon it by its separation from its end-organs and neighboring neurons.
In their final atrophic state, these cells may readily be recognized after staining
with methylene blue or toluidin blue. They exhibit a swollen and eccentric nu-
cleus as well as indistinct and diffusely stained chromophil granules.
(b) Physiological. — The early view of VanDeen and Schiff, that the white
matter of the spinal cord is non-receptive to electrical stimuli, has been thoroughly
disproved by the work of Fick, Biedermann, and others. It must be admitted,
however, that the results of the direct stimulation of the different tracts of the
cord leave much to be desired, because the paths are not suflBciently separated
from one another to be able to obtain sharply differentiated effects. In spite of
this difficulty this method has proved distinctly helpful as an adjunct to other
procedures. By applying a galvanometer or capillary electrometer to the different
spinal paths, Eckhard, Gotch and Horsley^ have succeeded in tracing the action
current which is produced whenever the motor areas of the cerebrum are stimu-
lated. This method has been amplified by the procedure of fractional division
of the spinal cord. Obviously, the division of certain spinal tracts enables us to
determine whether these electrical variations continue even after the establishment
of this block between the motor area and the level of the galvanometer. This
procedure is also applicable to the tracing of the circuits of the common spinal
reflexes.
^ Employed by Ttirck in 1851 upon sections of the diseased spinal cord of man.
2 Proc. Royal Society, London, 1888.
612
THE FUNCTION OF THE SPINAL CORD
(c) Clinical Observations. — A study of the
clinical pictures of diseases of the spinal cord
must prove of especial value if the symptoms
are subsequently compared with the record of
the autopsy. Naturally, the difficulties con-
nected with an accurate localization of motor and
sensory defects are minimized in man, owing to
his ability to observe and to describe his own
symptoms.
Classification of the Fasciculi of the
Spinal Cord. — The white matter of the
spinal cord is divided into three fascicuh,
an anterior, a lateral and a posterior.^
The first two are often called the antero-
lateral fasciculi, because the rather scat-
tered distribution of the axons forming
the anterior root, causes the boundary
line between these two columns to become
somewhat indefinite. Furthermore, as
the cervical and upper thoracic segments
of the cord show slight furrow-like depres-
sions at the points of exit of the fibers of
the anterior roots, the anterior funiculus
seems to be composed of two fasciculi,
namely, the anteromedian and the antero-
lateral. A similar condition exists pos-
teriorly, this funiculus appearing as the
posteromedian and posterolateral fasciculi.
The following subdivisions may easily be
made out:
1. The anterior funiculus comprises the area
between the anterior median fissure, and the an-
terior root. It is motor in its function and is
divided into the:
(a) Fasciculus cerebrospinalis anterior, also
known as Tiirck's column, or the direct (anterior)
••WERCURY pyramidal tract.
•SULPHURIC ACID 10%
^^
Fig. 303. — Schema Illustrating the Experiment for De-
termining THE Number of Separate Nerve Impulses Passing
Down the Spinal Cord upon Stimulation of the Cortex.
(Horsley.)
E, E, electrodes, intended to be on the "leg area." Where
the cord is interrupted, one non-polarizable electrode is placed
over the cut end of the pyramidal fibers going to the lumbar en-
largement; 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.
It lies next to the
median fissure and
extends downward
l-,_.>cv^ ^s far as the mid-
MICROSCOFE pUj^ thoracic region.
Its caliber de-
- -MERCURY creases constantly,
because the fibers
composing it enter
1 Von Bechterew,
Die Funktionender
Nervencentra,
Jena, 1908-1911,
and Edinger, Vergl.
Anat. des Gehirns,
Leipzig, 1911.
THE SPINAL CORD AS A CONDUCTING PATH 613
the gray matter of the opposite side by way of the anterior white commissure.
We shall see later on that these fibers arise in the motor cortex of the cerebrum
(cells of Betz) of the same and opposite side, and are therefore descending in their
character.
(6) Fasciculus anterior proprius, also called the anterior ground bundle or
root zone. This column occupies the area next to the anterior root and extends
throughout the cord. The fibers composing it are commissural in their character,
i.e., they bring different segments of the gray matter into functional relation.
This end they accomplish by passing to higher as well as to lower levels of the cord,
where they reenter the gray matter and make connections with other cells.
2. The lateral funiculus embraces the white matter between the anterior and
posterior roots and is composed of the :
(a) Fasciculus cerebrospinalis lateralis, also called the lateral or crossed pyram-
idal tract. It occupies the posterior area of this funiculus, but its position varies
somewhat at different levels of the cord. In the lumbar region, it comes right to
the surface, while in the cervical and thoracic regions it remains at some distance
from it. It is covered here by a layer of fibers composing the fasciculus cere-
bellospinalis. Its fibers arise in the motor area of the cerebrum (cells of Betz),
but cross to the opposite side of the body in the medulla. In their downward
course through the cord they terminate successively at different levels of the gray
matter so that the size of the entire column diminishes gradually from above
downward.
(b) Fasciculus spinocerebellaris, also designated as the direct cerebellar or
Flechsig's column. It lies externally to the crossed pyramidal tract. Its fibers
take their origin in the cells of Clark's column. From here they pass obliquely
outward and upward and finally terminate in the cerebellum, where they decussate
in part in the superior vermiform lobe of this structure.
(c) Fasciculus anterolateralis superficialis, also known as Gower's tract. It
occupies the external realm of the lateral funiculus in front of the crossed pyra-
midal tract and extends forward as far as the anterior roots. It begins in the
lumbar segment and forms a compact strand through the entire cord. I'he largest
number of its fibers arise in the opposite gray matter and cross the midline by way
of the white commissure. The uncrossed fibers find their origin in relation with
axons which have passed through the gray commissure and have come from cell-
bodies in the gray matter of the opposite side. In the brain-stem this column
divides into several groups of fibers which terminate in the reticular nuclei, the
cortex of the cerebellum, the tectum, the substantia nigra and the thalamus.
(d) Fasciculus lateralis proprius or lateral ground bundle. This tract forms a
narrow layer next to the external surface of the gray matter. It is believed to be
composed of efferent and afferent fibers, the former being situated in front. Its
function seems to be associative, because its fibers originate in cells of the spinal
gray matter and terminate at levels above and below their points of origin.
3. The posterior funiculus comprises the white matter between the posterior
median fissure and the posterior roots. It consists of the :
(a) Fasciculus gracilis, also called the column of GoU or the posteromedian
tract. It is situated next to the posterior fissure and begins with the posterior
root of the coccygeal nerve. Beginning at this level, it gradually increases in size
owing to the acquisition of the root fibers of higher nerves of the same side. Above
the fifth thoracic nerve it retains its caliber or becomes even somewhat smaller,
because whUe it ceases here to receive root fibers, it continues to give off collaterals
to the successive segments of the gray matter. It terminates in the nucleus funi-
culi gracilis of the medulla.
(b) Fasciculus cuneatus, also known as the column of Burdach or posterolateral
tract. It lies next to the posterior horn and begins in the middle thoracic region.
As it acquires new fibers constantly, its size increases from below upward until it
terminates in the nucleus funiculi cuneati of the. medulla. Its fibers are derived
from the successive posterior roots of the spinal nerves of the same side as well as
614
THE FUNCTION OF THE SPINAL CORD
from cells of the corresponding gray matter. The latter are short fibers, i.e.,
associative in their function, while the former belong to the projection system.
Classification of the Tracts of the Spinal Cord. — In accordance
with the foregoing histological discussion, it will be seen that the
Fig. 304. — Diagram Showing the Course, Origin and Termination of the Fibers of
THE Principal Tracts of the White Matter of the Spinal Cord.
Descending tracts: la, a fiber of the crossed pyramid or corticospinal tract; 16, an
uncrossed fiber of the pyramid or corticospinal tract passing to the lateral column of
the same side; 2, a fiber of the ventral pyramid or cortico-spinal tract; 3, a fiber of the
ventrolateral descending or pontospinal tract; 4, a fiber of the rubrospinal tract; 5,
a fiber of the common tract. Ascending tracts: 6, a fiber of the dorsomesial spino-
bulbar tract; 7, fibers of the dorsolateral spinobulbar tract; 9, one belonging to the
dorsal spinocerebellar; 10, a fiber of the ventral spinocerebellar tract. (Quain, Ele-
ments of Anatomy.)
different fasciculi of the spinal cord constitute different descending
and ascending tracts. In this connection brief reference should also
be made to a number of small and narrow tracts which have been
THE SPINAL CORD AS A CONDUCTING PATH
615
localized in these fasciculi at different levels of the cord. But, the
origin and distribution of the latter are still rather obscure so that the
following physiological classification must necessarily be subject to
frequent revision.
1. Descending Tracts, (a) Pyramidal tracts. — We have previously seen that
the fibers composing the direct (anterior) and crossed (lateral) pyramidal tracts,
originate in the large cells of Betz of the motor
areas of the cerebrum. Hence, an injury to
these regions or a transverse division of these
paths at a lower level must result in a down-
ward degeneration of these tracts. It should /
be remembered, however, that by far the largest/ ''
number of these fibers cross to the opposite side^'
so that, say, the left cerebral hemisphere eventu-
ally obtains control over the musculature of the
right side of the body, and vice versa. Only a
few fibers remain on the same side, where they
eventually enter the lateral column. The afore-
said crossing is effected principallj^ in the pyra-
midal decussation in the lower region of the
medulla, but in part also in the spinal cord itself.
Thus, it appears that the crossed pyramidal
tract is made up of fibers which have gained
the opposite side in the medulla, while the an-
terior pyramidal tract comprises in addition a
certain number of fibers which have failed to
cross in the medulla but which seek the opposite
side gradually by way of the anterior commis-
sure. As this crossing is completed in the mid-
dorsal region, these anterior tracts disappear
at this level. In fact, it is said that they are
entirely wanting in about 15 percent, of human
spinal cords, because in these cases the decussa-
tion is had solely in the medulla, the fibers being
distributed from here exclusively to the crossed
pyramidal tract. ^ This condition also prevails
in the cat, while in the mole the fibers remain
uncrossed and descend anteriorly. In the frog
this system is absent.
It may be concluded, therefore, that the
pyramidal tracts are efferent in their nature and
form the motor path for those impulses which
originate in the motor cells of the cerebrum and
are finally transferred to the large motor neurons
in the anterior horn of the spinal gray matter,
whence they are distributed to the skeletal mus-
culature. From this discussion it may be in-
ferred that they are the chief constituents of
the efferent side of the cerebral projection sys-
tem. Hence, any injury to this path must re-
sult in a loss of voluntary control over the action of the corresponding skeletal
muscles, but naturally, the ordinary reflex movements of the cord are not inter-
fered with unless the lesion is situated at a low level. High lesions of the pyra-
midal system, as has been stated above, really tend to exaggerate the activity
^Simpson, Quart. Jour, of Exp. Physiol., viii, 1914, 79; also: Lenhossek, Bau
des Nervensystemes, 1895.
Fig. 305. — Schema Represent-
ing THE Course of the Fibers of
THE Pyramidal System.
1, Fibers to the nuclei of the
cranial nerve; 2, uncrossed fibers
to the lateral pyramidal fasciculus ;
3, fibers to the anterior pyra-
midal fasciculus crossing in the
cord ; 4 and 5, fibers that cross in
the pyramidal decussation to
make the lateral pyramidal tract
of the opposite side. {Howell.)
616 THE FUNCTION OF THE SPINAL CORD
of the spinal cord. It is to be noted, however, that these defects differ in different
animals in accordance with the state of development of these tracts. They are
most apparent in the apes and man and less evident in lower animals, in which
the pyramidal system is always rather incomplete. In the latter, other motor
paths serve to bring the spinal nuclei into unison with the higher centers. This
is also true of the dog, because the division of the pyramids causes merely a par-
tial paralysis of the muscles, and still permits the stimulktion of the cerebral
cortex to evoke certain movements.^ Clearly, therefore, the results obtained by
experiments upon lower animals cannot be directly applied to man.
(6) The anterior tectospinal bundle, or Held's bundle, lies just beside the entrance
to the anterior median fissure. It has its origin in the superior quadrigeminal
colliculus and descends through the dorsal tegmented decussation, midbrain, pons
and upper half of the medulla to a place between the pyramidal decussation and
the isolated head of the anterior columna. It is concerned with the production of
the ocular and pupillary reflexes, of ^ which circuits it forms the central division.
(c) The rubrospinal or prepyramidal tract, also called Monakow's bundle. It
is triangular in outline and is situated anterior to the crossed pyramidal tract.
Its fibers may be traced from the red nucleus, a group of cells situated in the midbrain
anterior to the nucleus of the third nerve. Shortly after their origin they cross the
midline of the body and descend through the pons, medulla and cord to the level of
the lumbar region, where they arborize around the cells of the posterior extent of the
anterior horn. This tract appears to be an adjunct of the pyramidal system,
because the red nucleus is connected with the cerebrum and cerebellum.
(d) The vestibulospinal tract is composed of descending fibers which are scattered
through the anterior funiculus in the immediate vicinity of the root fibers. They
arise in the lateral vestibular nucleus (Deiters') in the medulla and terminate in
the spinal gray matter. It may be inferred, therefore, that this tract constitutes
an important transmitting system between the cerebellum and the cord, being
directly concerned with the adjustment of the musculature to sensory stimuli from
the semicircular canals.
(e) The olivospinal tract or bundle of Helweg. It is a small tract and is situated
near the surface of the cord just lateral to the anterior roots. Its fibers are said to
arise in the thalamus and to extend through the inferior olive of the medulla as far
as the lower cervical region.
(J) The comma tract of Schultze is situated in the posterior funiculus of the
cervical and upper thoracic regions. It occupies the anterior realm of the column
of Burdach, and appears to be formed by the descending branches of the posterior
root fibers. Many of the latter divide into ascending and descending branches and
thus connect afferently with different levels of the cord. For this reason, they
cannot be regarded as forming true descending tracts. A similar origin is ascribed
to Lissauer's bundle which embraces the tip of the posterior horn, as well as to the
oval field of Flechsig and the median triangle of Gombault and Philippe.
(g) The septomarginal bundle is oval in shape and borders upon the posterior
median fissure. It contains short fibers, but has been said to embrace also certain
fibers from the midbrain.
2. Ascending Tracts. — (a) The posterior tracts occupy the fasciculi gracilis and
cuneatus, and are formed almost wholly by the axones of the cells situated in the
ganglia of the spinal roots. Several of them also arise from different segments of
the spinal gray matter. The former are characterized as exogenous and the latter
as endogenous; moreover, while some of these fibers terminate at different levels
of the gray matter, others extend through the entire length of these columns and
eventually end in the nucleus gracilis and nucleus cuneatus of the medulla. The
former, very clearly, are spinal associative in their function, while the latter belong
to the projection system and form a part of the afferent side of this cerebral con-
ducting path. During their course through the cord, these fibers remain on the side
iRothmann, Zeitschr. f. klin. Med., xlviii, and Schafer, Quart. Jour, of Exp.
Physiol., iii, 1910, 355.
THE SPINAL CORD AS A CONDUCTING PATH
617
on which they have arisen, but finally cross the median line by way of the sensory
decussation of the medulla. It is also to be noted that the fibers which
have their origin at a low level, are gradually pushed toward the median fissure
by those fibers which enter at higher levels, and naturally, as this displacement
affects the exogenous fibers only, the upper thoracic and cervical segments of the
fasciculus gracilis gradually assume the character of the conducting path for the
root fibers of the lumbar and sacral regions.
cerebral
cortex
trigeminal lemniscus
sKin
Tnedial lemniscus
nucleus of dorsal
funiculus
spinal lemniscus
ventral pyramidal
tract
dorsal funiculus
lateral pyramidal tract
spinal ^an^lion
A sKin
muscle
Fig. 306. — Diagram of the Chief Connections Between the Spinal Cord and the
Cerebral Cortex.
The spinal lemniscus complex carries the ascending exteroceptive systems (touch,
temperature, and pain) ; the dorsal funiculus and medial lemniscus complex carry
chiefly ascending proprioceptive impulses (a nerve of muscle sense is the only member
of this group included in the drawing) . The diagram also shows the sensory path from
the skin of the head to the cerebral cortex through the V cranial nerve (trigeminus)
and the trigeminal lemniscus. The pyramidal tract (tractus corticospinalis) is the
common descending motor path for both exteroceptive and proprioceptive nervous
impulses from the cerebral cortex. (Herrick.)
(6) The direct or spinocerebellar tract (Flechsig's) is one of the two best known
tracts in the lateral funiculus. As its fibers arise in the cells of Clark's column,
they are endogenous in character, and serve for the inward conduction of those
impulses which have attained the aforesaid cells by way of certain fibers of the
posterior root. While most of them enter the inferior peduncle of the cerebellum
and terminate in the posterior and median areas of the vermiform lobe, some also
618
THE FUNCTION OF THE SPINAL CORD
pass into the gray matter of the upper spinal cord. The cerebellar groups remain
largely uncrossed.
(c) The superficial anterolateral tract (Gower's). — The origin of these fibers in
the lower spinal gray matter and their distribution to the cerebellum and related
parts suggest that they convey afferent impulses from the posterior roots to the
cerebellum/ and hence, their function must be similar to that of the fibers of
Flechsig's tract. They are concerned with the coordination of muscular move-
ments, their immediate purpose being to aid in the conduction of the impulses from
the receptors in the muscles, tendons and joints to the coordinating organ, the cere-
FiQ. 307. — Diagram or the Spinocerebellar, Bulbotegmental, Cerebellotegmental,
PONTOTEGMENTAL, AND PONTOCEREBELLAR TRACTS.
OT, Optic thalamus; F, fillet; RN, red nucleus. {After v. Gehuchten.)
bellum. For this reason, they may be regarded as forming a part of the afferent
arc required for the production of the muscle sense and coordination of muscular
action. That this is true may also be gathered from the fact that the division of
this tract is followed by a moderate degree of atonia and ataxia^ below the seat of
the lesion.
{d) The spinothalamic and spinotectal tracts are really a part of Gower's tract.
These fibers traverse the medulla and pons and terminate very largely in the optic
* Bruce, Quart. Jour, of Exp. Physiol., iii, 1910, 391; also see: Lewandowsky,
Untersuchungen iiber die Leitungsbahnen d. Truncus cerebri, etc., Jena, 1904.
2 Bing, Archiv fiir Physiol., 1906, 250; also see: Horsley and Macnalty, Brain,
1909, 237.
THE SPINAL CORD AS A CONDUCTING PATH 619
thalamus of the same side but in part also in the corpora quadrigemina of both
sides.
(e) A few scattered bundles of ascending fibers are also found in the anterior
funiculus. They intermingle here with the descending tracts mentioned previously.
The fasciculi proprii or ground bundles are not mentioned separately in this enu-
meration, because parts of them have already been described under the heading
of the septomarginal and comma tracts.
The Function of the Roots of the Spinal Cord. The Bell-Magendie
Law.^ — The general conclusion to be derived from the preceding
discussion is that the white matter of the spinal cord of the higher
animals is arranged in definite tracts which connect:
(a) Different segments of this structure with one another, thus
forming the propriospinal paths, ^.e., a short or reflex system of
conduction.
(6) The cord with the hindbrain, midbrain and forebrain, forming
a long or projection system of conduction. With the hindbrain the
connections are made over the posterior cerebellar tracts, the tracts
of GoU and Burdach, the spino-olivary and vestibulospinal bundles.
The midbrain receives its impulses by way of the spinotectal tracts
and discharges them over the rubrospinal. The forebrain (thalamus)
is entered through the spinothalamic tracts. From here the impulses
are relegated to the cerebrum, which organ, as has been stated above,
is not in direct afferent communication with the cord, because the
impulses directed to it from the latter structure, are first relayed
into lower nuclei and centers before they are finally distributed to the.
cerebral cortex. On the efferent side, however, the cerebrum is in
possession of a direct path in the shape of the anterior and lateral
pyramidal tracts. As has been emphasized repeatedly, the mere
entrance of an impulse into the cerebrum does not admit it to conscious-
ness; in fact, many of the reactions resulting in consequence of cerebral
activity "retain their reflex character as strictly as those evoked
exclusively with the help of the spinal cord. It is true, however,
that many of them are controlled by consciousness. They are then
converted into volitional acts, the p'receding afferent impulses haying
been received in consciousness as sensations of different qualities.
We are now in a position to go one step farther and to inquire
how the different spinal tracts and especially those belonging to the
projection system, are connected with the distant receptors and ef-
fectors. It will be remembered that each spinal nerve arises by two
roots, an anterior or ventral, and a posterior or dorsal, and that these
roots finally unite to form a nerve. Centrally to their point of union,
the posterior group of fibers is associated with a colony of cells, which
form the so-called intervertebral ganglion. In 1811 Ch. BelP found
that the mechanical stimulation of the anterior group of fibers gives
rise to movements, while the posterior behaves negatively in this
' Longet, Anat. et physiol. de la syst. nerv., 1847.
"^Ab. idea of a new anatomy of the brain, London, 1811.
620 THE FUNCTION OF THE SPINAL CORD
regard. In 1822 Magendie^ succeeded in demonstrating that the
division of the anterior roots destroys motion, while the section of the
posterior roots produces a loss of sensation. Owing, however, to the
fact that the former is in possession of a perfectly local system'
of sensory fibers and that the latter is connected with motor reflex
paths, this investigator did not succeed in fully establishing their
function. This end was finally attained by Joh. v. Miiller as a result
of his experiments upon the spinal roots of the frog.
In its modern form the Bell-Magendie law holds that the afferent
impulses from the superficial and deep parts of the trunk and ex-
tremities are conducted into the cord by way of the posterior roots,
while the efferent impulses to these parts leave this structure over the
fibers of the anterior roots. Thus, a most perfect localization of
sensory and motor function is had in this region of the nervous system.
To prove this, we may resort to the methods of division and stimulation,
as follows:
1. Section:
(A) Anterior root: loss of motion in the regions supplied by this nerve.
(B) Posterior root: loss of sensation (contralateral) in the region innervated by
this nerve (ataxia and loss of reflex movements).
2. Stimulation:
(A) Anterior root:
(a) Distal end : motor results of the kind ordinarily produced by this nerve.
(6) Central end : no motor results, but retrogressive sensation.
{B) Posterior root:
(a) Distal end : no results.
(6) Central end : sensations of the kind ordinarily conveyed by this nerve.
In its complete form the Bell-Magendie law also takes cognizance
of certain minor facts which are as follows: It has been mentioned
above that the anterior root as such is not devoid of sensation and
hence, does not differ in this regard from other tissues. For this
reason its excitation must give rise to ''retrogressive" sensory impulses
which are purely local in their origin, and should therefore be sharply
differentiated from those which arise at the periphery and attain
consciousness by way of the posterior group of fibers. ^ In the second
place, as the sensory impulses traversing the posterior roots also in-,
elude those which help in the formation of the muscle-sense, the divi-
sion of these fibers must necessarily be followed by a certain degree
of ataxia; in other words, in the absence of the sensory impressions
from the muscles and tendons, the muscular movements must lose
their coordinated character. In the third place, it should be re-
membered that the stimulation of the central end of the divided
posterior root may also give rise to movements, but these occasional
motor effects are reflex in their nature and cease immediately after the
division of the anterior roots. Being desirous of simplifying this topic
as much as possible, I refrain at this time from a discussion of certain
1 Jour, de Physiol., ii, 1822, 276.
2 CI. Bernard, Legons sur la physiol. et la path, du syst. nerveaux, i.
THE SPINAL CORD AS A CONDUCTING PATH
621
other facts which, however, do not put the general applicabihty of
this law in question. I also omit for the present the structural and
functional relationship existing between the spinal cord and the
sympathejbic system. We shall see later on that the anterior roots also
contain efferent fibers for the autonomic organs and that these in turn
send impulses to central parts by way of the rami communicantes
and the posterior roots.
The Trophic Function of the Spinal Cord. The Wallerian Law
of Degeneration. — It has been discovered by Nasse^ that a nerve-
fiber, when disconnected from its cell-body, undergoes certain very
characteristic alterations in its structure. In applying this fact to
t
k
r"
v./l»
; %
^k
Fig. 308. Fig. 309.
Fig. 308. — Schema to Show the Course of the Degeneration Following the
Division of the Roots of the Spinal Cord.
A, Division of the anterior root; B, division of the posterior root distally to spinal
ganglion; C, division of the posterior root centrally to spinal ganglion. The degen-
erated portions are indicated in solid black.
Fig. 309. — Schema Illustrating the Course of Degeneration in Motor and
Sensory Neurons.
A, Motor neuron of the anterior root; B and C, sensory neurons of the posterior
root. The portion separated from the cell degenerates, as is indicated by the dotted
lines.
the spinal nerves, A. Waller^ succeeded in demonstrating that a cut
made distally to the intervertebral ganglion, leads to a degeneration
of both roots in an outward direction, involving finally the entire
nerve as far as its end-organs (secondary degeneration). Quite
similarly, it was shown that the division of the spinal roots centrally
to this ganglion gives rise to degenerative changes which pursue
a tjourse in opposite directions from the seat of the lesion, i.e., the
anterior root degenerates toward the periphery and the posterior
1 Mailer's Archiv, 1839, 405.
2 Compt. rend., Acad, des sciences, xxxiv, 1852.
622 THE FUNCTION OF THE SPINAL CORD
root toward the cord. The deduction immediately to be derived
from these facts, is that the trophic center (cell-bodies) of the fibers
composing the former, is situated in the spinal cord, while that of the
posterior root fibers lies in the ganglion with which this root^is associ-
ated. Having been told previously that the efferent fibers composing
the anterior root originate in the ganglion cells of the gray matter of the
anterior horn, and that the afferent fibers of the posterior root are derived
from the cells of the spinal ganglia, we are now able to localize the
degeneration in these neurons in the manner indicated by Fig. 309.
It might be mentioned that the descending type of degeneration, ob-
served in anterior poliomyehtis, is represented by neuron A of this
figure, because it is commonly accepted that the active agent of this
disease destroys the cells of the anterior horn, and thus produces a
functional uselessness of the corresponding nerve fibers and motor
organ. A degeneration very similar to that represented by neuron
C, occurs in the course of tabes dorsalis, or locomotor ataxia. In this
disease the lesion remains localized at first in the terminals of the pos-
terior root fibers with the result that the muscle and tendon sense is
rendered defective, thereby preventing the proper coordination of
mviscular movements.
These facts, however, do not justify us in repognizing the existence
of special neurons with an exclusive trophic function, because the
nutrition of a tissue is dependent primarily upon its activity, and the
latter in turn upon the excitatory and regulatory power of the nerve
cells. Thus, an injury to these nervous elements invariably leads to
trophic disturbances in the tissues even without their being equipped
with special trophic qualities. For this reason, we find that the skele-
tal muscles atrophy when separated from their ganghon cells. Ex-
ceptions to this rule are few in number and are referable to the fact that
some muscles, such as the sphincter ani, are not under the direct
control of the central nervous system. Upon this basis, we are
also able to explain the trophic disturbances which are frequently
observed in the course of degenerating afferent nerves (Fig. 309, B),
Thus it is found that the inflammation of the ganglia upon the posterior
roots leads to the condition of herpes zoster (*' shingles") in the area
from which the corresponding fibers are derived. ^ The skin may also
become glossy and desquamate, which condition may eventually give
rise to a loss of the hair and nails, or to a formation of ulcers. In-
clusive of this trophic influence, the functions of the spinal cord may
therefore be summarized as follows:
(a) It is an important seat of reflex action.
(6) It forms one of the principal conducting paths.
(c) Its centers are automatically active and give rise to the tonicity of the
musculature. •
{d) It regulates the activity and trophic condition of the tissues and plays an
important part in the heat production of our body.
1 Head and Campbell, Pathology of Herpes Zoster, Brain, xxiii, 1901, 353.
THE SPINAL CORD AS A CONDUCTING PATH
623
The Distribution of the Impulses Derived from the Posterior
Roots. — The posterior roots of the cord are very important "feeders"
of the central nervous sytem. Together with the afferent fibers of
the cranial nerves, they constitute the only means by which the higher
centers may be influenced by impulses generated peripherally. These
impulses embrace first of all the superficial and deep sensations of
touch, pain and temperature, as well as those derived from the re-
ceptors in the muscles and tendons, having to do with the muscle-
sense. On their arrival in the terminals of the posterior root fibers,
BotMlaleral impulsRS WnSerlyiru) muscular eensibililij—i.e. seme of passive posilion and of
movement, also nf touch and pressure for a few segments.
I,
Z.,
1. Helerolaieral
uriconscioua afferent
impulses underlying
I muse, co-ordination
and reflex tone.
8. All impulses
of pain, of heal,
and of cold
{Helerolaieral).
9. Heterolateral impvleea of
touch and presswe,.
Fig. 310. — Diagbam to Illustrate the Termination op Peripheral Afferent
Fibers in the Spinal Cord, and the Origin of the Secondary Central Paths, with a
Brief Summary of Their Function.
1, Bundles of fibers passing up in the posterior column — many myelopetal (to sp.
cord) and the remainder bulbopetal (to p. col. nuclei) ; 2, fibers terminating around the
cells of Clarke's column; 3, fibers arborizing around cells in the posterior horn, and inter-
mediate gray matter; 4, ditto around the anterior horn-cells; 5, ditto swerving into the
lateral column to neighboring gray matter; 6, direct, or dorsal spinocerebellar tract;
7 and 8, Gowers' tract, i.e. (7) ventral spinocerebellar tract; (8) spinothalamic and
tectal tracts; 9, ascendingtract in the anterior column. {Starling after W. Page May.)
they are distributed to those particular groups of cells and fibers
which are directly concerned with their conduction to other parts.
Their distribution is effected as follows:
(A) Impulses Retained at the Level of their Entrance into the Cord. — They are
reflex in their nature and gain the corresponding effector by way of the anterior
root fibers. This transfer of the afferent impulses into efferent ones is accomplished
directly through the intervention of the cells of the anterior and lateral horns of the
neighboring gray matter. While the largest number of these impulses remain
confined to the same side of the cord, some also seek the opposite spinal gray matter
and opposite anterior root by way of the posterior white commissure.
{B) Impulses Seeking Levels above and below their Level of Entrance. — They are
distributed to:
624 THE FUNCTION OF THE SPINAL CORD
(a) Higher or Lower Segments of the Cord. — These are also reflex in character,
but involve the spinal gray matter and anterior roots of segments situated above
or below the point of their entrance. These segments are reached over the fibers
of the ground bundles or by way of the terminals and collaterals of the fibers of
the posterior columns. In the latter case, they are not relayed, because many of
the fibers of the posterior roots divide inside the cord into an upper and a lower
branch, the former eventually arborizing at a higher and the latter at a lower level
than their point of bifurcation. The connection between the terminals of this
afferent fiber and the anterior gray matter is effected in either case in the manner
just described.
(6) Higher Centers in the Cerebellum and Cerebrum. — The cerebellar impulses
are concerned with the muscle-sense and the coordination of muscular movements.
They are transferred from the posterior root to posterior cells and subsequently
to the cerebellar tracts in the lateral funiculus and the cerebellum. Some of these
are no doubt transferred directly to efferent channels, while others pass from this
organ to the cerebrum, where they may either enter consciousness or remain sub-
conscious. They then seek the efferent tracts by way of the motor areas. The
cerebral impulses leave the fibers of the posterior roots and enter either the pos-
terior tracts or those of the lateral funiculus. Inasmuch as no separate tract is
set aside for them by means of which they could reach the cerebrum directly,
they are relayed in the medulla and basal ganglia to secondary bundles of fibers.
These impulses serve conscious and subconscious reactions. In the first instance,
they enter consciousness as sensations of touch, pain and temperature.
Nothing further need be said regarding .the afferent impulses of
touch, pain and temperature, when concerned with reflex action.
Their course has been mapped out above under the headings of A
and B, a. Much controversy, however, has arisen as to their course
when they enter consciousness, and give rise to their respective sen-
sations which ar^ then followed by voluntary reactions. This con-
troversy finds its origin in the diversity of the symptoms following
lesions of the posterior and lateral fasciculi. Thus, it has been ob-
served that the posterior tracts may be divided in lower animals
without destroying the sense of touch. Cases have also been recorded
of persons with extensive lesions of the same columns whose sense of
touch was not seriously impaired. But this evidence does not prove
that the tactile impulses do not enter the posterior tracts at all, but
merely suggests that two paths are open to them, namely, the long
projection fibers of the posterior funiculus and the short fibers of the
lateral funiculus. Thus, if the former fibers are destroyed, these im-
pulses are still able to gain the cerebrum by way of the latter. This
view, however, is not fully in accord with the results of experiments
upon lower animals, but is in agreement with the symptoms presented
by persons suffering from certain affections of the spinal cord. While
this matter cannot be definitely decided at the present time, it appears
that these differences are chiefly dependent upon the fact that the
spinal paths vary somewhat even among the mammals.
If we confine ourselves to man, we may draw the conclusion
that the impulses of touch and pressure are transmitted under normal
conditions to the posterior tracts of the same side, but may be trans-
ferred in the upper cord to the opposite anterolateral columns. Head
THE SPINAL CORD AS A CONDUCTING PATH 625
and Thompson 1 have elucidated this matter further by dividing the
sense of touch into tactile discrimination and tactile localization. The
former term is employed to designate the ability of being able to
discriminate between two mechanical stimuli applied simultaneously
to the skin. This sensation may be evoked most easily by touching the
integument with a compass the points of which have been separated
from one another. Tactile localization is the ability accurately to
designate the area which has been stimulated. In certain spinal
diseases, these two forms of touch sensation have been found to be
dissociated. The former was lost, while the latter persisted. In
explanation of this phenomenon, it is held that the fibers allotted to
touch discrimination, are contained in the posterior tracts of the same
side, while those conveying the impulses of touch proper, are included
in the anterolateral fasciculi and cross the median line below the
medulla.
In addition to this dissociation of the tactile impressions into
touch discrimination and touch localization, the cutaneous sensations
may also be divided into two groups, namely, those of touch and those
of pain and temperature. The former impulses, as we have just seen,
select in part the posterior columns, while the latter appear to enter
the cells of the posterior gray matter, whence they attain the tracts
of the opposite anterolateral fasciculi. The evidence which may be
submitted in support of this view, is the fact that in syringomyeHa the
sensations of touch and pressure are retained, while those of pain and
temperature are lost. In other words, the patient exhibits an anal-
gesia and thermo-anesthesia below the seat of the lesion. These
symptoms are suggestive, because this disease affects chiefly the gray
matter of the cord, causing a vacuolization of the cells and, therefore,
a destruction of the connection between the posterior roots and the
anterolateral fasciculi of the same and opposite sides. It would seem,
therefore, that the loss of the sensations of pain and temperature is
dependent in this case upon the fact that they cannot reach their desti-
nation on account of this block upon the path usually selected by them
in gaining the opposite anterolateral tract.
The impulses serving the muscle-sense, may also be divided into
two groups, namely, those which pass directly to the cerebellum and
always remain subconscious and those which are relayed to the cere-
brum and finally involve volition. It has been stated above that the
former select the anterior and posterior cerebellar tracts of the lateral
funiculus of the same side, while the latter ascend in the posterior
columns of the same side. The latter, however, cross finally to the
opposite cerebral hemisphere by way of the optic thalamus. Our
muscular movements are executed in accordance with the character
of the impulses received from our muscles and tendons. This regula-
tion is primarily cerebellar, but may be modified by volition, i.e., the
activity of our muscles may be controlled by the cerebellum and cerebrum
1 Brain, 1906; also see: Saunders, Brain, xxxvi, 1913, 166.
40
626 THE FUNCTION OF THE SPINAL CORD
either without or with the help of consciousness, especially of volition.
In the first case, the control is involuntary or reflex, and in the second,
volitional and based upon an accurate conception in consciousness of
the state of contraction of our muscles and of the position of our limbs.
The Effects of Hemisection of the Spinal Cord.^ — The symptoms
following the division of one-half of the spinal cord, are homolateral
and contralateral in their nature, i.e., they may or may not be con-
fined to the side of the lesion.
A. Homolateral:
(a) Motor paralysis, affecting (o) the skeletal muscles innervated by the efferent
fibers which leave the cord below the level of the section, and (6) the smooth
musculature of the blood-vessels. The latter is made evident by the injection
of the blood-vessels of the parts affected and the consequent rise in tempera-
ture. The skin becomes dry which fact points toward a secretory motor
paralysis.
(6) Sensory paralysis (anesthesia) in the region of those afferent fibers which
enter directly at the seat of the injury. This zone is, of course, limited. Loss
of *the muscle-sense and tactile discrimination. The other parts show a cer-
tain degree of hyperesthesia.
B. Contralateral:
(a) Motor paralysis, negative,
(&) Sensory paralysis, affecting pain, temperature and tactile localization in
the region innervated by those fibers which have crossed below the level of
the lesion.
This syndrome, consisting of unilateral loss of motion and contra-
lateral loss of sensation, is not very evident in the lower animals, but
this need not surprise us, because the localization of conduction in the
simple spinal cords differs somewhat from that found in the human
cord. 2 In addition, we are confronted here by the difficulty that an
animal cannot interpret sensory disturbances for us.
1 Brown-S^quard, Jour, de Physiol., vi, 1863, 124; also see: Petr^n, Archiv fiir
Psychiatrie, xlvii, 1911, 495.
2 Karphus and Kreidl, Pfliiger's Archiv, clviii, 1914, 275.
SECTION XVI
THE AUTONOMIC NERVOUS SYSTEM
CHAPTER LI
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS
General Arrangement. — It has been stated above that the nervous
system consists of a central and a peripheral division, and that the
latter in turn is built up of (a) the cranial and spinal nerves, and (6)
the ganglia and nerves of the sympathetic system. The term sympa-
thetic, however, is somewhat misleading, because, as originally em-
ployed, this system included merely those ganglia which are situated
along the spinal cord, beginning above with the superior cervical and
ending below with the coccygeal. Its function was said to be the
regulation of the activities of the internal organs or viscera. In the
course of time a number of ganglia have also been found which, al-
though innervating the viscera, do not occupy a position within the
realm of the sympathetic system as originally mapped out. These
are said to form the so-called parasympathetic system. On account
of this conflict, Langley^ has advocated the use of the more general term
visceral or autonomic. Hence, in its modern conception the autonomic
nervous system is composed of a number of ganglia and plexuses of
nerves which are rather sharply differentiated from the cerebrospinal
system by certain anatomical, histological and physiological character-
istics. It is formed, on the one hand, by the sympathetic system as
originally conceived and, on the other, by certain ganglia which are
situated in the realm of the cranial and sacral nerves. The latter are
collectively known as the parasympathetic system. In making these
distinctions the student is cautioned not to regard the autonomic
system as a functional curiosity, or to separate it completely from the
cerebrospinal system, because it forms after all a closely correlated
division of the whole nervous mechanism.
The entire autonomic nervous system is composed of a series of
ganglia which are scattered through the regions of the head, neck,
thorax, abdomen and pelvis, beginning above with the superior cer-
vical and terminating below with the coccygeal ganglion. These col-
onies of cells are united by nerve-fibers which are frequently augmented
into networks or plexuses. It consists of:
1 Ergebn. der Physiol., ii, 1903, 2, and Zentralbl. fiir Physiol., xxvii, 1913, 149.
627
628
THE AUTONOMIC NERVOUS SYSTEM
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS 629
A. The sympathetic chain, situated on each side of the vertebral column and con-
sisting of ganglia which are connected by strands of fibers. It is divided into a :
(a) Cervical portion which is placed along the neck and is beset with the superior,
middle and inferior cervical ganglia. This delicate string of non-medullated
fibers may pursue an independent course along the carotid artery (rabbit)
or be intermingled with the medullated fibers of the vagus (dog).
(6) Thoracic portion, consisting of eleven or twelve ganglia, the first three of
which are united into the large ganglion stellatum.
(c) Lumbar portion, embracing the three or four ganglia of this region.
(d) Sacrococcygeal portion, formed by an equal number of sacral gangUa
terminating with the ganglion coccygeum.
B. A system of large ganglia which may be grouped as :
(a) Cranial, for example, the ganglion ciliare upon the third nerve, the gangUon
sphenopalatinum upon the second branch of the trigeminus, the ganglion
oticum et ganglion submaxillare upon the third branch of the same nerve.
The vagus and glossopharyngeus also embrace certain fibers which connect
with the sympathetic system.
(6) Thoracic, for example, the plexus cardiacus upon the arch of the aorta.
(c) Abdominal, for example, the plexus Solaris, embracing the right and left
suprarenal, the superior mesenteric, the celiac and certain smaller gangHa in
the region of the stomach. The greater and lesser splanchnic nerves unite
this complex with the thoracic ganglia. The distalmost ramifications of the
sympathetic system in this region form the plexuses of Meissner and Auerbach.
(d) Pelvic, for example, the ganglion hypogastricum.
Characteristics of the Autonomic Nervous System. — The preceding
outline teaches us that the autonomic nervous system occupies an
anatomically distinct position; in fact, its gross anatomical charac-
teristics are such that we are tempted to regard it as a nervous system
within a nervous system. On the histological side, we find that the
sympathetic cells are usually multipolar, rounded in outline, and some-
what smaller than those belonging to the cerebrospinal structures.
The nerve-fibers are characterized by an absence of the myelin sheath
which imparts to them a grayish color. The only exception to this
rule is to be found in the medullated fibers, forming the connection
between the gray matter of the cerebrospinal system and the neighbor-
ing sympathetic ganglia. These bridges of fibers are known as the
white rami communicantes. On the physiological side, we observe
that the reactions occurring in the realm of the sympathetic system,
are for the most part subconscious. This implies that they are not
under the direct guidance of volition and are, therefore, typically
reflex in their character. Besides, as they are relatively independent
of the central nervous system, and may continue even after the de-
struction of the latter, they are usually described as autonomic. . On
the pharmacological side, we find that the sympathetic elements behave
in a very characteristic manner toward certain drugs. Nicotin acts
as a cell poison, i.e., it paralyzes the synapses and thus separates the
distal from the central neuron. Efferent impulses are in this way
prevented from reaching the peripheral motor organ. Adrenalin
exerts a specific action upon the thoracic and lumbar divisions of the
sympathetic system, while atropin, muscarin and pilocarpin are said
630
THE AUTONOMIC NERVOUS SYSTEM
to act primarily upon the parasympathetic system, and chiefly upon
the cranial gangha and their ramifications.
The Function of the Autonomic System. — The innervation of the
striated musculature is effected by fibers which arise in the cerebrum,
cerebellum and spinal cord and pursue a perfectly straight course
to the periphery. Those fibers, on the other hand, which are con-
cerned with the vegetative processes, do not pass directly to the
motor end-organs, but are first relayed into the sympathetic system.
The latter, therefore, may be regarded as a siding upon the cerebro-
spinal tract. In its amplified form this statement signifies that the
impulses apportioned to striated muscle are distinctly cerebrospinal
in their origin and remain so throughout their course, while those
Fig. 312. — Cells from the Gangl. Cervicale Supremum of Man.
A and B, Cells with short dendrites; C, cell with long dendrites; a, axon. (Cajal.)
distributed to smooth and cardiac muscle tissue, as well as to the glands,
do not remain so, but presently assume the characteristics of the auto-
nomic or sympathetic system. It has been stated above that the
effectors are limited in number, because only two structural units
enter into their formation, namely, muscle tissue and glandular tissue.
The former, however, presents itself as striated, smooth and cardiac
muscle. We nO'W observe that the smooth and cardiac muscle tissues,
together with the glandular tissue, form the typical motor organs
of the autonomic system, while the striated muscle alone remains dis-
tinctly cerebrospinal in its character.
In further analysis of this fact it becomes immediately apparent
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS 631
that the motor units of the autonomic system are moulded into an
array of end-organs presenting a most perplexing structural and of
functional diversity. Naturally, all of them are concerned with vege-
tative processes and as such give rise to movements as well as to se-
cretions. The former embrace the musculomotor effects' along the
aHmentary and urinary tracts, the vasomotor and pilomotor actions,
the movements of the iris, and others. It would lead us altogether too
far to discuss these different autonomic functions in detail; many of
them, in fact, we have become acquainted with in the course of our
studies upon respiration, the circulation of the blood and reflex action.
For this reason, we shall confine ourselves at this time to a more
general summary, such as the following:
A. The Cranial or Parasympathetic System.
(a) The region of the midbrain. These fibers pass through the nervus oculo-
motorius and end in the gangl. cihare. Motor fibers are sent to the muse,
sphincter pupillse and muse, ciharis.
(6) The region of the bulb. (1) The facial nerve conveys fibers to the gangl.
sphenopalatinum (nerv. petrosus superfic. major), whence they gain the
mucous membrane of the nose, palate and upper pharynx as well as the
lacrimal, submaxillary and sublingual glands. They are vasomotor and
secretomotor in their function. (2) The glossopharyngeus contains fibers
for the gangl. oticum (nerv. tympanicus et nerv. petrosus superf. minor),
whence they gain the parotid gland. They are vasodilator and secreto-
motor in their function. (3) The vagus nerve embraces inhibitor fibers for
the heart, motor fibers for the musculature of the bronchi, esophagus,
stomach and intestine, and secretomotor fibers for the glands of the stomach
and pancreas.
B. The Cervical Sympathetic System.
1. Musculomotor fibers for the muse, dilator pupillse and the smooth muscle tis-
sue of the orbits and eyelids.
2. Vasomotor fibers for the blood-vessels of the ears, face, conjunctiva, iris,
choroidea, salivary glands, esophagus, larynx, thyroid, and brain.
3. Secretomotor fibers for the sweat glands of the head region, and the salivary
and lacrimal glands.
C. The Thoracic Sympathetic System.
(a) Vertebral ganglia :
1. Vasomotor fibers for the skin of the trunk and extremities.
2. Pilomotor fibers for the same regions.
3. Secretomotor fibers for the sweat glands of the same areas.
(b) Thoracic and abdominal ganglia:
1. Musculomotor fibers for the heart (gangl. stellatum).
2. Vasomotor fibers for the abdominal viscera (splanchnic system and solar
ganglia).
3. Vasomotor fibers for the colon descendens, rectum, bladder and uterus
(gangl. mesent. inf. and nerv. hypogastrici).
D. The Sacral Sympathetic System {Parasympathetic in Character).
1. Musculomotor fibers for the colon descendens, rectum, bladder and
genital organs.
The Connections between the Cerebrospinal and Autonomic
Systems. — Inasmuch as the vegetative processes are under the
direct control of the autonomic system, it must be evident that those
impulses which are relegated to this system from the brain and cord,
632 THE AUTONOMIC NERVOUS SYSTEM
musfc leave the cerebrospinal channels and enter the sympathetic
ganglia. This transfer is accomplished in three different regions,
namely, by way of the:
A. Cranial nerves.
(a) Midbrain, third nerve and gangl. ciliare.
(b) Bulb. (1) Second branch of the trigeminus, gangl. sphenopalatinum. (2)
Third branch of the trigeminus and gangl. oticum et gangl. submaxillare.
(3) Vagus and glossopharyngeus.
B. Thoracic and lumbar divisions of the spinal cord, from the first thoracic to the
fourth lumbar nerves.
C. Sacral division of the spinal cord, over the nerv. pelvicus.
We have previously seen that the sympathetic system as originally
described, consists of a chain of ganglia and their connections situated
along the vertebral column in the region of the thoracic and lumbar
segments of the spinal cord. But the autonomic system also includes
a number of ganglia and plexuses which do not belong to this particu-
lar region of the nervous system, but form the anatomically distinct
parasympathetic system. The latter embraces the cranial and sacral
ganglia. To summarize, the autonomic nervous system consists of
the sympathetic and parasympathetic systems. The latter includes
all those ganglia and plexuses which are not directly related to the
thoracic and lumbar divisions of the spinal cord. A glance at Fig. 311
will show that the largest number of the viscera receive a double
nerve supply, namely, one from the synipathetic system proper and
one from the parasympathetic system.^ Peculiarly enough, the func-
tions of these two groups of fibers are generally antagonistic to one
another. In illustration of this statement might be mentioned the
variations in the size of the pupil, or in the action of the heart. In
the former case, the stimulation of the oculomotor nerve representing
the autonomic pathway from the midbrain, gives pupillar constriction
and the excitation of the cervical sympathetic, pupillar dilatation.
In the case of the heart, the bulbar autonomic fibers contained in
the vagus nerve, are cardio-inhibitory in their function, and the sym-
pathetic, cardio-acceleratory.
Having found that the cerebrospinal and autonomic systems
are connected by definite bridges of fibers, let us for a moment examine
the structural details of one of these. I select for this purpose the
spinosympathetic rami, because their course has been made out with
at least a fair degree of accuracy (Fig. 313). We have seen that the
axons of the cells in the anterior horn seek their corresponding motor
end-organs by way of the anterior roots (I). In tracing these fibers
outward to the point where they intermingle with the afferent fibers
tending toward the posterior root, it is noted that a number of them
leave the mixed nerve and pursue a straight course toward the sympa-
thetic gangUon at the side of the vertebral column (II and III).
1 Gottlieb and Meyer, Die exper. Pharmak. als Grundlage der Arzeneibehand-
lung, Berlin, 1912.
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS
633
These fibers retain their medullary sheath and form the so-called ramus
albus communicans (W), i.e., a bridge by means of which certain effer-
ent cerebrospinal impulses are enabled to enter the sympathetic
system (S). The cell-bodies of these neurons form the later omedian
group of cells of the anterior horn in the thoracic and lumbar regions
of the spinal cord. It is to be noted, therefore, that the anterior
root is made up of two groups of efferent fibers, one of which conveys
impulses directly to the striated muscles and the other, to the sympa-
thetic system. The former are musculomotor (striated muscle) in
their function, and the latter, musculomotor (smooth muscle) vaso-
motor, secretomotor and pilomotor.
Fig. 313. — Diagrammatic Representation op the Connection Between the Cerebro-
spinal AND Sympathetic Systems.
AR and PR, Anterior and posterior roots of the spinal cord; SG, spinal ganglion;
N, spinal nerve; W, white ramus; G, gray ramus; S, sympathetic ganglion; I, ordinary
motor neuron, the axon of which pursues a straight course to peripheral effector;
//, motor neuron, the axon of which enters sympathetic ganglion through the white
ramus. Ill, secondary neuron carrying the impulses from II to other parts of sympa-
thetic system; IV, secondary neuron; carrying impulses from sympathetic system
through the gray ramus to the peripheral effector in the domain of the cerebrospinal
system; V, neuron carrying afferent impulses from sympathetic system into cerebro-
spinal system by way of spinal ganglion and posterior root.
Immediately adjoining the ramus albus is another bridge which
unites the sympathetic ganglion with a somewhat more peripheral
point of the mixed nerve. Its gray color suggests that the fibers
composing it are non-medullated and are, therefore, of sympathetic
origin. This is the ramus griseus communicans (G) . In some animals,
however, the white and gray rami are united into a single trunk and
arise from the same segment of the mixed nerve immediately beside
the spinal ganglion. It need scarcely be emphasized that the gray
ramus forms an afferent connection which enables sympathetic
impulses to reach the spinocerebral tracts (IV and V).
634 THE AUTONOMIC NERVOUS SYSTEM
At the hand of these details, we are now in a position to explain
why typically autonomic functions may also be had in regions which
on casual observation seem to be innervated exclusively by a cerebro-
spinal nerve. Thus, we observe that vasomotor and secretomotor
actions are not restricted to the viscera, but are also enacted in the
integument and deeper structures of the trunk, arms and legs. It
must be inferred, therefore, that the spinal nerves innervating these
parts, derive their supply of sympathetic fibers by way of the gray
rami (IV). In this way, their original power of regulating the activity
of the striated musculature is augmented by the control of the smooth
muscle and glandular tissue. To illustrate, the sciatic nerve contains
first of all a certain number of fibers for the skeletal muscles of the
leg, secondly, fibers for the smooth muscle of the blood-vessels (vaso-
motor) and skin (pilomotor) and thirdly, fibers for the sweat glands
(secretomotor) of this part. The former pursue a straight course
from the spinal cord to their peripheral effectors (I), while the latter
are first ' diverted into the sympathetic ganglia by way of the white
rami (II), whence they are again directed into this spinal nerve by
way of the gray rami (IV). For this reason, they are frequently desig-
nated as recurrent fibers. It seems quite probable that a similar
arrangement exists at the points of union between the cranial nerves
and the sympathetic, or more correctly speaking, the parasympathetic
system.
The peculiar manner of distribution of these fibers is well illustrated
by that of the pilomotors.^ Using the cat as an example, it is found
that the latter leave the spinal gray matter by way of the anterior
roots of the fourth thoracic to third lumbar nerve. They enter the
sympathetic system through the white rami, where they arborize in the
ganglia of this chain to form connections with neighboring ganglia
above and below their point of entrance. Each gangUon in turn
remits a certain number of secondary fibers which again reach the
corresponding spinal nerve by way of the neighboring gray ramus.
From here they are distributed to the smooth muscle cells of the skin
of that particular region. The fact that the sympathetic gangUa
permit of a spreading of the primary impulse may be proved by the
stimulation of the neighboring white and gray rami. For example,
while the excitation of a certain gray ramus will yield pilomotor effects
only in that segment of the body to which the corresponding mixed
nerve is distributed, the stimulation of the neighboring white ramus
most generally evokes these effects in the areas of the three or four
adjoining spinal nerves. Obviously, this result can only be obtained
if the primary impulse is relayed to neighboring efferent paths, and
naturally, there is every reason to believe that this spreading is not
1 While the production of "goose flesh" and the erection of the hairs are usually
classified as involuntary phenomena, cases have been placed on record which
show that individuals may acquire an accurate voluntary control over these
otherwise purely sympathetic reactions.
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS 635
confined to the pilomotor impulses, but also involves other sympathetic
impulses.
Afferent Conduction in the Autonomic System. — We have noted
that those fibers of the anterior horn which eventually enter the white
ramus communicans, terminate around the cells of the first sympa-
thetic ganglion (Fig. 314, S). The axons of the latter either return
to the spinal nerve by way of the gray ramus communicans or continue
within this system to other more distant ganglia. The neuron form-
ing the connection between the cord and the sympathetic ganglion
constitutes the preganglionic path (P), and the one situated on the
distal side of the ganglion, the postganglionic path (Po). This termin-
ology, however, is not always indicative of real conditions, because
some of the preganglionic fibers rnay pass directly through the first
sympathetic ganglia without entering into communication by synapse
with these cells. According to Langley, the precise nature of a
certain sympathetic fiber may be ascertained by moistening the
gangUon with a solution of nicotin (N), This agent, it will be remem-
"^ 4
i
Fig. 314. — Diagram to Illustrate the Action of Nicotin.
C, Spinal cord; P, preganglionic path; S, sympathetic ganglion; Po, postganglionic
path; E, effector; /, neuron which does not form a synapse in »S; II, neuron forming
synapse in S; N, destroys connections in synapse, blocking nerve impulse in neuron
// but not in /.
bered, first stimulates and then paralyzes the cells, preeminently at
their junction with the axon terminations of the central neurons.
Consequently, the stimulation of the preganglionic path must remain
without effect if the fibers composing the latter actually enter into
synapses within the nicotinized area (II). The reason for this is
that the nicotin has produced a block within the ganglion. Conversely,
if the central fibers traverse the ganglion without entering into com-
munication with other cells (I), they must necessarily retain their
power of conducting impulses to peripheral parts, because the nicotin
does not affect the nerve-fibers. In the latter case, therefore, the
excitation of the preganglionic path must give rise to motor effects.
It is true, however, that this method does not allow of a universal
application, because certain animals, such as the dog, are very re-
sistant against this agent; in fact, its action differs even in the same
animal when applied to different structures. Thus, it has been found
that the cervical ganglia are much more susceptible to it than the
ganglia of the splanchnic area.
The autonomic nervous system is essentially a distributing mechan-
ism and hence, its ganglia may be said to serve primarily the purpose
636 THE AUTONOMIC NERVOUS SYSTEM
of relay centers. As such they effect a considerable increase in
the number of the efferent channels, because when the preganghonic
path terminates in a certain sjnnpathetic ganglion, its fibers arborize
and form various new connections with these cells. The postganglionic
path, therefore, must be numerically stronger than the preganglionic.
A similar multiplication of paths results in the next ganglion and so on
until the periphery has been reached, where we find such intricate
ramifications of fibers as the plexuses of Meissner and Auerbach, or the
plexus cardiacus. Obviously, this fan-like expansion of the primary
path into multiple secondary and tertiary paths, enables the principal
center to control a large number of effectors and a wide area of tissue.
In the second place, it renders the distal ganglia and plexuses partially
independent of the cerebrospinal centers, because they can intercom-
municate with one another without that the impulses need be relayed
within the cerebrospinal system.
The formation of these relatively local centers for the control
of particular processes, necessitates the development of a certain
number of afferent channels, without which the motor actions could not
attain the preciseness required of them. While it cannot be doubted
that these afferent elements are present, it must be admitted that they
are fewer in number and retain for the most part a local importance.
It is also evident that their number varies considerably in different
parts of the autonomic system. This must necessarily be so because
certain structures, such as the glands along the intestinal tract, re-
quire a closer functional correlation than other organs. In general,
it may be said that these afferent sympathetic neurons serve two
purposes, namely, to effect perfectly local reflexes and to consummate
reactions in parts remote from the seat of the stimulation. In the
latter case, the impulses may even enter consciousness and give rise
to voluntary actions. This, however, is rather the exception. To
illustrate, the stomachtor intestine may be excised and if kept under
proper conditions of moisture and temperature, may be made to move
and to secrete in a manner not widely different from normal. This
implies that these organs are in possession of local nervous mechanisms,
consisting of afferent and efferent arcs and their corresponding end-
organs, which enable them to continue their actions even when iso-
lated from the cerebrospinal system or from neighboring sympathetic
ganglia. But it is also evident that these organs are constantly sub-
jected to stimuli arising elsewhere in the autonomic system or even
in the cerebrospinal system itself. Thus, a flow of gastric juice or of
any other digestive secretion may be evoked by stimuli arising else-
where in the abdominal cavity or in the receptors of the mucous mem-
brane of the mouth, the taste-buds, olfactory cells, and others. The
fact that the different sympathetic paths contain afferent fibers, finds
ample proof in the pressor and depressor reactions following in the wake
of the excitation of the hepatic and mesenteric plexuses. ^ It may be
1 Burton-Opitz, Quart. Jour, of Exp. Physiol., iv, 1911, 93.
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS 637
concluded that these different local reflex circuits are associated by
commissural fibers.^
Lastly, it should be noted that the afferent impulses of the auto-
nomic system may pass into the cerebrospinal system to be received
eventually in consciousness (Fig. 314, V). The fact that a path of this
kind exists, may be gathered from the work of Dogiel,^ who has found
that afferent visceral fibers arise in certain sensory cells of the sympa-
thetic system which then enter the posterior root and arborize around
the cells of the spinal ganglion. From here these visceral impulses
are conveyed inward over the usual afferent tracts of the spinal cord.
Thus we may. obtain at times distinct sensations of visceral pressure,
pain and temperature, such as arise in the course of the movements
of the stomach, intestine, bladder, and other organs. It must be
admitted, however, that the viscera are relatively insensitive to ordi-
nary stimuli, as may be gathered from the fact that the handling or
cutting of internal organs does not give rise to a decided sensation of
pain, whereas the mere opening of a body-cavity by an incision through
the integument can scarcely be effected without local or general anes-
thesia. It should be noted, however, that the sensation of visceral
pain need not be restricted to the area in which it has been produced,
but may also be projected to the surface layers of the body by way
of the corresponding cutaneous somatic fibers. Thus, a diseased organ
may give rise to a hypersensitiveness (hyperalgesia) and tenderness
to mechanical and thermal stimuli in an area of the integument cor-
responding to the distribution of these fibers. As examples of referred
visceral pain might be mentioned the radially disseminated pain ex-
perienced in the course of the passage of calculi through the biliary
ducts or the extreme painful sensations which may be elicited by
pressing upon the integument in the region of a gastric ulcer.
In general, therefore, it may be said that the autonomic system
possesses the same functional powers as the cerebrospinal system, be-
cause it serves as a :
(a) Conductor of efferent and afferent impulses,
(6) Center for reflex action,
(c) Tonically automatic center which retains the parts innervated by it in a
condition of tonus, and as a
(d) Center for the regulation of the trophic condition of these parts.
Pseudo- or Axon-reflexes.^-The question has frequently been
asked whether reflexes may also be elicited with the help of single
ganglia and their peripheral connections? This should remind us
first of all of the controversy pertaining to the nature of the patellar
reflex which has finally been decided in favor of the view that it is
not an axon-reflex, but is actually effected with the help of the cor-
responding spinal center. The only other structure which need be
considered in this connection is the spinal ganglion. It has been found
1 Hoffman, Jahresber. fiir die ges. Med., cclxxi, 1904, 113.
2 Der Bau der Spinalganglien des Menschen und der Saugetiere, Jena, 1908.
638
THE AUTONOMIC NERVOUS SYSTEM
that, in the lower forms, its cells are typically bipolar, while in the
mammals they are unipolar, possessing a single process which divides
into two branches, one of which enters the spinal cord and the other, '
the spinal nerve. As commonly conceived, the function of these
fibers is to conduct impulses from the periphery to the posterior region
of the spinal cord. Naturally, the severance of the corresponding pos-
terior root would render these fibers useless for reflex action, because
they would thereby be disconnected from their efferent channels
and motor-organs. A moment ago, however, we have noted that the
spinal ganglia receive certain afferent fibers from
the sympathetic system. Under experimental con-
ditions these afferent sympathetic fibers may also
be made to conduct in a centrifugal or eft'erent
direction. It need not surprise us, therefore, to
learn that the stimulation of these spinal ganglia
frequently gives rise to vasodilator effects in that
region of the body from which the aforesaid afferent
fibers have been derived. It is highly improbable
that an effect of this kind is produced under normal
conditions, although it may arise in consequence of
inflammatory reactions in the region of the spinal
ganglia, multiple neuritis and other conditions.
While our search for axon-reflexes within the
realm of the cerebrospinal system has thus proved
negative, it cannot be doubted that the ganglia of
the autonomic system are well adapted for this
form of reflex action, because practically every one
of them is a reflex center .dominating the function
of a rather circumscribed region of the body. No
definite facts, however, are at hand to prove that
the sympathetic system is especially constructed
for true axon-reflexes. The example usually given
is the following: If the inferior mesenteric ganglion
(Fig. 315) is isolated from the central nervous
system by the division of its preganglionic path
(P), but is left in functional relation with the blad-
der (B) through the two hypogastric nerves (H), the stimulation
of the central end of one of these nerves invariably evokes a con-
traction of the musculature of the opposite half of this organ. If
the aforesaid ganglion is now moistened with a solution of nicotin,
this motor effect cannot be obtained. The conclusion to be de-
rived from this experiment is that this ^' reflex'^ cannot be effected
without the help of the cells of the inferior mesenteric ganglion, but
since the normal conditions of conduction have been reversed in this
case, we cannot justly regard this reaction as a true reflex. For this
reason, Langley and Anderson^ have applied to it the term of pseudo-
1 Jour, of Physiol., xvi, 1894, 410.
Fig. 315.— Dia-
gram Showing Ner-
vous Innervation
OF Bladder.
C, Spinal cord;
JM, inferior mesen-
teric ganglion; P,
preganglionic path ;
Po, post-ganglionic
path formed by H,
the hypogastric
nerves; B, bladder.
THE SYMPATHETIC AND PARASYMPATHETIC SYSTEMS 639
or axon-reflex. Obviously, the stimulus is applied here to normally
efferent fibers from which the impulse is then transferred at the central
synapses to the efferent fibers of the opposite side. This transfer
is made possible by the fact that each preganglionic fib^r arriving
in this ganglion, divides into two branches, one of which pursues a
direct course to the corresponding side of the bladder, while the other
makes connections by synapse with the fibers forming the opposite
hypogastric nerve.
On closer analysis, however, it becomes evident that this particular
experiment does not prove anything further than that the normal
direction of conduction in the hypogastric fibers may be reversed by
experimental means. This is not a new fact, because Ktihne has shown
that a similar reversion may be effected in the motor nerves of skeletal
muscle. It will be remembered that the nerve innervating the gra-
cilis muscle divides into two branches, one of which supplies the
upper, and the other, the lower end of this muscle (Fig. 74). * Inas-
much as a contraction may be evoked in its upper end by the stimula-
tion of the nerve terminals in its lower end, the fibers of this normally
efferent branch must be able to conduct the impulses so generated in
an afferent direction. It should not be assumed, however, that this
reversal of conduction may also take place under perfectly normal
conditions. The same statement applies to the manner of conduction
within the sympathetic system, because we have not been able to
observe these phenomena under other than experimental conditions.
There is one reaction, however, which may be of positive value and
that is the following: If an irritant, such as mustard oil, is applied to
the skin, this area becomes red, swollen, warm and painful in con-
sequence of the dilatation of its blood-vessels. These changes may also
be brought about after the sensory fibers from this region have been
severed, but are much diminished if the sensitiveness in this part is
first abolished by a local anesthetic. It appears, therefore, that
this vasomotor reaction is not effected in a direct manner, but reflexly.
Now, inasmuch as this area may be isolated from its center by the
division of its afferent fibers, the resultant dilatation of the blood-
vessels must have been brought about by a local reflex accomplished
solely with the help of peripheral axons and their collaterals./
1 Bardy, Skand. Archiv fur Physiol, xxii, 1908, 194.
SECTION XVII
THE MEDULLA OBLONGATA AND THE CRANIAL
NERVES
CHAPTER LII
THE FUNCTION OF THE MEDULLA OBLONGATA
The Medulla as a Reflex Center. — While the medulla oblongata
or bulb may be regarded essentially as a part of the spinal cord, it
really possesses a much greater functional importance than the latter,
because it gives lodgment to a number of centers which control the
most vital processes in our body. Thus, a separation may be effected
Vagoglossopharyngeal
roots Nucleus of the
Restiform | fasciculus solitarius
body I Tsenia
Vagus nucleus
Faso'culus solitarius
Descending root of vestibular
nerve (VIII)
yago-glossopharyngeal
roots
Fasc. long, medialis
Nuc. spinal V. tract
Spinal V. tr.
N. ambiguus
Olivo-cereb. tract
Dorsal acces. olive
xternal arcuate fibers
Medial lemniscus
Medial acces. olive
Inferior olive
Pyramid
External arcuate fibers
Fig. 316. — Cross-section Through the Adult Human Medulla Oblongata at the
Level op the IX Cranlvl Nerve. (From Cunningham's Anatomy.)
between this structure and the other parts of the central nervous sys-
tem without actually destroying the life of the animal, but its isola-
tion must be brought about by sections through the region of the
pons and through the spinal cord below the nuclei of the phrenic nerves.
If the latter section is made above this point, the ensuing paralysis
of the diaphragm would, of course, make life impossible. Similarly,
640
THE FUNCTION OF THE MEDULLA OBLONGATA 641
the destruction of the medulla itself is followed by an almost immediate
cessation of the respiratory movements, a relaxation of the vascular
channels and a stoppage of the heart.
The centers situated in the domain of the bulb are of two kinds,
namely, simple reflex and dominating or automatic. Regarding
their function, nothing further need be said, because the manner in
which reflex action is effected has already been discussed in detail
in an earlier chapter. The following bulbar reflex centers have been
localized with some degree of accuracy:
(a) Closure of the eyelids. The sensory impulses reach the medulla from the
cornea, conjunctiva, and vicinity of the eyelids by way of the trigeminus nerve.
They are transferred to the motor fibers of that branch of the facial nerve which
innervates the orbicularis palpebrarum. The center itself extends from the ala
cinera to the posterior border of the pons. While this reflex is bilateral in character,
the volitional closure of the lids may be unilateral and may be intensified by the
contraction of the neighboring muscles of the face.
(6) Center for sneezing. The afferent arc is formed by the trigeminus, and the
efferent arc by the nerves innervating the different muscles of respiration. In
addition, afferent impulses may be received by way of the olfactory and optic
nerves, because this reflex is also evoked by intense odors and sudden high intensi-
ties of light.
(c) Center for coughing. It is situated above the center for respiration. The
sensory side of this reflex circuit is formed by the afferent fibers of the vagus, and
the efferent arc by the nerves innervating the muscles of the larynx and the expira-
tory muscles of the thorax.
(d) Center for mastication and sucking. The sensory path includes the second
and third branches of the trigeminus and the glossopharyngeus. The motor
path includes the facialis to the muscles of the lips, the hypoglossus to the tongue,
and the third branch of the trigeminus to the muscles raising and lowering the
lower jaw.
(e) Center for deglutition. It is situated near the floor of the fourth ventricle
above the respiratory center. The afferent side of this circuit is formed by the
second and third branches of the trigeminus and the vagus. Its efferent side is
formed by the vagus.
if) Center for the secretion of saliva. It is placed near the floor of the fourth
ventricle and may be activated by different sensory impulses. Its efferent fibers
enter the parasympathetic system and appear peripherally as the chorda tympani
and the auriculotemporal branch of the inferior maxillary division of the trigeminus.
(g) Center for vomiting. Besides the afferent fibers of the vagus, these im-
pulses may also be derived from other sensory tracts, such as the optic and ol-
factory. The chief efferent fibers are contained in the vagus.
The Medulla as an Automatic Center. — The foregoing discussion
shows that the reflex centers of the medulla are practically identical
with the nuclei of the different cranial nerves concerned in these
reactions. For this reason, the latter may be considered as gene-
rating a state of nervous activity very similar to that displayed by
the spinal nuclei or by the cells of the automatic centers regulating
the most vital processes in our body, namely, respiration, the action
of the heart, and the distribution of the blood. These functions are
of such great importance that the medulla is capable of assuming
through them a position almost independent of the cerebrum and
41
642
MEDULLA OBLONGATA AND THE CRANIAL NERVES
allied structures. Inasmuch as it is thus placed in a position to in-
fluence the respiratory, cardiac and vasomotor activities, it must also
dominate in an indirect way, the function of the cerebral centers.
Lastly, the medulla must be considered as an organ of conduction,
because it occupies a position directly in the path of the cerebro-
spinal tracts. It also gives origin to several of the cranial nerves which
in this way are enabled to gain access to the higher centers. All in
all, therefore, the medulla is one of the most widely connected struc-
tures of the nervous system.
Nuc. dorsalis vagi'
Nuc. fasc. solitarius'
Fasc. solitarius
Nuc. fasciculus
cuneatus
Nuc. XII
Spinal V nuc
Spinal V tr.
Nuc. sal. inf.'
X root
Nuc. ambiguus'
Reticular
formation
Inferior olive
XII root
Ala cinerea
Trigonum hypoglossi
Nuc. vestibularis spinalis
Fasc. long. med.
Lemniscus V
Corpus restiforme
Tr. spino-cereb.
dorsalis
Tr. rubrospinalis
Tr. spino-cereb.
ventralis
Lemniscus spinalis
^Tr. tectospinalis
^Lemniscus medialis
-Pyramidal tract
Fig. 317. — Diagrammatic Cross-section Through the Human Medulla Oblongata
AT THE Level of the Vagus Nerve, Illustrating Details of Functional Localization.
{Herrick.)
CHAPTER LIII
THE CRANIAL NERVES
The Functional System of the Cranial Nerves. — We have seen
above that the spinal nerves enter the cord by a series of roots
arranged in strict agreement with segmentalism. The sensory fibers
and corresponding gray matter occupy the dorsal realm of this struc-
ture, while the motor fibers with their gray matter are situated ante-
riorly. The cranial nerves show a similar functional arrangement,
because the sensory centers are situated dorsally to the motor, but the
segmentalism observed in the case of the spinal fibers has here given
way to a perfectly definite grouping of the different units. This enables
all impulses of like character to become closely associated. In general,
therefore, it may be said that the twelve pairs of cranial nerves repre-
sent twelve pairs of interlocking systems, regulating one or several
independent functions, irrespective of their anatomical location. This
fact shows that the grouping of the components of the cranial nerves
THE CRANIAL NERVES
643
is based upon function rather than upon structure, and implies that
these components are arranged in accordance with their terminations.
Thus, the classification of these nerves should be based upon the
Out edge of eeretellar peduncle
Pineal body
ColUculus superior , , ,
- ColUculvs inferior \ "f '"^- 1"^^'
Pulvinar of thala^mua
iteaial geniculate body
Jjateral geniculate body
Funiculus gracilis
funiculus cu)i
tndeenieal *'^ ventricle
Fig, 318. — View from Dorsal Aspect of Upper Part of the Spinal Cord, Medulla
Oblongata, Pons, Fourth Ventricle, Mid-brain, Thalamus, etc.. Dissected in situ.
(J. Symington.)
type of organ with which they are united peripherally or upon the
type df center in which they arise or terminate. ^ Thus, it happens
that a certain cranial nerve may embrace fibers from two different
1 Herrick, Wood's Reference Handbook of the Med. Sciences, iii, 1914, 321.
644
MEDULLA OBLONGATA AND THE CRANIAL NERVES
sense-organs which then diverge centrally to seek the respective centers
for these functions. Again, a certain sense-organ may distribute its
ingoing fibers to two different cranial nerves, after which they reunite to
attain a common center.
This structural divergency implies that the cranial nerves may be
efferent or afferent in their function, as well as mixed. The
efferent fibers arise, of course, in cells situated within the domain of
the cerebrum, isthmus and medulla, while the cells of the afferent
fibers are situated in special ganglia at some distance from these parts.
In the latter case, the same arrangement is found to exist as in
the spinal ganglia, i.e., the sensory cell sends out an axon which soon
divides into two branches, one of them tending toward the brain, and
the other toward the peripheral sense-organ. The trophic centers
of the motor fibers, therefore, are situated within the brain, and those of
the sensory fibers in the peripheral ganglia.
With the exception of the first and second pairs, the cranial nerves
arise from the medulla oblongata and neighboring parts, their nuclei
being situated chiefly in the gray matter below the floor of the fourth
ventricle and its prolongation below the aqueduct.
1. The olfactory nerve, or nerve of smell, forms the connection be-
tween the olfactory region of the nose and the olfactory center. These
Olfactory tract
Granule cell
' Mitral cell
Glomerulus
Olfactory nerve
Ethmoid bone
'""^---^ Olfactory epithelium
Fig. 318a. — Diagram of the Connections of the Olfactory Bulb. (Herrick.)
fibers arise in the olfactory cells of the aforesaid area, whence they
attain the primary center within the olfactory bulb by passing through
the cribriform plate of the ethmoid bone. The arborizations formed by
these fibers in this particular locality, are known as glomeruli and repre-
sent synapses between the primary and secondary olfactory neurons.
The latter, which begin here, are known as the mitral cells. Their
axons continue inward and form the so-called olfactory tract, ending
finally in the secondary olfactory nucleus,^ at the base of the olfac-
tory bulb. The olfactory center is then attained by three paths which
are known as the medial, intermediate and lateral olfactory striae. -
1 Zwaardemaker, Ergebn. d. Physiol., i, 1902; also: Edinger, Vergl. Anat. des
Gehirns, Leipzig, 1908.
THE CRANIAL NERVES 645
The center itself contains the following subdivisiofis: (a) The lateral
olfactory nucleus which extends backward into the tip of the temporal
lobe of the cerebrum as far as the point of contact between the ventro-
lateral extremities of the hippocampus and hippocampal gyrus,
(b) the medial olfactory nucleus into which the medial olfactory striae
are discharged, and (c) the intermediate olfactory nucleus in the anterior
perforated substance in which the intermediate olfactory striae termin-
ate. These nuclei are intimately connected with other cerebral centers
and diverse motor paths, thereby enabling the sensory impressions
of smell to become associated with other sensations as well as with
the different motor mechanisms. This close correlation permits these
nuclei to play the part of reflex centers, in which the olfactory impulses
are transferred to efferent paths and to the motor end-organs. In
man, these olfactory reflex centers are dominated by a psychic or
cortical center which, as will be shown later, occupies the hippocampal
convolution, especially its distal end, the uncus. Different association
paths connect this area with other cortical centers.
2. The optic nerve, or nerve of sight, conveys the impulses from
the retina to the thalamus, where they are transferred onward to the
center for vision in the occipital region of the cerebral cortex. The
, essential receptive element of the eye is the retina which forms the
'innermost coat of this sense-organ and contains neurons of the fol-
lowing four types: (a) The rods and cones, (6) the bipolar cells, (c)
the ganglion cells, and (d) the horizontally arranged association neu-
rons. The fibers of the optic nerve take their origin from the ganglion
cells, but this does not mean that these elements constitute neurons
[of the first order. In fact, as the real receptors of the retina are the
[rods and cones, these elements should be regarded as forming the
peurons of the first order of the optic path. Their impulses are
[transmitted across the external molecular layer to neurons of the sec-
[ond order, the cell bodies of which are situated in the internal granular
flayer. These data tend to show that the ganglion cells of the retina
[are already neurons of the third order which then leave the eye through
:he optic papilla to form the optic nerve proper.
Having reached the optic chiasma at the ventral aspect of the
jrebrum, these fibers enter into a decussation which carries them either
part or as a whole to the opposite side of the brain. A complete
jrossing is effected in fishes, amphibians, reptiles and most birds, and a
)artial one in man and the mammals, namely, in those animals in
rhich the visual fields overlap and which possess stereoscopic vision.
'here is, however, no evidence at hand to show that the crossing in
ihe latter is absolutely symmetrical, because the number of fibers
remaining on the same side seems to become the greater, the higher
the rank of the animal in the scale of the Animal Kingdom. In man,
lowever, the fovea centralis or yellow spot seems to be innervated
bilaterally, i.e., the fibers emerging from this area pass to both visual
centers. This crossing carries the fibers from the inner halves of the
646 MEDULLA OBLONGATA AND THE CRANIAL NERVES
retinae to the opposite side and leaves the fibers from their outer
halves on the same side. Thus, the right occipital center innervates
the right halves of both retinae, and the left center their left halves.
The yellow spot of each eye, on the other hand, is innervated by both
centers. 1
Posteriorly to the chiasma, these crossed and uncrossed fibers con-
tinue upward and backward in the form of the optic tracts. Having
passed the surface of the thalamus, they divide into two groups, one
of which terminates in the lateral geniculate body and the other in
the roof of the colliculus of the midbrain. In this way, certain reflex -M
centers are established which are concerned with the movements of the ^
LEFT RETINA RIGHT RETINA
Fig. 319. — Diagram Showing the Probable Relations Between the. Parts of the
Retina and the Visual Area of the Cortex. The Bilateral Representation of the
Fovea is Indicated by the Course of the Dotted Lines. (Schdfer.)
eyeballs, the process of accommodation, and other reactions. This is
true especially of the colliculus, while the thalamus seems to be set
aside rather as a relay station in the path leading to the visual center
situated in the occipital cortex of the cerebrum. The latter, therefore,
forms a direct dependency of the cortical center and hence, its impor-
tance must increase with the development of the center for vision. We
find here, therefore, an arrangement very similar to that previously
noted in the case of the olfactory mechanism, i.e., the light impressions
received by the retinae, may actually reach the center for vision to be
associated or may be transferred unto a motor path in the lower reflex
center situated in the superior colliculus. In the former case, they must
first give rise to a psychic impression, and, in the latter, to a simple
* Wilbrand and Sanger, Die Neurologie des Auges, Wiesbaden, 1904.
THE CRANIAL NERVES
647
reflex reaction. This lower center is intinlately connected with the
path for tactile and auditory sensations by way of the neighboring
cerebral peduncle and is closely associated with the nuclei of the third
and fourth cranial nerves. Connection is also made here with the
other cranial and spinal nerves by way of the fasciculus longitudinalis
medialis.
3. The oculomotor nerve arises from the oculomotor nucleus
situated in the central gray matter near the floor of the aqueduct of
Fig. 320. — Diagram of the Principal Components op the Optic Apparatus.
{Cunningham.)
Sylvius. The latter is composed of three groups of cells, namely,
(a) a lateral colony of large ganglion cells situated next to the median
line below the aqueduct, (5) a smaller median colony consisting of large
cells, and (c) a median colony composed of much smaller cells. This
nerve is motor in its function and embraces fibers for:
(a) The internal rectus, superior rectus, inferior rectus and inferior oblique
muscles of the eye. According to Bernsheimer, ^ these fibers arise in the group of
cells constituting the lateral subnucleus. The coordination of these muscles with
those of the opposite eyeball, is not under the guidance of the will. This nerve
also innervates the muse, levator palpebrse superioris.
1 Handbuch der Augenheilkunde, Leipzig, 1900.
648
MEDULLA OBLONGATA AND THE CRANIAL NERVES
(6) The sphincter muscle of the iris. These fibers take their origin in the
median colony of small cells and terminate in the ciliary ganglion. Here they make
connection with postganglionic fibers formed by sympathetic neurons (nervi
ciliares breves).
(c) The ciliary muscle. These fibers arise in the median colony of large cells
and end in the ciliary ganglion. Their postganglionic continuations are formed by
sympathetic neurons (nervi ciliares breves).
We shall see later that the contraction of the ciliary muscle allows
the lens of the eye to become more convex, a condition necessary for
near vision. This change is usually accompanied by a constriction
of the pupil. These two reactions occur simultaneously and constitute
accommodation reflexes. In addition, the pupil is also constricted
whenever a high intensity of light is permitted to strike the eye. This
* Edinger-Westphal nucleus.
Principal nucleus.
Median nucleus.
Nucleus of 4th nerve.
Fig. 321. — Nuclei or Origin of the Third and Fourth Nerves. — {From
Poirier and C harpy.)
reflex constitutes the so-called light reflex. In accordance with the
preceding discussion, it must now be evident that the afferent arc of the
circuit for the light reflex is formed by the optic tract, and the efferent
arc by the oculomotor nerve. Its center lies in the reflex area of the
optic tract, i.e., in the colliculus and corpora quadrigemina near the
aqueduct of Sylvius. The constriction of the pupil associated with
near vision and constituting the so-called accommodation reflex, finds its
origin in certain sensory stimuli which are set up in the eye muscles
whenever the eyes are converged for a near point. The afferent arc
of this reflex circuit, therefore, does not encroach upon the optic tract
and is not directly concerned with vision.
THE CRANIAL NERVES
649
4. The trochlear nerve arises in the trochlear nucleus which is
situated in the central gray matter below the floor of the aqueduct just
posteriorly to the lateral subnucleus of the oculomotor nerve. These
fibers pass horizontally backward and emerge behind the posterior
corpora quadrigemina, where they cross in the anterior medullary
velum. It is a motor nerve supplying fibers to the superior oblique
muscle of the eyeball. The action which this muscle gives rise to,
simultaneously with the muscle attached to the opposite eyeball, is not
under the control of the will.
5. The trigeminus nerve originates from two roots, a small anterior
or portio minor, and a large posterior or portio major. The former is
motor and the latter sensory in its function. Its motor root arises
in part from a small nucleus in the pons and partly from ganglion
Accessory
N. opht
ly ^i^\ Principal
^i>^ i motor
-jT^y^ji^j nucleus
Descending
spinal root
N. max. sup. N. max. inf.
Fig. 322. — Nuclei of Origin op the Fifth Cranial Nerve.
after Van Gehuchten.)
(From Poirier and Charpy,
cells situated in the region of the corpora, laterally to the aqueduct
of Sylvius. Its musculomotor fibers are distributed peripherally
through the ramus masticatorius to the different muscles of mastica-
tion, as well as to the muscles of deglutition, inclusive of the muse,
mylohyoid eus, the tensor veli palatini and muse, azygos uvulae. It also
contains secretomotor fibers for the lacrimal gland and sweat-glands,
and vasomotor fibers for the tongue and face. The latter, of course,
are of sympathetic origin and use the path of this nerve merely as a
highway to reach distal parts.
This nerve is of importance chiefly on account of its sensory power,
because it conveys the sensations of touch, pain and temperature from
the skin of the face, the adjoining region of the scalp, the mucous
membrane lining the nasal and oral cavities, and from the teeth and
650 MEDULLA OBLONGATA AND THE CRANIAL NERVES
eyes. Stimuli brought to bear upon its distant receptors, give rise
to a large array of reflex actions, such as inhibition of the respiratory
movements, closure of the glottis, slowing of the heart-beat, and secre-
tion of the tears and saliva. The trigeminus is also said to convey the
sensations of taste from the anterior third of the tongue, but it is more
than probable that the taste fibers contained in this nerve, have been
derived from the glossopharyngeus or nervus intermedins. The
sensory fibers of this nerve arise in the Gasserian ganglion in a manner
similar to the fibers of the spinal ganglion. Their peripheral branches
pass to the sense-organs, while their central branches divide and are
arranged as two roots which end (a) in the sensory nucleus situated
laterally to the motor nucleus and (6) in a long nucleus which extends
through the entire dorsal portion of the medulla. This arrangement
enables the impulses to be relayed from the sensory nucleus of this
nerve through the median raphe to the cortex of the cerebrum. In
addition, collaterals are sent to all the nuclei of the cranial nerves
• arising in 'the medulla, with the exception of the nucleus abducens.
It should also be mentioned that this nerve communicates with the
ganglion sphenopalatinum and ganglion submaxillare which form the
outposts of the sympathetic system of this region.
6. The abducens nerve originates in a nucleus situated below
the colliculus facialis, and emerges from the posterior edge of the pons.
It is a motor nerve and innervates the external rectus muscle of the
eyeball. Like the third and fourth cranial nerves, it is under the con-
trol of the will, but not when made to act synchronously with others to
produce those movements of the eyeballs which are necessary in
binocular vision and accommodation.
7. The facial nerve arises from a conspicuous nucleus in the teg-
mental region of the pons and leaves the brain at the inferior margin
of this structure, somewhat lateral to the point of emergence of the
sixth nerve. It is chiefly a motor nerve and supplies the muscles of
the face, those of a part of the scalp, and those of the ear, inclusive of
its intrinsic muscles. As such it governs the expression of the face.
This may be gathered from the fact that its division is soon followed
by a distortion and a drawing over of the paralyzed side of the face
toward the normal. This deviation which eventually may also in-
volve some of the bones, is produced by the tonic pull exerted by the
muscles of the normal side. In many cases, however, the paralyzed
muscles finally show a condition of contracture which then tends to
antagonize this pull so that the face again assumes a more normal
appearance. Another muscle which takes part in this paralysis is the
orbicularis. The inability to close the space between fhe eyelids
exposes the cornea to mechanical and thermal influences which in
turn give rise to a copious secretion of lacrimal fluid, and possibly
also to inflammatory processes. The paralysis of Horner's muscle
prevents the offlow of the tears into the nasal cavity. In view of the
fact that the facial nerve als6 innervates the muscles which have to do
THE CRANIAL NERVES
651
with nasal respiration, its division leads to a loss of movement of the
nostrils. Phonation is impaired.
This nerve also contains secretomotor and vasomotor fibers for
the submaxillary and sublingual glands which reach their destination
by way of the chorda tympani. It also embraces secretomotor fibers
for the lacrimal glands which pass through the ganglion sphenopala-
tinum and reach the second branch of the trigeminus and subsequently
the nervus zygomaticus and nervus lacrimalis. Its sensory fibers
convey taste impressions from the front part of the tongue. They
form the nervus intermedins and are affixed to the chorda tympani
and lingual nerves.
fy/A
Fig. 323. — The Oeigin of the Sixth and of the Motor Paet of the Seventh Nerve.
F/m Sixth nerve; YII., seventh nerve; a.VII., ascending part of the root of seventh
shown cut across near the floor of the fourth ventricle; gr, genu of seventh nerve-root;
n.YI., chief nucleus of the sixth nerve; n.'VI., accessory nucleus of sixth; n.VII., nucleus
of seventh; d.V., descending root of &i th ; pyr., pyramid-bundles; VIII.v., vestibular
root of eighth nerve. (Schdfer.)
8. The auditory nerve consists of two groups of fibers possessing a
certain anatomical and functional independency. One of them is con-
cerned with hearing and forms its cochlear branch, and the other with
the sense of equilibrium and forms its vestibular branch. In the horse
and sheep these fibers are in fact absolutely separated from one another
throughout their course.
The auditory nerve enters the bulb in two parts, an external and
an internal. The fibers of the former are derived chiefly from the
cochlea, and those of the latter from the semicircular canals and the
vestibule of the. internal ear. The first connect with the spiral gan-
glion of the cochlea and the latter with the vestibular ganglion of the
semicircular canals. These peripheral stations are comparable to
the spinal ganglia, because the cells composing them send out processes
which soon divide into two branches. One of these connects with the
652
MEDULLA OBLONGATA AND THE CRANIAL NERVES
peripheral receptor, and the other with the central nucleus. If we
now follow these fibers in the latter direction, we will find that they
pursue a separate course; those contained in the vestibular branch
ending in the nuclei of Deiters and Bechterew in the cerebellum, and
those belonging to the cochlear division in the ventral and dorsal
nuclei of the pons. From these primary relay stations the auditory
impulses are conveyed onward to the auditory center in the superior
gyrus of the temporal lobe of the cerebrum, but the course pursued
by them, has not been fully made out as yet. It seems, however,
that the largest number of the fibers arising in the ventral or accessory
nucleus acusticus, cross to the opposite side of the cerebrum. They
TO VERMIS
TO HEMISPHERE
fiJ.b
FIBRES OF
VESTIBULAR
ROOT
NERVE
ENDINGS
IN MACUL>E
4.AMPULL/&
Fig. 324. — The Course and Connections of the Fibers Forming the Vestibular
Root of the Auditory Nerve.
r., Restiform body; F, descending root of fifth nerve; p., principal nucleus of ves-
tibular root; d, fibers of descending vestibular root; n.d., a cell of the descending ves-
tibular nucleus; Z>, nucleus of Deiters; B, nucleus of Bechterew; n.t., nucleus tecti
(fastigii) of the cerebellum; pZ6., posterior (dorsal) longitudinal bundle. {Schafer.)
select, however, somewhat different routes. -Some of them tend
directly across through the corpus trapezoideum, while others reach
this structure by passing around the restiform body and through the
tegmental region. From here they attain the superior olivary body
of the same and opposite sides and subsequently the lateral fillet or
lemniscus. Having traversed the colliculus or median geniculate
body, they terminate eventually in the psychic area for audition,
situated in the superior gyrus of the temporal lobe. .
The dorsal nucleus or tuberculum acusticum is connected with
this center by secondary sensory neurons which form the medullary
or auditory striae, a band of fibers traceable along the floor of the
fourth ventricle. At the median raph^ these fibers turn and a large
THE CRANIAL NERVES
653
number of them cross the midhne to attain the lateral lemniscus of
the opposite side, whence they reach the gray matter of either the
inferior colliculus or median geniculate body. These structures are
connected with the psychic area for hearing by way of the auditory
radiation which passes through the inferior extremity of the internal
capsule.
We observe, therefore, that the auditory nerve finally gives rise to
a decussation which bears a close resemblance to that effected by the
optic nerve, but the degree of crossing has not been determined as
yet with certainty. As we shall see later, this fact is very important,
because it helps to explain some of the symptoms resulting from uni-
lateral destruction of the center of hearing. In the second place, it
FIBRES TO NUCL.LEMNISCI
&CORPORA QUADRIGEMINA
NERVE-ENOINGS
• N ORGAN OF CORTi
Fig. 325. — The Course and Connections of the Fibres Forming the Cochlear Root
OP the Auditory Nerve.
r., Restiform body; V, descending root of the fifth nerve; tub.ac, tuberculum
acusticum; n.acc, accessory nucleus; s.o., superior olive; n.tr., nucleus of trapezium;
n.VI, nucleus of sixth nerve; VI, issuing root-fiber of sixth nerve. (Schafer.)
will be seen that the median geniculate body may serve the purpose of
a secondary auditory center and hence, assume a position similar to
that of the lateral geniculate body which is really a subordinate center
for vision. Thirdly, sufficient experimental evidence is at hand to
show that the auditory centers form the starting points of certain motor
paths which are used in the reflex actions resulting in consequence
of auditory stimuli.
9. The glosso'pharyngeus nerve is motor and sensory in its function.
It emerges from the side of the medulla, its motor fibers originating
from two nuclei, known as che nucleus ambiguus which forms the
ventral area of the vagus nucleus, and the nucleus dorsalis which is
situated below the floor of the fourth ventricle. Its sensory fibers are
derived from the ganglion superiore and ganglion petrosum. The
peripheral branches of these pass to the receptors and their central
654
MEDULLA OBLONGATA AND THE CRANIAL NERVES
branches in part to the nucleus alae cinereae and in part to the nucleus
tractus solitarii. Its sensory and motor fibers are thereby brought
into close relationship with those of the vagus nerve.
Its musculomotor function is restricted to the muscles of the
pharynx (muse, stylopharyngeus) and its secretomotor function to
the parotid gland. The latter is reached by way of the ganglion
petrosum, nervus tympanicus, nervus petrosus superficiahs minor,
ganglion oticum and nervus auriculotemporalis. Its sensory fibers
are in relation with the mucous membrane of the tongue, pharynx,
Fig. 326. — Diagram Showing the Bra.in Connections of the Vagus, Glossopharyngeal,
Auditory, Facla-l, Abducens, and Trigeminal Nerves. {After Obersteiner.)
tonsils, tympanic cavity and Eustachian tube. It also conveys
the sensations of taste from the posterior third of the tongue and the
lateral aspect of the fauces.
10. The vagus or pneumogastric nerve arises from the same nuclei
as the ninth nerve, and emerges from the side of the medulla posterior
to the superficial origin of the preceding. It is a mixed nerve. Its
motor fibers are traceable to the nucleus ambiguus and the dorsal
or vagus nucleus. Its sensory fibers take their origin in the ganglion
jugulare and ganglion nodosum and pass to the nucleus alse cinereae
and, in small numbers, also to the nucleus tractus solitarii. While
the function of this nerve will be considered in detail in connection with
THE CRANIAL NERVES
655
the organs innervated by it, it may be stated at this time that it is
primarily concerned with respiration, the action of the heart, and the
musculomotor and secretomotor processes of the digestive organs.
(a) Respiration. It supplies motor fibers to the muscles of the larynx, trachea
and bronchi. The most important nerves to be mentioned in this connection are
its superior and inferior laryngeal branches. It also serves as the sensory nerve
of the larynx (sup. laryngeus) and the lungs. The latter are directly concerned
with the self-regulation of respiration.
(6) The Heart. The vagus conveys inhibitor impulses to this organ, and also
sensory impulses from this region by way of its "depressor fibers."
ycuLA
vagus]
\
ARCUATE
NUCLEUS
XII.
[HYPOGLOSSAL]
FiQ. 327.
-Cross-section of Medulla Showing Nuclei of Nerves x and xii.
(Cunningham.)
(c) Digestive Organs. The vagus innervates the sphincters of the pharynx
and the musculature of the esophagus, stomach and intestine. It sends secreto-
motor fibers to the stomach, intestine, pancreas and possibly also to other abdom-
inal organs. The vasomotor mechanisms of these organs are supplied with fibers
from the solar plexus. While the latter in turn communicates with the thoracic
sympathetic system through the splanchnic nerves, it is also intimately connected
with the vagus system.
11. The accessory nerve is formed from several upper roots which
take their origin in the medulla, and from a series of lower roots which
arise from the anterior gray matter of the spinal cord as low as the
fifth to seventh cervical vertebrae. It is a motor nerve and suppHes
the sternocleidomastoid and trapezius muscles.
656 MEDULLA OBLONGATA AND THE CRANIAL NERVES
12. The hypoglossal nerve emerges from the furrow between the
anterior pyramid and olivary body of the medulla. Its deep origin
is formed by a nucleus situated in the floor of the fourth ventricle.
A commissure unites the nuclei in the two halves, and each nucleus
receives fibers from the opposite cerebral hemisphere. It is a motor
nerve and innervates the muscles of the tongue, inclusive of the muse,
geniohyoideus and thyreohyoideus.
SECTION XVIIi
THE CEREBRUM
CHAPTER LIV
THE GENERAL FUNCTION OF THE CEREBRUM
General Arrangement of the Gray Matter. — The investigation of
the function of the brain of which the cerebral hemispheres form the
largest part, is usually carried on along structural, experimental
physiological, and clinical lines. A complete functional picture,
however, can only be obtained if the data derived from these sources,
are compiled and compared with one another. On the histological
side, it is of interest to note that the chief neurons of the cerebral
cortex are pyramidal in shape and are directed in such a way that their
apices are turned toward the surface and their bases toward the white
matter. The three poles of these cells are usually occupied by den-
drites, the principal one of which arises from the apex. The axon
is derived from a hillock in the middle of the base of the cell-body
and pursues a rather straight course into the white matter, giving
off collaterals in its course.
While this cell is typical of the cerebral cortex, it does not exhibit
the same size and form in all parts of this organ. Throughout the
cortex, however, it is united with others to form four or five separate
layers which border immediately upon the central core of white matter.
(a) The most superficial layer lies, of course, in contact with the enveloping
lembranes of the cerebrum, i.e., with the pia mater, and is known as the plexiform
lor molecular layer. Its thickness amounts to 0.25 mm. Besides the neuroglia
icells, it contains chiefly dendrites from the deeper layers and a few small cells, the
[processes of which are directed parallel to the surface of the cortex. These proc-
fesses terminate within this layer and do not penetrate the white matter. It
fis believed, therefore, that their function is chiefly associative for the cells of the
Icortex. •
(6) The layer of pyramidal cells lying directly underneath the former, is char-
|acterized by the presence of a large number of cells possessing a pyramidal shape.
Campbell^ arranges them in three layers, this classification being based upon
fdifferences in their size. The inner ones are larger than the outer. As has been
;mentioned above, their apices are directed outward and send their dendrites into
Hihe molecular layer. The axon arises from the basal margin of the cell and enters
}the white matter underneath. The dendrites of the pyramidal cells are rough and
^ Hist. Studies on the Local, of Cort. Function, Cambridge, 1905.
42 657
658
THE CEREBRUM
thorny; in fact, it has been claimed that these projections form actual synaptic
connections with neighboring neurons.
(c) The stellate or granular layer contains numerous cells possessing a stellate
shape and short irregular axons. It is also known as the middle cell lamina.
(d) The inner fiber lamina contains numer-
ous large and medium-sized cells which are
known as the cells of Betz. The latter are not
present in all parts of the cerebral cortex, but
are most conspicuous in its motor area next to
the fissure of Rolando. Their axons pass into
the white matter.
(e) The layer of fusiform or polymorphous
cells is situated next to the white matter. It
is also known as the inner cell lamina and is com-
posed of different types of cells of which the
spindle-shaped ones are the most prominent.
It also embraces a number of pyramidal cells
similar to those found in the outer realm of the
more superficial layer, but their tips are directed
inward and their bases toward the surface.
These are the cells of Martinotti. In addition,
this layer contains a cell resembling the second
type of Golgi with branching axons. The latter
terminate in the neighboring gray matter.
General Arrangement of the White
Matter. — The medullary portion of the
cerebrum begins directly below the poly-
morphous layer. When stained in ac-
cordance with Weigert's method which
brings out the meduUated nerve fibers,
the white matter is seen to be arranged
in radial striae, i.e., its fibers expand fan-
Hke from a common center formed by
the internal capsule. Some of these ra-
dial streamers may be followed to the
surface of the cortex and may be seen to
give rise here and there to networks of
fibers which are placed transversely to
the course of the former. A layer of
this kind is found directly underneath
the surface of the cortex, but it does not
extend throughout the brain. It is
most conspicuous in the hippocampal
region. Another layer is situated be-
tween the molecular and pyramidal
zones, and still another internally to the
granular zone. These layers are known
respectively as the outer and inner
stripes of Baillarger. A special layer
of transverse fibers is found in the visual
area of the occipital lobe where it bisects the granular layer. This is
Fig. 328. — Postcentral Convolu-
tion. Golgi Method.
i; Plexiform layer; 2, small
pyramids; 3, medium pyramids;
4, superficial large pyramids; 5,
granules; 6, deep large pyramids;
7, deep medium pyramids. (Cajal.)
THE GENERAL FUNCTION OF THE CEREBRUM 659
the line of Gennari, which really corresponds to the outer stripe of
Baillarger.
It will be seen, therefore, that the cortex of the cerebrum presents
a definite histological structure which, however, does not remain the
same in its different regions. Certain minor differences appear here
and there, which enable us to tell from which particular area a certain
section has been taken. In making this distinction, we should be
guided by (a) the thickness of the entire cortex, (6) the relative thick-
ness of its different zones, (c) the type of cells found in each layer,
and (d) the character of the radial and transverse striae of fibers. Thus,
it is to be noted that the thickness of the human cortex varies from about
4 mm. in its motor region to about 2 mm. in other parts. In the
/
Fig. 329. — Neuroglia Cells of Cortex Cerebri. Golgi Method. (G. Retzius.)
former area are found the large pyramidal cells of Betz which are char-
acteristic motor elements. In addition it is to be observed that the
layer of pyramidal cells is very thick, while the granular layer is thin.
The visual area of the occipital lobe is characterized by a very
prominent granular layer which, as has been stated above, is really
divided into two by a broad band of transverse fibers. The distinguish-
ing feature of the association areas of the frontal, parietal and oc-
ciptal lobes is the highly developed outer layer of pyramidal cells.
Classification of the Tracts of the Cerebrum. — The fibers of the
cerebral white matter are arranged in three distinct groups, namely:
(a) Those which connect the hemispheres with the outlying
structures of the nervous system, i.e., with the thalamus, pons, medulla
and spinal cord.
1 Brodmann, Vergl. Localisationslehre der Grosshirnrinde, Leipzig, 1909; also
Ramon y Cajal, Stud, tiber die Hirnr. des Menschen, Leipzig, 1906, or Lewan-
dowsky, Handb. der Neurologie, Jena, 1910.
660
THE CEREBRUM
(6) Those which unite different parts of the same hemisphere
with one another, and
(c) Those which extend from one hemisphere to the other. The
first group forms the so-called projection system, the second, the
association system and the third, the commissural system. Naturally,
each area of the cortex must be equipped with two sets of fibers, one
of which conducts away from it and the other toward it. In the case
of the projection system, the terms of afferent and efferent may be used
FiQ. 330. — Schema of the Projection Fibers of the Cerebrum and of the Peduncles
OP the Cerebellum; Lateral View of the Internal Capsule.
A, Tract from the frontal gyri to the pons nuclei, and so to the cerebellum (frontal
cerebro-cortico-pontal tract) ; B, the motor (pyramidal) tract; C, the sensory (lemniscus)
tract; Z), the visual tract; E, the auditory tract; F, the fibers of the superior peduncle
of the cerebellum; G, fibers of the middle peduncle uniting with A in the pons; H,
fibers of the inferior peduncle of the cerebellum; J, fibers between the auditory nucleus
and the inferior coUiculus; K, motor (pyramidal) decussation in the bulb; Vt, fourth
ventricle. The numerals refer to the cranial nerves. {After Starr.)
to distinguish these fibers from one another, but this terminology
is not applicable to the association and commissural systems, because
these fibers establish communication between different central parts and
do not possess a true motor or sensory function. The projection system
is made up of the following afferent and efferent tracts:
A. Aferent. (a) Thalamocortical. — These fibers arise in the gray matter of all
parts of the optic thalamus and radiate outward to every area of the cerebral cor-
tex. In accordance with their distribution, they are grouped in the form of a
frontal, parietal, occipital and ventral stalk. Those forming the first group, do not
invariably pass directly to the frontal lobes, but may end in the caudate and
lenticular nuclei. Those destined for the occipital lobes, form the so-called optic
THE GENERAL FUNCTION OF THE CEREBRUM 661
radiation. They emerge from the outer part of the pulvinar and external genicu-
late body.
(6) The Fillet System of Fibers. — ^This is the tract which enables the impulses
from the different sensory paths of the cerebrospinal system to reach the thalamus
and subthalamic region.
(c) The Superior Cerebellar Peduncle. — This tract connects the central ganglia
of the cerebellum with the thalamus and subthalamic region. Some of them may
pass directly through and around this structure to reach the region of the fissure
of Rolando.
(d) The Auditory Radiation. — These fibers extend from the internal geniculate
body to the temporal lobe. They traverse the posterior extremity of the internal
capsule under the lenticular nucleus.
B. Efferent, (a) The Pyramidal Tract. — These fibers arise in the motor area
of the cortex and pass through the corona radiata into the internal capsule. Here
they are grouped in the genu and anterior two-thirds of the posterior limb. In
their downward course they enter the crusta and pyramids of the pons and medulla.
Most of them cross the midline in the upper part of the spinal cord to enter the
crossed pyramidal tract. The others continue onward on the same side where they
form the direct pyramidal tract, but cross over gradually in the lower part of the
cord.
(6) The frontopontine fibers take their origin in the cortex of the frontal lobes
and eventually gain the mesial extent of the crusta of the crus cerebri. They
terminate in the formatio reticularis of the pons or nucleus pontis.
(c) The temporopontine fibers originate from the two upper temporal convolu-
tions and enter the outer extent of the crusta. From here they enter the pons,
where they terminate in the nucleus pontis and are brought into relation with the
middle peduncles of the cerebellum. This path, therefore, serves as the chief
efferent bridge between the cerebrum and cerebellum, the afferent connection
between these organs being represented by the fibers passing between the cere-
bellar cortex and dentate nucleus to the superior cerebellar peduncle, red nucleus,
optic thalamus and the cerebral cortex of the opposite side.
The association system unites the different areas of the cerebral
cortex of the same side with one another. • Some of these fibers merely
dip downward into the white matter to clear the bottom of the sulci
tand to enter the cortex immediately adjoining, while others pass to
^more remote regions. For this reason, these fibers are said to form
[short and long association paths, the most prominent of which are the :
(a) Uncinate fasciculus which connects the orbital convolutions of the frontal
[lobe with the anterior segment of the temporal lobe.
(6) Cingulum which passes between the anterior perforated space and the
■ hippocampal gyrus and temporal lobe.
(c) Longitudinal superior fasciculus which forms the connection between the
'frontal, perietal and occipital cortex.
{d) Longitudinal inferior fasciculus which extends along the occipital and
temporal lobes.
(e) Occipitofrontal fasciculus which is situated internally to the corona radiata
^and next to the caudate nucleus.
f The commissural system consists of three chief bridges which unite
the two hemispheres, namely :
(a) The corpus callosum consists of fibers which arise in all parts of the cortex
with the exception of the anterior and posterior segments of the temporal lobes and
,'the olfactory bulb. They originate in cells of the cortex but may also be the
^collaterals of certain projection axons. Having reached the other side, they arborize
extensively.
1 K!(MlO'l
662
THE CEREBRUM
(6) The anterior commissure connects the olfactory and certain portions of the
temporal lobes. It pursues a course through the anterior wall of the third ventricle
anterior to the pillars of the fornix.
Fig. 331. — Lateral View op a Human Hemisphere, Showing the Bundles of Asso-
ciation Fibers.
A, A, Between adjacent gyri; 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.N, caudate nucleus; O.T, thalamus. {After Starr.)
:rv»T^"i£i>^>
Fig. 332. — Dligram of Association, Commissural, and Projection Fibers of Brain.
A, Corpus callosum; B' anterior commissure; C, basal ganglia; D, endings of com-
missural fibers; E, sensory cortex; M, motor cortex; F, endings of association fibers from
motor cortex (collaterals of projection-fibers) ; G, ending of association-fibers from
sensory center; H, projection-fibers from motor cortex passing to spinal centers; /,
projection-fibers from sensory cortex; a, h, c, collaterals. (Adapted from Cajal.)
(c) The hippocampal commissure ia formed in the hippocampus of one side and
ends almost wholly in the same structure of the opposite side. It is closely con-
cerned with the sense of smell.
Mode of Development of the Cerebrum. — In early embryonic
life the nervous system first presents itself as a dorsal tube, known as
THE GENERAL FUNCTION OF THE CEREBRUM
663
the neural tube. It is formed by an invagination of the epiblast.^
Its cavity possesses a somewhat larger caliber in front than in the
region of the spinal cord, and becomes subdivided into three vesicles
■by two constrictions. These are designated respectively as the fore-
brain, midbrain and hindbrain. To begin with, the walls of this tube
are thin, being composed solely of epithelial cells. The nervous
elements develop a little later and show a differentiation into neuro-
blasts and spongioblasts, the former eventually giving rise to nerve-
cells and the latter to the supporting tissue or neuroglia. In several
places, however, the original epithelium remains undifferentiated and
interior heurepere
iPalliuiti of telencephalon
Corpui striatum
"Optic vesicle
Future pontine
fJeKure
encephalon
/Interior neuropore
Mesencephalon
Isthmus
Mesencephalon
optic recess
Future pontine
Rhombeneephahn tley^ure
Fig, 333. — An Enlarged Model of the Brain of a Human Embryo 3.2 Mm. Long
(About Two Weeks Old). The Outer Surface is Shown at the Left, and on the
Right the Inner Surface After Division of the Model in the Median Plane. The
Anterior Neuropore Marks a Point Where the Neural Tube is Still Open to the
Surface of the Body. The Pallium is the Region from Which the Cerebral Cortex
Will Develop. The Optic recess Marks the Portion of the Lateral Wall of the
Diencephalon from Which the Hollow Optic vesicle Has Evaginated. (After His, from
Prentiss' Embryology S)
finally gives rise to a layer of similar cells, known as the ependyma.
^This relationship is shown best in the hindbrain, where the posterior
'■all of the neural canal fails to develop nervous elements and reaches
laturity merely as a layer of epithehal cells covering an expanse of
the tube. This is the fourth ventricle. In other places, again, the
lervous elements grow very rapidly and lead to the formation of more
)r less circumscribed structures. The cerebellum, for example, is
^developed by an offshoot from the dorsal wall of the tube, while the
>ns and medulla are formed by a more even outgrowth round the entire
[central canal. The details of the development of the brain lie, of
[course, outside the scope of this book and must be obtained from
works of more specialized character.
^Keibel and Mall, Manual of Human Embryology, PMladelphia, 1912.
664
THE CEREBRUM
Comparative Physiology of the Cerebrum. — In the course of verte-
brate evolution, the primitive reflex stem of the nervous system event-
ually acquires a number of structures which collectively make up the
brain. Its constituent elements are the hindbrain (rhombencephalon),
midbrain (mesencephalon), tweenbrain (diencephalon) and forebrain
(prosencephalon). The one named last is formed by the cerebral
hemispheres. Obviously, these complex masses find their origin in
the adjuncts to the head ganglia of the lowest forms which, as has
previously been pointed out, are primarily concerned with the forma-
tion of the sense of smell, sight, touch, etc. The point to be empha-
sized is that these areas are developed from small beginnings and that
Fig. 334.— Diagram-
matic Representation of
THE HeXAJD of a TuRTLE, TO
Show the Position of the
Cerebrum C and Optic
Lobes O,
Fig. 335. — Diagrammatic Representation of the
Brain of a Frog {A) and Shark {B).
ON, Olfactory nerves; OL, olfactory lobe; C, cere-
brum; T, tween brain; OpL, optic lobes; Ce, cerebellum;
M, medulla; Co, spinal cord; OC, olfactory capsules;
OB, olfactory bulb. The cranial nerves are indicated
by Roman numerals.
their mass and complexity is in accord with the position of the animal
in the scale of the Animal Kingdom.
Thus, we find that the olfactory realm occupies almost the entire
cerebrum of the fishes, and forms the most conspicuous part of the brain
of the reptilia and amphibia. This condition permits of only one con-
clusion, namely, that the sense of smell is especially well developed in
these animals, and that their existence is mainly dependent upon ol-
faction. Moreover, while their reactions are almost wholly reflex,
they must also possess a moderate power of associating these sensa-
tions. As we ascend the scale of the Animal Kingdom, this sense
becomes retrogressive. A constantly increasing number of other
mechanisms are added to the hemispheres which enable the animal
THE GENERAL FUNCTION OF THE CEREBRUM
665
to assume a more diversified position in nature. This is true partic-
ularly of birds, their more elaborate powers being directly attributable
to a greater development of the corpus striatum and cerebellum. In
mammals, on the other hand, these bodies remain relatively small,
whereas the external shell of the cerebrum, or pallium, is brought into
much greater prominence. These differences have led to the division
of the contituents of the cerebrum into two groups, namely, those
which are intimately associated with the sense of smell, and those
which are chiefly concerned with vision, hearing and touch. The
Body of corpus calloaum
Intermediate mass
Fornix
Septum pellucidum
MargiruU
Genu of co^-piu cailomm
CHngulate
Tela choroidea ventriculi tertii
Cingulate gyrus
Callosal fissure
Splenium of corpus callosum
Paracentral lobule
Central fissure
Suhparietal fissure
Precuneate lobule
Parieto-occip. fissure
Calcarine fissure
Cuneate lobuU
Lamina terminalis
Optic recess
Optic nerve
Optic commissure
Hypophysis
Corpus mamillarei
Zrd ventricle
Cerebral peduncle
Pons
Suprapineal recess
Pineal body
Cerebral aqueduct
Cerebellum
Medulla oblongaia
4th ventricle
' Superior medullary telum
Corpora quadrigemina
Fig. 336. — Median Section of an Adult Brain. (/. Symington.)
former are spoken of collectively as the archipallium, and the latter as
the neopallium. The first system is the more primitive. Its impor-
tance gradually diminishes in favor of the second.
As a natural consequence of this evolution we find that the cerebral
hemispheres increase in volume and complexity until, in the mammals,
they become larger than the whole of the rest of the brain put together.
They overshadow the primitive olfactory apparatus completely, and
extend backward across the brain-stem as far as the middle of the
cerebellum. In this way, it comes to pass that the primitive reflex
cerebrum of the lower forms which is largely apportioned to smell,
666 THE CEREBRUM
is finally changed into the complex association organ of the higher
animals. As such it is destined eventually to dominate all processes
of life, because it gives rise to the psychic products involved in con-
sciousness, perception, vohtion, thought and memory. In the higher
forms, therefore, all reactions are referable in last analysis to the
psychic processes, because while they may not always be the direct
outcome of cerebral activity, the latter unfaiHngly determines the
condition of the body as a whole and hence, also the power of reaction
of its constituent tissues and organs.
The brain of the higher animals, therefore, possesses a distinguish-
ing feature in its many areas of nervous tissue which are primarily
intended to be adjuncts to the different motor and sensory mechanisms.
This statement, however, should not imply that they are all psychic in
their function; in fact, they are not so to begin with. These additions,
as has been stated, bring about an increase in the mass and weight of
the brain. Thus, we find that the human brain weighs about 1400
grams in the male and 1240 grams in the female, and is heavier than
that of any of the lower forms, excepting the whale and elephant.
Even a casual study of the beh&,vior of these three types of animals
will show that man is distinctly superior to the other two, and even
to those animals which, relatively speaking, possess the same amount
of brain tissue.
The reason for this is not difficult to detect. It Hes in the fact that
a large part of the human brain is taken up by nervous material which
gives rise to those associations which are necessary for reflection,
intelligence, and volition. In other words, the human brain possesses
the distinguishing feature of being more of a psychic mechanism than
that of any other animal. It will be seen, therefore, that while the
absolute amount of brain tissue of such animals as the dog, ape and
man remains practically the same in all three, the human brain has
lost much of that kind of nervous material which is ordinarily set
aside for motor action and sensation. Instead, it has acquired certain
units for the formation of those associations which add a distinct
psychic quality to these fundamental processes. This gradual evolu-
tion of the cerebral hemispheres, therefore, accompHshes a shifting
of function from lower centers to a higher psychic realm situated in the
cortex. In the human brain, this transfer of function is portrayed
best by the relationship existing between the cortical or psychic
centers for vision and hearing and the corresponding lower '^ reflex"
centers situated in the thalamus and geniculate body. In other words,
man's position in the scale of the Animal Kingdom is determined by
the gradual subordination of these lower centers of the brain-stem
to the more recently formed cerebral hemispheres and especially
to their cortical portions.
This functional metamorphosis displays itself in an increase in the
complexity of the brain rather than in an increase in its weight.
Thus, we find that the rabbit's brain presents a very smooth surface,
THE GENERAL FUNCTION OF THE CEREBRUM
667
while that of the cat, dog and ape is decidedly uneven, i.e., it is crossed
by furrow-like depressions or sulci which divide it into numerous convolu-
tions and lobes. Its greatest complexity it attains in man, but even here
certain differences are apparent in that the brain of the more, primitive
S./rontaUtir/mor
S.frmlalu
8. firontalu vutUut
Bamua ptft. of Sylvuin f.
8. iemparalU mediu9
S. ocdpitdLu lateralis
8. occipUalit trannemts
Fig. 337. — Left Cerebral Hemisphere from the Lateral Aspect. (J. Symington.)
8. centraltt {Itolandt)
Pan marffinaltf $. cingitl
Fatciadtntata
Fig. 338. — Left Cerebral Hemisphere from the Mesla.l Aspect.
The label "caput hippocampi" has been placed too far forward. The caput hippo-
campi does not extend in front of the incisura temporalis. (/. Symington.)
races is poorer in convolutions than that of the more advanced peoples.
In addition to these external differences, we are also able to make out
certain internal peculiarities which pertain chiefly to the structure of the
668 THE CEREBRUM
cortex. In the rabbit, for example, the poljnnorphous layer displays a
thickness three times greater than that of the pyramidal layer, whereas
in man just the reverse relationship exists. The inference to be drawn
from this is that the pyramidal cells are the association units of the
brain, excepting, of course, the cells of Betz which are motor in their
function, while the polymorphous elements are concerned with the lower
types of function. By exclusion, we may then assign a sensory func-
tion to the constituents of the granular layer.
This analysis should also take into account that the ^'psychic"
brain of man exhibits certain minor differences in regard to the relative
size and complexity of its different association areas. One or the other
of these may be more highly developed with the result that the mechan-
ism of which the area so favored forms a part, possesses a greater
functional adaptability. In other words, it frequently happens that
these association centers are not evenly balanced. It need scarcely
be emphasized that such differences may also be displayed by one and
the same association area belonging to the brains of different indi-
viduals, i.e., one or the other person may excel in certain motor or sen-
sory actions.
Removal of the Cerebrum. — The preceding discussion may well
be amplified by a study of the behavior of animals which have suffered
a partial or complete loss of the cerebral hemispheres by disease or
surgical operation. While the symptoms appearing subsequent to the
latter procedure vary somewhat in different animals, they present
nevertheless the same general characteristics. The essence of these
changes is that an animal, the cerebrum of which has been removed, is
devoid of associations. Its psychic life, whether simple or complex,
has been destroyed. It has been converted into a simple reflex ma-
chine. This fact will be brought out more clearly by a brief considera-
tion of the functional capabilities of decerebrated fish, amphibia and
reptilia. These animals are selected for this purpose partly because
their cerebrum is sufficiently compact and easy of access to permit of
its quick removal, and partly because the positive results following
this operation are so few that they do not overshadow the principal
effect briefly alluded to above. As this operation is performed under
ether, these animals should, of course, be permitted to fully recover
before they are studied.
Emphasis should be placed upon the fact that the loss of the
cerebrum destroys the sensorium. The decerebrated bony fish (shark) '
shows the same power and manner of movement as a perfectly normal
animal. It tends, however, to be more inactive, assuming a rather
continuous position of rest which is changed to one of activity only
upon stimulation. But when made to move, its motor reactions show
no deviation from normal. More decided defects, however, appear
when the lesion is extended to the midbrain, because the animal then
is rendered blind and loses its sense of equilibrium.
^ Bandelot, Ann. d. sc. nat., 105, 1864.
THE GENERAL FUNCTION OF THE CEREBRUM 669
Quite similarly, a decerebrated frog^ shows few modifications in
its behavior, excepting those directly referable to the loss of the sense
of smell. It retains a normal posture and jumps and swims normally.
It rights itself when placed upon its back, and executes centrifugal
and balancing motions when placed upon a rotating disc. Provided
that the thalamus has not been injured, it avoids obstacles placed in
its way, and reacts to stimuli applied to the nasal mucous membrane by
various protective movements. These reactions, however, it shows
only when stimulated. Its normal attitude is one of inactivity, be-
cause it has lost the memory of past experiences and instincts. For
this reason, it need not surprise us that an animal of this kind takes no
food but must be fed ; in fact, the food must be placed directly into its
mouth. The processes of deglutition and digestion are in no way
impaired, and hence, it is possible to keep this animal for many months
or even for years. A general idea regarding the function of the cere-
brum may be had from the character of the croaking reflex before and
after the removal of the hemispheres. Under normal conditions,, this
act is a complex association phenomenon; i.e., this sound is produced
only in consequence of definite cortical processes, and is under the
guidance of the will. In the absence of the cerebrum, on the other
hand, it is a pure reflex, so that it may be eUcited at any time by the
proper kind of stimulation consisting in a gentle pressure upon the
lateral aspects of the chest and abdomen. Furthermore, if we pass
our hand over a number of normal frogs, these animals will immediately
make motor efforts to escape from the area of stimulation, while the
decerebrated animals will not. In brief, we may say that the latter
have lost their associations and are no longer under the control of
motives or sensations of fear.
The same general effects are manifested by birds^ when deprived
of their cerebral hemispheres. They assume a position of rest, generally
upon one leg with the head drawn in and the bill buried in the
feathers. Every now and then they will open their eyes, stretch
themselves, and walk about in the cage. This nonresponsive attitude
may be disturbed at any time by stimulation, i.e., the animal may
be made to fly by throwing it some distance into the air, or it may be
made to execute balancing movements upon a rope swung back and
forth. It will right itself immediately if placed upon its back, and
continues to move about if made to do so. In all these cases, however,
the position of rest is sought very soon after the stimulation ceases.
Its reactions are machine-hke, and are executed without definite purpose
or regard to environment. This is well shown by the decerebrated
pigeon which, when made to fly, soon alights upon any object situated
in its path even if it should endanger its life. As all its digestive
processes and spinal reflexes are perfectly normal, this pigeon may be
kept for an indefinite period of time provided, of course, that it is
^Blaschko, Sehzentrum der Frosche, Berlin, 1880.
2 Bechterew, Archiv fur Physiol., 1890, 489.
670 THE CEREBKUM
fed and properly attended to. In fact, its initial lethargy is partially
compensated for in time, owing to the gradual development in the lower
centers of certain activities previously suppressed.
The removal of the cerebral cortex in mammals presents several
technical difficulties and is attended by certain motor and sensory
defects which do not permit of a precise analysis. Still, it is easily
noted that this operation does not destroy the ordinary spinal and basal
reflexes and does not lead to a complete disarrangement of the motor
functions. This is true not only of rabbits, guinea pigs, and cats,^
but also of dogs. Directly after the operation, these animals showed
a spastic rigidity of their extremities, the so-called decerebrate
rigidity, 2 as well as an extensor tonus and an upward deviation of the
head, or opisthotonos. These symptoms disappeared in the course
of a few days, whereupon the animal was capable of making relatively
precise muscular movements.
The dogs of Goltz^ were operated on at intervals of several months,
a part of the cerebrum being removed each time. They were kept
for 51 and 92 days and one 'for 18 months. On autopsy it was found
that they had retained small portions of the striate body, optic thala-
mus and uncus. All these parts, however, were soft and atrophic and
in all probability functionally useless. The animals began to move
about within a few days after the operation and even walked across
inclined planes. They rested by assuming the usual position, but
could not be kept in a normal nutritive condition, in spite of the fact
that they were rather overfed. They reacted to sensory stimuli
by snarling, barking and the erection of the ears, but not in a way to
display recognition or to effect an intelligent motor response. Their
spinal reflexes remained normal. The animal which was kept longest,
finally acquired the power of taking food without being helped,
although it had to be held directly under its nose. Food with a dis-
agreeable taste was not swallowed. In general, therefore, these ani-
mals displayed the same defects as the birds, reptilia and amphibia,
namely, a loss of understanding and memory which made willful and
purposeful motor responses impossible. Only the simple reflexes were
retained, namely, reactions which do not involve complex associations.
The condition of these animals was one of general imbecihty.
It has previously been emphasized that the development of the
cerebral hemispheres in the higher animals leads to the gradual
transfer of at least a part of the motor processes to this realm. This
implies that they are finally subjugated to the activities of the cortex.
As this higher control must, of course, be most complete in the apes and
man, it may be inferred that the destruction of parts of their cere-
brum must give rise to symptoms which are much more intense and
lasting than those previously noted in the case of birds, reptilia and
1 Probst, Jahrb. fiir Psych, und Neurologie, 1904.
2 Sherrington, Phil. Transactions, London, 1896.
3 Pfluger's Archiv, iii, 1892, 570.
THE GENERAL FUNCTION OF THE CEREBRUM 671
amphibia. It appears, however, that the general deductions then
made, also hold true in the case of man. We know this from a study
of the behavior of infants born with cerebral defects as well as from a
study of the symptoms following accidental injuries to the cerebral
cortex. The cases of inherited absence of the cerebrum ' or anen-
cephalus, recorded by Vaschide and Vurpas^ as well as by Sternberg
and Latzko,^ have shown that the spinal reflexes are preserved and that
muscular movements are possible, and especially those concerned with
mastication, sucking, crying and grasping. The anencephalous infant
described more recently by Edinger and Fischer,^ lived for nearly four
years. At autopsy it was shown that its cerebral hemispheres had been
displaced by fluid, creating a condition similar to hydrocephalus. During
this time it showed no signs of intelligence, but its motor defects
were so slight that even its mother did 'not believe that anything was
wrong with it until, when about two and a half years old, it began
to show extensive contractures and absolute lethargy.
The destruction of considerable portions of the brain does not
prove fatal as a rule unless the injury extends beyond the cortex of the
anterior and central convolutions. In fact, the superficial region of
one whole hemisphere may be rendered functionally useless without
terminating the life of the individual. A process of gradual exclusion
of the cerebral cortex is at work in advanced stages of insanity, when
the psychic life is terminated more and more until the human body
is finally reduced to a machine-like reflex existence, effected with the
help of the more deeply seated subsidiary centers.
CHAPTER LV
CEREBRAL LOCALIZATION
THE MOTOR AREA
The Functional Separation of the Cerebral Cortex. — The doctrine
that consciousness in its various aspects is the product of several
individualized functions of the brain, was first developed by Galenus
(131-203 A.D.), although the cerebral hemispheres have really been re-
garded as the material basis of consciousness since the time of Hippo-
crates (460-377 B.C.). In fact, it is claimed that this view was first
expressed by Alkmeon of Grot on in about the year 500 B.C. The
imaginative qualities were said to be seated in the frontal, intelligence
in the central, and memory in the posterior regions of the cerebrum.
This conception that consciousness is composed of separate units and
1 Compt. rend, de Facad., cxxxii, 1901.
2 Deutsche Zeitschr. fiir Nervenheilk., xxiv, 1903, 209.
3 Pfliiger's Archiv, clii, 1913, 535.
672 THE CEREBRUM
that, therefore, the cerebral cortex is divisible into several, minor or-
gans, has been made use of by Gall, ^ a physician of Vienna, in framing
his system of cranioscopy, or, as it was called later on by Spurzheim,
the science of phrenology. Being of the firm belief that the psychical
power of an individual is seated in the cerebrum, he outlined definite
areas upon the external surface of the cortex in accordance with defi-
nite mental qualities. This localization he based upon a study of the .
external characteristics of the cranium of people who showed especially
well-marked mental faculties. He reasoned that the cerebral area
controlling a certain function must increase in volume in proportion to
the state of development of the latter; moreover, this internal change
must betray itself in a greater prominence of the skull plate of this
particular area. While this deduction is in general correct, Gall
carried it too far, and was in no position to furnish experimental
proof for his assertions. These facts were subsequently exploited
for commercial purposes and no definite scientific good was derived
from them, at least, not immediately.
This assumption of Gall that the cerebrum is not a single organ or
functional unit, was first criticised by riourens,^ and his followers
Magendie, Longet, Budge and Schiff. It was finally pointed out that
the mental life of man cannot be subdivided into a series of independent
faculties, this conclusion being based upon the theoretical and experi-
mental data of different writers. Thus, Flourens showed that the
destruction of the cerebrum of pigeons is followed by a loss of intelli-
gence which it is impossible to grade by a partial destruction of this
organ. In other words, the successive removal of certain parts of the
cerebrum did not give rise to a progressive series of psychic defects,
but to a uniform lowering of the sum total of the psychic processes.
This inability to localize certain functions in definite areas of the
cortex led him to believe that the cerebral hemispheres act as a uni-
form whole and produce the phenomena of consciousness jointly.
This conclusion found substantiation in the symptoms displayed by
individuals who had suffered accidental injuries of the brain. It will
be shown later on that this conception of Flourens is correct only in
part, because subsequent researches have proved beyond doubt that
there is a distinct difference in the functions of the different parts of
the cerebrum, or rather in the quality of the contribution which they
severally make to consciousness. Mourens, however, was correct in
his belief that the psychic life is really dependent upon a proper
functional interaction of the different constituents of the brain.
This doctrine of Flourens was commonly accepted until Broca
(1861) gave final proof of the fact that the loss of speech so frequently
associated with apoplexy, is due to the destruction of the left inferior
1 Recherches sur la syst. nerv. en general et sur celui du cerveau en particulier,
1810.
2 Rechersches experimentales sur les proprietes et les fonctions du syst. nerv.
dans les animaux vertebres, 1824.
CEREBRAL LOCALIZATION 673
frontal convolution. This conclusion was based in part upon the
earlier work of Bouillaud (1825) which tends to show that the speech
center is situated in the anterior extremities of the frontal lobes.
[Furthermore, it was proved by M. Dax and G. Dax (1830) that in
[right-handed people this area is confined to the left cerebral hemisphere.
Lttention has also been called repeatedly to the observation of Galenus
that a paralysis of the body results in consequence of lesions to the cere-
>ral hemisphere of the opposite side. These data, however, were
lot considered of sufficient importance until Broca called special
bttention to them.
In 1864 H. Jackson, stimulated by the work of Broca, proved that
bhe muscular spasms characterizing epilepsy, are due to an excitation
>f the cerebral cortex. A firm basis was given to this view in 1870
)y Fritsch and Hitzig,^ who showed that the cortex of the cerebrum
|is irritable and that its stimulation evokes perfectly definite muscular
responses. These tests were first made upon dogs, but were later on
extended to other animals and also to the apes and man by Ferrier,
[orsley, Schaffer, Sherrington, Luciani, and others. As a direct
result of this work, we find a complete abandonment of the doctrine
|of Flourens and the acceptance of a view which may be said to be more
lirectly in line with the conception of Gall. As has been pointed
|out above, the latter regarded the cerebrum as a plurality of organs,
[n its modified form this doctrine holds that the cerebrum is composed
)f circumscribed areas possessing different sensory and motor func-
|tions. Emphasis is placed upon the fact that these parts are not
separated from one another, but are intimately associated and inter-
related with one another so as to yield coordinated function. This
fundamental conception is in no way altered by the doctrine of Flechsig
[(1894) which asserts in addition that the different areas of the cerebral
jeortex consist of projection and association fields. In other words,
pthe different cerebral spheres seem to be built up of a central core
id a peripheral zone which possesses a true psychic character.
The Location of the Motor ^rea. — The discovery of Fritsch and Hit-
dg, that the cortex of the brain is irritable, completely overthrew the
)ld conception of Haller, which assumed that only the underlying
rhite matter is pervious to stimuli. The latter view prevailed for so
long a time, because it was advocated by such experimenters as Mag-
jndie, Longet, Mateucci, Budge and Schiff, and was based chiefly upon
iheir inability to evoke motor reactions by the stimulation of any area
)f the cerebral surface. As Fritsch and Hitzig made use of the galvanic
|current, which tends in time to induce electrotonic alterations, their
localization left much to be desired. They showed, however, that
the muscular effects are confined to the opposite side of the body
and may be varied in their intensity by changing the strength of the
1 Arch, fiir Anat. und Physiol., 1870, 300.
43
674
THE CEREBRUM
current. The finer details were brought out subsequently by Ferrier^
by means of faradic stimulation.
The motor area is situated along the fissure of Rolando (sulcus
cruciatus) of each hemisphere and occupies the anterior and posterior
central convolutions. Each area is composed of a number of motor
points, so-called, because their stimulation with fine electrodes gives
rise to contractions of only one particular muscle or group of muscles.
In mapping out this field, it is also to be noted that these motor points
are arranged in a definite manner, those governing the activity of the
muscles of the trunk being situated very close to the longitudinal
fissure, and those controlling the posterior extremity upon the upper-
FiQ. 339. — Lateral View of the Brain of a
Dog. Diagram I>a)iCATiNG the Location of the
Motor Area.
CS, Crucial sulcus; T, L, A and i^, areas for
the muscles of the trunk, leg, arm and face.
Fig. 340.— Diagram Showing
THE Motor Points in the Cere-
brum OF THE Dog.
most convexity of the cerebral surface.. Directly below this field we
find the motor points for the anterior extremity and at a still lower
level those for the facial muscles. In general, therefore, it may be
stated that each motor area is composed of four minor fields which
control respectively the movements of the trunk, leg, arm, and face.
Each minor field is subdivided in turn into still smaller ones, the so-
called motor points.
This finer subdivision of the motor areas is not apparent in such
mammals as the rabbit, cat, and dog, but becomes unmistakable in the
monkeys and reaches its highest development in the apes and man.
While only very general reactions can be evoked in rabbits, the cat and
dog show movements of a more specialized character. This may be
gathered without difficulty from the preceding Fig. 340, illustrating
1 Les fonctions du cerveau, Paris, 1878.
CEREBRAL LOCALIZATION
675
the position and functional character of the motor points in the dog.
It is to be noted especially that they are situated on both sides of the
crucial sulcus and are sufficiently centralized to permit, for example,
the separate activation of the flexors of the anterior and posterior
extremities and other rather specialized movements, such as the re-
traction and abduction of the fore limbs, movements of the tail, closure
of the eyelids, constriction of the pupils, movements of deglutition, and
others.
The movements themselves are in no way different from those
produced in the course of the normal volitional efforts of the animal.
Toes
Hip--.
Elbotu
Wri
Tinyers
jCh£st
Eyelid /Closure \ "^X^ "'^^''Z^Suleus Centrals
Mose ^j"^"*" Oberting s/oaa.1 Mastieatiojt,
Fig. 341. — Location op Motor Areas in Brain op Chimpanzee.
The different motor points lie in front of the fissure of Rolando, partly within the
feSulci. The area marked "eyes" yields conjungate movements of the eyes, but is
generally not taken to be a part of the motor area. {Sherrington and Greenbaum.)
[This implies that they are never antagonistic to one another, for the
treason that, having evoked a contraction of the flexors, the extensors
[are momentarily inhibited, and vice versa. This preponderance of
[one set of muscles, even when the stimulation involves the motor points
lof both groups, may be destroyed by rendering the nervous structures
fmore irritable by means of strychnin or the toxin of tetanus. Under
this condition the cerebral stimulation spreads, activating the entire
reciprocal mechanism. We then obtain a strife between the antagonis-
tic muscles with the result that the stronger ones predominate.
As has been emphasized above, the effect of the stimulation of
the motor area is unilateral, and is restricted to the side opposite the
excitation. There is one exception to this rule and that is conjugate
movement. Thus, it will be noted that the stimulation, say of the
676
THE CEREBRUM
right motor points controlling the muscles of the eyes, produces a
deviation of both eyes toward the left. In this case, therefore, an
activation of the right internal and left external recti results which
is associated with an inhibition of the right external and left internal
recti. The same holds true of other movements which are carried
on with the help of corresponding muscles on the two sides of the
body, such as the erection and flexion of the trunk, the approximation
of the jaws, and the contraction of the muscles of the abdominal wall.
Clearly, these movements must be bilaterally controlled and coordi-
nated. A bilateral representation is also had in the case of the respi-
ratory muscles, because, as will be pointed out later, the destruction
of one motor area does not affect the respiratory movements.
The observations of Sherrington and Greenbaum^ have shown that
in the anthropoid apes the motor area is confined to the anterior
SulacaUoso
SulcparieCo
occip.
Sulc. Central. ^""^ * ^'^^
\ ./ StUc.jjrecenCrmarff.
SulccalcaTin.
C.S.S. del.
Fig. 342. — Mesial Surface of Chimpanzee, Showing that the Motor Areas also
Dip into the Longitudinal Fissure. {Sherrington and Greenbaum.)
central convolution, but this discovery is not wholly new, because
a very similar condition has already been proved by Fritsch and Hitzig
to exist in the monkey. These 'tests have been extended to man by
Bartholowand Sciamanna, but particularly by Terrier (1890), Horsley,
Brevior (1890), and Bechterew (1899). The more recent work of F.
Krause^ in particular te/ids to prove that the localization in man is
very similar to that found in the anthropoid apes. The motor points
are concentrated in the precentral convolution and neighboring por-
tions of the frontal furrows and permit of the production of very
specialized movements.
The Motor Area is a True Center. — Fritsch and Hitzig character-
ized the motor area as a center for the production of muscular motion.
1 Proc. Royal See, London, Ixxii, 1903.
2 Lewandowsky, Die Funktionen des zentralen Nervensystems, Jena, 1907.
CEREBRAL LOCALIZATION 677
This conception is correct, because it has subsequently been shown
that the stimulus arises in the gray matter of the cerebral cortex and
not in the fibers leading away from this area. This is proved by the
fact that the latent period, i.e., the time elapsing between the moment
of the appHcation of the stimulus and the beginning of the muscular
movement, is longer when the stimulus is applied to the surface of the
gray matter than when brought to bear directly upon the underlying
white matter. This result clearly betrays the controlling influence of
the cells composing this area. Central formative processes always
consume a much longer time than the mere passage of the impulses
over nerve-tissue. In addition, it has been proved that the gray matter
possesses a lower threshold value of stimulation than the white matter.
In other words, a lesser strength of current is required for its activation
than for that of the underlying fiber substance. This relationship,
however, may be reversed by painting the cerebral surface with cocain
or chloral.^
In this connection it should be stated that muscular movements
may also be evoked by the stimulation of very restricted areas of the
occipital and temporal lobes. These movements, however, remain
confined to the extrinsic muscles of the eyes and ears and seem, there-
fore, to be the direct outcome of the psychic processes occurring in
these particular areas. The impulses here generated are transferred
first of all to the motor area in the precentral convolution and later
on to the distant motor organs. Hence, neither the occipital nor the
temporal lobes should be regarded as true motor centers, although
both are in a position by means of close association paths to activate
the chief motor center in the anterior central region.
Traumatic Epilepsy. — It has previously been stated that the
muscular spasms associated with epileptic seizures, have been attributed
by Jackson^ (1864) to a mechanical irritation of a particular area of
the cerebral cortex. This assertion, which was made sometime before
the publication of the work of Fritsch and Hitzig, was based upon the
fact that certain types of epileptics present definite lesions of the cere-
bral gray matter. A few years later it found confirmation in the ob-
servation of Fritsch and Hitzig proving that the application of a strong
galvanic current to the surface of the motor region gives rise to
powerful and lasting muscular contractions. Ferrier, Luciani and
Unverricht^ showed subsequently that these seizures need not remain
localized, but may acquire a progressive character until they involve
the musculature of practically the entire body. So generalized, they
constitute the clinical picture which is commonly seen during the con-
vulsive seizures of epileptics. It is true, however, that an increase
in the strength of the current is not the only means by which these
1 Francois — Frank and Pitres, Arch, de Physiol, norm. et. path., 1883.
2 Hitzig, H. Jackson und die motor. Rindenzentren im Lichte der physiol.
Forschung, Berlin, 1901; also: H. Jackson, A Study of Convulsions, London, 1870.
^ Archiv fiir Psychiatric, xiv, 1880, 175.
678 THE CEKEBRUM
general seizures may be evoked. In many cases even weak stimuli
suffice, provided, of course, that the nervous system has been rendered
especially susceptible. Conditions of this kind often arise in the
course of eclampsia, uremia, and diabetes, after the toxins contained
in the blood have led to a constant discharge of supraminimal im-
pulses. Thus, Landois^ has succeeded in evoking tonic and clonic
spasms by spraying the motor areas with creatin, creatinin and urates.
The same results may be obtained with such agents as santonin,
physostigmin and bile, and even more readily in pregnant animals, ^
in which the nervous system is in an especially irritable condition.
Traumatic or Jacksonian epilepsy most commonly finds its
origin in tumors or in the pressure exerted upon the motor area by the
projecting pieces of bone of an old fracture. These seizures are
ushered in as a rule by a feeling of numbness and a tingling sensation
in the part to be affected first. Thus, if the motor points of the
muscles of the thumb are the seat of the excitation, the contractions
begin in this part and then spread to the muscles of the hand, forearm,
arm and shoulder, and later on to those of the face, trunk and leg.
Eventually they also involve the muscles of the opposite side of the
body. This orderly sequence or ''march" is also observed if the
contractions begin with the muscles of the toes or foot. When these
seizures are reproduced in animals, it is quite impossible to prevent
the spreading of the contractions from one side of the body to the
other by cutting the corpus callosum. Single muscles, however,
may be prevented from participating in the general convulsion by
ablation of the corresponding motor district. It seems, therefore, that
the aforesaid spreading is made possible through the mediation of the
subcortical paths and centers.
These seizures may last a few seconds or several minutes. They
consist as a rule of a tonic and a clonic phase. To begin with, the
muscles remain tonically set, but presently show repeated attempts at
relaxation: These relaxations are separated from one another at first
by intervals of several seconds, but gradually become more frequent
toward the end of the convulsion. In consequence of these violent
muscular contractions, the body temperature most generally shows a
rise of several degrees, but consciousness is not lost unless the attack
is severe. This fact really serves as one of the differential signs between
Jacksonian and idiopathic epilepsy. The latter is a type of epilepsy
which must be assigned to general retrogressive changes of the cortex.
It need scarcely be mentioned that the traumatic type may be remedied
by removing its cause, the seat of the lesion being suggested by the
manner of progression of the muscular contractions. For example,
if the epileptic seizure begins with tonic and clonic spasms of the
muscles of the thumb, it is to be inferred that the difficulty chiefly
1 Wiener med. Presse, 1887.
^Bickel, Pfliiger's Archiv, Ixxii, 1898, 190, also: Blumenreich and Zuntz, Arch,
fiir Physiol., 1901.
CEREBRAL LOCALIZATION 679
involves the motor points of this particular part. The location of
the trephine opening may then be determined with almost mathe-
matical precision.
Effects of the Ablation of the Motor Area. — In dogs, the destruc-
tion of one motor area results in an incomplete paralysis of the muscles
of the opposite side of the body. This condition is known as hemi-
plegia, the term biplegia being used when both sides are affected.
While this muscular disturbance usually attains its height within a few
hours after the injury, it gradually becomes less acute later on and
disappears in the course of a few days. During the interim, however,
the dog betrays a decided weakness of the muscles situated on the side
opposite to the injury, and generally walks upon the back of the paws.
Furthermore, those muscles which usually act together, never exhibit
so decided a degree of paralysis as those which are not directly related.
Fig. 343. — Diagbam Illustkating the Disposition of the Motor and Sensory Points
IN THE Brain op the Dog (A) and the Brain or the Monkey (B).
In the former animal motor and sensory paralysis generally occur together, because
their points intermingle, while in the apes and man they do not.
Consequently, the muscles of respiration and those of the trunk in gene-
ral are weakened but never paralyzed. This fact indicates that they
are innervated by both hemispheres.
These motor disturbances are associated as a rule with a very
decided loss of the tactile sensations and the muscle sense. It ap-
pears, therefore, that the motor area of the dog, i.e., the anterior
and posterior central convolutions of each side, also embraces certain
sensory points, representing the end stations of the incoming fibers
pertaining to these sensations (Fig. 343). This intermingling of the
motor and sensory points, however, is not in evidence in the monkeys,
apes and man. It will be shown later on that in these animals the
former are concentrated more and more in the precentral and the latter
in the postcentral convolution, inclusive of the neighboring region of
the parietal lobe. Hence, it is possible to obtain in these animals
a motor paralysis which is not accompanied by disturbances of sen-
sation. Conversely, they may show sensory anesthesias without loss
of motion.
680 THE CEREBRUM
In the monkey, the ablation of the motor area gives rise to very-
marked and permanent symptoms. Very instructive observations
have been made by Goltz upon macacus whose left frontal and parietal
cortex had been removed by two operations. The animal remained
under observation for eleven years. The decided hemiplegia fol-
lowing directly after the operation, gave way in the course of two
months to a more moderate paralysis of the muscles of the right side.
This disturbance, however, persisted so that the animal always retained
a certain clumsiness of movement. It also showed certain sensory
defects for the obvious reason that the lesion also involved the post-
central and parietal gyri. In walking, climbing and jumping the muscles
of the left side were always relied upon most; in fact, unless made to
use the right hand, the animal preferred to employ the left hand. It
appears, therefore, that the motor area of the monkey is of much
greater functional importance than that of the dog for the reason
that it is concerned with those higher forms of movements which
can only be acquired by training and experience. Obviously, it is more
difficult to reestablish a center for skilled movements than it is to
compensate for the loss of a center controlling the less specialized
movements of the dog. This deduction is in complete harmony
with the greater specificity of the pyramidal system of the higher
animals as well as with the fact that the motor functions of the latter
have gradually been brought under the control of the cerebral hemi-
spheres. This is true especially of man in whom almost all muscular
actions are dominated by the cerebrum. It need scarcely be em-
phasized that this higher innervation necessitates experience and
education, two processes which are not essential to the- lower forms,
because their actions are largely determined by subcortical centers.
For this reason we cannot be surprised at the helplessness of infants
as against young animals much lower in the scale of the Animal
Kingdom.
In further analysis of this subject matter it may be inferred that the
recovery from lesions of the motor area must be least complete in
man. The histories of such cases show that this injury is invariably
followed by a contralateral paralysis, the extent of which is propor-
tionate to the size and severity of the central defect. Moreover, in
those cases in which the lesion remains confined to the anterior central
convolution, no true sensory disturbance arises.^ It is also to be
observed that the paralysis involves chiefly those muscles which
are under the guidance of the will and are not paired in function.
In other words, the muscles of respiration, such as the diaphragm,
the abdominal and intercostals and those of the larynx, are excepted.
While a certain recovery from the immediate effects of the lesion may
take place in the course of time, hemiplegic muscles never regain their
normal usefulness.
It has been mentioned above that hemiplegia is frequently asso-
1 Monakow, Ergebn. der Physiol., 1902.
CEREBRAL LOCALIZATION 681
ciated with contractures of the paralyzed muscles, while paraplegia
resulting in consequence of the division of the spinal cord or higher
conducting paths, is not. This hypertonic setting of the muscles
may be explained by the assumption that the injury to the cerebrum
has removed those inhibitory impulses which ordinarily tend to hold
the tonic discharges of the ganglion cells in check. In consequence of
this removal of cerebral inhibition the lower reflexes have full sway
and are enabled to play upon these muscles repeatedly until they
are thrown into a state of spastic rigidity or contracture. ''High''
lesions, therefore, increase the spinal reflexes, while ''low" lesions tend
to diminish them, thereby allowing the muscles to remain continuously
in a flaccid condition.
The foregoing discussion should also have made it clear that the
motor area constitutes a center for voluntary movements. This
statement, however, does not imply that this area, in conjunction with
the faculty of volition, is the primary exciting agent of all muscular
movements. A conclusion of this kind cannot be correct for the reason
that all our actions result in consequence of sensory impressions, and
are, therefore, not spontaneous. As the motor area, together with the
pyramidal system, forms merely the efferent arc of the association or
reaction circuit necessary for motion, it cannot be regarded as a thor-
oughly independent unit capable of generating centrifugal impulses
unaided. The afferent impulses and subsequent sensory impressions
ordinarily responsible for the activation of this motor system, are
derived from the different association centers of the cerebrum with
which we will become acquainted in the chapter now following.
CHAPTER LVI
CEREBRAL LOCALIZATION (CONTINUED)
THE BODY-SENSE AREA
The Location of the Body-sense Area. — While it is undoubtedly
true that, in the lower animals, the sensory and motor areas overlap
to such an extent that it has been suggested by Bastian to apply
to them the more general term of kinesthetic area,^ the more recent
experimental work has shown that, in the apes and man, these fields
find a natural boundary in the fissure of Rolando.^ Thus, it is now
commonly accepted that the motor area lies in front of this sulcus and
the sensory area posterior to it. It must be evident, therefore,
that a hemiplegia need not be associated with a hemianesthesia, unless
^ Luciani and Seppilli, Le Localsizzazioni funz. del cervello, Napoli, 1885.
2 Von Monakow, Ergebn. der. Physiol., 1902.
682
THE CEREBRUM
the^ lesion also involves the posterior Rolandic region. Hence, an
injury, involving the entire centro-parietal field, must always be ac-
companied by a loss of cutaneous sensation.
Monakow does not give a definite boundary for this sensory region,
but merely states that it embraces the posterior central gyrus and the
^'^^fi^L AZ^:d^
Fig. 344. — Human Brain Showing Outer (A) and Mesial {B) Surfaces, and the
Situation op the Chief Motor and Sensory Areas.
The different shading represents the extent of each of these areas as determined by a
study of the histological structure of the cortex. (Campbell.)
anterior realm of the superior to inferior convolutions of the parietal
lobe. Flechsig's view^ coincides with this localization. He especially
emphasizes the fact that the sensory points are centralized in the con-
^ Sachs. Gesellsch. der Wissenschaften, Leipzig, 1904.
CEREBRAL LOCALIZATION
683
vexity of the posterior central convolution, while the Rolandic sulcus
itself is already partly motor. This deduction which is based chiefly
upon histological evidence, has been greatly strengthened by Gushing,^
who, for reasons of diagnosis, resorted to the stimulation of the centro-
parietal region in two conscious patients. The positive statement is
made that distinct sensations of numbness and touch were aroused
which persisted as long as the stimulation remained confined to the
post-Rolandic area. This evidence is in agreement with the distri-
Centrcd Sulcus
Mid-^^^^"-
Nucltus of funiculus
ciracilis ^fun.cunealus
^Internal arcuate fibers
QJ Id in at CorcL
Fig. 345. — Schema Repeesenting the Origin and Course of the Fibers of the Median
Fillet — the Intercentral Paths op the Fibers op Body Sense. {Howell.)
bution of the afferent paths of the spinal cord and principally of those
fibers which form its posterior funiculi. We know that the impulses
arriving in the nuclei of these tracts, are transferred to secondary
neurons forming the internal arcuate bundle, which crosses the mid-
line in front of the decussation of the motor (pyramidal) tracts. This
fact is important, because it explains the contralateral character of
defects in these sensations. Beyond their decussation the sensory
^ Amer. Jour, of Physiol., xxiii, 1909.
684 THE CEREBRUM
fibers form a longitudinal bundle which is designated as the median
fillet or lemniscus. They terminate chiefly in the thalamus superior
colliculus of the corpora quadrigemina, receiving in their course nu-
merous fibers from the sensory nuclei of the cranial nerves of the oppo-
site side. The thalamus is connected by tertiary neurons with the
parietal region of the cerebrum. This explains the observation of
Campbell/ that the degenerative changes associated with tabes dor-
salis, finally progress into these central paths and also affect the cells
of the post-Rolandic region.
Regarding the character of the sensations mediated by this area,
it has been stated by Luciani and Seppilli that they subserve the
muscle and cutaneous senses. But as pain is not felt as a result of
the stimulation of this area, it may be said that it is chiefly concerned
with muscular and tactile sensibility, and in a lesser degree also with
the temperature sense. The fact that the perceptions and judgments
based upon these sensations are mediated in the association realm of
this region, is especially' well betrayed by the diminution and loss of
the stereoscopic acuity (astereognosis) invariably following lesions of
this area. In other words, defects of the post-Rolandic region give
rise to a more or less imperfect judgment of the shape and texture of
objects when handled. Doubtlessly, therefore, this psychical difficulty
must be dependent upon a loss of those associations which are ordina-
rily obtained with the help of the cellular units of this area. Another
psychic defect frequently associated with injuries to this region, is
tactile agnosia, i.e., an inability to form judgments regarding the
ordinary sensations of touch.
THE PSYCHO-VISUAL REGION
The Visual Center. — The fact that vision is under the control of
a definite region of the cerebral cortex was discovered by Panizza in
1855. It was found that an injury to one posterior tip of the cerebrum
of the dog gives rise to blindness in the opposite eye. This same obser-
vation was made subsequently by Hitzig (1874), but without knowing
that it had already been called attention to previously. It was left
to Munk (1878) to prove that the destruction of certain parts of the
occipital lobes leads to total psychical or cortical blindness. These
terms were used to indicate that the loss of vision is not due in this
particular case to a functional uselessness of the retina or of the re-
fracting media of the eyes, but to a central defect involving the
perceptions and judgments pertaining to visual sensations. Omitting
the controversial discussions arising in consequence of this discovery
which were participated in by Goltz and Luciani, it may be stated
in brief that the more recent experiments have fully substantiated
these results of Munk.^ Thus, Schaeffer (1888), Brown (1890), and
1 Histol. Studies on Localization of Cerebral Functions, Cambridge, 1905.
2 Uber die Funkt. der Grosshirnrinde, Berlin, 1890, and Berliner Akad. der
Wissenschaften, 1892-1901.
r
CEREBRAL LOCALIZATION 685
others, have shown that in the monkeys the ablation of the occipital
lobes produces a permanent and total blindness. This result has
also been obtained by Panichi (1895), with this difference, however,
that the blindness can only be made permanent by extending the
ablation somewhat beyond the commonly accepted boundaries of the
occipital lobes.
With the exception of certain minor details, the visual center may,
therefore, be said to be situated in the occipital realm of the cerebrum,
and this conclusion is well borne out by the defects following the
extirpation of only one of these lobes. Under this condition we obtain
a blindness which is confined to the corresponding halves of the retinae,
in other words, a bilateral hemianopia. The term of hemianopsia
may also be used to indicate this condition, because it refers to a loss
of vision in one-half of each visual field, while the former more directly
applies to a loss of function of one-half of each retina.
The results of this operation, however, differ somewhat in different
animals, but this should not surprise us, because attention has already
been called to the fact that the fibers emerging through the optic
nerve, do not pursue a uniform course. We have seen that they
cross the mid-line completely in some animals and only partially in
others. In the first instance, the ablation of the occipital cortex of
one side must, of course, lead to a total blindness in the opposite eye.
It seems advisable, however, not to extend this discussion unduly,
but to confine ourselves to the conditions met with in man. We find
here that the destruction of one occipital lobe is followed by disturb-
ances in vision of hemiopic character, i.e., by a bilateral homonymous
hemianopsia. Thus, an injury to the left center produces a blindness
in the outer half of the left and the inner half of the right eye, and a
loss of vision in the opposite half of the visual field of each eye.
Quite similarly, a lesion affecting the right centef causes bhndness in
the two right halves of the retinae and left halves of the visual fields.
This implies that the crossing of the retinal fibers is about equal. It
is to be emphasized, however, that the foveae centrales are not involved,
and hence, the field of direct and most acute vision is always excepted
(Fig. 319). This peculiarity is explained by saying that the fovea cen-
trahs of each eye is connected with both centers, i.e., the foveae are
bilaterally represented.^
Very pecuhar types of blindness result if the lesion is situated in the
course of the fibers connecting the retinae with the cortical center for
vision. Thus, it must be evident that the destruction of one optic
nerve must lead to a total blindness in the corresponding eye, while a
lesion situated in the chiasma must produce bilateral defects in ac-
cordance with its location and extent. In a similar way, it may be
inferred that the destruction of the central optic tract posterior to
the chiasma must give rise to a hemianopia in the corresponding halves
^ Sachs, Der Hinterhauptlappen, Leipzig, 1892; also: Laqueur and Schmidt,
Virchow's Archiv, clviii, 1900, 466.
i^ (/'
686 THE CEREBRUM
of the retinae. In many of these cases, however, a tertiary type of
degeneration frequently results which involves certain neurons which
are not directly affected by the primary lesion. This spreading
gives rise to ^' sympathetic '' effects, so that bilateral defects in vision
may be obtained in spite of the fact that the original injury is con-
fined to, say, one of the optic nerves and should, therefore, have pro-
duced blindness in only the corresponding eye.
Visual Association. — Upon genetic grounds it must be granted that
the optic nerves are really not peripheral nerves at all, but true cerebral
tracts, bearing a close resemblance to the lemniscus and other systems. ^
Hence, the retina must be regarded merely as an exposed feeler of the
nervous system which is excited by the ethereal rays of light entering
its substance. The impulses here generated are transferred to central
parts over neurons, the cell-bodies of which are situated in the retinae.
It is true, however, that the optic nerves also embrace a small number
of centrifugal conductors which end in arborizations around certain
elements of the retinse. The function of these fibers is not known.
We have previously seen that the centripetal fibers of this tract con-
nect with the superior colliculus, lateral geniculate, and thalamic
nuclei, and that the psychovisual centers in the occipital realms of
the cerebrum are more directly reached by way of the thalamo-
geniculate bodies and the occipitothalamic radiations. In the course
of the development of this cortical area, the importance of the lower
visual centers formed by the aforesaid masses of gray matter, dimin-
ishes gradually. In the higher animals, the latter retain merely the
function of ordinary relay stations for reflex action, while visual per-
ception and memory are concentrated in the cortical area. In the
simpler forms, such as the fish, these lower centers form the terminal
stations of the optic tract and must, therefore, be capable to mediate
in addition the psychical processes connected with vision. ^ It may
be concluded, however, that the psychical activity of these animals
is at best extremely rudimentary.
The psycho-visual area is composed of two fields, one being re-
stricted to visual perception and the other to visual memory. Having
reached the visual sphere, the retinal impulses are transferred to con-
sciousness as perceptions which are then relegated to the memory field
by way of association fibers. Stress has been placed upon the fact that
the visual center cannot be restricted to a narrow sphere, although
Henschen^ has stated that the visual paths of man terminate around
the calcarine fissure on the mesial surface of the cerebrum. In support
of this contention it has been mentioned that the examination of the
brain of Laura Bridgman,^ the blind deaf-mute, has shown decided
1 Parker, Am. Nat., xlii, 1908, 601.
2 Harris, Brain, xxvii, 1904, 106; also: Vincent, Jour. Animal Behavior, ii,
1912, 249.
3 Brain, xvi, 1893, 170.
4 Donaldson, Am. Jour, of Psychol., 1892, 4.
CEREBRAL LOCALIZATION 687
atrophic changes m the region of the cuneus, which is situated above
this fissure.
In addition, Flechsig^ has proved by means of the myehnization
method that the optic fibers terminate largely in the region situated
along the calcarine fissure, ^>., in the cuneus as well as in the gyrus
lingualis. The same inference may be drawn from the clinical data
compiled by Crispolti (1902), which show that the most permanent
types of hemianopia result from lesions of this particular area.
The tendency, therefore, is to regard the cuneus as a more impor-
tant area of the visual center than the lobulus lingualis and fusiformis.
Besides these regions, however, which border upon the calcarine fissure,
the psycho-visual sphere also embraces the three occipital convolutions
and even encroaches upon the outlying districts of the parietal and
temporal lobes. Evidently, the fields named last are set aside for
visual memory. Any attempt, however, to localize these psychic
areas more sharply must meet with failure. Thus, it does not seem
correct to assume with Henschen and in accordance with the theory
of Munk, that the retinal elements are projected in the visual center
as individual units, because we are in no position to-day to support a
contention of this kind by facts. This projection would imply that
those elements which are situated in the upper area of the retina, are
associated by the cellular units of the cuneus, while those situated
below are associated by the lobulus lingualis. The point most
frequently mentioned against such an almost mathematical subdivi-
sion of the visual center into visual units of definite value, is the fact
that Monakow^ and Bernheimer^ have shown that the fibers innervat-
ing the yellow spot, are widely scattered through the occipital cortex,
and do not terminate in a circumscribed area of this region.
The Connection between the Visual Center and Others. — The
fact that the stimulation of the occipital cortex gives rise to muscular
movements, points toward the existence of definite anatomical con-
nections between the visual center and the musculomotor mechanism.
The stimulation of the upper surface of the right lobe causes the eyes
to be turned downward and toward the left, while the excitation
of its posterior region produces a deviation of the eyes upward and to
the left. Furthermore, a purely lateral movement to the left may be
evoked by stimulation of the mesial surface. It must be conceded,
therefore, that the visual sensations are expressed in this case in
accurate muscular movements, and that this end can only be attained
by efferent impulses which traverse the occipitothalamic radiation
and eventually find their way into the nuclei and distal ramifications
of the third, fourth and sixth cranial nerves. It need scarcely be
emphasized that connections of this kind also exist between this center
and other motor paths.
1 Sachs. Gesellsch. der Wissensch., 1904.
2Ej.gebn. der Physiol., 1907.
3Archiv fiir Ophthalm., Ivii, 1904, 363.
688 THE CEREBRUM
Visual perception and memory play an important part in all our
reactions. This is well shown by the fact that lesions of the occipital
region lead not only to hemianopia but also to psychical or cortical
blindness. The latter condition, however, is not always complete,
but may vary between a slight disturbance of our associations per-
taining to a certain number of visual sensations, and an absolute
inability on our part properly to recognize and rate all our visual impres-
sions. In some animals, for example, certain lesions may be produced
which permit sensations of sight as such to continue, while their ability
to recognize and properly associate these impressions is lost absolutely.
This constitutes true psychic blindness.
In man, this condition which is known as word-blindness, was
first recognized in 1877 by Kussmaul.^ It is characterized by an
inability to comprehend printed or written words, without, however.
Fig. 346. — Lateral View of a Human Hemisphere; Cortical Area V, Damage to
Which Produces "Mind-blindness" (Word-blindness); Cortical Area H, Damage
TO Which Produces "Mind-deafness" (Word-deafness); Cortical Area ;S, Dajviage
TO Which Causes the Loss of Audible Speech; Cortical Area W, Damage to Which
Abolishes the Power of Writing. (Donaldson.)
involving the faculty of expressing our thoughts by words or in writing.
A person so afflicted is capable of seeing and even of copying the letters,
but he has no associations pertaining to them. For this reason, they
remain absolutely meaningless to him. He is, therefore, in the same
position as a person who attempts to read a language with which he is
not familiar, say Arabic or Chinese. The condition of word-blindness
forces us to assume that the psycho-optical region embraces a cir-
cumscribed area which is set aside for the perception and memory of
letters. As primitive man, in all probability, was not in possession
of an association zone of this kind, it has been developed in the course
of time. Its location has not been definitely established as yet,
although those cases of word-blindness which have come to autopsy,
have shown lesions in the second parietal convolution and gyrus
1 Storungen der Sprache, 1885.
CEREBRAL LOCALIZATION 689
angularis of the left side. This area forms the outlying district of
the memory realm of the psycho-visual region.
THE PSYCHO-AUDITORY REGION
The Auditory Center. — The first tangible data regarding the loca-
tion of the auditory center, have been furnished by Ferrier in 1875. It
was found at that time that the excitation of the surface of the temporal
lobes gives rise to muscular movements involving the ear of the oppo-
site side. Somewhat later, when these experiments were extended to
include ablation of this particular area of the cerebral cortex, it was
established that the destruction of both temporal lobes produces total
deafness, while the ablation of only one lobe leads solely to an impair-
ment of hearing. Subsequent experimentation by Munk (1878-81),
Luciani and Tamburini (1879), and Bechterew (1887) has proved this
localization to be essentially correct. In addition, it has been pointed
out that the psycho-acoustic region embraces not only the temporal
lobe but also the fields extending from here in the direction of the
parieto-occipital convolutions and the gyrus hippocampi.
These outlying districts appear to be set aside for memory, while the
chief area of this center seems to be restricted to the superior temporal
convolution. This deduction is based upon the results of stimulation
of the surface of the temporal cortex as well as upon the manner of dis-
tribution of the incoming fibers, as determined by the myelinization-
method of Flechsig.^ It seems that the fibers of the auditory radia-
tion terminate chiefly in the superior convolution of this lobe
(Monakow). This area also embraces a sphere for musical sounds.
The experiments of unilateral extirpation of the temporal lobes
have also brought out the fact that the deafness resulting therefrom,
is only temporary, and that the symptoms are chiefly confined to the
ear of the opposite side.^ This result strongly suggests a crossing of
the auditory fibers which, as we have seen in an earlier chapter, takes
place in the corpus trapezoideum. This decussation is incomplete and
may, therefore, be likened to that occurring in the optic chiasma.
Thus, it may be gathered that, in the dog, the organ of Corti in the coch-
lea is bilaterally represented. Besides this rather incomplete and
temporary deafness, the destruction of the temporal cortex also gives
rise to psychic or cortical deafness, which means that the animal
hears the sounds, but is quite unable to understand them.
This condition has also been observed in persons who at autopsy
showed characteristic lesions of the temporal cortex. They appeared
to be able to hear even whispers, but could not comprehend their
meaning. In analogy to word-blindness, Kussmaul (1876) designated
this condition later on as word-deafness. Luciani and Seppilli local-
ized the seat of this difficulty in the first and second temporal con-
1 Neurol. Zentralblatt, 1903, 202.
2 Tamburini, Re vista di Freniatria, Reggio Emilia, 1903.
44
690 THE CEREBRUM
volutions of the left side. A person so afflicted is in the same position
as one who is spoken to in a foreign language, i.e., he hears the words,
but is unable to depict their meaning, because he cannot properly
associate them. Wernicke^ recognized at an early date that this con-
dition, together with word-blindness, must lead to a loss of speech,
because individuals who thus fail in their associations, cannot react
to auditory and visual impressions by the production of coordinated
sounds. It may also be inferred that they cannot react to these im-
pressions by the act of writing for the same reason. The latter condi-
tion is known as agraphia, and the former as aphasia.
THE CENTERS FOR SMELL AND TASTE
The Location of the Olfactory Center. — The sense of smell is very
unequally developed. We have seen that it forms the dominant sense
in many of the lower vertebrates; for example, in the fish in which
almost the entire., cerebrum is concerned with this function. These
animals, however, are not in possession of a true cerebral cortex, the
first indications of it appearing in the amphibia and reptilia. Other
animals are entirely lacking in olfactory organs ; for example, the dol-
phin, porpoise and whale. ^ This divergency enables us to divide
animals into two groups, namely into osmatic and anosmatic, and the
former again into macrosmatic and microsmatic. As examples of the
first kind, might be mentioned the dog, rabbit, rat and opossum and as
an example of the second kind, man.
The acuity of this sense is in keeping not only with the complexity
of the olfactory cells in the nasal cavity, but also with that of the
association area in the cortex. In the fish, the reactions following
olfactory impressions, are still chiefly reflex. A true cortical or psychic
element is first imparted to them in the amphibians and reptiles.
This statement implies, that beginning with these animals, the ol-
factory reflex realm is gradually amplified by a cortical center. As
far as man is concerned, this psycho-olfactory region has been lo-
calized by Ferrier in the gyrus hippocampi, and particularly in its
distal limb, the uncus. This conclusion has been reached partly in
accordance with the anatomical data pertaining to the distribution
of the olfactory fibers, and partly because the stimulation of this area
in monkeys produces movements involving the muscles of the Hps
and nostrils of the same side. This effect is similar in character to
that produced by inhaling an irritating vapor. It should be remem-
bered, however, that reactions of the latter kind are due chiefly to
the excitation of the receptors of the trigeminus nerve. Luciani
came to the same conclusions as Ferrier, but extended this area some-
what to include the subiculum cornu Ammonis. Bechterew,^ on the
^ Der aphasische Symptomenkomplex, Breslau, 1874.
2 Zwardemaker, Ergebn. der Physiol., i, 1902, and Herrick, Evolution of
Intelligence and its Organs, Science, xxxi, 1910, 7.
3 Archiv fur Physiol., 1899, SuppL, 391.
CEREBRAL LOCALIZATION 691
other hand, beUeves that Amnion's horn does not form a part of the
olfactory area.
The Center for Taste. — The psychic area for the sensations of taste
has not been definitely located as yet. As the taste buds are widely
scattered, their excitation involves the seventh and ninth cranial
nerves; in fact, Wilson^ states that a few of these receptors are also
situated in the mucous membrane of the larynx and epiglottis. The
latter seem to be innervated by the vagus nerve. In the medulla
these afferent fibers are intimately connected with the motor mechan-
ism concerned in mastication and deglutition, as well as with the
spinal nuclei. They terminate finally in the gyrus hippocampi near
the anterior end of the temporal lobe. In fishes these fibers may be
traced to the region of the hypothalamus.
THE CENTER FOR SPEECH
The Speech Circuit. — The psychic area for the associations required
in the production of intelligent sounds and speaking, should, of course,
not be confounded with that region of the cerebral cortex which has to
do with the innervation of the muscles of the larynx and functionally
allied structures and forms a part of the general motor area. In
fact, these motor points are under the direct control of the psychic
speech center. In the latter area the various revalent associations
from the visual, auditory and other centers are brought together and
are psychically adapted to speech. The speech center, therefore, is
the seat of those memories which are required for the execution of the
perfectly definite and coordinated movements necessary for speaking.
Sounds are a common phenomenon in nature. We cannot, how-
ever, concern ourselves at this time with the reflex-like production of
noises, such as result in insects in consequence of the rubbing together
of the legs or mandibles. The first indications of true associated
sounds are present in amphibians and reptiles, but only in a rudimen-
tary manner, because the cerebral cortex of these animals is largely
concerned with olfaction. Such noises, however, as are produced by
means of resonating pouches, seem to contain at least a slight cortical
element. Somewhat higher in the scale of the Animal Kingdom this
psychic admixture becomes unmistakable. Its increasing conspicuous-
ness pursues a course parallel to the retrogression of the olfactory
apparatus and the development of the association areas pertaining to
other senses. Undoubtedly, this change is far advanced in the birds
and is almost complete in the monkeys and apes. In the mammals,
the production of sounds is universal and diversified, but the range of
these sounds is relatively limited. In other words, the sounds which
they produce are few in number, but are nevertheless made for very
specific purposes. In this connection, brief reference might be made
to certain seemingly authentic cases which suggest that it is possible
1 Brain, xxviii, 1905, 339.
692 THE CEREBRUM
to train animals to produce a definite number of associated sounds.
Instances of this kind are the ^ talking dog" and the ''talking horse."
The higher monkeys, it is said, are capable of uttering a few coordinated
sounds in expression of particular mental concepts.
A true coordination of sounds in the form of speech, however,
is shown only by man. This achievement is made possible very
largely by the development of the association area pertaining to
this function and not by a correspondingly much greater intricacy
of the motor apparatus necessary for speaking. Already dur-
ing infancy, man is equipped with a phonetic mechanism which is
practically complete as far as its structural complexity is concerned,
but is still in need of functional development. This it acquires
in the course of the succeeding years. This
awakening of the associations concerned in speech,
is one of the most interesting and instructive phe-
nomena in the life of man. The primary cooing
sounds of the infant are gradually amplified by a
number of successive sounds having a definite
meaning. This augmentation indicates an exten-
sion and melting together of intracerebral paths,
so that various impressions from other association
centers may be brought to bear upon speech.
Once this union has been effected, the develop-
ment of speech is much more rapid, being subject,
of course, to differences in the training of the child.
. . Speaking is the outcome of certain mental pro-
W^ Y^ cesses; in other words, it is the result of particular
afferent impulses which may enter the body by
^'''* ^^Cmcu™ ^^^^"^ ^^y ^^ practically any receptor. They are then
R Receptor- V as- associated in the perception and memory realms
sociation center; c/cen- of the corresponding regions of the cerebral cortex,
ter for speech ;iW, motor ^s Speech follows visual, auditory, tactile and other
poiijts for muscles of • • •. i -j xi_ x ai, i, •
larynx; L, larynx. impressions, it may be said that these mechanisms
are really tributary to the speech center. Hence,
speech is the product of a harmonious interaction between different
peripheral and central nervous mechanisms. It is true, however, that
these tributary complexes are not developed simultaneously but suc-
cessively, and that training has much to do with their functional
adaptability to speech. Thus, it is a common experience that the
memory sphere of vision becomes functional at an earlier date than
that of audition; at least, it seems more difficult for the infant to
make the latter subservient to its speech requirements.
The morphological and functional arrangement of the adult
mechanism of speech may be illustrated best in the form of a diagram.
It has been said that speech is under the control of an association area
situated in the cortex of the cerebrum (Fig. 347). This center stands
in communication with the phonating organs, the larynx and allied
CEREBRAL LOCALIZATION
693
parts (L), by means of an efferent path through the motor area (M).
This entire complex, inclusive, so to speak, of one-half of the center of
speech, forms the motor arc of the speech circuit. But, inasmuch as
speech results only in consequence of incoming impulses, inclusive
of those of pure psychic origin, this circuit can only be completed
by bringing it into relation with a sensory or afferent arc. The latter
may embrace either the visual, auditory, or any other mechanism.
Supposing that we are now dealing with a visual impression, we would
say that the stimuli are received upon the retina (R) and are then
conveyed to the visual center in the occipital
cortex for proper association (V). From
here they are conducted to the center of
speech by way of definite association fibers.
In the chief center they are then remodelled
and transferred upon the efferent path by
way of which they attain the larynx. Natur-
ally, if speech is the outcome of an auditory
impression, the organ of Corti and the audi-
tory center would have to be substituted for
the retina and the visual center, but the
motor path remains the same.
The Location of the Center for Speech.
Aphasia. — Adult persons are capable of com-
municating their mental products to one
another by means of mimic movements,
speech and writing. The second of these
means has been shown by Broca^ to be lost
whenever the base of the left inferior frontal
convolution is extensively injured. For this
reason, this investigator recognized in this
area the cortical regulatory factor of speech. Speech Cibcuit, Illustrating
or more correctly speaking, of the motor ap- ™ Position of the Lesions
, I,- I, J • -J. ■ i- j> Which Give Rise to Sensory
paratus which derives its innervation from and Motor Aphaslv.
the fifth, seventh and ninth to twelfth cranial r, Receptor; v, association
nerves. He designated the aforesaid condi- center; c, speech center; M,
tion as cortical motor aphasia, thereby fur- 7J^of:^^^ryLXZ^:Mt
nishmg the basis for the commonly accepted realm of motor aphasia.
view that the speech center is situated in the
left inferior frontal convolution. We shall see later on that this locali-
zation is not quite correct, because it is restricted to too narrow a
sphere. In this connection attention should also be called to the fact
that cerebral localization should never be attempted upon a strictly
anatomical basis. Function should really be the deciding factor.
The term aphasia signifies a loss of the power of speech (Fig . 348) . An
individual so afflicted is unable to express his ideas in spoken words.
The difficulty, however, does not lie in the larynx nor in the paths con-
1 In amplification of the observation of Bouillaud, 1825.
^
R
Fig. 348. — Diagram of the
694 THE CEREBRUM
necting this organ with the cerebrum. This is shown by the fact that
its movements dm-ing respiration, mastication and deglutition are
executed with perfect precision, and may even be used for mimic ex-
pressions, singing and whisthng. Aphasia, therefore, is an intracere-
bral defect involving the spontaneity or power of phonetic expression
(Fig. 348). This implies that the aphasic person is no longer in a
condition to express his thoughts in words which form his principal
means of communication with his fellow-men. To be sure, man is
also subject to a number of conditions in which the intellectual facul-
ties are in abeyance, either from birth, as in idiots, or from disease, as
in coma, stupor, dementia and certain states of hysteria. This type of
speechlessness, although due to cerebral defects, cannot be classified
as aphasia.
Motor aphasia is the result of an injury either to the efferent or motor
realm of the speech center or to the path connecting it with the motor
area situated along the fissure of Rolando. The motor area itself,
however, is not affected in cases of pure aphasia, as is evinced by the
fact that the muscles used in speaking are not paralyzed but have only
lost their central directing influence. For this reason, we must think
of the motor realm of the center of speech as a storehouse of those
memories which are directly concerned with articulation and the
phonetic construction of words. To be sure, an injury may be so
extensive that it also involves the motor area, in which case the aphasia
is associated with a hemiplegia. This is not at all uncommon.
It is possible to amplify these associations and to impart to them
a specificity which in turn will tend to render the action of the laryn-
geal parts more and more effective. In other words, while the laryn-
geal parts may be fully developed, they cannot attain their greatest
functional efficiency unless the association realm is trained and made
to progress in a corresponding measure.
An injury to this center most frequently results in consequence of
traumas and hemorrhages in the region of the middle cerebral artery.
These lesions may be very extensive or more or less restricted; hence,
the resulting motor aphasia or aphemia may be either complete or partial '
in character. In the former case, the person loses his power of speech
absolutely, while in the latter he retains the faculty of uttering a limited
number of words. Thus, Broca has described a person suffering from
a loss of all numerical concepts with the exception of the term ^' three,"
this number being employed by him constantly in referring to all nu-
merical values. Quite similarly, a person may lose the use of certaii
nouns and pronouns, or persistently employ words in wrong combina-
tions (paraphasia). The point to be emphasized is that these defects
in speech may be so specific that they may almost be compared to the
loss of one of the strings of a piano or other musical instrument.
Another point to be noted is that the mental faculties of a persoi
afflicted with motor aphasia, are generally preserved, provided, of
course, that the injury is perfectly localized. This implies that hi
CEREBRAL LOCALIZATION 695
power of associating the various sensory impressions is relatively normal,
although he absolutely fails in his attempts to give verbal expression to
these concepts. Indee'd, a person of this kind may be told the missing
words repeatedly without being able to utter them, for the reason that
his power of forming words has been lost. It is true, however, that
any statement which definitely asserts that there is no impairment of
the intellectual faculties in motor aphasia, should be accepted with
reserve, because aphasias unaccompanied by a lowering of other
faculties are not common. A pure motor aphasia is designated as
aphemia. The real determining factor of the loss of intelligence,
associated with aphasia, is the cause and extent of the lesion, because it
is more than probable that a degenerative process affecting the frontal
convolutions, most generally passes beyond the confines of this region
and also involves more distant areas of the cerebrum. Thus, while
these patients may deport themselves reasonably well and even con-
tinue to transact ordinary business, their difficulty in speech is in
many cases associated with others, such as an at least partial paralysis
of the skeletal muscles, showing an involvement of the motor area
(hemiplegia), or an anarthria, proving an impairment of the motor
power of expression (Marie). The latter condition usually indicates a
lesion of the white matter of the external capsule as its winds around
the lenticular nucleus.
In many cases of aphasia, we also observe a loss of the power of
writing (agraphia), or a loss of the power of making purposive move-
ments of a familiar kind (apraxia). The latter condition may be
tested by handing the patient a comb, drinking glass, matches, or other
articles and noticing whether he knows how to use them. Apraxia
may be sensory or motor in its character.
This discussion inadvertently leads us to the further consideration
of the data supplied by Bouillaud and Broca in support of the contention
that the speech center is located in the left inferior frontal convolution.
It has been stated that this is true only in right-handed persons, ^.e., in
about 95 per cent, of people, and that this center is situated on the right
side in left-handed individuals (Noison, 1862). Moreover, it is a
common experience that reeducation is difficult to accomplish in the
adult, but not in children. ^ This fact seemsjto suggest that the destruc-
tion of the aforesaid area in children, allows the elements in the opposite
frontal lobe to develop into a true center. Very difficult to understand
are those cases which prove that aphasia may be present in an individual
whose inferior frontal lobe was shown at necropsy to be free from
lesions . Again, it has been demonstrated that aphasia may be absent in
cases of undisputed destruction of Broca's area. ^ Montier presents the
records of 108 trustworthy cases. Of these, 19 support Broca's conten-
tion, while 84 are against it. , In 57 of them motor aphasia was present
in spite of the fact that Broca's area was intact, while the others showed
1 Gowers, Diseases of the Brain, London, 1885.
2 Monakow, Gehirnpathologie, 1906, and Collier, Brain, 1908.
696 THE CEREBRUM
a destruction of this region, but no aphasia. It seems, therefore, that
we cannot adhere to the old view of Broca, but must regard this
particular area merely as a link in the chain of 'the speech circuit. As
speech is a skilled act, involving several cerebral regions, Marie^
believes that it cannot be referred to any particular group of cells to
the exclusion of another. The latter point will be brought out more
clearly during the succeeding discussion upon sensory aphasia. ^
Sensory Aphasia. — Speaking, as well as writing, necessitates the
presence of distinct concepts which may be memories of visual sensa-
tions, auditory sensations, tactile sensations and others. Hence,
it may be gathered that speech must be lost whenever these associa-
tions are absent, because it then lacks its causative factors. In other
words, a person may be in complete possession of the power of articu-
lation and phonation, but be quite unable properly to construct those
mental pictures or concepts which ordinarily give rise to speech.
In this case, therefore, the difficulty lies on the sensory side of the speech
circuit.
We have previously seen that an injury to Wernicke's area of the
temporal lobe gives rise to word-deafness, i.e., to an inability of cor-
rectly associating sounds or words, in spite of the fact that they are
clearly heard. In the same way, a lesion to the parietal realm of the
psycho-visual field may give rise to the condition of word-blindness,
i.e., to an inability of associating written or printed language. In
both cases, of course, the peripheral afferent paths are in perfect condition,
and hence, the difficulty must be situated in the auditory and visual
centers. Under ordinary conditions, these two centers are the chief
contributors to the speech center proper, but not in an equal measure,
because the auditory realm is no doubt more directly associated with
it than the visual. This is shown especially by the fact that a loss of
speech is more frequently associated with word-deafness than with
word-blindness. This constitutes the so-called sensory aphasia of
Wernicke,^ so designated to differentiate it from the motor aphasia
of Broca. A simple word-blindness, on the other hand, rarely leads
to sensory aphasia, but presents itself rather as an inability to read
(alexia) and an inability to write from copy (agraphia). It may
happen, however, that the primary lesion does not remain confined
to the psycho-optic realm but also involves the psycho-auditory field,
in which case, of course, the aphasia is associated with both conditions,
word-deafness and word-blindness, as well as with alexia and agraphia.
It should also be added that auditory aphasia is often combined with
at least sHght defects in hearing, and visual aphasia, with certain
defects in sight (hemianopia). This cannot surprise us, because the
lesions involving these areas, are rarely so precisely placed as not to
affect neighboring units.
1 Semaine medicale, Nos. 21, 42 and 48, 1906.
2 A. Meyer, Harvey Lectures, New York, 1910, 228.
3 Der aphasische Symptomenkomplex, Breslau, 1874.
CEREBRAL LOCALIZATION
697
Strictly speaking, however, the condition of sensory aphasia
must result in consequence of any lesion producing a loss of the intel-
lectual recognition of external objects through any one of our senses,
at least, of those which ordinarily give rise to concepts enxployed in
speech. On this account, the different association centers may really
be regarded as subsidiary or tributary centers to the speech center.
This failure of intellectual recognition has been designated as agnosia;
hence, word-deafness is really auditory agnosia, and word-blindness,
visual agnosia, while stereognosis is tactile agnosia. Thus, practically
any agnosia may give rise to defects in expressing our ideas in words
or deeds. The location and extent of these sensory lesions determine
the intensity of the aphasia or agraphia; and hence, these conditions
Fig. 349. — The Speech Circuit Projected to Show the Location of Lesions Which
May Give Rise to Aphasia.
E, Eye; V, visual association area; SC, speech center; M, motor points; L, larynx.
Sensory aphasia follows injuries to the association center (A) its transcortical connecting
path (B) or the receiving side of the center for speech (C). Motor aphasia may be
produced by an injury to the motor neurones of the center for speech (Z>) or its con-
necting path (E) with the motor area.
may be either complete or incomplete. At all events, sensory apha-
sics suffer in most instances a greater deterioration of their mental
faculties than the simple motor aphasics, because their primary as-
sociation spheres are more directly involved. For the present, there-
fore, we must adhere to the belief that the speech circuit consists of
a number of distinct centers, the several activities of which are com-
bined into the single product of speech. This circuit may be broken
at different points, namely, at (a) the tributary association center, (6)
the association path connecting this lower center with the chief center,
(c) the chief center on its ingoing or sensory side, (d) the chief center
on its outgoing or efferent side, and (e) the association path connecting
the latter with the motor area. Injuries at points a, fe, and c, must
give rise to sensory aphasia and injuries at points d and e, to motor
aphasia.
698 THE CEREBRUM
Agraphia. — As a second means of communicating our ideas to our
fellow-men, we employ a code of written signals which are in no way
less arbitrary than those of speech. They differ with the character
of the language and hence, also with the intelligence of the people
employing them. Like speech, writing is a skillful act and is controlled
by a number of cortical centers. Both faculties are acquired and may
be perfected by training. First of all, we observe that the muscles of
the hand and fingers are controlled by certain units of the motor area.
These in turn are under the guidance of a psychomotor area of the
cortex which, as far as is known, occupies a position in or very near to
the psychomotor center for speech. Secondly, as writing is the direct
outcome of associative processes in different sensory regions of the
cortex, the latter may be regarded as tributary areas to the chief psy-
chomotor center.
Theoretically considered, therefore, we might recognize the exist-
ence of a distinct writing-circuit, similar in its outline to the speech
circuit. In strict analogy to the latter, it might be said to possess
a sensory and a motor side, the ingoing impulses being derived chiefly
from the visual and auditory centers. While this conception is un-
doubtedly correct physiologically, no pathological cases have been
recorded as yet which might prove the power of writing to be a separate
cortical entity. In fact, the records show that agraphia or loss of the
power of writing, is present only in connection with at least a slight
degree of aphasia. This is also true of paragraphia, i.e., the writing
of wrong words, syllables and letters. Agraphia, however, is due to a
lesion of those psychic centers which are directly concerned with the act
of writing. Hence, writer's cramp is not an agraphia, but is due in all
probability to a neurosis of psychogenic origin. Thus, this condition
is comparable to those disturbances in speech which are classified
as stuttering and stammering. Very characteristic defects in writing
are exhibited in different psychoses. The paralytic writes carelessly,
leaving out words and syllables, while the maniac writes very hastily
and the katatonic in a peculiar stilted manner. It may be concluded,
therefore, that speech and writing are closely related, acquired and
educative faculties. Their motor centers, paths and end-organs are
quite distinct, but on the sensory side we find that practically the same
psychic areas are involved in the two processes. This fact accounts
for the close relationship existing between agraphia and aphasia.
It has also been claimed by Kussmaul that our musical faculties
are "separately represented in the cerebral cortex. This implies that
the psycho-visual and psycho-auditory regions embrace a circumscribed
area in which musical symbols and sounds are associated. This con-
clusion is based upon the fact that the power of reading musical notes
may be preserved in alexia.^ A condition of amusia, however, has
been repeatedly observed in consequence of cerebral lesions.
1 Oppenheim, Charity Ann., 1888, 345.
CEREBRAL LOCALIZATION • 699
THE FRONTAL ASSOCIATION AREA
^ The preceding localization of the different motor and sensory areas
has undoubtedly led us to believe that the cerebral cortex embraces
a number of island-like fields which are concerned with particular
functions. While this conception is correct, it should not be forgotten
that still larger areas are situated in between those already explored,
which have not as yet been shown to possess a specific functional
value. Guided very largely by the fact that the aphasics may lose
their power of word-formation without suffering a decided impair-
ment of their intelligence, the clinicians have assumed that thought
is quite independent of auditory, visual and other impressions and
memories. In accordance with this assumption, it was then believed
that the psycho-optic, the psycho-acoustic, and other psychic areas are
apportioned severally to the different sense organs, and are amplified by
definite areas in which solely the more general psychic activities are
situated.
This at first purely hypothetical center of thought received a firmer
morphological basis by the investigations of Flechsig^ pertaining to the
time of myelinization of the fibers of the embryonal brain. It is
conceivable that those association areas of the cortex attain their
function first which are first placed in possession of myelinated fibers,
and thus antecede the others in gaining connection with the outgoing
paths of the white matter. By this method Flechsig succeeded in
outlining thirty-six different cortical fields which he further divided
into primary, intermediary and terminal. The first attain their myelin-
ated fibers at birth and constitute the primary sense centers, namely,
those of smell, cutaneous and muscle sense, sight, hearing and touch.
These areas are characterized by large numbers of radial, transverse
and projection fibers which eventually make connection with the more
distant projection centers apportioned to the different sensations
and motor actions. The intermediary fields contain fibers which
attain their medullary sheath during the first month of extra-uterine
life. The terminal regions possess few transverse fibers, but numerous
association paths which unite them with the different projection cen-
ters. They form the association areas which amplify the individual
primary sensory centers and thus form the memory realms for vision,
audition, olfaction, etc. In addition, they form those independent
association realms which give rise to the higher psychic concepts.
For this reason, they may be regarded as the organs of perception
and thought. In this connection it should be stated, however, that
many physiologists do not admit that the highest psychical activities
are mediated by special and individualized association centers (Munk),
but are produced in the association realms belonging to the different
primary sensory regions.
1 Die Lokalisation der geist. "Vorgange, Leipzig, 1896; also: Sachs. Gesellsch.
der Wissensch., Leipzig, 1904.
700 * THE CEREBRUM
Whichever view is accepted, it must be evident that these different
association regions are used for purposes of synthetizing the sensory-
impressions into perceptions and concepts. In accordance with Flech-
sig, it may thus be held that the association areas are the places in
which sense impressions are built up into organized knowledge, and
where a complex mental image is formed of conditions in our internal
and external world. Typical association regions are, of course, the
parietooccipital and frontal realms. Regarding the latter, little prog-
ress has been made. It has been stated by Bolton ^ that mentally defi-
cient persons (amentia) exhibit a thinning of the cortex which is especially
marked in the frontal region. These atrophic changes are also appar-
ent in idiotic and demented persons; in fact, it is claimed that they
bear a direct relationship to the degree of the idiocy. Moebius^
calls attention to the fact that the laterobasal portions of the frontal
lobes are strongly developed in mathematicians. Thus, the brain of
Helmholtz showed a uniform massiveness, but especially in the region
between the gyrus angularis and the g5rrus temporalis superior. ^
According to Guzrhann,* the gyrus angularis is very prominent in
people who possess a special talent for music. Mills^ argues that the
intellectual states are controlled by the frontal lobes, while Spitzka's^
observations rather tend to prove a predominance of the posterior
association fields in intellectual men.
Cases of extensive destruction of the frontal lobes have been cited
repeatedly. Most commonly, however, reference is made to that of a
workman whose frontal lobes were extensively lacerated by the end of a
crowbar, driven through his skull by a premature explosion of dynamite
(1850). In all these instances a decided change in the character and
intelligence of the individual was noted. The more recent observa-
tions of Phelps,^ Mtiller^ and Schuster,^ however, have shown that a
deterioration or loss of the higher mental qualities does not always
follow, although minor mental changes, suchas weakness of the memory,
insane desires, and depression, are usually present. In all those cases
in which these symptoms were the result of circumscribed tumors
(glioma), the removal of the growth was generally followed by a com-
plete mental recovery. In this connection, mention should also be
made of the experiments of Franz ^° which have proved that the removal
of the frontal lobes in cats and monkeys leads to the loss of habits
previously formed by brief periods of training. The habits so lost,
1 Brain, 1903, 215, and 1910, 26.
2 tJber die Anlage der Mathematik, Leipzig, 1900.
3 Hansemann, Zeitschr. fiir Psych, der Sinnesorgane, xx, 1899, 1.
* Anat. Anzeiger, xix, 239.
6 Univ. of Pennsylvania Med. Bull, xvii, 1904, 90.
6 Med. Record, 1901, and N. Y. Med. Jour., 1901.
' New York Med. Jour., Ixi, 1895, 8.
8 Allg. Zeitschr. fiir Psychiatrie, lix, 1902, 830.
^ Psych. Storungen bei Hirntumoren, 1902.
1° Archives of Psychology, March, 1907.
CEREBRAL LOCALIZATION 701
may be relearned in about the same period of time. Long-standing
habits, on the other hand, seemed to be retained, in spite of the injury
to this lobe.
As far as the higher functions of the association regions are con-
cerned, much work must still be done to obtain more definite data.
For the present, we can go no further than to state that the cortex of
the cerebrum is the seat of special sensory and motor projection areas
which may be mapped out with varying definiteness. We are also
fairly well acquainted with the sensory and motor paths leading to and
away from these regions. Around and in between these primary
cortical fields certain association areas are situated which are inti-
mately connected with the centers to wMch they belong, and in turn
also with one another. Their destruction affects first of all the par-
ticular sensory or motor function to which they are assigned, and
secondly, the functional equiHbrium of the cerebrum as a whole.
This constitutes the so-called diaschisis effect of Monakow,^ consisting
in a disturbance of the dynamics of the cerebral processes as a whole
which, however, is rather transitory in its nature.
It is conceived that the higher mental concepts are not the product
of special areas of the cortex, but are the result of discharges of nervous
energy from one center to another as well as to more remote regions
of the body. This interaction of nervous energy gives rise to a com-
plex product, the analysis of which is at present impossible. This
constitutes the so-called dynamic theory of cortical function, in accor-
dance with which the different sensory and motor centers of the cere-
brum are to be regarded merely as fixed points of action of a complex
system of neurons and not as independent generators of mental
actions. The result of this reverberation of discharges through the
nervous system depends in each case upon the number and kind of
neurons involved. Thus, the higher cortical function results in con-
sequence of the correlation of its different products, and cannot be
ascribed exclusively to one or the other of its constituent areas.
THE CORPUS CALLOSUM
The cerebral hemispheres are connected with one another by three
tracts of commissural fibers, namely, the anterior commissure, the for-
nix, and the corpus callosum. The most conspicuous of these is the
corpus callosum which forms the floor of the great longitudinal fissure
and may be brought into view by separating the hemispheres. The
fibers composing this structure, do not enter the main paths of the
internal capsule, but extend directly across from cortex to cortex.
According to Ferrier,^ Brown-Sequard,^ Koranyi,^ and others, its divi-
sion at the point where it crosses the longitudinal fissure, is not followed
1 Die Lokalisation des Grosshirns, Wiesbaden, 1914.
2 Proc. Royal Soc, London, 1875.
3 Compt. rend. Soc. biol., 1887.
^Pfliiger's Archiv, xlvii, 1896, 35.
702
THE CEREBRUM
by motor or sensory defects of any kind. Mott and Schaefifer, ^ how-
ever, have shown that its stimulation gives rise to symmetrical move-
ments on the two sides of the body. Moreover, there is sufficient
experimental evidence at hand to prove a distinct localization of these
^Central fissure
Posterior central gyrus
Anterior central gyrus
Corpus callosum
Fornix
Lateral ventricle
Thalamus
Caudate nucleus
Internal capsule
Lentiform nucleus
Insula
Second temporal gyrus
First temporal gyrus
Clauitrum
Inferior horn of lot. vent.
Hippocampal fissure
Optic tract
'Hippocampal gyrus
Uncus
Cerebral peduncle
pons
Pyramid of. medulla oblongata
Fig. 350.
-View from the Front of a Coronal Section of an Adult Brain Made
Three Inches Behind the Frontal Pole. (J. Symington.)
fibers, because their stimulation evokes successively movements of
the eyes, head, trunk, shoulder, arm, fingers, hip, tail and foot.
Obviously, therefore, this commissure forms a connection between
the two motor areas for the association of symmetrical points of these
regions. This fact may be substantiated by the ablation of one motor
1 Brain, xiii, 1890, 174.
CEREBRAL LOCALIZATION 703
area, when the excitation of the corpus will evoke movements on that
side of the body which is still connected with the uninjured area.
Although generally associated with idiocy and epilepsy, certain cases
have been recorded by Wahler^ which show that lesions of the corpus
callosum in man give rise to a disturbance of the muscular movements.
Liepman^ describes cases in which dyspraxia existed without any ap-
parent injury to the motor cortex, the inference being that this
disorder resulted from defects in the power of conduction of the
corpus.
THE BASAL GANGLIA
The Corpus Striatum. — The nuclei caudati and nuclei lenticulares,
constituting the corpora striata, are intimately connected with the frontal
cortex by the corticocaudal bundle as well as with the thalamus, red
nucleus, and through the latter with the longitudinal bundle. They
form, therefore, important relay stations upon these paths and medi-
ate reflexes of the more complex kind. In the lowest vertebrates,
these bodies form almost the entire telencephalon and really serve as
the basal stem from which the hemispheres of the higher animals are.
developed. Their importance seems to be greatest in the birds,
because the more complex processes of these animals appear to be
mediated by these bodies, rather than by the palhum, or hemispheres.
The question whether they possess an independent function, can-
not be answered with certainty, because their destruction by means
of injections of chromic acid, as well as their stimulation, has yielded
very conflicting results. Their close connection with the internal cap-
sule makes a direct involvement of these paths not improbable, and
hence, many of the effects described by earUer investigators^ may be
due to this cause. It seems to be established, however, that these
gangHa are closely associated with heat production and the regulation
of the body temperature,^ because their stimulation invariably results
in a rather lasting rise in temperature, amounting to as much as 1.6° C.
Mayer and Barbour have substantiated these results by permitting
warm and cool water to flow upon these bodies. CooUng the water
produced shivering and a rise in the body temperature, while warming
it lowered the body temperature.
THE THALAMUS OPTICUS
This body consists of three parts, known as the median, lateral,
and anterior nuclei. It is intimately connected with the corpus stria-
tum and the cerebral cortex by ingoing and outgoing fibers, and also
forms the end-station of the secondary sensory tracts of the spinal cord
^ Balkentumoren, Leipzig, 1904.
2 Med. Klinik, 1907, 725.
3 Schuller, Zentralbl. ftir Physiol., 1902, 222.
^ Jto., Archiv fiir Physiol., 1898, 537, and Zeitschr. fur Biologie, xxxciii, 1898, 36;
also Nicolaides and Dontas, Archiv fiir Physiol, 1911, 249.
704 THE CEREBRUM
and medulla oblongata. In addition, its pulvinar prominences, to-
gether with the lateral geniculates and anterior corpora, form the end-
station of the primary division of the optic tract, while the median
geniculates and posterior corpora receive the auditory tract. It is
also connected with the cerebellum, and sends a few fibers to the red
nucleus and medulla oblongata.^
In accordance with its connections with the cutaneous, sensory,
optic and auditory tracts, Monakow^ regards the thalamus opticus,
together with the lateral and median geniculates, as a subsidiary cere-
bral cortex, the purpose of which is to transfer these sensations to the
proper association areas. Lesions of this body, therefore, must give
rise to very diverse sjrmptoms. This also holds true of the outgoing
impulses. Bechterew, ^ for example, calls attention to the loss of the
emotional movements concerned with laughing and crying, and the im-
pairment of the mimic play of the facial muscles. This investigator
also states that this body contains the reflex center for the secretion of
the tears. Its activation also produces a dilatation of the pupils, a
bulging of the eyeballs and a retraction of the eyelids. Injury to this
body also gives rise to the so-called phenomenon of Romberg, i.e.,
to an inability to stand erect when the eyes are closed. This symptom
serves as a diagnostic sign in tabes dorsalis and other degenerative
affections of the nervous system. ■*
THE CORPORA QUADRIGEMINA
The anterior corpora receive a part of the optic fibers and direct
them to the cortex of the occipital lobes. The posterior corpora, to-
gether with the median geniculates, serve as end-stations of the second-
ary auditory fibers, and communicate with the cortex of the temporal
lobes and other parts of the cerebrum. In the lower forms, the destruc-
tion of these bodies occasions blindness in both eyes, while their
unilateral laceration gives rise to blindness either in the corresponding
eye or in that of the opposite side. This diversity in the effects is caused
by differences in the crossing of the optic fibers. In the monkeys and
man, blindness does not result,^ for the reason that the loss of these
relay stations is compensated for by a transfer of their optic impulses to
other tracts.
The anterior corpora contain the center for the constriction of the
pupils, the impulses being transferred in this place from the optic tract
to that of the oculomotor. Furthermore, this transfer is distinctly
reciprocal, because the stimuli brought to bear upon the retina of one
1 Wallenberg, Neurol. Zentralblatt, xx, 1901, 50.
2 Gehirnpathologie, Wien, 1904.
3 Neurol. Zentralblatt, x, 1894, 481.
*Wilbrand and Sanger, Die Neurologie des Auges, Wiesbaden, 1904; also
Sachs, Brain, i, 1909.
^ Deutsche Zeitschr. fiir Nervenheilkunde, xvii, 1900, 428.
CEREBRAL LOCALIZATION
705
eye, affect both pupils in a corresponding degree. It need scarcely be
emphasized, therefore, that the occipital cortex may be removed with-
out destroying the Ught-reflex. An injury to the posterior corpora
produces deafness in some animals, but not in monkeys. ^ These bodies
also exert an inhibitor influence upon reflex action and are concerned
with the orderly execution of movements. This is true especially of
fishes, amphibians and reptiles, in which animals these functions are
centered in the corpora bigemini, also known as the optic lobes.
1 Ferrier and Turner, Brain, cciv, 1900, 27.
45
SECTION XIX
THE CEREBELLUM. THE PROTECTIVE MECHAN-
ISMS OF THE NERVOUS SYSTEM
CHAPTER LVII
THE CEREBELLUM
The Structure of the Cerebellum. — Anatomists have been accus-
tomed to divide this organ into a median lobe or vermis and a right
and left lateral lobe, or hemisphere. Bolk/ however, does not recog-
Sulcus prepyramidah
Uvula
Tonsilla
Lobulua biventralit
Sutctn intragracilis
Sulcus poatgracUia
Svlcus horizontalis magnua
Fig. 351.
Lobulus postero-superior
Lobulua semilunaris inferior
Lobulus gracilis posterior
Lobulua gracilis anterior
Pyramis
View of Cerebellum from Below. (J. Symington.)
nize this transverse arrangement, but advocates a division in the
anteroposterior direction. Thus, it is stated that the sulcus primarius
separates this organ into an anterior and a posterior portion. The
former embraces the superior vermis, the monticulus and lobus quad-
ratus anterior, while the latter includes the remaining portion of this
organ, namely, the lobulus simplex, lobulus medianus posterior (ver-
mis inferior) and the lobuli complicate
^ Das Cerebellum der Saugetiere, Jena, 1906.
706
THE STRUCTURE OF THE CEREBELLUM
707
The external surface of the cerebellum presents numerous deep furrows or
sulci which limit narrow leaf-like gyri or convolutions. Thus, when cut trans-
versely across, the section presents a number of lamellae, or leaf-like subdivisions,
which bear a close resemblance to the sprigs of the evergreen cedar tree, designated
as arbor vitse. Each lamella is made up of a central core of white matter and an
external envelope of gray matter. The latter consists of three layers. At the point
of contact between the cortical gray and the white matter lies a broad zone of very
minute granular cells. These elements possess a scanty amount of cytoplasm and
very short claw-like dendrites. Their axones are thin and non-medullated, and
connect with the constituents of the superficial molecular layer. Here they divide
into two branches which pursue a course parallel to the longitudinal axis of the
lamellae and terminate among the dendrites of the cells of Purkinje,i composing the
Culmen
Sulcus predivalis
Clivus
Sulcus postcentraUs
Sulcus precentraUs
Sulcus postclivalis
Folium cacuminis'
Sulcus horizontalis
magnus
Sulctts precentraUs
Lincfula
Sup. med. velum
Dorsal recess of
ith ventr.
Nodulus
Sulcus post-
nodtdaris
./
Tuber valvulce
Sulcus postpyramidalis
Uvula
3
ell*
Fig. 352. — Median Section of the Worm.
Sagittal section of the cerebellum to show its internal structure, the relative depth
of the fissures, and the grouping of the laminae. (Schdfer.)
central layer. The cells just mentioned are the most characteristic constituents of
the cerebellar cortex. They present large pear-shaped bodies and a bushy fan-
shaped network of dendrites, which is directed transversely to the long axis of the
lamellae. Their axons are myelinated and form the chief efferent path between the
cortex of the cerebellum and the more deeply seated nuclei, to be described later.
The most external zone is known as the molecular. It is occupied by the dendrites
of the cells of Purkinje and those of the cells of the granular layer. A few neurons
are interposed in this place for purposes of association. The most characteristic of
these are the so-called basket cells.
The fibers composing the white matter are of three kinds — two afferent and one
efferent. The former pass either directly into the molecular layer where they
terminate among the dendrites of the cells of Purkinje, or extend only as far as the
1 Named after their discoverer, Johannes Purkinje, Professor of Physiology at
Breslau, from 1822 to 1850.
708
THE CEREBELLUM
cells of the granular layer. The long ascending ones are known as tendril fibers
and the short ones as moss fibers, so-called on account of the peculiar thickenings
which they exhibit close to their points of termination. Ramon y Cajal believes
that the tendrils are the terminals of the fibers of the middle peduncle, while the
moss fibers are derived from the afferent fibers of the inferior peduncle. The
efferent fibers are formed by the axons of the cells of Purkinje. They end in the
deep nuclei, whence their impulses are conveyed onward by secondary neurons.
Fig. 353. — Section of Cortex of Fig. 354, — A Purkinje Cell of the
Cerebellum. Cerebellar Cortex. Golgi Method.
a, Pia mater; h, exterior layer; c, a, Axon; b, collateral; c, d, ramifications
layer of cells of Purkinje; d, inner
or granular layer; e, medullary center.
(Sankey.)
of dendrons. (Cajal.)
The cerebellum also contains certain collections of gray matter beneath its
cortex. Within the vermis and above the fourth ventricle are found the so-called
roof ganglia, consisting of the nuclei fastigii situated near the middle line, the
nuclei emboliformes located in a dorsal direction from the former, and the nuclei
globosi. Directly embedded in the white matter of the hemispheres are the deep
nuclei of which the nuclei dentati are the most conspicuous. As has been stated
above, the latter form stations upon the efferent paths, and the former stations upon
the afferent paths. Each incoming fiber divides into many branches and is thus
brought into relation with the greatest possible number of cells of the granular layer.
THE CONNECTIONS OF THE CEREBELLUM
709
The peculiar position of the latter toward the cells of Purkinje gives rise to very close
and multiform synapses so that the widest possible ramifications are established.
Functionally, this intricate union of the different neurons greatly facilitates the
spreading and summation of impulses, and leads to the so-called avalanche conduc-
tion, i.e., to an unusually extensive involvement of neurons.
The Connections of the Cerebellum. — The cerebellum is expanded
upon a central stem formed by its three connecting strands of fibers,
which are known as the superior, middle and inferior peduncles.
Fig. 355. Fig. 356.
Fig. 355. — Basket-work of Fibers Around Two Cells of Purkinje.
a, Axis-cylinder or nerve-fiber process of one of the corpuscles of Purkinje; h, fibers
prolonged over the beginning of the axis-cylinder process; c, branches of the nerve-fiber
processes of cells of the molecular layer felted together around the bodies of the cor-
puscles of Purkinje. (Cajal.)
Fig. 356. — Figure Showing the Three Pairs of Cerebellar Peduncles.
On the left side the three cerebellar peduncles have been cut short; on the right
side the hemisphere has been cut obliquely to show its connection with the superior
and inferior peduncles. The cut ends of the cerebellar peduncles have been artificially
separated from one another and are displayed diagrammatically. 1, Median groove
of the fourth ventricle; 2, the same groove at the place where the atlditory striae emerge
from it to cross the floor of the ventricle; 3, inferior peduncle or restiform body; 4,
funiculus gracilis; 5, superior peduncle: on the right side the dissection shows the
superior and inferior peduncles crossing each other as they pass into the white center
of the cerebellum; 6, lateral fillet at the side of the pedunculi cerebri; 7, lateral grooves
of the pedunculi cerebri; 8, corpora quadrigemina. (From Sappey after Hirschfeld &
Leveille.)
The superior peduncle is made up very largely of fibers which arise in the dentate
nuclei.and pass toward the region of the midbrain. They cross the midline below
the corpora quadrigemina and connect with the red nucleus and the optic thalamus.
The afferent fibers of this peduncle are few in number and seem to be derived from
the thalamus.
The middle peduncle is made up chiefly of afferent fibers which are derived from
the nuclei of the pons. They cross the midline within this structure and pass into
the lateral cerebellar hemisphere of the opposite side. A certain number of fibers
also extend efferently from the cerebellum into the same region of the pons. In this
way, a connection is formed with the corticopontine fibers which brings the cere-
710
THE CEREBELLUM
bellum into relation with the cortex of the frontal and parietal lobes of the opposite
side. The middle peduncle also embraces efferent fibers which are derived from
the cells of Purkinje and, after their decussation in the pons, descend in the lateral
funiculus of the cord. They eventually terminate around the motor cells of the
anterior horns.
^erebeffufT)
Tr olivo-cereb.
tr.spino-
cereb. dors.
(Flechs
brachium"
conjuncTivum
V: tecto-cereb.
tr. ponto-ceretx
mesencephalon
Tr Spino-oljvan
tr cortico-spinalis^
central
tegmental
tract.
tr. cortico-
olivQ interior pontd.'s
tr spino - cereb- ventr. (Gowers)
Fig. 357.-
-DlAGRAM OF THE ChIEF AFFERENT TrACTS LeADING INTO THE CEREBELLUM.
(Herrick.)
The inferior peduncle is composed principally of afferent fibers which take their
origin either in the spinal cord or in the bulb. The former constitute the continua-
tion of the direct cerebellar tract and ascend through the corpus restiforme into the
vermis of the cerebellum. ^ We have seen that this tract includes the axons of the
cerebellum
nuc. dentatus
roof nuclei
corpus restiforme
rachium pontis
brachium ^ ,
conjunctivum
tr. cereb.-teqmenTaiis
hali
mesencephalon'
bro-thol..
oliva infei
1r. cerebejlo-
tegmentojis
pontis
tr. cerebeilo-tegmentalis buibi,
Fig. 357a. — Diagram of the Chief Efferent Tracts leading out of the Cerebellum.
(Herrick.)
cells of Clark's column and collaterals from the posterior roots of the cord. The
medullary fibers form the continuation of the vestibular division of the auditory
nerve and connect the nuclei of Deiters and Bechterew with the nucleus fastiguus
1 Thomas, Le Cervelet, Paris, 1897.
I
THE ABLATION OF THE CEREBELLUM 711
and nucleus globosus of the cerebellum . In this way, this organ is brought into rela-
tion with the semicircular canals of the internal ear. It also receives a few fibers
from the trigeminus, vagus and accessory nerves. The efferent fibers of the in-
ferior peduncle arise in the dentate nucleus and form the direct anterolateral bundle
which connects with the spinal tracts.
The Ablation of the Cerebellum. — The size and complexity of the
cerebellum differ greatly in different animals. It reaches its highest
development in the apes and man. In these animals we also find the
greatest relative development of the cerebrum, although these organs
do not display a perfect structural correspondence. We have seen
that the cerebral cortex is made up of complexes of neurons which show
very decided differences in their structure and arrangement, and medi-
ate different nervous processes. The cerebrum, therefore, presents
unmistakable evidence of a division of function. A precise locahza-
tion of this kind is not in evidence in the cerebellum. On the contrary,
this organ exhibits a decidedly homogeneous structure, and hence, we
cannot go wrong in assuming that it possesses a single specific func-
tion. The correctness of this conclusion will become more apparent
later on.
While repeated attempts have been made by Rolando (1809),
Flourens (1824), Magendie (1825), Vulpian (1866), Nothnagel (1876),
and others, to apply to the cerebellum the methods previously used
in experiments upon the cerebrum, the results have proved very
unsatisfactory on account of the difficulties which surgical interferences
with this organ must necessarily be confronted by. Subsequent to
the time of Galvani and Volta, when an undue stress was placed
upon the electrical phenomena in nature, it was believed that the
cerebellum supplies the ''nerve force" which is required for our bodily
processes. No doubt, this now ridiculous contention was based chiefly
upon the observation that the lamellated outline of this organ in cross-
section presents certain characteristics which remind one of the Vol-
taic pile. Later on Gall advocated the hypothesis that it is concerned
with the sexual emotions. The first tangible view of its function was
presented by Flourens, who regarded it as an organ for the coordination
of muscular movements and particularly of those concerned in locomo-
tion and the preservation of the equilibrium.
This view is widely accepted to-day and finds its origin in the array
of S5nnptoms "displayed by pigeons whose cerebellar hemispheres
have been removed either in part or in their entirety. Birds, in par-
ticular, are closely dependent upon a properly balanced muscular
apparatus, inclusive of its central coordinating mechanism, the cere-
bellum. It may be inferred, therefore, that the excessive development
of this organ noted in these animals, is in keeping with their muscular
power, and that its removal must give rise to especially disturbing
symptoms. Thus we find that a pigeon deprived of its cerebellar
hemispheres, shows a spasdic position of the wings, legs and head which
renders standing, walking and flying impossible. Any attempt to
712 THE CEREBELLUM
make it move results in excessive and asymmetrical muscular contrac-
tions which make it tumble in all directions. It is to be noted, however,
that this loss of the power of coordinated movement is not caused by
a paralytic condition of the different muscles but by an inability to
correlate their actions for the attainment of a particular purpose.
This swaying, staggering behavior constitutes the condition of ataxia.
It is true, however, that these symptoms are not permanent, but grad-
ually disappear in the course of time until merely a certain unsteadiness
in the gait is left behind. In reptilia and amphibia the cerebellum
is rudimentary. It cannot surprise us, therefore, to find that its
ablation produces no noticeable defects in these animals.
Luciani^ has extended these experiments to the mammals. He
states that a dog, after unilateral removal of the cerebellum, shows a
rigidity of the extremities, a curvature of the spine toward the operated
side (opisthotonos), a deviation of the head toward the normal side,
a slight nystagmus, and strabismus. The latter condition presents
itself as a deviation of the eyes downward and inward on the operated
side, and upward and outward on the normal side. Among the
dynamic symptoms are mentioned atonia, or loss of the tonus of the
musculature, asthenia, or loss of force, astasia, or loss of steadiness,
and ataxia, or loss of the purposeful action of the musculature. These
defects are chiefly unilateral and produce forced movements toward
the abnormal side.^ The latter consist in rolling motions toward the
injured side as well as in movements in a circle toward the same side.
Most generally, however, the more intense symptoms disappear in
the course of from eight to ten days and are superseded by tremors.
The general character of these defects as well as their rather short
duration, led Luciani to assume that the cerebellum is an organ which
by processes that remain below the threshold of consciousness, produces
a reinforcement of the activity of the musculomotor centers. In
this beUef, however, he merely followed the views of du Petit (1710),
Laf argue (1838), and others.
A number of cases are on record of inherited defects of the cere-
bellum in man, as well as of tumors which in the course of time de-
stroyed large segments of this organ. ^ The symptoms noted in these
persons, show a decided similarity to those observed in the lower
mammals. Briefly stated, cerebellar disease produces a condition
of asynergia, ^.e., an inability properly to associate movements of
greater or less complexity into functionally definite acts. If we adhere
to this view, that the cerebellum is the seat of synergia, this organ
assumes a position very similar to that of an association center of the
cerebrum. It then becomes the center for the coordination of all
muscular activity by reason of its power of associating those sensory
impulses upon which movements depend.
1 Arch. ital. de Physiol., xxi, 1894; Fisiol. et Pathol, del Cervelletto, Padova,
1897, and Ergebn. der Physiol., iii, 1904, 259.
2 Eckhard, Herrmann's Handb. der Physiol., ii, 1883, 102.
3 Mills and Weisenburg, Jour. Am. Med. Assoc, Nov. 21, 1914.
CEREBELLAR LOCALIZATION 713
The asynergia developed in the course of cerebellar disorders, pre-
sents itself in various forms, namely, as:
(a) Hypermetry, or dismetry, i.e., a faulty measurement of the movements.
In this particular instance, the patient is unable to associate the motor constituents
of such acts as putting the index finger to the tip of the nose when the eyes are
closed. Invariably, the finger misses its mark by a distance which increases with
the degree of the hypermetry.
(6) Adiadochokinesis, or an inability to produce fine motor associations of an
antagonistic character. This is shown by the fact that the patient is quite unable
to pronate and supinate the hand when the forearm is flexed upon the arm.
(c) Tremors, shown in grasping for objects or in walking. The gait is trunkal,
i.e., the trunk constantly leaves its accustomed position, but is immediately sup-
ported in its new place by the legs in a stilt-like, sprawling manner. The cere-
bellar patient, however, knows his difficulty and makes compensatory movements
to counteract these forced movements. In this regard he differs very decidedly
from a person who is under the influence of alcohol. The latter reels in any direc-
tion without, at least in the final stage, being able to antagonize his movements.
This loss of compensation is due, of course, to the fact that the alcohol has rendered
the cerebral centers inactive. Cerebellar defects, on the other hand, need not be
accompanied by cerebral depression. The cerebellar patient also exhibits an asyn-
ergia of the tongue and laryngeal muscles which gives rise to a jerky and crackling
speech. The head is generally carried in the plane of the trunk. The eyes are
seldom at rest.
(d) Atonia, or loss of tonus and relaxation of the muscles. This condition is
dependent upon the fact that the tonic impulses from the cerebral cortex cannot
become effective when the movements are asynergic.
(e) Asthenia, or loss of force. This condition is due to the exhaustion which
results whenever the efforts to perform purposeful movements can no longer be
properly controlled,
(/) Astasia, or loss of steadiness.
(g) Ataxia, or loss of the purposeful action of the muscles. This is a complex
symptom resulting in consequence of the other defects.
Cerebellar Localization. — It has been shown by Ferrier that the
stimulation of the surface of the hemispheres of the cerebellum or of
its superior vermis, gives rise to movements on the same side of the
body. In order to evoke these motor results, it becomes necessary to
use much stronger stimuli than are ordinarily required for the excitation
of the cortex of the cerebrum. This observation is in keeping with
the histological arrangement of the cerebellar neurons, because the
cortex is really the end station of the afferent paths, while the efferent
paths as such begin in the more deeply seated nuclei.
Naturally, when we speak of localization of function in the cere-
bellum, we realize that this organ, contrary to the cerebrum, mediates
only one kind of activity, namely, that of coordinating the movements
of skeletal muscle. Thus, the only question before us is, whether
different muscles or groups of muscles are controlled by different regions
of this organ. That such a division of labor actually exists, has been
shown very clearly by the experiments of Horsley and Clarke^ which
yielded movements of the eyes and head on excitation of the roof nuclei,
and movements of the trunk and limbs on stimulation of the para-
1 Brain, xxviii, 1905, 13.
714
THE CEREBELLUM
cerebellar nuclei (Deiters'). Very similar results have been obtained
by destroying circumscribed areas of the cerebellar cortex. Thus,
it has been observed by Ryerberk^ that the excision of the lobulus
simplex produces forced movements of the head (head-nystagmus), a
condition which is caused by a faulty control of the muscles of the
neck. Quite similarly, the destruction of the ansiform lobule next to
the crus primum, gives rise to a disordered action of the muscles of the
foot of the same side, while lesions of the crus secundum cause a dis-
turbance in the movements of the foot. In accordance with the older
schema of Bolk, the present state of cere-
bellar localization may be represented as
in Fig. 358, A and B. Stress should, how-
ever, be laid upon the general fact that
different areas of the cerebellum control
different groups of muscles, rather than
upon the kind of muscle actually domi-
nated by any particular area of this organ.
The observations of Holmes^ upon
soldiers suffering from lacerations and gun-
shot wounds of different portions of the
cerebellum, have failed to yield positive
results. In many of these cases, however,
the exact location of the lesion could not
be made out. It is true that injuries to
the vermis most generally produced affec-
tions of the n uscles of the head, neck and
trunk, including those of phonation and
articulation. Small superficial lesions pro-
duced only slight and transient symptoms
which involved whole limbs rather than
particular muscles, but the defects were
invariably hmited to the side of the lesions.
But, though these clinical observations do
not lend support to the physiological con-
tention that the localization in the cere-
bellum is perfectly definite, they cannot
be considered as proof that such a minute localization does not exist.
The Function of the Cerebellum. — The foregoing data pertaining to
the ablation and excitation of the cortex and intrinsic nuclei of the
cerebellum, have been employed repeatedly as a possible basis for
a more precise doctrine regarding the function of this organ. But
while the general activity of this organ is clearly discernible, physi-
ologists have not succeeded as yet in detecting the precise nature of the
mechanism by means of which it is able to consummate its action.
It has been stated above that Flourens regarded this organ as a center
lErgebn. der Physiologie, vii, 1908, 643, and xii, 1912, 533.
2 Brain, xl, 1918,461.
Fig. 358. — Diagram Illustrat-
ing Cerebellar Localization.
A, Upper surface and B,
lower surface of human cere-
bellum; PrF, primary fissure;
PcF, postcleval fissure; GLF,
great longitudinal fissure; GHF,
great horizontal fissure; PF,
pyramidal fissure; ACL, anterior
crescentic lobe; SSL, superior
semilunar lobe; JSL, anterior
semilunar lobe; BL, biocentral
lobe.
THE FUNCTION OF THE CEREBELLUM 715
for the coordination of voluntary movements, while Rolando (1809),
Weir Mitchell (1869), and Luciani considered it as an organ for the
reinforcement of the activity of the musculomotor centers of the
cerebrum and spinal cord. Munk ascribed to it the fijnction of
preserving the equilibrium of the body, while Hitzig saw in it the
association center of the muscle sense. The last view has been
advocated more recently by Lewandowsky^ and Sherrington.
In last analysis we are dealing here with a reflex or excitomotor
function of the cerebellum, in consequence of which the musculature
of our body is forced to act within perfectly definite channels. We
obtain an absolutely set condition of tonus, a certain amplitude of
contraction, and a coordination of the activities of the different muscles.
Thus, the only factor to be determined as yet is the intrinsic stimulus
which causes the cerebellum to discharge these regulatory impulses.
In the nature of this process, the latter may be either acceleratory
or inhibitory.
In accordance with the view of Lussana, Hitzig and Lewandowsky,
the cerebellum is to be regarded as the center for the muscle-sense,
in which the different centripetal impulses from these sense organs
are associated to give rise to coordinated motion. This association,
however, does not involve consciousness, as does the association
taking place in the cerebral centers, but remains subconscious, or
more correctly speaking, reflex in its nature. Sherrington has gone
a step farther and designates this organ as the head ganglion of
the proprioceptive system, in which the different impulses from the
muscle-spindles and from the labyrinth are brought together and asso-
ciated subconsciously. From here the resulting impulses are conveyed
through the superior peduncle into the cerebrum, where they influence
the function of the motor areas. Other impulses are made to travel
outward by way of its connections with the pons and bulb, and to
direct the activity of the distant musculature. In this way, a com-
plex mechanism is established which is concerned with the coordina-
tion of the musculature in general, but more particularly with that
having to do with the maintenance of the equilibrium of the body
as its position in space is changed to suit particular purposes.
lArchiv fiir Physiol., 1903, 129.
716 THE CEREBELLUM
CHAPTER LVIII
THE PROTECTIVE MECHANISMS OF THE NERVOUS
SYSTEM
SLEEP AND NARCOSIS
The Enveloping Membranes. — The encephalon is contained in a
rigid box formed by the cranial bones. The periosteal lining of the
latter is displaced by the dura mater, a strong fibrous membrane
which is lined internally with endothelial cells, and sends firm parti-
tions inward for the support and protection of the different parts of
the brain. A membranous process of this kind invades the great
longitudinal fissure separating the hemispheres of the cerebrum.
It is called the falx cerebri, because it possesses the shape of a sickle,
being narrow in front and broad behind. Another, the tentorium
cerebelli, extends transversely across between the cerebrum and cere-
bellum, while a third, the falx cerebelli, dips into the fissure between
the cerebellar hemispheres. In several places, the dura mater is
split into two layers for the reception of the sinuses which return the
blood from the brain. In the spinal canal, the dura is not attached
to the bone, but forms a long extended sac which closely invests the
spinal cord and is held in place by the prolongations which pass out-
ward to invest the individual spinal roots. Its outside surface is
covered with networks of veins.
Directly underneath the dura and in intimate contact with it,
lies a delicate transparent membrane, known as the arachnoid. Its
outer surface is covered with endothelial cells and borders upon the
subdural space which, in reality, is of capillary size and does not seem
to have a special functional significance. Its under surface is placed
in relation with the pia mater, but in such a way that a distinct cleft
arises between them which is known as the subarachnoidal space.
The latter is intersected by fine fiber connections and septa of con-
nective tissue, the meshes of which are filled with a lymph-like fiuid.
It becomes especially conspicuous over the different sulci for the
reason that the pia mater follows the surface of the brain into these
furrows, while the arachnoid and dura pass directly across them in the
form of bridges. In certain localities, however, the subarachnoid
space is much increased in size, forming here the so-called cisternse which
in turn are connected with one another by delicate canals. Reflections
of the arachnoid frequently dip into the fissures. One of these is
found between the cerebral hemispheres and the third ventricle,
where it extends into the lateral ventricle, becoming covered on one
side by the ependyma of this cavity, and, on the other, by the epen-
dyma of the roof of the third ventricle. It envelops a rich network
PROTECTIVE MECHANISMS OF THE NERVOUS SYSTEM
717
of blood-vessels forming the choroid plexus. A similar vascular fringe
is suspended from the roof of the fourth ventricle.
This subarachnoid system is in direct communication with the
ventricles of the biain by way of the foramen of Magendie and the
foramina of Luschka. It also connects with the lymphatic spaces
accompanying the cranial nerves, as well as with the central canal tra-
versing the commissure of the gray matter of the spinal cord. In
addition, it is placed into relation with the venous sinuses by the
Pacchionian bodies. The latter are pouch-like protrusions from the
surface of the arachnoid formed by enlargements of the normal vilU
of this membrane. Most of these bodies are lodged in irregular pits
Fig. 359. — Transverse Section Through the Longitudinal Fissure to show the
Relation of the Cerebrum to the Meninges.
C.C., Corpus callosum; W, white matter; G, cortical gray matter; P, pia mater
closely investing it; A, arachnoid with its membranous prolongations forming the
subarachnoid space {S.S.)', D, dura mater; B, skull consisting of the external and
internal plates separated by a spongy center; F, falx cerebri enveloping LS, the longi-
tudinal sinus. Into the latter extend the Pacchionian bodies.
in the calvaria, but some of them also project into the sinuses. They
are particularly numerous along the superior longitudinal sinus. The
close contact which is thus established between the liquid filling this
entire system and the venous blood, might lead us to suppose that these
saccules serve as a means for returning some of the liquor to the blood.
They do not, however, constitute perfectly open outlets, and hence the
escape of the lymph must be brought about very largely by processes
of filtration and osmosis.
The Growth of the Brain. — Broca^ states that the weight of the pia
mater amounts to:
1 Elements d'Anthropologie generale, 1885.
718 THE CEREBELLUM
45 grams in individuals between the ages of 20-30
50 grams in individuals between the ages of 30-40
60 grams in individuals between the ages of 50-60
The capacity of the ventricles is 26 c.c, and the specific gravity of
the entire encephalon 1.036. Its weight varies considerably even when
members of the same race and social standing are compared. Thus,
the compilations of Marshall^ which are based on the records of
Boyd, show immediately that the male possesses a heavier encephalon
than the female and that all its subdivisions are heavier. Further-
more, a comparison of individuals of the same sex and age will show
that those having the greater stature, exhibit a greater brain weight,
and that the weight decreases with advancing years. This decrease
in weight is most clearly indicated between the seventy-first and
ninetieth years.
Vierordt^ has collected a series of observations illustrating the
changes in the weight of the brain between birth and the twenty-fifth
year; which show that the greatest increase takes place during the
first year. It grows rapidly to the fourth and fifth years, and then
more gradually to the seventh year. From this time on its growth is
very slight up to maturity. Social environment may be expected to
be of influence, because the least favored individuals in any community
usually show a certain retardation. The observations of Manouvrier
have proved, however, that the average weight of the brains of murder-
ers permits of no conclusions when compared with the average weight
of the brains of the usual inmates of hospitals. Moreover, with the
exception of, the microcephalics, the insane as a class are not
characterized by an especially slight brain weight. The examination
of the brain capacities of a series of skulls belonging to different
races, favors the western Europeans. ^
The total number of neurons present in the central nervous
system, has been estimated at 13,000,000,000. This estimate is
based upon the records of Hammarberg,^ which in accordance with
Thompson,^ give 9,200,000,000 well-marked cell-bodies to the cortex
of the cerebrum alone.
The Cerebrospinal Fluid. ^ — The subarachnoidal and subdural
spaces, as well as the encephalic ventricles, are filled with a colorless
liquid, the quantity of which varies between 60 and 200 c.c. in accord-
ance with the age and size of the individual. The subdural space
being chiefly potential, about one-half of this quantity is held in the
subarachnoidal clefts, and 20-30 c.c. in the ventricles We have noted
^ Jour, of Anat. and Physiol., 1892.
2 Archiv fur Anat. u. Physiol., 1890.
3 Davies, Jour, of the Acad, of Nat. Sciences, Philadelphia, 1869; also: Donald-
son, The Growth of the Brain, 1895.
* Studien iiber die Path, der Idioten, Upsala, 1895.
6 Jour, of Comp. Neurol., 1899.
^ First described by Haller, Physiol, des Menschen, 1766.
PROTECTIVE MECHANISMS OF THE NERVOUS SYSTEM 719
before that this subarachnoidal space does not possess the same height
throughout the encephalon, but shows cistern-Hke enlargements at
different points, and especially over the corpus callosum and the optic
lobes. Over the upper and lateral aspects of the brain- it is very nar-
row. It has also been mentioned that it is traversed by numerous
fibers and bands, so that it really becomes subdivided into a multitude
of intercommunicating cells which in turn connect with the lateral
ventricles, the central canal and subarachnoidal space of the spinal
cord, the lymphatic channels of the cranial and spinal nerves, and the
Fig. 360. — Right Lateral. Aspect of the Skull and Cerebral Hemisphere Out-
lined IN Black, with Orthogonal Projection of the Structures in the Median Plane
AND OF the Right Lateral, the Third and the Fourth Ventricles in Red. (Quain.)
Man aged fifty-six years, o, nasion; b, bregma; c, lambda; d, union; t.r., temporal
ridge; s.c, sulcus centralis; s.p., Sylvian point.
lymphatics of the nasal cavity and neck.^ It seems, however, that
the subdural and subarachnoidal spaces are not directly connected
with one another, although colored fluid injected into either cavity,
eventually reaches the lymphatics of the nasal cavity as well as those
of cranial nerves.
Cerebrospinal fluid may be obtained from animals by introducing
a cannula through a slit in the sheath, of a nerve root into the subarach-
noid space of the spinal canal or by inserting it through the atlanto-
occipital membrane into the cistern-like enlargement of the subarach-
noid over the fourth ventricle. In man, it is now a rather common
procedure to introduce a hollow needle directly into the spinal, canal
1 Walter, Monatschrift fiir Psych, und Neurol., 1910, 28.
720 THE CEREBELLUM
of the lumbar region, the needle being pushed inward between the
laminae of the vertebrae. This constitutes the procedure of lumbar
puncture^ which is made necessary whenever small quantities of this
fluid are to be obtained for chemical and histological analysis. Several
cases are also on record, showing that a spontaneous discharge of cere-
brospinal liquid may take place at times from the nasal cavity, aver-
aging as much as 500 c.c. in 24 hours.
The fact that this fluid escapes from the cannula with some force
snows that it is held under a certain pressure, equaling 5 to 7.3 mm. Hg.
The flow decreases later on until only droplets appear. Various symp-
toms, such as vertigo, nausea and headache, result if it is allowed to
drain off for too long a time. It is also of interest to note that the
pressure of this fluid is about equal to that existing in the venous sinu-
ses of the cranial cavity. Thus, if salt solution is injected into the
subarachnoid space, it will be found to escape with relative ease, one
of its channels of escape being the Pacchionian bodies. It seems,
therefore, that these protrusions of the arachnoid membrane serve as
filters, allowing a quick interchange of pressure between the cerebro-
spinal fluid and the blood in the sinuses. A similar interchange may
be effected between this fluid and the lymph filling the lymphatics of
the nerve roots, but the resistance interposed here seems to be much
greater.
The cerebrospinal fluid is commonly regarded as a true secretory
product (Mott) of the epithelial fining cells of the choroid plexus
(Luschka). Others, however, consider it as a Ijmiphatic fluid formed
by transudation as well as by secretion (Lewandowsky). It cannot be
doubted that this fluid possesses a certain independency, because bil-
iary pigments frequently appear in the content of the subarachnoid
space but not in that of the ventricles; and furthermore, the former
often shows certain chemical characteristics which are not displayed
by the latter. ^ It has also been found that its flow may be increased
by extract of choroid plexus.^ Its formation, however, is slow under
ordinary conditions, as has been shown by the experiments of Cavaz-
zani,^ which prove that it takes about one hour before an easily recog-
nizable salt injected into the general circulatory channels, may be de-
tected in the subarachnoid fluid. ^ In a similar way, it has been found
that potassium iodid injected into the encephalic arachnoid cavity, ap-
pears in the urine only after about twenty minutes. In view of this
close connection between the cerebrospinal fluid and the lymph, it
seems best to consider the former as being derived from three sources,
namely, (a) by secretion into the ventricle from the choroid plexus, (b)
^ Quincke, Deutsche med. Wochenschrift, 1905.
2 Thomson, The Cerebrospinal Fluid, New York, 1899.
3 Halliburton, Proc. R. Soc, London, 1916.
^ Centralbl. fiir Physiol., xiii, 14.
^ Plant, Rehm and Schottemiiller, Leitfaden zur Unters. der Zerebrospinal-
fliissigkeit, Jena, 1913.
PROTECTIVE MECHANISMS OF THE NERVOUS SYSTEM 721
by transudation into the subarachnoid and subdural spaces, and (c) by
transfer from the intra-adventitial lymphatic spaces of the cortex.
Regarding its function it should be mentioned first of all that it
serves the general purpose of lymph, because it bathes the nerve-cells.
It forms a nutritive medium, which, in addition, is chemically protect-
ive, because it tends to exclude such harmful substances, as proteins
and toxins. In the second place, it is mechanically protective, be-
cause it serves as a water-bed upon which rests the base of the middle
and posterior parts of the encephalon, and which in other regions mini-
mizes the force of blows upon the integument. In the third place, it
may be conjectured that this fluid subjects the nervous tissue to a
certain pressure which keeps it under a tension best adapted for its
function.
Sleep. ^ — Activity must always be followed by rest, because con-
tinued catabolic processes lead to fatigue and exhaustion. This holds
true of the motor as well as of the sensory mechanism. A heart or
skeletal muscle, when made to contract repeatedly, soon loses its irri-
tability, because it is not allowed sufficient time to replenish the mate-
rial lost during its periods of activity. This is also true of glands if
made to secrete excessively, and of all sense-organs, if stimulated for a
long period of time. What is true of individual tissues, is true of the
body as a whole. It requires a period of recuperation during which its
receptive power is at a minimum and during which it reestablishes
proper physico-chemical conditions. Sleep is a universal phenomenon
among animals; even the fish, reptiles and amphibians pass long
periods of time in absolute quietude. The fundamental reason for
sleep must, of course, be sought in chemico-physical changes, but our
present knowledge of metabolism is not sufficiently advanced to ex-
plain the cause of this phenomenon in more than a very general
manner.
While the daily requirement of sleep is about 7-8 hours for the
adult, this time varies considerably under different conditions. In
childhood, the amount of stored energy is small, owing to the immature
development of the cells, while the metabolism, relatively rated, is
intense, and hence, children require longer periods for recuperation.
In old age, on the other hand, the small amount of stored energy is due
rather to retrogressive changes and is associated with a lower meta-
bolism, both factors combining to produce shorter hours of sleep. In
either case, however, loss of sleep is injurious and even more so than
the withholding of nourishment. Thus, Manaceine^ has found that
young dogs may withstand a starvation period lasting twenty days,
but fail to recover from a loss of sleep extending over more than four or
five days. These animals exhibited a fall in the body temperature of as
much as 8° C. below normal, a diminution of the reflexes, fatty de-
generation of diverse tissues, and hemorrhagic extravasations into the
1 Pieron, Le probleme physiol. du sommeil, Paris, 1913.
2 Contemp. Science Series, London, 1897.
46
722 THE CEREBELLUM
nervous tissue. Very similar changes have been observed in men
deprived of sleep during a period of ninety hours. ^
The desire to sleep most commonly manifests itself by drowsiness,
a general malaise, a heaviness and dryness of the eyelids, a difficulty
in keeping the attention fixed, and other symptoms. This initial
state soon gives way to a condition of unconsciousness during which the
cortex is at least moderately impervious to external and internal
stimuli. All volitional actions, therefore, cease, while the reflexes are
in part preserved, although greatly diminished in their intensity.
This shows that some parts of the central nervous system remain more
active than others and this is true even of the cerebral cortex, because
the motor center becomes inactive before the sensations have been
lost entirely. Thus, a person may have reached the state of muscular
flaccidity while still capable of receiving sensations of sound and touch.
The sense-organs themselves are in part protected against stimuH.
The eyelids are closed and the eyeballs rolled far upward and inward.
The pupils are markedly diminished in size. The latter effect may be
explained in the same manner as the constriction resulting on near
vision, i.e., it may be said to find its cause in afferent stimuli set up in
consequence of the convergence of the eyes. The conjunctival mem-
brane becomes dry owing to a diminished secretion of lacrimal fluid,
and is thus rendered less responsive to stimuli. A similar diminution
in the sensitiveness is noted in the oral and nasal cavities. Their
mucous lining also exhibits a certain dryness as a result of diminished
secretion. The ears are protected by a relaxation of the conductors
of sound situated in the middle ear, i.e., the ear drum and ossicles.
Sleep having set in, the respirations become slower and deeper and
are frequently accompanied by loud noises produced by the air as it
rushes across the relaxed fauces, uvula, and edges of the laryngeal folds.
In many cases the respirations assume a periodic character, a certain
number of them being separated from others by a distinct interval of
comparative rest. The frequency of the heart is greatly reduced; the
vascular channels are relaxed and the blood pressure lessened. From
these changes it may justly be inferred that the tissues have entered
upon a state of relative inactivity; their low oxygen requirement and
small output of carbon dioxid clearly betraying a decided reduction in
their oxidations.
Changes in the Depth of Sleep.; — Although sleep lasts as a rule for
a certain number of hours, it does not retain the same depth through-
out this period. This has been shown by endeavoring to awaken a
person at different intervals by sounds of measured intensity. A pen-
dulum beating against a metal plate, or small lead balls falling upon a
metal surface, have usually been used for this purpose.^ While in-
dividual variations are very common, the results show that the
intensity of sleep increases steadily until it reaches its maximum
1 Patrick and Gilbert, Psychol. Review, iii, 1896.
2 Monninghofif and Piesbergen, Zeitschr. fiir Biologie, xix, 1883.
PROTECTIVE MECHANISMS OF THE NERVOUS SYSTEM 723
between the first and second hours after its beginning. It then
decreases and remains rather Ught during the third and fourth hours.
A second but much sUghter increase takes place during the fifth hour.
From here on it again decreases up to the hour of awakening.
Theories of Sleep. — The theories pertaining to the causation of sleep,
may be conveniently arranged as follows:
(o) Anemia Theory (Coppie, 1854). — It is held that the diminution and loss
of the irritability of the cerebrum, and especially of its cortical zone, is dependent
upon a decrease in its blood-supply. This view is based chiefly upon the experi-
ments of Mosso^ which have shown that the volume of the arms and legs increases
during sleep, presumably on account of a transfer of blood from the cerebral into
the cutaneous circulatory channels. This transfer may be effected in two ways,
namely, by a constriction of the cerebral blood-vessels ^ or by a relaxation of the
blood-vessels in other parts of the body. The extracerebral circuits which could
be concerned in producing this diminution in the vascularity of the brain, are those
of the integument and portal organs.
These facts have been made use of by HilP in formulating a theory which has
as its chief element the fatigue of the vasomotor center. It is assumed that sleep
results in consequence of the loss of tonus of this center brought on by the con-
tinued activity during the working hours. This loss of the vascular tonicity in
turn leads to lower pressures and diminishes the blood flow throughout the body,
but more particularly that through the brain. The blood withdrawn from the
cerebral circuit, is said by Hill to be accommodated in the blood-vessels of the portal
organs, while Howell believes that it is transferred into those of the skin and sub-
cutaneous tissues. Brodmann^ and Shepard^ however, claim that the volume of
the brain is increased, during sleep, as is also that of the limbs. This contradiction
of the results of the investigators just cited, necessitates a certain modification of
the anemia theory, because it places the transfer of blood from the brain into other
blood-vessels into question. At best, therefore, we can go no further than to state
that the vascular relaxation and depression resulting during sleep, is general and
does not produce an actual anemic condition of the brain.
(6) Inhibition theory, advocated by Brown-Sequard, ^ refers sleep to an inhibition
of cortical function, such as may be produced by passing an induction current of
low tension through the cranium (Leduc). This view has few points in its favor,
because it does not attempt to explain the mechanism by means of which this
inhibition is brought about.
(c) The mechanical block theory refers sleep to an interruption of the conduction
paths caused by a retraction of the terminal fibers of the synapses.^ This view
must also be said to contain a decided element of speculation, because it has never
been demonstrated that a retraction of this kind actually takes place.
{d) The chemical theories of Preyer,^ Pieron* and Pfliiger^^ refer the loss of the
irritability of the brain to a fatigue brought on by chemical means. Thus, it has
^ Ueber den Kreislauf des Blutes im menschl. Gehirn, Leipzig, 1881; also:
Brush and Fayerweather, Am. Jour, of Physiol., v, 1901, 199.
2 Jensen, Pfliiger's Archiv, ciii, 1903, 171.
3 Physiol, and Pathol, of the Cerebral Circulation, London, 1896, and Howell,
Jour, of Exp. Med., ii, 1897, 313.
* Jour, fiir Psych, und Neurologie, i, 1902, 10.
5 Am. Jour, of Physiol., xxiii, 1909.
« Archiv de physiol., 1889, 333.
' Duval, Compt. rend, de la Soc. biol., 1895; Cajal, Archiv fiir Anat. und Phy-
siol., 1895, and Nicard, Le sommeil normal, Lyon, 1904.
8 Centralb. f. d. med. Wissensch., xiii, 1875.
^ Le probl^me physiol. du sommeil, Paris, 1913.
i« Pfluger's Archiv, x, 1875, 468.
724 THE CEREBELLUM
been suggested that the constant activity of the muscles and other organs during
the waking hours gives rise to waste products which accumulate in the system,
because they cannot be gotten rid of as rapidly as they are produced. In the course
of time, these substances cause a nervous depression which eventually culminates
in sleep. While this theory also lacks experimental confirmation, it has certain
points in its favor. Thus, it is a well-known fact that the activity of muscle is
associated with the production of fatigue substances, such as carbon dioxid, sar-
colactic acid and monopotassium phosphate. The accumulation of these sub-
stances in muscle finally causes the latter to lose its irritability. Furthermore, if
the serum of a fatigued animal is injected into the circulatory channels of a normal
animal, the latter will show all the phenomena of fatigue.
Some physiologists, among them Pieron, have gone a step farther and have stated
that these fatigue substances are augmented by a special toxin which might be
designated as a hypnotoxin. It is this agent which is assumed to produce the
histological changes in the cells of the brain after forced deprivation of sleep. Its
presence has been established by injecting the blood serum or cerebrospinal fluid
of such animals into the circulatory channels of normal animals. The latter then
showed a condition simulating sleep as well as structural changes in the cerebral
cortex.
Pfliiger explains sleep by assuming that the cells of the brain are quite unable
to replace their store in intramolecular oxygen as rapidly as it is used up and hence,
their irritability must decrease gradually with the length of the period of activity.
This idea, however, that oxygen is stored in the cells as a product of a distinct
synthesis is not commonly accepted to-day. The foregoing brief discussion must
show that this subject is still in a very indefinite form, so that it might seem advisa-
ble to adhere for the present to the chemical theory and to consider the changes in
the pressure, flow and distribution of the blood as secondary phenomena.
Hypnotic Sleep. — This condition is by no means identical with
sleep. It is brought about by producing the picture of hypnosis by
suggestion, a process which may be greatly facilitated by fixing the
attention of the subject upon a constant visual, auditory or tactile
stimulus, such as a glistening object, a monotonous sound, or slight
stroking of the skin. Facilitation of this process is effected in time by
repeated hypnoses until eventually a condition of autohypnosis may be
induced, ^.e., an ability on the part of a person to self -induce this state
(Cardanus, 1553).
Contrary to sleep, the hypnotized person exhibits a decided blanch-
ing of his features, a muscular relaxation, a drooping of his eyelids,
slow and deep respirations and a peculiar change in his conscious-
ness which is characterized by a decided vulnerability to suggestions.
The vascular changes are betrayed by a decrease in the volume of
the arms and legs, when determined by means of the phlethysmograph.
Deep hypnosis, moreover, insures a loss of voluntary control of the
muscles and certain sensory disturbances, such as amnesia, analgesia
and anesthesia for touch and temperature. Curiously enough, this
loss of the self-regulation of muscular movements does not include the
control of the * voluntary muscles through suggestion. Thus, it is
possible to force a hypnotized person to assume different positions or
to inhibit the action of his muscles, so that he cannot extricate himself
from the most awkward idiomuscular situations. In fact, his muscles
may be tonically set, so that the body becomes perfectly rigid and may
PROTECTIVE MECHANISMS OF THE NERVOUS SYSTEM 725
be subjected to most unusual conditions. Quite similarly, it is pos-
sible to influence his mental concepts in such a way that memories
of certain past experiences are lost, while others are artificially created,
thereby changing the entire character of the person. He may assume
the character of a typical paralytic, bUnd or deaf person. Some of
these suggestions may even produce posthypnotic results many days
and weeks after the hypnosis. Thus, when a postage stamp was placed
upon the skin of a hypnotic and it was suggested to him that it would
raise a blister, such a formation was actually found beneath it on the
following day. Subcutaneous hemorrhages may be induced in the
same way, and so may ''brand-marks" by simply suggesting to the
hypnotic that, say, a piece of chalk used upon the skin, is a red hot
iron.
Hypnotic states may also be evoked in animals. Thus, it is not
difficult to render frogs, birds and rabbits motionless by a continued
gentle pressure upon the dorsal aspect of their body, such as may be
produced by holding them in the palm of the hand. A lobster may in
this way be made to stand upon its head supported only by the first
pair of appendages. Kircher's experimentum mirabile (1644) con-
sists in rendering a fowl temporarily quiescent by placing a straw across
its bill or by fixing its head in such a way that the eyes look directly
at a chalk line drawn across the table. Verworn,i however, states
that this is not an instance of true hypnosis but solely one of optical
inhibition of reflexes.
Narcosis. — Omitting the largely speculative theories regarding
the causation of narcosis, it has always been supposed that the nar-
cotics enter into a chemical combination with the constituents of the
protoplasm. In analogy to this union might be mentioned the action
of curarin upon the motor nerve-endings or that of carbon monoxid upon
the hemoglobin. Peculiarly enough, certain narcotics of the aliphatic
series are chemically inactive, although capable of inducing a character-
istic narcotic action. It was subsequently found that all possess the
property of being dissolved in water and fats, this property being
responsible for their absorption and distribution to the cells of the
body. Bibra and Harless,^ therefore, conceived the idea that the action
of the anesthetics is dependent upon their power of dissolving fat. This
hypothesis, however, seems untenable, because it fails to explain the
rapid restitution of function following the anesthetization. In other
words, *it seems unlikely that the fat dissolved out of the nervous tissue
to institute narcosis, can again be replenished in so short a time.
While no definite theory of narcosis has been formed to supplant
the preceding, some interesting data have been gathered which partly
explain the anesthesia. Thus, it has been shown by Meyer^ and
1 Die sogenannte Hypnose der Tiere, Jena, 1898.
2 "Qber die Wirkung des Schwefelathers, 1847.
3 Archiv fiir Exp. Path, und Pharm., vi, 1901, 12.
726 THE CEREBELLUM
Overton^ that the narcosis depends upon the solubility of the narcotic
agent in fats and oils. In general, those substances act as narcotics
which are more readily soluble in fat-like media than in water; in
fact, the power of these agents is directly proportional to their fat
solubility. It has also been established that their action is produced
by the free molecule and not by the products of their decomposition.
Thus, the esters of the fatty acids narcotize only while they remain
unsaponified. They lose this property as soon as they are spUt
into the corresponding alcohol and fatty acid. This characteristic
effect upon the nervous system is made possible by their going into
solution with the fat-like constituents of this tissue, the lipoids.
As nervous tissue contains an especially large amount of these sub-
stances, the narcotics must be capable of entering this tissue much
more easily than others.
Having shown that the accumulation of the narcotics in the nervous
tissue is due to their solution-affinity for the lipoids, we may go one
step farther and state that the essential cause of narcotic action is the
solution-reaction between them and the lipoids. In this connection,
it might be mentioned that Hober^ has found the colloidal state of
the cells to be changed during narcosis, and that Winterstein^ has
proved that narcotized tissue ceases to take up oxygen even when
made to produce work in a superfluity of this gas. The evidence tends
to show, however, that while the inhibition of oxidation constitutes
a factor in narcosis, it is not actually its cause.
1 Studien iiber die Narkose, Jena, 1901.
2 Zeitschr. fiir allg. Physiol, xi, 1910, 173.
» Ibid., vi, 1907, 316.
PART VI
THE SENSE-ORGANS
SECTION XX
SPECIAL SOMATIC AND VISCERAL RECEPTORS
CHAPTER LIX
CLASSIFICATION OF THE SENSE-ORGANS
The DijBferent Manifestations of Energy. — Until now we have re-
garded the central nervous system as a mechanism controlling our
various motor actions in a way to conform with the conditions existing
in our environment. As such it occupies a position intermediate
between the different afferent and efferent paths, fulfilling the function
of a machine which converts or synthetizes the incoming impulses into
motor responses. We have previously seen that the efferent side of
this circuit is not greatly diversified, because all the effectors in our
body are built up either of muscle tissue or glandular tissue. On the
afferent side, on the other hand, we find a decided multiplicity in
structure to correspond with the diverse character of the influences
to which we may be subjected.
Our body is surrounded by a medium which is teeming with mani-
festations of energy in its different forms. Against these the body
is partially protected by a relatively impervious capsular investment,
the skin. Here and there, however, this investment is beset with
orifices for the admission of those stimuli which are essential to our
life. These perforations really correspond to the windows of a house
which enable us to come into functional relationship with the outside
world. This is also true of the lower animals and even of those
forms which are not in possession of a nervous system. In the latter,
the different manifestations of energy are brought to bear directly
upon their hving substance, but not in an indiscriminate manner, be-
cause, with the exception of a few, these organisms are all at least
partly protected against excessive stimuli by some sort of an enveloping
membrane or calcareous shell. Furthermore, all these organisms pos-
sess a much more limited range of excitation than the higher forms, so
that they are open to only a few types of stimuli, principally to those
of mechanical and thermal origin.
727
728 SPECIAL SOMATIC AND VISCERAL RECEPTORS
Recurring to the analogy of the house with the many windows, it
may then be said that these different openings are beset with a special-
ized form of protoplasm which, owing to its chemico-physical constitu-
tion, is especially sensitive to energy impressions from without, and is
also modified in such a way that it can receive only one particular kind
of stimulus. In other words, these sense-organs or receptors show
individual differences which render them more particularly adapted to
a certain type of energy manifestation. Thus, the retina of our eye
cannot be activated by sound waves, nor can the organ of Corti be
stimulated by the ethereal impacts of light. Each receptor, therefore,
is set aside for only one kind of stimulus and remains impervious
to others not specifically suited for it. It is true, however, that in
most cases these receptors may be subjected to non-specific stimuli
artificially, but the effects are then quite different from normal.
Thus, it is possible to stimulate the retina either mechanically or
electrically, in which case visual sensations in the form of phosphenes
will be obtained, but these sensations are obviously very different from
ordinary light impressions.
This specificity of the different sense-organs is to be attributed to
the peculiar structure and composition of the neuroplasm forming
them. Their function, however, is materially enhanced in many cases
by the fact that the nervous terniinals are amplified by certain acces-
sory structures which tend to concentrate the stimuli precisely upon
the receptor so as to intensify their force. Thus, we find that the
essential receptive element of the eye is the retina, while the different
refractive media of this organ, together with the iris, merely serve the
purpose of concentrating the light rays upon its most sensitive con-
stituent. The same is true of the organ of Corti, because the exter-
nal ear, the eardrum, and ossicles merely serve to increase the striking
force of the sound waves and to direct them to the sensitive epithelium
in the cochlea.
The orifices in our integument in which the different sense-organs
are placed, form, so to speak, points of least resistance through which
the energy manifestations in space may reach the interior of our body.
But, as has been stated above, each gateway permits of the entrance
of only one particular kind of impact, because its resistance toward the
others is heightened sufficiently to exclude them. In general, it
may be said that we are subject to two types of energies, namely, the
vibratory and the chemical, which in turn have been classified by
Herrick^ as follows:
A. Vibratory Energy.
1. Mechanical impacts received by the tactile corpuscles of the skin at a rate
of as high as 1552 vibrations in a second.
2. Slow vibrations in material media received by the organ of Corti, and sub-
jectively perceived as sound. The human ear is activated by vibrations varying
between 30 and 30,000 in a second. In some cases, however, this range may be
extended to 40,000 and 50,000 vibrations per second.
1 An introduction to Neurology, Saunders Co., Philadelphia, 1915.
CLASSIFICATION OF THE SENSE ORGANS 729
3. Rapid vibrations in ether, or waves in immaterial media, received by the
temperature corpuscles of the skin (heat-rays) and the retinae of the eyes (light-
rays). These vibrations, however, also include some to which we are absolutely
insensitive or which can only be perceived with the help of certain accessory means.
The Hertzian electrical waves attain a vibratory frequency of 3000 billions per
second, the ultra-violet rays one of 5,100,000 billions per second, and the Roentgen-
rays one of 6,000,000,000 billions per second. In between these two extremes
lies the receptive scala of man. Thus, we find that our retina is capable of receiving
impacts, the vibrations of which vary between about 400,000 and 800,000 billions
per second. This range covers the solar spectrum. Between these vibrations and
those attaining a frequency of 3000 billions per second, lies the realm of the radiant
heat which stimulates the temperature receptors of our skin.
B. Chemical Energy.
The different chemical impacts to which we may be exposed, are received in a
relatively imperfect manner. The organ of smell covers a much wider range than
the organ of taste; in fact, the latter gives rise to only four fundamental sensations,
namely, sweet, bitter, salty and sour.
Classification of the Sense-organs. — The foregoing discussion
shows first of all that under ordinary conditions only a limited number
of the energies developed in space, are made accessible to man. This
statement, however, is not meant to imply that the equipment of other
animals is as good as that of man; in fact, the chances are that it is
not, for the reason that the human nervous system attains the most
perfect all around development. It cannot be doubted, however, that
the sensory mechanisms of a particular group of animals may be more
fully developed along certain lines than those of others. This is especi-
ally true of the olfactory apparatus ; but may also be true, for example,
of the visual and auditory mechanisms of the birds as against those
of man. At all events, provision has been made in each case to equip
the different animals more especially with those sense-organs which
are of greatest practical use to them.
Man has been placed in a position to analyze the energy manifes-
tations in space by means of five senses, i.e., he is able to bring five
different means to bear upon the forces of nature for purposes of
orientation. The sense-organs concerned in this analysis, are com-
monly said to be the eyes, ears, nose, tongue and skin. In agreement
with this classification the layman recognizes five senses, namely, sight,
hearing, smell, taste and touch. One discrepancy, however, must
occur to us immediately, namely, that this classification does not em-
brace the large number of different receptors which are concerned with
the reception of stimuli arising in the interior of our body. In the
second place, attention should be called to the fact that several of the
original five senses are really composite in type. Obviously, the ear
contains not only the organ of hearing, but also separate receptors for
the static and dynamic senses. Quite similarly, the skin is not only
concerned with touch, but also mediates the sensations of pressure,
pain, and temperature. To be brief, it will be brought out later on
that there are in reality more than twenty different receptors in our
body.^
^Ohrwall, Skand. Archiv fiir Physiol., xi, 1901.
730 SPECIAL SOMATIC AND VISCERAL RECEPTORS
The preceding discussion must have shown that the central nervous
system really performs two important functions, namely, to control
the activities of the different tissues and organs, and secondly, to bring
the latter into a proper relation with the outside world. Since this
control is effected with the help of two different groups of nervous
structures, the central nervous system tnay be divided theoretically into
a visceral and a somatic part. For the same reason, the sense-organs
may be classified as visceral and somatic, the former having to do with
the sensations arising within our body, and the latter with those pro-
duced by the energies in space. It should be noted, however, that
these groups of organs are not functionally isolated from one another,
but are closely correlated so that they can always influence one another.
Thus, we find that a visceral sensation may give rise to a somatic
response, and vice versa. This classification has been made more em-
bracing by Sherrington,^ who divides the somatic group of receptors
into exteroceptors and proprioceptors, and the visceral group into
general and special interoceptors, as follows :
A. Somatic receptors, having to do with the orientation of the animal toward its
environment.
1. Exteroceptors, are stimulated under ordinary conditions by outside forces
They embrace the end-organs for: (a) touch and pressure, (6) pain, (c) heat and
cold, id) general chemical sensibihty, (e) hearing, and (/) vision.
2. Proprioceptors, are situated in the muscles, tendons and joints and are con-
cerned with the production of the muscle-sense. To this group also belong the
end-organs which have to do with the sensations of equilibrium, namely, the oto-
Uthic cavities (static sense) and the semicircular canals (dynamic sense).
B. Visceral receptors, are concerned with the stimulations arising within the body,
principally in connection with digestion, secretion, the action of the heart, and
other functions.
1. General interoceptors, embrace the end-organs, mediating the sensations of
hunger, thirst, nausea, respiratory and circulatory sensations, sexual sensations,
visceral pain, and others.
2. Special interoceptors, consist of the end-organs for taste and smell. Both
are excited by chemical stimuli and while both are typical interoceptors to begin
with, the organ of smell eventually becomes more closely associated with outside
conditions. 2 In the amphibians and allied animals it is really the chief extero-
ceptor, although its more primitive interoceptive qualities are still in evidence.
Like the animals, plants are also exposed to varying conditions in the environ-
ment and are in possession of intensifying receiving organs. As such may be
classified the bristles upon the leaf of Dionaea as well as those upon the stems and
leaves of Mimosa pudica.
The Doctrine of the Specific Nerve Energies. — It is by no means
difficult to see that the energy manifestations give rise to very specific
sensations and reactions. The question then arises, whether this
specificity is due to peculiarities in the energy or to pecuharities in the
structure of the sense-organs. Johannes von Miiller favors the second
view without, however, positively referring it to any particular segment
of the neuron. In more recent years physiologists have gone a step
1 The Intergrative Action of the Nervous System, New York, 1906.
* C. J. Herrick, Jour. Comp. Neurol., xciii, 1908, 157.
CLASSIFICATION OF THE SENSE ORGANS 731
farther and have rather generally concluded that the specific quality of
a sensation in consciousness is dependent upon the center and not upon
the conducting path nor upon its receiving organ. The second pos-
sibiUty may, of course, be justly ruled out, because nerve fibers are con-
ductile elements and nothing more than that. The third possibility
cannot be excluded so easily, because the sense-organs exhibit particu-
lar structural details which- render them especially adapted for the
reception of single kinds of energy manifestations. On the other hand, it
is evident that this specificity of the end-organ could not be of any avail,
were it not for the fact that the center possesses a similar specificity.
. Besides, since the latter is commonly regarded as the controlling factor
of all nervous processes, it may also be considered as the determining
agent of these impressions in consciousness. Consequently, the end-
organ merely enables a particular stimulus to enter, and determines
whether or no the latter should become effective centrally. Thus, if
it were possible to cross the optic and auditory nerves, so as to connect
the retina with the auditory center and the organ of Corti with the
visual center, we would hear pictures and see sounds.
The experimental evidence which might be mentioned in favor of
the doctrine of specific nerve energy, includes such positive data as
the following:
(a) An impression in consciousness is often obtained without the help of the
sense-organ and conducting path. For example, subjective sensations of light are
frequently gotten in a perfectly dark room and when the eyes are closed. Ringing
in the ears is another common subjective phenomenon. Central causes must also
be held responsible for the multitude of concepts obtained during dreams and in
consequence of pathological conditions, such as arise during hysteria and states of
excessive sensitiveness of the nervous system.
(6) The different sense-organs may also be activated by stimuli other than
those ordinarily received by them. Thus, sensations of light may also be produced
by exerting a slight pressure upon the eyeball or by passing an electrical current
through it. Quite similarly, an electrical current directed through the tongue,
evokes sensations of taste, but sensations of touch, when applied to the skin. A
tuning fork made to vibrate in the vicinity of the ears, gives rise to sound sensations,
and when allowed to beat against the skin, to the pecuhar tactile impression
known as tickling.
(c) Very similar effects may be obtained by the stimulation of the nerve fibers
leading away from these sense-organs. Thus, the cutting of the optic nerve evokes
flashes of light, while the excitation of the chorda tympani during its course through
the tympanic cavity gives rise to sensations of taste upon the tip of the tongue.
In many cases, these diverse sensations are elicited in consequence of tumors,
exudations, and hyperemic conditions in the course of sensory nerves.
(d) Sensations may be dissociated. A degree of pressure may be brought to
bear upon the skin which destroys the sensation of touch and temperature, but not
that of pain. This preservation of one particular cutaneous impression to the ex-
clusion of others, is frequently observed in the beginning stages of degeneration and
regeneration following the division of peripheral nerves. This dissociation may
also be effected by chemical means, for example, the taste of bitter may be destroyed
by cocain and that of sweet by gymnemna sylvestris.
The Modality of a Sensation.— It is a matter of common experience
that the different sensory impressions are not referred to the brain at
732 SPECIAL SOMATIC AND VISCERAL RECEPTORS
all, but are projected to the sense-organ in which they have arisen and
even beyond the latter to the area in space from which they have been
derived. Thus, the sensations of touch are referred to the surface of
the body and those of taste to the tongue and mouth. Quite similarly,
the sensations of sight and hearing are always interpreted as having
been received from a particular realm in space. It must be evident,
therefore, that a sensation cannot be regarded as a definite cortical
concept, because since judgment enters this act, which always com-
prises other activities, the resultant impression is really the symbolical
picture of the conditions mediated from without.
Each sensation, however, is symbolized independently of the others,
because the sensations of light are distinct from those of taste, smell,
hearing and touch. This implies that every one of them possesses a
definite quality or modality which we have learned to recognize in
the course of time. In spite of this fact, however, it would be quite
impossible for us to compare these modalities with one another. To
be sure, we clearly understand what is meant by the sensations of bit-
ter, an intense Hght, a low pitched sound, and other impressions, al-
though we are unable to estimate the precise character of these quahties
so as to be able to say, for example, that this sound is louder than this
taste is sweet. Consequently, each sensation possesses a modality
which is absolutely specific to it. Sensations mediated by one and
the same sense-organ, however, we are able to rate in a quantitative
manner, because we clearly recognize differences in the pitch of the
sounds and in the intensity of the light, and are able to tell that the
sweet taste of a given substance is more pronounced* than that of
another.
Fatigue and Adaptation. — While the different receptors may be
activated by stimuli of a non-specific character, they are usually open
to those kinds of impacts only for which they are especially con-
structed. It may be said, therefore, that the sense-organs form
channels of least resistance through which appropriate stimuli are
allowed to pass with the least possible loss of energy to them. Be-
ginning with this minimal or threshold value, an increased strength of
stimulation always gives rise to a more intense sensation, but an upper
limit is finally reached beyond which a further augmentation is impos-
sible. This augmentation, however, is not always proportional to the
intensity of the stimulus, because an undue strength or duration of the
stimulation invariably results in a fatigue which seems to affect pri-
marily the recipient centers. It is also evident that the sense-organs
are much more receptive toward repeated stimuli of minimal strength
than toward single stimuli of maximal strength. In addition, they
possess the power of adaptation, which in many cases may be employed
to intensify the primary sensation. Thus, we speak of a dark-adapted
eye, i.e., an eye which is at first kept in complete darkness so that
it may later on be activated by much lower intensities of light than are
ordinarily required to stimulate one which has just been exposed to light.
CLASSIFICATION OF THE SENSE ORGANS 733
Weber's Law. — While it is true that the intensity of a sensation
increases with the strength of the stimulus, the former does not pre-
serve a direct relationship to the latter. Clearly, the different sense-
organs are adjusted in such a way that they can receive their specific
stimuli with the greatest possible ease; in other words, their threshold
value is low. This implies that the maximum value of a sensation is
attained very quickly and that stimuli of greater intensity do not aug-
ment the primary impression in any appreciable measure; in fact, their
tendency is to produce fatigue. Now, while it is a relatively simple
matter to determine the strength of the stimulus which is required to
evoke a certain sensation, it is difficult to obtain comparative values
of sensations, whether of the same or of different character. This in-
ability on our part of rating sensations in an absolute quantitative man-
ner forces us to rely solely upon our power of perceiving slight differences
in them. One way of doing this is to ascertain how greatly a stimulus
must be increased in order to give rise to an appreciable sensation of
difference. Consequently, the only two means at our disposal for rating
sensations in a quantitative way are first, the determination of the
threshold value of the stimulus required to elicit a certain sensation, and
secondly, the determination of the increase in the strength of the
stimulus necessary to produce a distinct difference in the sensation.
E. H. Weber, 1 who first attempted to obtain such values, made the
observation that the stimulus necessary to cause a sensation of differ-
ence, is proportional to the intensity of the stimulus then acting, ^.e.,
it forms a fractional increment of the latter. Subsequent determina-
tions, however, have shown that this law holds true only for stimuli of
moderate intensity. Thus, if a weight of 30 grams is placed upon
the tip of the index finger of a hand supported at the wrist, and is
properly adjudged by means of the muscle-sense, an additional weight
of 1 gram must be added to or subtracted from these original 30 grams
before a distinct difference in this sensation will be obtained. If this
test is now repeated with a primary weight of 60 grams, it will be found
that 2 grams are required in order to produce a sensation of difference,
and with 90 grams an additional weight of 3 grams, and so on, until
the physiological limit is reached at about 1000 grams. In this par-
ticular case, therefore, the increment is lio of the original stimulus.
Naturally, this law holds true for any quality of stimulus, provided
that the latter is of moderate intensity. For sounds the appreciation
difference is 3^, and for light Jf20 of the original stimulus. Conse-
quently, the eye is the most sensitive organ.
Fechner's Psychophysical Law. — The attempt has been made by
Fechner^ to generalize the preceding law and to place it upon an ac-
curate quantitative basis. It is stated that the sensations show the
same relationship to the stimuli as the logarithms to their numerals.
Fechner's law, therefore, may be expressed by the formula S = C
^ Wagner's Handworterbuch der Physiol., iii, 1846, 481.
^Elemente der Psychophysik, Leipzig, 1860.
734
SPECIAL SOMATIC AND VISCERAL RECEPTORS
log Rj in which S indicates the sensation, R the stimulus and C the
constant represented by the difference in the sensation. But this
conception, that the sensation is proportional to the logarithm of
the stimulus, must meet with serious objections, because it has been
proved that Weber's law is not applicable to stimuli of low and high
intensity. In addition, Fechner has assumed that the smallest
appreciable increase in the sensation must always remain the same,
i.e. J the difference in the sensation obtained when 1 gram is added to 30
grams, must be the same as that evoked by the addition of 2 grams
to 60 grams. Physiological observation has proved this assumption to
be incorrect, and hence, we may justly advocate the view of James,
that the attempt to measure sensations with mathematical precision,
is a mere speculation.
CHAPTER LX
THE SENSES OF PRESSURE OR TOUCH, PAIN, AND
TEMPERATURE
The Structure of Cutaneous Receptors, — The integument of our
body is permeated by two sets of nerve-plexuses, one of which is situ-
ated in the panniculus adiposus and the other
in the stratum subpapillare. Both ramifi-
cations give rise to fibrils which terminate
in peculiar end-organs in almost all layers
of the skin. The most common of these
consist of meduUated fibers from the dermal
plexus which give off branches and soon lose
their medullary sheath. The latter pierce
the epidermis and then form arborizations
among the cells of the Malpighian layer.
The different fibers end bluntly or are ex-
panded into distinct sensory plates. Phylo-
genetically considered the latter formation is
the more recent.
The corpuscles of Meissner (1852) are found m
* '^ the papillary and subpapillary layers of the skin.
FiQ. 3 61. — Tactile Cor- They acquire a length of from 40-lOOjU and exhibit
puscLE WITHIN A Papilla OF au oval OF Tound-elUptical outline. Their outer zone
THE Skin OF THE Hand. Stained consists of connective tissue lamella which invest a
WITH Chlobid OF Gold. {Ran- ^^^^ ^^ reticular tissue through which one, two, or
several non-medullated nerve fibers wind their way
n Two nerve-fibers passing spirally to the tip of this structure. A very similar
arrangement is presented by the Golgi-Mazzoni cor-
puscle (1880) as well as by that described by Vater
and Paccini (1840). The latter are small oval
bodies which attain a length of from 2-4.5 mm. and a breadth of 1-2 mm. Their
outer zone consists of concentric lamellae, while their core is penetrated by a nerve
to the corpuscle; a, a, varicose
ramifications of the axis-cylin-
ders within the corpuscle.
THE SENSES OF PRESSURE OR TOUCH
735
fiber which may be single or split up into a delicate ramification. These end-organs
are very numerous in the subcutaneous connective tissue. The corpuscle of Herbst
which is chiefly found in birds, is somewhat smaller, but very similar in structure
to the preceding. Another cutaneous receptor has been described by Krause (1860).
It is globular in shape and its central region is taken up by the arborization of the
nerve fiber. Equally characteristic and suggestive of their function are' the corpus-
cles of Grandry and Merkel. They consist of two or several hemispherical cells with
flattened surfaces, between which the nerve fiber is expanded. Their height
measures 15 fi and their breadth 50/x. The composite type of these corpuscles is
present in great numbers in the skin of the bill and tongue of birds. Several
different types of endings have been found around and in the immediate vicinity
of the roots of hairs.
Fig. 362.
-Paccinian Corpuscles from the Peritoneum of a Cat.
Bohm-Davidoff-Huher' s Histology.)
{After Sola, from
Methods Used to Evoke Tactile Sensations. — The skin is exposed
to influences which are capable of eliciting several kinds of sensations,
namely, pressure, touch, pain, cold, warmth, tickling, and others of a
more composite type. The sensations of pressure and touch are depen-
dent upon mechanical stimuli and find their origin in a displacement
of the surface layers of the skin.^ They represent sensations caused by-
different grades of the same mechanical impact, but the displacement
need not take place in an inward direction but may also result in
consequence of pull upon the surface. In the former case we obtain
a positive and in the latter a negative imprint.
The tactile sensations are usually tested by means of an instrument,
which is known as an esthesiometer. In its simplest foi:m it con-
sists of a hair or fiber of glass-wool attached to a handle, the tip of which
^ Frey and Kiesow, Zeitschr. fiir Psych, und I'hysiol. der Sinnesorgane, xx,
1899.
736
SPECIAL SOMATIC AND VISCERAL RECEPTORS
is pressed upon the skin with a force sufficient to eHcit different in-
tensities of tactile impressions. This method permits of the deter-
mination of the acuity of these sen-
sations as well as of our ability to
localize them with accuracy. Esthes-
iometers are also in use which possess
two points of contact adjusted at
varying distances from one another.
This arrangement allows us to deter-
d mine how far these points must be
separated from one another in order
.J to give rise to two distinct sensations.
Our ability to tell whether a tactile
stimulus is single or double, is known
as tactile discrimination.
Tactile Acuity, Localization and
Discrimination. — We have seen that
the adequate stimulus for sensations
of touch is a mechanical impact which
causes a deformity of the surface of
the skin and thus activates the sen-
sory nerve-endings contained therein.
This activation, however, is accom-
plished under normal condition with
the help of certain adjuncts consist-
ing in peculiar capsular investments
of the terminals of the sensory nerve
fiber. Thus, we find that the threshold value of a stimulus applied
to the tactile capsule, is very much lower than that required to
363. — Herbst Corpuscles of
Dtjck.
n, Medullated nerve-fibre; a,, its
axis-cylinder, terminating in an en-
largement at end of core; c, nuclei of
cells of core; t, nuclei of cells of outer
tunica; i' , inner tunica (Sobotta) X
380 diameters.
Fig. 364. — Krause's Corpuscle. A and B, Genital Corpuscles from the Clitoris of
THE Rabbit (Izquierdo) ; C, from the Human Clitoris. (W. Krause.)
ehcit a sensation from the nerve fiber itself. It is evident, there-
fore, that the skin is in possession of what might be termed tactile
THE SENSES OF PRESSURE OR TOUCH
737
points, but experimentation has shown that these points are not
evenly distributed throughout the skin, but are more numerous and
A n — B
Fig. 365. Fig. 366.
Fig. 365. — Corpuscles of Grandey feom the Duck's Tongue. (Izquierdo.)
A, compound of three cells, with two interposed discs, into which the axis-cylinder
of the nerve, n, is observed to pass; in B there is but one tactile disc enclosed between
two tactile cells.
Fig. 366. — Grandry Corpuscle in Transverse Section. {After Dogiel.)
more sensitive in some regions of the integument than in others.
Fig. 367. — Sensory Nerve Terminating in Arborizations Around the Ends of Mus-
cle-fibers. (Ceccherelli.)
Their total number has been estimated at 500,000, excluding the
region of the head. Upon the back of the leg, 1.0 sq. cm. of the skin
47
738
SPECIAL SOMATIC AND VISCERAL RECEPTORS
is said to contain about 15 of these tactile receptors.^ The succeed-
ing table shows how great a pressure must be brought to bear upon
different regions of the skin in order to evoke minimal sensations ; the
degree of pressure being indicated here in grams per square millimeter
of area:
• » • • • •
• * • . • •
111
:•:::
Fig. 368. — Cold and Hot Spots from the Anterior Surface of the Forearm.
a, Cold spots, b, Hot spots. The dark parts are the most sensitive, the hatched
the medium, the dotted the feebly, and the vacant spaces the non-sensitive. (Landois
and Stirling.)
Tongue and nose 2
Lips 2.5
Finger-tip and forehead 3
Back of the finger 5
Palm of the hand, arm and thigh 7
Forearm 8
Back of the hand 12
Back of the leg and shoulder 16
Abdomen 26
Sole of the foot 28
Back of the forearm 33
Gluteal region 48
The acuity of the discriminating sense also varies in different regions of the
skin, as may be gathered from the succeeding table :
Tip of tongue 1.1 mm.
Palm of the last phalanx of the finger 2.2 mm.
Palm of the second phalanx of the finger 4.4 mm.
Tip of the nose 6.6 mm.
Back of the second phalanx 11.1 mm.
Back of the hand 29.8 mm.
Forearm 39 . 6 mm.
Sternum 44 . 0 mm.
Region along spine 54 . 0 mm.
Middle of the back 67 . 0 mm.
* Vitreg, Ber. der sachs. Gesellsch. der Wissensch., xxiii, 1896, and Kiesow,
Wundt's phil. Studien, xix, 1902.
THE SENSES OF PRESSURE OR TOUCH 739
It will be seen that the tongue, tips of the fingers and nose are
the most sensitive regions. Other areas are frequently beset with
hairs which tend to increase the intensity of the excitation in a per-
fectly mechanical way, because they act as levers upon the tactile
corpuscles lying in the immediate vicinity of their roots. Moreover,
the pressing down of their shafts tends to augment the displacement
of the surface layers. Hairs, therefore, tend to lower the threshold
value of the excitation and to impart to the latter a peculiar quality
which renders stroking movements and all laterally applied impacts
especially effective. Variations in tactile acuity may be produced
by increasing or decreasing the blood-supply, by the administration
of such drugs as morphin, strychnin and alcohol, and by training.
Thus, we find that the tactile sense is especially keen in blind persons
and in type-setters.
Touch Illusions. — Weber conceived the skin as being subdivided
into a number of touch circles or, as Hermann has called them, touch
areas, within the boundaries of which the two points of an esthesiometer.
are perceived as one. The size of these fields differs, a fact which may
readily be deduced from the preceding table. It was assumed further
that every one of these touch points is represented in consciousness
by a local sign or quality which, however, does not retain a local
character but is projected outward to the area of the skin stimulated.
Furthermore, this sensation is not perceived as a rule in the form of a
simple deformation of the surface of the skin, but as an actual re-
production of the object. In many instances, this projection is even
extended to a point beyond the skin. Thus, we find that the peculiar
grating sensation produced when cutting into bone, is not referred
to the fingers, but to the knife itself.
Our associations pertaining to tactile sensations, m^^y easily be
upset by subjecting them to unusual conditions. This fact is
typically illustrated by an experiment first described by Aristotle.^
If the index and middle fingers of the right hand are crossed, a marble
rolled around between their tips in the palm Of the left hand will appear
as two. This illusion is due to the fact that the crossing of the fingers
brings two sets of tactile corpuscles together which are ordinarily
far removed from one another and are rarely called upon to act in
unison. Consequently, the corpuscles upon the radial side of the
index finger, as well as those upon the ulnar side of the middle finger,
give rise to separate sensations. Quite similarly, it has been observed
that the tactile sensations obtained from a flap of the skin of the fore-
head which has been turned downward to cover a defect of the nose,
are at first referred to the forehead. Later on, however, new judg-
ments are formed, which enable the individual finally to localize these
sensations correctly. If the tip of the nose is palpated between the
tips of two crossed fingers, it appears as two.
1 Metaphysics, iii, Chapter 6.
740 SPECIAL SOMATIC AND VISCERAL RECEPTORS
The Sense of Pain. — Uncomfortable and painful sensations may be
mediated by any sense-organ and even if the intensity of the stimulus
is slight. This is true particularly of obnoxious odors, noises, very loud
sounds and high intensities of light. As commonly interpreted, how-
ever, the word pain refers to a very definite sense quality which allows
of a rather precise localization, while the painful sensations just alluded
to, are indefinite and general in their character. Pain is widely dis-
tributed throughout the body, and is a common phenomenon even in
the deeper tissues and organs. The most sensitive part, however, is
the skin, as may be gathered from the fact that an incision in the
integument always elicits a more intense pain than the handling and
cutting of the deeper structures. According to Von Frey,^ more than
one hundred pain points are allotted to each 1 sq. mm. of skin. It
also appears that the visceral receptors for pain cannot be activated
by ordinary mechanical means. Thus, it is possible to operate upon
the stomach and intestine without causing an acute sensation of pain,
while inflammatory reactions in these organs or their distention by
gases and subsequent spasmodic contraction give rise to intense
gastralgia and colic. Quite similarly, it is commonly noted that the
passage of biliary calculi through the common duct or of renal cal-
culi through the ureters, evokes an intense pain in otherwise practically
insensitive structures. In all these cases, it appears that the adequate
stimulus is distention, pain resulting only if the degree of the distention
exceeds that ordinarily required to obtain the sensation of physiological
fulness.
As far as the cutaneous sensation of pain is concerned, it may be
held that it is caused either by an overstimulation of the receptors
for pressure and touch or by the excitation of specific sense-organs for
pain. The second view is more commonly accepted to-day, ^ because
the sense of pain possesses a punctiform distribution and is mediated
by end-organs which yield solely this particular sensation. Thus,
while the hyperexcitation of the touch points may give rise to an
unpleasant sensation, the quality of the latter is distinctly different
from that of true pain.^ In addition, it might be mentioned that the
tactile and temperature senses may be absent in certain regions of the
body, but not the pain sense. Thus, while the stimulation of the
cornea readily elicits a painful sensation, it does not give a distinct
sensation of touch. Furthermore, it is a common observation that
pathological processes may give rise to an analgesia or loss of the pain
sense, but not to an anesthesia or loss of the sense of touch.
Assuming, therefore, the separate existence of pain points, it seems
most plausible to refer this sensation to the free endings of the nerve
1 Arbeiten aus dem physiol. Inst, zu Leipzig, 1896.
2 Brown-Sequard, Jour, de physiology, vi, 1864, and Funcke, Hermann's
Handb. der Physiol., ill, 1883.
3 Blix, Zeitschr. fur Biol., xx and xxi. 1884-85.
THE SENSES OF PRESSURE OR TOUCH 741
fibers.^ These sense-organs possess a high threshold value, i.e., they
remain insensitive until a certain upper limit has been reached when
their excitation suddenly evokes pain. It is also evident that the latent
period elapsing between their stimulation and the sensation, is unusually
long; moreover, the quality of this sensation may be materially varied
by the simultaneous excitation of other cutaneous receptors. For
example, a burning pain results whenever the nerve-endings for pain
and heat are activated together and a throbbing pain, whenever the
receptors for pain and touch are jointly involved. A peculiar alter-
nating character is imparted to the latter sensation by the systolic dis-
tention of the blood-vessels, and especially if it meets the resistance of
hyperemic and infiltrated tissues. In this group of the composite
sensations of pain also belong itching and tickling. Alrutz,^ however,
considers these impressions as being evoked by special nerve-endings,
which implies that they represent two varieties of one and the same
modality of sensation.
The pain sense forms an important protective mechanism of the
body, because it acts as a danger-signal, by means of which abnormal
processes may be detected. In many cases, it compels rest and there-
by favors the healing of a diseased part. It should also be noted
that a certain tissue may become painful by sympathy, i.e., it may
develop a decided tenderness in consequence of a diseased condition
existing elsewhere. Diseases of the heart or aorta are sometimes
associated with pain between the shoulders or with pain radiating out-
ward into the arms. Referred sensations of pain are also experienced
in inflammatory conditions of the appendix, gall-bladder and biliary
ducts. Head^ has shown that the innervation of certain areas of the
skin is intimately related to that of certain internal organs, because
any particular segment of the spinal cord sends out an autonomic
supply of nerve fibers as well as one to the corresponding region of the
integument. In certain lesions of the central nervous system, the
tactile sensations are sometimes wrongly referred to regions of the
body which are actually far removed from those in which they have
arisen. Most commonly, however, the corresponding area on the
opposite side is believed to be the seat of the excitation. This faulty
localization is designated as allochiria and constitutes a frequent
tabetic symptom.
The Temperature Sense. — Contrary to the view that the sensa-
tions of heat and cold arise in consequence of the excitation of one and
the same end-organ, it is now commonly believed that they represent
two distinct modalities which are mediated by separate receptors.
Thus, if a pencil-like probe through which warm water is made to cir-
culate, is slowly drawn across the surface of the skin, a very decided
sensation of heat is generally obtained in one place and none at all
1 Thunberg, Nagel's Handb. der Physiol., iii, 1905.
2 Skand. Archiv fiir Physiol., xvii, 1905.
3 Brain, xvi, 1893.
742 SPECIAL SOMATIC AND VISCERAL RECEPTORS
in the area immediately adjoining. Quite similarly, the mapping out
of the surface with a thermaesthesiometer through which cool water
is made to flow, yields sensations of cold within fields of no thermal
stimulation. It appears, therefore, that the integument embraces
a series of warm and cold points which when properly marked in dif-
ferent colors, will be seen to occupy dissimilar areas. The cold spots
are more numerous than the warm spots, their relationship being as
13 : 1.5. In between these positive fields we have areas which do not
give rise to a distinct temperature sensation and are, therefore, called
indifferent fields. But these temperature points are not confined to the
skin alone but are also disseminated through the mucous membranes
of the mouth, nose, external auditory meatus, and anus.^
Cold spots. Heatspots.
Fig. 369. — Heat and Cold Spots on Part of Palm of Right Hand.
The sensitive points are shaded, the black being more sensitive than the lined, and
these more sensitive than the dotted parts. The unshaded areas correspond to those
areas in which no special sensation was evoked. (Goldscheider.)
The acuteness of the temperature sense varies in different regions
of the body. Thus, it has been observed that the areas situated in
the midline of the trunk, are less sensitive than those situated more
laterally, and that the left side, in general, is more sensitive than the
right. 2 The lateral aspects of the extremities are relatively insensi-
tive. The same holds true of the mucous surfaces, when compared
with the skin. Inasmuch as the latent period is shortest in the case
of the cold points, the stimulation of a certain area of the integument
most generally elicits the sensation of cold before that of heat. More-
over, the former sensation develops more rapidly than the latter and
seems, therefore, to be the more intense. Much depends, of course,
upon the size of the area stimulated. Thus, a finger immersed in
water of a certain temperature always gives a more moderate sensation
than the entire hand.
Von Frey believes that the sensation of cold is mediated by the
corpuscles of Krause. The activation of these endings may also be
1 Zeitschr. fiir Biol., xx, 1884, 141 ; also Goldscheider, Uber denSchmerz, Berlin,
1894, and Gesellsch. Abhandlungen, Leipzig, 1898.
2 E. H. Weber, Wagner's Handworterbuch der Physiol., iii, 544.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 743
effected by pressure or by the electrical current, a fact which is fre-
quently cited in proof of the law of the specificity of nerve energy.
Under ordinary conditions, these receptors are exposed to a constant
temperature by reason of the steady stream of heat which escapes from
the blood and permeates the tissues. The escape of this heat may be
retarded by warm and increased by cold applications. Consequently,
these thermal stimulations can only arise if the heat stagnation or
dissipation surpasses the physiological minimum. This fact explains
the sensation of cold, experienced whenever the circulation of a part is
impeded or when especially good conductors of heat are applied to the
body-surface. Since a more rapid fall in temperature is effected by
the latter procedure, the nerve-terminals for cold are more vuickly
reduced below the point of minimal thermal stimulation. In other
words, the chief factor in the production of the sensations of heat and
cold is the temperature of the nerve-terminals mediating these senses.^
Rather difficult to explain are the so-called paradoxical temperature
reactions. Menthgl applied to the skin, gives rise to a sensation of
cold, while carbon dioxid elicits a sensation of warmth. A sensation
of cold may also be evoked by stimulating a cold spot with an object
possessing a temperature of 45-50° C. Very peculiar sensations of
contrast arise in consequence of the adaptation of these sense-organs
to certain temperatures. If the index finger of one hand is placed in
water of 10° C, the primary sensation of cold eventually gives way to
one of indifference. If this finger is then quickly transferred into
water of 11° C, a distinct sensation of warmth will be obtained. Quite
similarly, a sensation of cold may be evoked by transferring the finger
from water of 39° C. into water of 38° C. Furthermore, having adapted
the fingers of one hand to water of 35° C, and those of the other to water
of 25° C, their simultaneous transfer into water of 30° C. produces a
sensation of cold in the former and a sensation of warmth in the latter.
If a warm coin is applied to the skin for some time, its removal gives
rise to a sensation of cold, and even when the temperature of the sur-
rounding medium is only very slightly below that of the skin.
CHAPTER LXI
THE SENSES OF SMELL, TASTE, HUNGER AND THIRST
A. SPECIAL INTEROCEPTORS. SMELL AND TASTE
The Structure of the Olfactory Organ. — The mucous membrane
of the nose consists of ciliated reticular cells which are augmented, in
the so-called olfactory area, by cells possessing all the characteristics of
1 Hering, Sitzungsber., Akad. zu Wien, Ixxv, 1877, 101.
744
SPECIAL SOMATIC AND VISCERAL RECEPTORS
receiving elements. This particular area occupies the nasal septum
and adjoining region of the superior turbinated bone, and .measures
about 250 sq. mm. on each side. It is sharply differentiated from the
general lining membrane of this cavity by its yellowish brown color.
Each nasal cavity may be divided into two regions, namely, into
the so-called regio respiratoria and regio olfactoria. The former oc-
cupies the space between its floor, its median septum and the inferior
and middle turbinated bones. It receives its sensory nerve supply
chiefly from the second ramus of the fifth cranial nerve or trigeminus,
while its upper part is innervated by the first branch of this nerve.
These fibers end free among the
lining cells and mediate general
sensations, namely, those of
touch, pain and temperature. As
such they may also be stimulated
by irritating emanations, such as
are derived from ammonia and
acetic acid. In this region are
also found numerous mucous
glands, while those in the upper
part of the nose are tubular.
Fig. 370. — Cells of the Olfactory
Region.
The olfactory regions proper con-
sist of non-ciliated columnar cells
which are intermingled with a large
number of modified epithelial cells. ^
The free ends of these slender nerve cells
are beset with six to eight hair-like pro-
jections which extend through the limit-
ing membrane into the lumen of the
nasal cavity. Their basal portions are
directly continuous with the fibers of
the olfactory nerve, which pass through
the pores in the cribriform plate of the
ethmoid bone and eventually terminate
,, ^ 11 7 -xu 1- 1 11 in the olfactory bulb. They end here in
a, olfactory cells; o, epithelial cells; n, i • ,• • xi. ir j. i i-
central process prolonged as an olfactory arborizations in the olfactory glomeruli
nerve fibril; I, nucleus; c, knob-like clear Their further course has been mapped
termination of peripheral process; h, olfac- out in one of the precedmg chapters,
tory hairs. {After v. Brunn.) In the lowest vertebrates the olfac-
tory organ appears in the form of a
rounded or long drawn out depression, which is connected with the olfactory nerve.
In the selachia?, these grooves are connected with the cavity of the mouth by a
gutter-like prolongation. In the frog, this connecting passage is distinctly tubular.
The cephalopods are in possession of ciliated olfactory pockets which are situated
behind the eyes, while those of the arthropods are located upon the antennae.
The Specific Action of the Olfactory Cells.^ — The respiratory currents
of air traverse chiefly the lowest part of the nasal cavity, while the
air in its upper region remains practically stationary. From this it
^ Found in the frog by Eckardt in 1855, and in mammals by Ecker in 1856.
M. Schultze gave an adequate description of these cells in 1863.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 745
may be inferred that the odoriferous particles reach the olfactory area
by diffusion. Their passage upward, however, may be greatly facili-
tated by the act of sniffing which tends to displace the air in the vicinity
of the olfactory cells by air drawn upward through the fore part of
this cavity. This act is, of course, inspiratory in its character, but it
cannot be denied that the aforesaid cells may also be activated by the
odoriferous particles derived from food and diverted into the nasal
cavity by the expiratory air. The senses of smell and taste frequently
act together, supplementing one another. In fact, it frequently hap-
pens that we project a sensation to the mouth which has actually
arisen in the olfactory cells. The preceding data also serve to explain
the long latent period usually intervening between the entrance of the
odors into the nostrils and the sensation, the largest part of this period
being required for the diffusion of the particles to the olfactory area.
Regarding the manner in which the olfactory cells are stimulated,
little is known. It is evident, however, that the odorous substances
emit particles which in most part are in gaseous form. Having
arrived in the vicinity of the olfactory area, they enter into solution
with the fluid bathing the lining membrane and eventually with the
olfactory cells themselves. But only those bodies are capable of acting
upon these cells which contain a chemical binder, the so-called odori-
phore group, which possesses a chemical constitution, enabling it to
unite with the substance of the olfactory epithelium.^ Hence, smell is
essentially a chemical process, consisting in an interaction between the
activating body and the protoplasm of the olfactory cells. It is diffi-
cult to show this fact, because it is practically impossible to fill our
nasal cavity completely with a fluid which is non-irritating. Aron-
sohn,2 however, claims to have succeeded in evoking sensations of
smell by means of isotonic solutions of sodium chlorid to which odorif-
erous substances had been added. In support of this chemical
theory it might be mentioned that the aquatic animals are in posses-
sion of- a projected chemical sense of smell which, in the nature of
things, can only be evoked by substances held in solution.
The Power of Reaction of the Olfactory Cells — Olfactometry.—
While the sensations of smell may also be evoked by stimulating the
olfactory area with an electrical current, the adequate stimulus is,
of course, the odorous molecule. Zwaardemaker^ has attempted to
determine the stimulating quantity of different odoriferous substances
by means of an instrument, known as the olfactometer. It consists
as a rule of two tubes which are curved at their ends so as to f aciHtate
their introduction into the upper part of the nasal passage. The
free ends of these* tubes are surrounded by somewhat larger tubes
(6 mm. in diameter) which are imbibed with some odorous material.
Naturally, the farther the outer tubes are shoved over the inner, the
iHaycraft, Brain, 1888, 166; also Pussy, Compt. rendus, 1892.
2 Archiv fiir Anat. und Physiol., 1886.
3 Die Physiologic des Geruchs, Leipzig, 1895.
746 SPECIAL SOMATIC AND VISCERAL RECEPTORS
smaller will be the surface capable of sending odoriferous particles
into the air inspired through this tube. This method enables the
experimentor accurately to grade the stimulating quantity.
The amount of substance necessary to excite the olfactory mechan-
ism, is extremely small. Thus, 0.01 mg. of mercaptan may be per-
ceived if diffused through 230 c. cm. of air, so that each liter of the latter
contains only 0,000,000,04 mg. of this substance. ^ The threshold value
of ether and oil of wintergreen is 0.0005 mg. per liter of air. Cam-
phor stimulates in a dilution of 1 part to 400,000, musk in the propor-
tion of 1:8,000,000 and vanilla in the proportion of 1 : 10,000,000.
The acuity of the sense of smell differs in different persons, and is
subject to various exherent factors. It is said that women, and espe-
cially children, are more sensitive than men; moreover, it is a matter
Fig. 371. — Single Olfactometer. (Zwaardemaker.)
of common experience that this sense is easily fatigued, but if fatigued
so as to be no longer excited by one kind of odorous substance, it
is still in a condition to receive other modalities. Quite similarly,
while the persons seated in a poorly ventilated room, are quite unable
to perceive the foulness of the air, one who has just entered immedi-
ately notices its quahty. Furthermore, some persons are absolutely
insensitive to certain odors; at least, they fail completely in recognizing
their respective qualities.
In this connection, attention should again be called to the fact
that the sense of smell is absent in some animals and is very unequally
developed in others. For this reason, the osmatic? group of animals
is commonly divided into a microsmatic and macrosmatic, the latter
class including such animals as the dog and rabbit. Clearly, the ability
of the dog to follow the trail of his master must depend upon a very
acute recognition of individual odors, the stimulating quantity of
^ Fischer and Penzoldt, Liebig's Annalen, 1887, 131.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 747
which must be infinitely small. In animals of this kind, the sense of
smell must, of course, become prepotent in determining their behavior,
both volitionally and reflexly.
Qualitative Differences in the Olfactory Sensations. — The modali-
ties of smell are very numerous and their number is increased still
further by newly acquired sensations. Thus, a chemist is generally
trained to recognize a much larger number of substances than the
layman, but even that person whose olfactory impressions have been
most minutely associated, is quite unable to classify them in accordance
with their qualities. In most cases, one must be content with charac-
terizing them as agreeable or disagreeable. A. von Haller, however,
has divided them into odores suaveolentes, odores intermedise and
odores factores. In this regard the sense of smell differs very greatly
from the others, because it does not permit of at least a general arrange-
ment of these sensations into a fundamental and a complex group.
The following classification of Zwaardemaker which is based upon the
observations of Linne, tends to overcome this defect in a slight degree
by recognizing at least certain vague similarities between them :
1. Ethereal odors, depend upon the presence of such substances as the esters.
They are emitted by different fruits.
2. Aromatic odors are given off by such substances as camphor, resinous oils
and citron.
3. Fragrant odors, comprise the various odors of flowers and perfumes.
4. Ambrosial odors, are typified by amber and musk.
5. Garlic odors, are emitted by the onion, garfic, sulphur, and the compounds
of selenium and tellurium.
6. Burning odors, are given off by benzol, phenol, tobacco smoke and similar
substances.
7. Caproic odors, find their origin in the caproic and caprillic acids of sweat,
cheese, and the spermatic and vaginal secretions.
8. Repulsive odors, are yielded by many plants, such as acanthtis.
9. Nauseating or fetid odors, are given off by putrefying substances of animal
origin.
A conflict between these sensations arises whenever two odors
are permitted to act at the same time. While the result then ob-
tained, is largely dependent upon the odors selected, the strongest
most generally predominates in consciousness. At other times, they
may alternate with one another without, however, being fused into an
intermediate compound sensation. An actual fusion does not* result,
as a rule, unless they belong to one and the same group of odors.
A mixture of two or more odors which presents a modality quite
different from those of the fundamental odors, may be effected by
such substances as vanillin and bromin, turpentine and xylol, and
others.^ Certain odoriferous substances may also be mixed in certain
proportions to annul their individual effects. A neutralization of
this kind is obtained by mixing 4 grains of iodoform with 200 grains
of balsam Peru.
1 Nagel, Zeitschr. ftir Psych, und Physiol, der Sinnesorgane, xv.
748
SPECIAL SOMATIC AND VISCERAL RECEPTORS
The Structure of the Taste Buds.— These peculiar bodies are
widely distributed through the mucous membrane lining the mouth
and pharynx. 1 They are found upon the tip, margins and posterior
region of the dorsal aspect of the tongue, but not upon its lower sur-
face. Limited numbers of them may also be detected in the mucosa
of the fauces and adjoining regions of the pharynx and epiglottis.
In children they are more numerous than in adults, invading even the
adjoining regions of the cheeks and posterior fauces. These outlying
taste buds atrophy in later years. This retrogression also involves
those occupying the median area of the tongue.
The taste buds appear as oval bodies, measuring 80/x in length
and 40jLt in width. Externally they are enveloped by the cortical
reticular cells, while their central portion is occupied by a number of
..^*--V.
Fig. 372.
Fig. 372. — Diagrammatic Representation of Circumvallate Papilla Showing the
Position of the Taste-buds.
Fig. 373. — Transverse Section Through a Taste-bud.
A, taste pore; B, spindle-shaped cells of the taste-bud; C, reticular cells; D, nerve
fibers terminating among its cells.
closely packed, elongated cells which send their hair-like projections
into the depression overlying them. This depression, which is known
as the taste-pore, is the seat of the stimulation leading to taste sensa-
tions. The nerve fiber enters through the basal pole of the taste-bud
and terminates in arborizations among the different gustatory cells.
These fibers lose their medullary sheath directly before entering.
It has just been stated that these end-organs communicate with
the general cavity of the mouth through the taste-pore. Many of
them, however, do not He directly upon the surface, but occupy a posi-
tion in the depressions between the different elevations of the mucosa.
The tongue, for example, exhibits three types of elevations which, in
accordance with their shape, are known as filiform, fungiform and
circumvallate papillae. Those mentioned last are found chiefly upon the
posterior aspect of this organ and are beset with an especially large
1 First described by Loven and Schwalbe in 1867.
SENSES OF SMELL, TASTE, HUNGER AND THIRST
749
number of taste buds. Sometimes as many as one hundred of these
may be congregated m the depression encircling a single papilla. It
is to be noted especially that they are well protected against the ordi-
nary mechanical stimuli which arise in consequence of the mpvements
of the tongue
The Innervation of the Taste Buds. — In accordance with their wide
distribution, it cannot surprise us to find that their innervation can
only be accomplished with the help of several nerves. Those directly
involved are the lingual nerve, a branch of the inferior maxiUary
division of the trigeminus, and the glossopharyngeal and vagus nerves.
The first innervates the anterior region of the tongue, or about two-
thirds of the entire organ; the second the posterior part and root of
the tongue as well as the adjoining soft parts, and the third the epi-
Gftssen'&n G&n^lion
Fig. 374. — Diagram Showing Obigin and Course of the Nerve Fibers of Taste.
glottis and mucosa of the larynx proper. It is to be noted, however,
that the fibers allotted to the lingual nerve, pursue a double course, i.e.,
while some of them remain within the system of the trigeminus, others
leave it to enter that of the chorda tympani. The latter, in turn,
either continue in this system of the seventh cranial nerve (portio
intermedia Wrisbergii) or pass over to the glossopharyngeal nerve.
It seems certain, however, that the fibers originally allotted to the
glossopharyngeus and vagus nerves, pursue a straight course to their
respective nuclei in the medulla.
The function of the glossopharyngeus is, of course, quite evident,
because cutting this nerve leads to a loss of the sensations of taste
in the region innervated by it and eventually to a complete atrophy of
the corresponding taste buds. The fact that the chorda tympani
takes part in the conduction of taste-impulses, may be evinced at any
time by stimulating this nerve as it traverses the tympanic cavity^
The usual effect of this procedure is a metallic or sour taste, but some
750 SPECIAL SOMATIC AND VISCERAL RECEPTORS
investigators also claim to have produced sweet and bitter sensations.^
Much diversity of opinion, however, prevails regarding the central
distribution of these fibers. Thus, Krause^ states that the total
extirpation of the Gasserian ganglion is followed by a loss of taste in
the corresponding anterior region of the tongue. Gushing, ^ moreover,
has found that this operation never impairs the taste sensations from
the posterior part of the tongue. It may be concluded, therefore,
that the fibers from this region traverse the petrosal ganglion and enter
the sensory nucleus of the glossopharyngeus in the medulla. The
fibers from the taste buds of the larynx must necessarily follow the high-
way of the vagus, while those from the anterior two-thirds of the tongue
must for the present be assumed, to enter by way of the trigeminus
and facial nuclei.
The Activation of the Taste Buds. — When food is taken into the
mouth, it is subjected to a mechanical as well as chemical reduction,
with the result that it is brought into intimate relation with the largest
possible number of taste buds. Substances to be tasted must, of course,
be in a fluid state. This end is generally attained with the aid of the
saliva which not only acts as a solvent, but also tends to carry the par-
ticles into the crevices between the base of the tongue and the fauces,
and facilitates their entrance into the furrows around the papillae
in which the taste buds are situated. Glearly, the movements of the
tongue are not essential to taste, but materially facilitate the reduction
and distribution of the food. It may be concluded, therefore, that
the sensation of taste arises in consequence of a reaction between the
sapid substance and the protoplasm of the gustatory cells, through the
intervention of their hair processes.^ It must also be evident that
this reaction can only take place if the sapid agent possesses definite
chemical properties. It is true, however, that chemically allied bodies
need not exhibit identical characteristics in this regard. Thus,
sugar, saccharin and lead acetate all give rise to a sweet taste, while the
starches do not. In addition, it should also be remembered that sensa-
tions of taste may be evoked by substances contained in the blood.
Thus, the j aundiced person frequently experiences a bitter taste, while the
diabetic perceives sweet. It has also been claimed that sensations of taste
may be evoked by electrical means, but not by mechanical or thermal
stimuli. Thus, it is usually stated that the anode gives rise to a sour
and the cathode to a bitter sensation. This phenomenon has been
referred by some experimenters to a direct excitation of the taste buds,^
while others contend that it arises only in consequence of electrolytic
dissociations at the seat of the electrodes.® At the present time no
^ Blau, Berliner klin. Wochenschr., xlv, 1879.
2 Miinchener med. Wochenschr., xlii, 1895.
3 Bull, of the Johns Hopkins Hospital, Baltimore, xiv, 1903, 77.
* Zwaardemaker, Ergebn. der Physiol., Wiesbaden, 1903.
6 Ohrwall, Skand. Archiv fiir Physiol, ii, 1891, and Zeynek, Zentralbl. fiir
Physiol., xiii, 1898.
« Hermann, Grundrisse der Physiol., 1872, 337.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 751
facts are at our disposal which could be used to exclude the second
view, and hence, we must regard the excitation of the taste buds by-
inadequate stimuli as not proven,
The Power of Reaction of the Taste Buds. Gustometry. — ^The
acuity of the sense of taste may be tested by bringing solutions of
different concentration in relation with different points of the tongue
and ascertaining the dilution which barely suffices to incite a sensation.
These fluids may be applied either with a camel's hair brush or a drop-
per, but inasmuch as the tongue is also equipped with tactile, temper-
ature and pain receptors, they must be non-irritating and should be
heated to a few degrees below the temperature of the body. Very
cold and very warm solutions diminish the sensitiveness of these end-
organs. Care must also be taken that the substances selected for
these tests, do not activate the olfactory cells, and that they are not
spread to other regions of the oral cavity by movements of the tongue.
All sensations of taste are preceded by a definite latent period,
which is caused in part by the delayed action of the sense-organs
themselves, and in part by the fact that the substances must first be
dissolved. Other factors to be controlled are the size of the field
stimulated, the length of the period during which the stimulus is allowed
to act and the general sensitiveness of the mucous membrane. It is
a matter of common experience that the receptive power of the latter
is materially altered by habits, such as the use of alcohol and tobacco.
The values of the latent period for the tip of the tongue are as follows:^
Sodium chlorid 0 . 308 sec.
Sugar 0 . 446 sec.
Sulphuric acid 0. 536 sec.
Quinine 1 . 082 sec.
The Topography of the Sense of Taste. — While the sensations of
taste are very numerous, it is possible to arrange them in four funda-
mental groups, namely, as sweet, bitter, acid and salty. Such modali-
ties as burning, astringent, aromatic and oily are composite in their
nature and require the simultaneous activation of the olfactory cells
as well as of the sense-organs for touch and temperature. Thus,
weak acids give an astringent sensation in addition to a distinct taste
of sour, while strong acids amphfy the primary impression by a
burning sensation. A similar amplification of common sensibility is
effected by alum and pepper.
Even the fundamental taste sensations may be combined to give
a fused or compound effect. Thus, weak solutions of sweet and salty
substances may yield a sensation of flatness or alkalinity, and a weak
sensation of sweet may be completely neutraUzed by the addition of
a few grains of sodium chlorid. Quite similarly, the addition of
sugar to lemon juice diminishes the acidity of the latter and gives rise
to a mixed sensation in which the components may be clearly recognized.
^Kiesow, Wundt's philos. Studien, ix, x and xii, 1894-96; also Zeitschr. fiir
Psych, and Physiol, der Sinnesorgane, xxvii, 1901.
752 SPECIAL SOMATIC AND VISCERAL RECEPTORS
It is also to be noted that the tongue is not equally sensitive to all
four primary tastes. By far the greatest acuity for sweet prevails
upon the tip of tongue, while bitter is most clearly perceived upon its
posterior aspect in the vicinity of the circumvallate papillae. The
acuity for sweet decreases gradually from before backward and that
for bitter in the opposite direction. The sour taste is most highly
developed in the central fields of the marginal regions of the tongue,
and the salty taste in its antero-lateral regions. PecuUarly enough,
these different sensibilities may be varied by means of certain drugs.
Thus, we find that the application of a solution of cocain to the sur-
face of the tongue first of all diminishes our acuity for the compound
impressions, so that acids produce merely a sour taste without any
astringent or burning admixture.^ Next in order follow the fundamen-
tal sensations, namely, bitter, sweet, sour and salty. A very similar
effect may be produced by chewing the leaves of gymnemna sylvestre.
In this case, the sensations of sweet and bitter are destroyed, while the
acid and salty tastes, as well as the general sensibility , are not impaired. ^
These facts recall to our minds the interesting question regarding
the specificity of the taste buds, it being entirely probable that the
four fundamental qualities of taste are mediated by four different
types of end-organs. Thus, Ohrwall has shown that certain papillae
react only to particular kinds of sapid substances. Of the total num-
ber of 125 examined, 98 could be activated by different substances.
Of this number, 60 yielded three modalities of taste sensations, while
12 gave sweet and acid, 12 only acid, 7 bitter and acid, 4 sweet and
bitter, and 3 only sweet. In addition, it has been pointed out that
parabrombenzoic sulphinid gives rise to a sensation of sweet when
placed upon the tip of the tongue, and to a sensation of bitter when
applied to its posterior surface. Quite similarly, sodium sulphate
tastes salty upon the tip of the tongue and bitter upon its posterior
region.
B. GENERAL INTEROCEPTORS, APPETITE, HUNGER AND THIRST
Appetite. — It has been mentioned above that in the lower forms
the sensations of smell and taste occupy the position of exteroceptors,
while in the higher animals, they assume more especially the function
of interoceptors. In addition, the latter group also embraces a large
number of peculiar internal sensations, chief among which are the
sensations of appetite, hunger and thirst. Regarding the first, it
has commonly been held that it is merely a mild form of hunger and is
not mediated by separate receptors. Cannon and Washburn,^
on the other hand, seem to differentiate sharply between these sensa-
^ V. Amrep, Pfliiger's Archiv, xxi, 1880, and Knapp, Archiv fiir Augenheilk.,
1885.
2 Edgeworth and Hooper, Nature, xxxv, 1887, 565.
2 Amer. Jour, of Physiol., xxix, 1912, 441.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 753
tions and characterize appetite as a pleasurable mental state, which has
its origin in an excitation of the mechanisms for taste and smell, while
hunger constitutes a more disagreeable and stronger sensation which
arises in certain receptors in the walls of the stomach. Carlson^ who
has studied this subject more recently, adheres to this classification.
These general contentions, however, do not aid us very materially
in establishing a physiological basis for these sensations; in fact, it
must be admitted that we know practically nothing regarding them.
Besides the sensory element imparted to them by the senses of smell
and taste, they also possess a gastric component introduced by the
simultaneous excitation of some sensory unit of the gastric mucosa.
Thus, it is a matter of common experience that the ingestion of food
blunts the appetite as well as the hunger, while both are evoked by
total abstinence. Still, certain conditions may be introduced which
lead to a dissociation of these sensations. For example, while a pro-
longed fast very frequently diminishes and destroys all the pleasurable
sensations connected with the thought of food, the sensation of hunger
may persist for some time thereafter. Again, the mere passage of the
food through the esophagus may satisfy the appetite, in spite of the
fact that the hunger contractions of the stomach continue. Quite simi-
larly, the gradual emptying of the stomach after a meal usually restores
the appetite at a time when actual hunger is not experienced as yet.
The contrary sensation of appetite is an aversion to food, which
arises whenever the gastric reservoir is well filled or when the body as
a whole is unable to assimilate a particular kind of food. Thus, it
frequently happens that we acquire an aversion to fat or gelatin in
spite of the fact that these substances possess a distinct nutritive value.
As in the case of appetite, this sensation arises in special interoceptors,
but also embraces a gastric element.
Hunger. — The sensation of hunger is primarily projected to the
region of the stomach, but may also make itself felt by the more
general sensations of mental and bodily fatigue and functional de-
pression. To begin with, there is a local feeling of emptiness in the
stomach which is intensified in the course of time into a painful sensa-
tion. Furthermore, this sensation shows a definite intermittency and
may be temporarily abolished by the ingestion of even indigestible
material. These three facts seem sufficient to disprove one of the hy-
pothesis which holds that hunger is a general sensation and is caused by
certain changes in the metabolism of the tissues, particularly in that of
the nervous tissues. ^ Another view is that hunger is caused by the
stimulation of certain afferent nerves in the gastric mucosa in conse-
quence of the distention of the glands by accumulated secretion (Beau-
mont). No facts can be mentioned in support of this hypothesis other
than that sensations of hunger are generally followed by a sudden out-
1 Carlson and Braafladt, Am. Jour, of Physiol., xxxvi, 1914, 153.
2 Turro, Zeitschr. fiir. Psych, und Physiol, der Sinnesorgane, xlv, 1911.
48
754 SPECIAL SOMATIC AND VISCERAL RECEPTORS
pouring of gastric juice. A third hypothesis is that hunger is due
to the stimulation of certain afferent nerves in the stomach by the
contraction of its musculature. In support of this view might be men-
tioned the contracted state of the empty stomach, the periodic peri-
staltic waves passing over it, the aboUtion of this sensation after the
introduction of indigestible substances, and the rumbling gastric noise
produced when this sensation is experienced. Cannon and Washburn
have proved that the sensation of hunger occurs simultaneously with
increases in intragastric pressure. In nervous persons, however, and
especially in women, loud rumbling noises are frequently heard
without being associated with this sensation.
Carlson^ has repeated these observations upon a man with a
gastric fistula established after the occlusion of the esophagus by a
cicatrix. It is stated that there is a fairly close correspondence be-
tween the duration of the contractions and the duration of the sub-
jective sensation of hunger. A similar relationship was noted between
the intensity of this sensation and the strength and rapidity of develop-
ment of the contractions. Moreover, while a distinct sensation of
hunger could be produced by suddenly inflating a balloon placed in
the stomach, it could not be evoked by tactile stimulation of the gas-
tric mucosa. The peripheral genesis of this sensation, therefore,
seems established, although no definite data have been obtained regard-
ing the nervous mechanism involved in it.
Attention should also be called at this time to the continued sensa-
tion of hunger experienced by the diabetic patient which prompts him
to eat superfluous amounts of food. A similar condition frequently
results in persons whose lower intestine has been made to open through
the abdominal wall in order to relieve an, obstruction in the rectum or
neighboring parts (Carcinoma). Under this condition the pangs of
hunger are experienced even when the stomach is comfortably filled
with food. In view of these facts, it might be well to recognize two
types of hunger, namely, gastric hunger which is present normally, and
general or somatic hunger which is brought into play under unusual
conditions.
Thirst. — The sensation of thirst is specifically referred to the
pharynx, unless there is a general scarcity of water, in which case this
local sensation is augmented by fatigue, anguish, pain and suffering.
In the first instance, the sensation is evoked in a circumscribed region
of the pharynx situated directly in the path of the currents of air ebb-
ing back and forth between the outside"*and the lungs. It is conceiva-
ble that the terminals of the glossopharyngeus nerve are specifically
adapted to perceive variations in the water content of the cells lining
this area, because thirst is experienced as soon as the latter becomes dry
and even at a time when the body as a whole is abundantly supplied
with water. A local moistening then suffices to give reHef without that
water is actually taken into the stomach. But, these lining cells may
1 Am. Jour, of Physiol., xxxi, 1912, 175.
SENSES OF SMELL, TASTE, HUNGER AND THIRST 755
also become dry when the general water content of the body is depreci-
ated, because water is constantly transferred by them to the respira-
tory air. While a local moistening also gives relief in this case, it is
not lasting and can only be made so by taking water into the stomach.
When water is long withheld, all the tissues become water-starved so
that the simple sensation of pharyngeal thirst becomes augmented by
more distressing symptoms, such as pain and a bodily and mental an-
guish and discomfort. It is conceivable that these sensations arise in
the receptors allotted to the different tissues. If this assumption is
correct, a second variety of thirst must be recognized which may be
designated as general or tissue thirst. The testimony of those persons,
however, who have been without food and water for long periods of
time, tends to show that these symptoms of extreme discomfort and
pain disappear in the course of time, so that death by starvation need
not necessarily be accompanied by extreme suffering.^
1 Hertz, The Sensibility of the Alimentary Canal, London, 1911; Sven Hedin,
in his travels through Thibet, alludes to many cases of self-imposed abstinence by
the Holy Men of Brahma.
SECTION XXI
THE SENSE OF HEARING
CHAPTER LXII
THE CAUSE AND CHARACTER OF THE SOUND WAVES
The Cause of Sound Waves. — Sound waves arise in consequence
of the vibration of elastic bodies. If a metal plate is suspended in
space and its central area is struck with the end of a rod, it suffers a
displacement of its constituents which permit it to deviate in the
direction of the stroke. Having attained its extreme position in this
direction, it immediately swings back toward the opposite side, and
so on until it has again attained its equilibrium. These deviations
of the plate in turn give rise to a vibration of the air surrounding it,
because those molecules which lie directly ia its path will be alternately
condensed and rarefied. In this way, the vibrations of the sonorous
body are transferred into undulations of an elastic medium, formed
by the air. The first are stationary and the second progressive in
their nature.
Vibrations of a sonorous body may be either transverse, as in a
string, or longitudinal, as in a rod. The undulations in a medium,
however, must of necessity be longitudinal, because only forward im-
pulses or pushes can be communicated from one molecule to another.
Thus, sound is conveyed onward by an undulatory or wave-like
motion in air, similar to that exhibited by particles of water during
the translation of a wave. In water, however, the different particles
move in a circle, while in air they move in a straight line, backward
and forward, in the direction in which the sound is projected.
The initial energy of the undulations in air is gradually reduced as
they pass away from the sonorous body, so that the sound diminishes
constantly until it becomes completely neutralized. This reduction,
however, takes place at a more rapid rate than is theoretically sug-
gested by the law of inverse squares. The reason for this discrepancy
is that vibration leads to friction and friction to heat, generated, of
course, at the expense of the initial energy.
Sound waves may also be propagated by media other than air, in
fact, in many instances with much better results. Thus-, they pass
along rods of wood with the greatest ease, and also along cords and
wires. Practical use has been made of this fact in the construction
756
THE CAUSE AND CHARACTER OF THE SOUND WAVES 757
of the earlier forms of stethoscopes (Laennec) which usually consisted
of a wooden cyUnder perforated through its axis and enlarged at its
ends. Furthermore, their initial energy may be protected against loss
by sending them through narrow tubes, because they are then no longer
propagated as concentric spheres, but are reflected from the walls of
the tube. We shall see later on that this is true of the sound waves
traversing the external auditory meatus.
Any sound produced near at hand, seems to reach our ears instan-
taneously. In reality, however, there is a distinct interval between
the moment of its production and the moment when it produces its
stimulation in the internal ear. This latency is caused in part by a
certain sluggishness of the receptor, and in part by the fact that sound
waves require time for their propagation through the medium. A
distant locomotive or steam boat is seen to discharge a certain volume
of steam through its vibrator long before the sound produced thereby
actually reaches our ears, and the flash of lightning is seen long before
I
Fig. 375. — Laennec Stethoscope.
the thunder is heard. While altitude, temperature and the general
character of the medium have much to do with the propagation of the
vibrations from molecule to molecule, it may be said that the velocity
of sound is 340 m. in a second. Its speed, however, is proportional to
its intensity, i.e., loud sounds travel more rapidly than those possessing
a low quality. Through water sound is propagated at the rate of
about 1450 m. in a second, and through wood at the rate of about
13,000 m. in a second.
Sound waves may be reflected and refracted. In the ear we deal
chiefly with reflections from curved surfaces in which the reflection
takes place on the opposite side of the perpendicular, drawn to the
point of impact of the incident wave. The angle of reflection in-
variably equals the angle of incidence, and both occupy the same plane.
In the ear we have curved surfaces which are constructed in such a way
that the inclinations of the planes of which any curved surface is com-
posed, gives rise to a convergence of the sound waves. Thus, the
external ear of man possesses a curvature arranged to reflect these
undulations into the auditory meatus. The same is true of the ear
trumpet and of the flexible stethoscope. Both appliances collect the
sound waves by means of their cup-shaped free ends and reflect them
into the meatus.
Noises and Sounds. — It is not always easy to distinguish between a
noise and a sound. In general, however, it may be said that the former
consists either of a brief vibration, as may be produced by the discharge
of a cannon, or of a mixture of vibrations as may be caused by the
wheels of a carriage. It lacks, therefore, a definite wave length and
758
THE SENSE OF HEARING
regularity. A true or musical sound arises in consequence of a sus-
tained vibration, and possesses an euphonious character by reason of
its relatively fixed and uniform rate. The difference between noises
and true sounds may be well illustrated by mean^ of sirenes placed upon
a rotating disc. If the openings through which the air is blown, are
placed at regular distances from one another, the result is a sound of
definite pitch; quality and loudness, while if they are arranged in an
irregular manner, the result is a noise.
Fig. 376. — Form of Wave Made by Tuning Fork.
Musical sounds result in consequence of the vibration of such
bodies as strings, rods, plates, bells, membranes and reeds. The waves
produced by them, however, do not affect our organ of hearing in a
like manner, because they differ from one another in their pitch, in-
tensity or loudness, and quality or timbre.
(a) The pitch or tone of a sound is determined by the rapidity of vibration of
the sonorous body and the number of undulations produced by it. The greater
their number, the shorter must be their wave length and hence, the higher the
pitch of the sound. Thus, if these oscillations recur at the rate of 500 in a second,
their time of vibration is }ioo of a second.
Fig. 377. — To Illustrate the Conception of Differences in Pitch and m Amplitude
OR Intensity.
In A, three pendular or sinus curves of the same period or pitch, but with different
amplitudes. In B, three pendular or sinus curves of the same amplitude, but with
different periods. {After Auerbach.)
(6) The intensity or loudness of a sound is referable first of all to the amplitude
of the vibrations of the sonorous body. Thus, if the bass string of a piano is
struck with slight force, it will be seen to execute a series of vibrations of small
amplitude, which give rise to a sound of low audibility. If this same string is
then struck more vigorously, the amplitude of the vibrations will be much greater
and the sound much louder. These changes in the intensity of a sound may also
be noted as the vibrating body gradually returns into its position of absolute rest.
In the second place, the loudness of a sound is determined by the striking force of
the waves, because the latter is inversely proportional to the square of the distance
THE CAUSE AND CHARACTER OF THE SOUND WAVES 759
of the vibrator from the ear and to the density or elastic quality of the medium.
Thus, the voice becomes remarkably feeble on top of a mountain and is much
stronger in a calm atmosphere.
(c) The quality, timbre, stamp or color of a sound is the product of a variety of
factors; primarily, however, of the form of the movement of the sonorous body
and of the form of the waves produced by it. Thus, a sound of a certain pitch and
intensity emitted by a piano, is quite different from that of a violin or of the phonat-
ing organs of man. If these sound waves are examined more closely, it will be
found that they appear in two distinct forms, namely, as a simple or pendular
and as a compound or non-pendular type. If we permit the pointed end of a simple
reed vibrator to record its excursions upon the smoked paper of a kymograph, the
record so obtained will show perfectly symmetrical deviations from the line of
rest, because the pointer has swung back and forth across the midline in a uniform
manner. A compound wave, on the other hand, presents asymmetrical deviations,
which, however, may be perfectly periodic.
FiQ. 378. — Schema by Helmholtz to Illustrate the Formation of a Compound Wave
FROM Two Pendular Waves.
A and B, pendular vibrations, B being the octave of A. If superposed so that e
coincides with d° and the ordinates are added algebraically, the non-pendular curve C
is produced. If superposed so that e coincides with d' the non-pendular curve D is
produced. {Howell.)
Fundamental Tones and Overtones. — If the string of a musical
instrument is set into transverse vibration by plucking it, a certain
sound will be emitted, the pitch, quality and loudness of which will
depend not only upon the length and the thickness of this vibrator,
but also upon the force with which it is displaced. If the string is
now firmly held midpoint between its two ends, the vibrations of
each half per unit of time will be doubled. Furthermore, if the
string is divided in this way into three segments, each division will
vibrate with a frequency three times greater than that of the entire
760
THE SENSE OF HEARING
string. Fourier has proved that every sonorous body, when made to
vibrate as a whole, also exhibits vibrations of its different segments.
For this reason, every compound wave should really be considered
as the product of the fusion of a number of simple waves, i.e., if a
sonorous body yields, say, 100 vibrations in a second, it also gives off
a series of notes in the ratio of 1, 2, 3, 4, etc. The former give rise
to the so-called fundamental tone and the latter to the partial tones,
overtones or harmonies.
Inasmuch as all musical instruments, inclusive of the mechanism
set aside for the production of the human voice, send forth funda-
mental tones as well as overtones, the sounds emitted by them,
a^
l.^--—
Fig, 379. — To Illustrate the Mechanism of the Formation of Overtones.
{Helmholtz.)
In a the string vibrates as a whole, giving its fundamental tone; in 6, c, and d, its
halves,.. thirds and fourths are vibrating independently. When a string is struck,
plucked, or bowed these movements may happen simultaneously and the fundamental
note due to the vibration of the whole string is combined with the notes due to the vibra-
tions of aliquot parts, the overtones. The combination gives a compound wave whose
form and musical quality vary with the number and relative strength of the overtones.
are really compound in their nature and not simple. The trained
ear is capable of analyzing these sounds, but naturally, they arrive
at the tympanic membrane as compound waves and are not separated
into their component wavelets. In other words, the tympanic mem-
brane is not activated by individual series of molecules of air vibrating
with different frequencies, but by whole waves, the form of which
varies in accordance with their component wavelets.
Reinforcement and Interference of Sound Undulations. — If two
stones are thrown into the water at some distance from one another, the
two systems of wavelets produced around their points of contact, fre-
THE CAUSE AND CHARACTER OF THE SOUND WAVES 761
quently interfere with one another so as to give rise either to a reinforce-
ment or a neutraUzation of the individual undulations. In quite the
same manner the simultaneous transfer of two sounds through the same
medium may give rise to waves which may be either the' sum total
or the difference of the two systems of undulations. The complete
neutralization of the two sets necessitates, of course, the coming to-
gether of the condensed molecules of one system with the rarefied
molecules of the other system.
If two tuning forks, the vibrations of which differ slightly per unit of
time, are being sounded simultaneously, the two systems of undulations
must interfere with one another. Consequently, the sound emitted by
them must vary from moment to moment, becoming louder when they
reinforce and softer when they neutralize one another. This consti-
tutes the phenomenon of ^' beats." If the difference in the number of
vibrations per unit of time is increased, the effect produced on the
ear becomes increasingly disagreeable. The sound then assumes
a harsh grating character and is said to be discordant or dissonant.
Helmholtz states that the dissonance assumes an intolerable character,
when the ''beats," or the difference in the vibration frequency of two
sounds, reaches 33 to the second.
In the absence of "beats" the general sound becomes consonant or
harmonic. This implies that the two sets of undulations correspond in
rhythm and amplitude, enabling them to be combined into an evenly
balanced compound wave. It must be evident, therefore, that a
perfect consonance can only be gotten if the two sets of waves are
identical in character. An almost complete consonance is also obtained
if a sound is elicited in conjunction with its octave. It is a well-known
fact that two sounds possessing a numerical relationship of 2:1, 4:1,
etc., must be closely allied. Thus, if the first is designated as C, the
second is called CI, and the interval between them an octave. If we
now strike the octave note of the second and then the octave of this
one, it will be found that their entire series of octaves or eighth notes
become fused into a sound which gives an agreeable sensation. Other
intervals giving consonance are the following:
1:2 octave
^ 2:3 fifth
3:4 fourth
4:5 major
5 : 6 minor third
5 : 8 minor sixth
3 : 5 major sixth
Sympathetic Vibration or Resonance. — If the end of the handle
of a vibrating tuning fork is placed upon a table or other elastic body, its
vibrations are immediately communicated to a large area of this
vibrator. Moreover, since the latter generally vibrates synchro-
nously with the tuning fork, its sound will be intensified. In a similar
way, it is possible to produce vibrations in a certain string of a piano
762 ITHE SENSE OF^ HEARING
by simply striking *a note of the same character upon some other instru-
ment. The piano answers back with a note very similar to that re-
ceived by it from the distance. Also, if a certain note is struck in
the vicinity of a series of tuning forks, only that tuning fork will
answer which possesses the same periodicity of vibration as the primary
sound. These phenomena are made possible by the property of
sympathetic vibration or vibration of influence. As has been pointed
out, the transmission of the sonorous undulations may be effected in
two ways, namely, by direct contact, and by the transfer of the waves
through air without actual contact. It is to be noted, however, that
while elastic bodies may be set into vibration by neighboring bodies and
media, they cannot be activated unless their own periodicity corre-
sponds precisely to that of the activator. Thus, a string possess-
ing a vibratory quality of 125 in a second, will not be
affected by vibrations in air of 100 to the second.
Helmholtz has devised an apparatus, called the
resonator, by means of which it is possible to analyze
sounds in accordance with their properties of sympa-
thetic vibration. It consists of a spherical capsule made
of copper or brass. Its two opposite sides are perfor-
ated. Through one of these the sound is conducted into
the interior of the resonator and from here through the
opposite opening into the external auditory meatus.
Konig has introduced an important modification of this
appliance by constructing it of two hollow cylinders. By
Fig. 380. — sliding these telescopically into one another, the size of
EoNiGs Re- |.j^-g capsule may be either increased or decreased. If
SONATOR. Y 111- 1 .
the rubber tube attached to its outlet is now introduced
into the auditory meatus of one ear while the other ear is closed, the
sounds entering through the opposite orifice, will appear stifled with the
exception of the one corresponding to this resonator. This particular
one sounds out clearly from among the confused monotone of the
others.
If resonators of varying size are employed, it is possible in this way
to determine the presence or absence of the different tones or overtones
represented by them. Any given sound may thus be separated into its
components. This power of analysis is also possessed by the auditory
apparatus, or rather, by the constituents of the organ of Corti of the
internal ear. As Ohm has stated: every motion of the air which cor-
responds to a composite mass of musical tones, may be reduced into
their simple pendular vibrations, and each single vibration corre-
sponds to a simple tone, sensible to the ear and having a pitch deter-
mined by the periodic time of the corresponding motion of the air.
These facts suggest that the organ of Corti acts in the manner of a
resonator, its different cellular elements being adjusted to conform to
these simple vibrations. The manner in which this activation is
brought about will be discussed in a succeeding chapter.
EXTERNAL AND MIDDLE PORTIONS OF THE EAR 763
CHAPTER LXIII
THE EXTERNAL AND MIDDLE PORTIONS OF THE EAR
The Pinna and Auditory Meatus. — The organ of hearing may be
divided into three parts, namely, into the external ear, including the pinna
or auricle and auditory meatus, the middle ear, or tympanum, and the
internal ear, or labyrinth. The first two are accessory structures and
merely serve to direct the undulations in air to the receptor, formed by
the organ of Corti of the cochlea. The pinna or auricle is the funnel-
shaped expanse of the auditory meatus, consisting essentially of yellow
elastic tissue covered with skin.
The cap-shaped depression in its
center is known as the concha.
The external ear is especially
adapted to collect the sound waves
and to reflect them through the audi-
tory meatus upon the tympanic
membrane. It may be taken for
granted, however, that it is not a
particularly important part, because
many animals lack the pinna entirely
without any apparent impairment in
the acuity of their hearing, and a
person whose pinna has been cut off,
can hear almost as well as previously.
In many animals, the pinna is beset ^^^' 3 8 1 . — Diagra^imatic Repbe-
.,1 I 1-1 1 xi SENTATION OF THE DIFFERENT PaBTS OF
With muscles which are under the the Ear.
control of the will and are employed l, Pinna; 2, external auditory meatus;
to change its shape and position and 3, ear drum ; 4, middle ear containing
to turn it in thp Hirppfinn nf thp the ossicles; 5, Eustachian tube; 6, vesti-
XO turn It m tne airection OI tne ^^^^^ ^^ ^^e internal ear; 7, auditory
sound waves. In many instances, nerve; dividing into two branches, one
the ears are moved in divergent ^^ ^^^^^ innervates the cochlea and the
J- ^„4.- ^ 1-1 , , n • other, the semi-circular canals; 8, paro-
directions which must naturally give tid gland,
a different reflection on the two sides
and hence, also impart a different quality to the sound as heard by
the two ears. This faculty is especially developed in horses and ro-
dents. Aquatic animals are in possession of a valve-like mechanism for
closing the auditory meatus and many terrestrial animals are capable
of enlarging the concha. In man these muscles are evidently of very
little importance, because they are retrogressive and cannot, therefore,
play a significant part in ascertaining the direction from which the
sound is received. The latter faculty seems to originate in the con-
jugate deviation of the eyes toward the side from v/hich the sound
waves have been projected.
764 THE SENSE OF HEARING
The external auditory meatus of man is a tubular passage 21-26
mm. in length, 8-9 mm. in height, and 6-8 mm. in width. It pursues a
slight spiral course forward, inward and upward, but may be straight-
ened very easily by pulling the pinna upward and backward. This
is made possible by the fact that the wall of this canal is cartilaginous
and movable for a distance of about one-half inch, while internally to
this point it becomes osseous. The dehcate skin hning this canal
contains numerous sebaceous and ceruminous glands which furnish
the cerumen, a yellowish wax-like secretion, possessing a bitter taste
and peculiar odor. This secretion is lubricating and protective in
its function, because it prevents, in conjunction with the hairs, the
entrance of dust and larger foreign
particles. Its excessive formation
and subsequent drying frequently
lead to the formation of chips and
plugs which greatly impair the pas-
sage of the sound waves, thereby
diminishing the acuity of hearing.
The Middle Ear or Tjrmpanum.
— The middle ear consists of an ir-
regular cavity hollowed out of the
petrous portion of the temporal bone.
It is broader above and behind than
below and in front, and is shut off
„ _ ^ from the external auditory meatus
Fig. 3 8 2. — Diagrammatic Repre- , ,, , . .
sENTATioN OF THE MiDDLE Ear OR Tym- by the eardrum or tympanic mem-
PANic Cavity. " brane. Anteriorly, it communicates
1, External auditory meatus; 2, the with the pharynx by means of a
ZleuTwUh rri:u"riutTo:;in'g long and narrow tube which is known
against the internal surface of the ear aS the Eustachian tube, while pOS-
drum; 4 incus; 5, stapes resting against tej-ioj-ly J^ jg connected with the
the membrane of the fenestra o vans; 6, , ' „ ,, . .
vestibule of the internal ear; 7, fenestra COmpleX System Ot Small caVltieS m
rotunda; 8, Eustachian tube; 9, saccule; the mastoid bone, knOWn as the
10. central canal of the cochlea; 11. j^astoid antrum and mastoid cells.
utricle; 12, muse, tensor tympani. . i . i • «.
Its inner wail, which is formed by
the bony septum of the internal ear, is perforated in two places. In-
asmuch as one of these openings is oval in shape and the other round,
they are designated as the fenestra ovalis and fenestra rotunda. Both
are closed by a membrane, the outer surface of which lies in contact
with the air of the tympanum, while their inner surface borders upon
the lymphatic fluid filling the labyrinthine spaces. The tympanic cav-
ity is occupied by three small bones known as the ossicles, which are
arranged in series between the inner surface of the eardrum and the
outer surface of the membrane closing the fenestra ovahs. These os-
sicles are freely suspended in this space and are held in position by
hgamentous bands attached to different points of the wall, as well as
EXTERNAL AND MIDDLE PORTIONS OF THE EAR 765
by two muscles, known as the muse, tensor tympani and the muse,
stapedius.
The Tympanic Membrane or Eardrum. — The tympanic membrane
is stretched across a cartilaginous ring which is placed obUquely in
the inner end of the auditory canal. It possesses a somewhat oval
shape and is tilted at an angle of 40° in a direction from above and with-
out to a point within and below, this pecuUarity in its position en-
abling it to present a much larger surface to the sound waves. The
membrane itself is 9.5-10 mm. in length and 8 mm. in breadth. Its
thickness measures 0.1 mm. and its area 50 mm. It consists of three
layers, its middle coat being formed of fibrous tissue which is en-
veloped externally by a dehcate layer of skin, and internally by the
mucous membrane, lining the general cavity of the tympanum. The
fibers of the median coat are chiefly arranged in a radial direction,
Membrana flaccida Posterior ligament
Anterior ^iff^^^i—M^^^^^^^^BM^ Long process of incus
- End of manubrium of malleus
Fig. 383. — Membrana Tympani, as Seen with the Orosc- i- (Heusman.)
but some of them are also adjusted circuUiiiy around its center. The
latter are especially numerous in the region where this membrane is
joined to the ring of cartilage.
The inner surface of the eardrum lies in contact with the handle,
or manubrium, of the first '>sicle, commonly known as the hammer-
bone or malleus. This process is securely fastened to its median
layer, the membrana propria, by an overlapping of its circular fibers.
When observed through the external meatus,' the line of contact be-
tween the malleus and tlie eardrum is sharply outlined by an opaque
ridge which commences o jar its upper anterior margin and extends
downward and backwrra to a point slightly below its center. The
surface of the eardrun- is not flat, but convex toward the outside. Its
apex points inward, Ih'S central depression, or umbo, being caused by
the inward traction o the tip of the manubrium. It will be seen,
therefore, that the di^ orent radial fibers uniting this process with the
membrane, are arr t^^ 'd as arches around a common center.
>^
9^
766
THE SENSE OE HEARING
It need scarcely be emphasized that the external auditory meatus
plays the part of a tube tending to conserve the character of the sound
waves. They are deflected from its walls into the pit of the funnel-
shaped tympanic membrane, but since the sides of the latter are
convex, their ampUtude must be diminished, while their striking force
is increased. In this way, this membrane is set into vibration in
complete harmony with the undulations in the air. Moreover, since it
is small in size, it is able to move as one whole and with a definite perio-
dicity. The latter peculiarity is of
particular value, because it prevents
the magnification of certain overtones
to the exclusion of others. In addi-
tion, its structure and position are
such that it is able to offer a certain
resistance to the oscillations of this
system which causes the latter to
cease almost as soon as the sound
has been completed. The dampen-
ing effect is of great functional im-
portance, because it keeps these parts
in a state of readiness to receive new
vibrations.
The Ear Bones or Ossicles. — The
connection between the eardrum and
the membrane of the fenestra ovaUs
is formed by three bones which are
known as the malleus, incus, and
stapes.
Fig. 384. — View of the Mem-
BBANA TyMPANI AND AuDITORY OS-
SICLES FROM THE Inner Side.
m, Malleus; i, incus; st, stapes; vy,
pyramid, frorr, which the tendon of the
stapedius musclb jg seen emerging; tt,
tendon of the tensor tympani cut
short near its insertion, la, anterior
ligament of the malleus; the anterior
process (processus gracilis) is concealed
by the lower fibers of this ligament; h,
superior ligament of the malleus; U,
ligament of the incus; ch, chorda tym-
pani nerve passing across the outer
wall of the tympanum.
The malleus or hammer bone, is 8-9
mm. in length and possesses an average
weight of 23 mgrs. It consists of a rounded
head, grooved on one side for its articulation
with the incus, a short massive neck and a
long handle, or manubrium. The latter is
eecurely fastened in the tissue of the eardrum
and presents two processes, one of which is
knovn as the processus brevis and the other
as the processus gracilis. The former presses
against the eardrum above the umbo, while the latter extends into the Gasserian
fissure in the wall of the tympanum. The malleus is held in place by three liga-
ments, a superior, anterior and posterior. The first of these holds the head of
this bone against the roof of the tympanic cavity, while the second and third
secure its neck in a position near the anterior wall of this space. Besides serving
as supports, these ligaments also force this bone to rotate around a perfectly definite
axis. This is true especially of the anterior and poisterior ligaments which tend
to fix its neck portion as if it were placed in a sling. Consequently, the inward
movement of the eardrum and manubrium must cause the head of this bone to
move outward, while their outward movement must force the latter inward.
The incus or anvil bone, weighs about 25 mgrs. and p6ssesses a shape somewhat
similar to that of a bicuspid tooth, its heavier upper portion being hollowed out for
EXTERNAL AND MIDDLE PORTIONS OF THE EAR 767
the reception of the head of the malleus. This articulation is effected in a plane
situated somewhat above the brim of the eardrum. This ossicle presents two
processes, the largest of which measures 4.5 mm. and the other 3.0 mm. in length.
To begin with the former extends downward, parallel to the manubrium of the
malleus, but suddenly turns inward to enter into articulation with the stapes.
The short process is fastened to the posterior wall of the tympanum by a thick
ligament which, however, gives rise to only a partial fixation of this bone.
The stapes or stirrup bone, is only 2.5 mm. in length and weighs about 3 mgrs.
Its base is oval in shape and is fastened to the membrane of the fenestra ovalis by
means of a number of radial fibers of connective tissue. This foramen measures
3 mm. in length and 1.5 mm. in width.
The Movements of the Ossicles. — It need scarcely be emphasized
that the function of the ear bones is to convert the vibrations of the
eardrum into vibrations of the membrane closing the fenestra ovalis.
This implies that the undulations in air are converted into oscillations
of the lymphatic fluid filling the spaces of the internal ear.^ The
latter then activates the constituents of the organ of Corti. In endeav-
oring to analyze the action of the ossicles it must be remembered that
the manubrium of the malleus is firmly anchored to the eardrum and
must, therefore, move in harmony with the latter. This fact may be
demonstrated in a very convincing manner by placing the umbo under
the ocular of a microscope, ^ inserted through a perforation in the
upper wall of the tympanum. When measured with the help of a
micrometer, these movements are seen to attain a maximal amplitude
of about 0.2 to 0.7 mm.
Inasmuch as the neck of the malleus is fixed by the anterior and
posterior ligaments, the inward movement of its manubrium must give
rise to an outward deviation of its caput. This simple pendular
motion, however, cannot become excessive, because the malleus
executes at the same time a rotatory movement around its long axis.
The outward inclination of the caput of the malleus in turn enforces
a movement of the head of the incus in the same direction. At this
very moment the latter is turned as a whole around the axis formed by
its short process, while its long process is raised and is forced inward
against the stapes, pushing the latter more deeply into the foramen
ovale. The outward movement of the eardrum produces a movement
of these ossicles in the opposite direction. Helmholtz has compared
the malleus-incus articulation to the joints of a Breguet watch-key,
possessing a row of interlocking teeth which force the stem of the watch
in one direction, but prevent its revolution in the opposite direction.
It will be seen, therefore, that this series of bones acts in the
manner of a bent lever, the fulcrum of which is placed at the tip of the
short process of the incus, while the power arm extends from here
through the tip of the manubrium, and the load arm, from here through
the tip of the long process of the incus. This arrangement is repre-
1 Helmholtz, Pfluger's Archiv, i, 1869, 34.
2 GoUtzer, Archiv fiir Ohrenheilkunde, i, 1864, 59, also see : Mach and Kessel,
Ber., Akad. der Wissensch., Wien, Ixix, 1874, 221.
768 THE SENSE OF. HEARING
sented in the adjoining diagram (Fig. 385). When combined into one
single mass, these bones act upon the axis a-b, the manubrium c
and stapes d then pursuing precisely the same course, inward as well as
outward (Fig. 386). This system is rendered especially sensitive by
the fact that a large part of the total mass of the malleus and incus
comes to lie above their axis of rotation a-b, so that their upper por-
tions are made to act as a counterpoise for the parts situated below
this axis. The latter constitute the real lever, sensitized, as has just
been stated, by this counterpoising weight. It should be noted, how-
ever, that the oscillations of the stapes possess a smaller amplitude
than those of the eardrum, the relationship between them being as.
Fig. 385. Fig. 386.
Fig. 385. — To Illustrate the Lever Action of the Ear Bones.
M, the malleus; e, the incus; a-b, the axis of rotation; a, short process of incus abut-
ting against the tympanic wall; a-p, the power arm; a-r, the load arm of the lever.
(McKendrick.)
Fig. 386. — Schema to Illustrate the Way in Which the Ear Ossicles Act To-
gether AS a Bent Lever in Transmitting the Movements of the Tympanic Membrane
to the Membrane of the Fenestra Ovalis.
1, The handle of the malleus; 2, the long process of the incus; 3, the stapes; a-b, the
axis of rotation. The arrows indicate a movement inward of the tympanic membrane.
(Howell.)
0.04 mm. to 0.4 mm. The force, however, with which they strike
against the fenestra ovalis, is increased in the proportion of 2 to 3,
because the length of the arms of the lever formed, on the one hand, by
the manubrium, and, on the other, by the long process of the incus, is
as 3 to 2. Furthermore, since the area of the eardrum is about twenty
times as large as that of the membrane closing the foramen ovale,
the initial energy is concentrated in this way upon an area twenty
times smaller than that exposed to the sound waves. Consequently,
the force of these waves is augmented % X 20 = 30 times, when pro-
jected against the fenestra ovalis.
It is also of importance to remember that this system is not given
to after-vibration, because it is made to act under a considerable
EXTERNAL AND IV. r^TIONS OF THE EAR 769
resistance which finds its origi > 1 conditions. Among these
we have cited the pecuUarities ii >. ture and position of the ear-
drum and also the unusual chara : < 'f the lever formed by the
ossicles. In addition, Helmholtz lias called attention to the fact that
the articulation between the malleus and incus may be broken at any
time by unusually strong inward movements of the eardrum.^ The
head of the malleus is then forced outward so far that the incus cannot
follow it. Doubtlessly, this dislocation serves to protect the internal ear
against sounds of extraordinary striking force. As we shall see later,
an additional factor of safety has been provided in the shape of the
stapedius muscle, the contraction of which pulls the head of the stapes
over so that this bone presses more firmly upon the membrane closing
the fenestra ovalis, thereby diminishing its vibratory qualities.
The Eustachian Tube. — A membrane, such as the eardrum, is
capable of developing the most perfect vibrations only when the pres-
sure upon its two surfaces is equal. If the tympanic cavity were
absolutely closed, the air contained therein would be absorbed in the
course of time, establishing a rarefaction which in turn would give rise
to an inward bulging of the eardrum, and a diminution in its oscillatory
power. Under ordinary conditions, however, a result of this kind
is obviated by the fact that the tympanum is connected with the
pharyngeal cavity by means of a membranous communication, known
as the Eustachian tube. While the pharyngeal end of this channel
is kept closed under ordinary conditions, it may be opened at any time
by the act of swallowing which involves a contraction of the muse, tensor
veli palatini. This permits of an interchange of air in both directions.
The closure of this orifice results immediately upon the cessation
of this muscular effort on account of the elastic recoil of its valve-like
lips, situated inside the ostium.
If we enter a tunnel in which the pressure is above that of the
atmospheric air, the tympanic membrane is forced inward. This gives
rise to a peculiar local sensation of pressure as well as to a diminution
in the acuity of hearing. The tube is then opened by the act of
swallowing which allows the required amount of air to rush into the'
tympanum. In a similar way, a diminution in the atmospheric pres^
sure gives rise to an outward displacement of the eardrum which is .
remedied immediately by permitting air to escape from the tympanum.
A condition of the first kind may be set up very easily by swallowing y^ .
during the act of inspiration while the lips and nostrils are held shut, '^^y'
The opposite condition may be produced by swallowing during expira- ' '^t-i^aJA^
tion while the lips and nostrils are kept closed.
Although this tube serves chiefly as a means for the ventilation
of the tympanum, it also forms a natural outlet for excess secretions.
Both functions are greatly impaired during catarrhal affections of the
^ This hypothesis has been criticized by von Frey (Pfliiger's Archiv, cxxxix, 1911,
548) upon the ground that the malleus and incus are not united by a true joint,
but are more or less ankylosed.
770
THE SENSE OF HEARING
pharynx involving this tube, as may be gathered from the diminution
in the acuity of hearing then commonly experienced. In many in-
stances, these simple catarrhal affections pave the way for suppurative
processes which spread from the lining of the tympanum to the ossicles,
destroying them in part or causing them to become ankylosed. The
exudations formed in the course of this process most commonly burrow
their way through the eardrum, but without permanently destroying
the oscillatory qualities of this membrane. The greatest danger of
an infection of this kind lies in the fact that it may spread to the
adjoining mastoid cells and, unless the latter are freely drained,
give rise to a septic infection of the neighboring meninges.
The Inherent Muscles of the Ear. — Besides the different muscles
attached to the pinna, the ear also contains two muscles which are
intimately concerned with the transmission of the sound waves through
the tympanum. These muscles are the tensor tympani and the
stapedius. The former is placed in a long furrow above the Eustachian
tube and is inserted by means of a long tendon
into the neck of the malleus directly below the
axis of rotation of this bone. It is innervated
by fibers derived from the trigeminus and re-
legated to the otic ganglion. When this muscle
contracts, it pulls the eardrum inward, thereby
placing it under a greater tension. This ful-
fills two purposes, namely to accommodate the
drum to sounds of higher pitch, and to lessen
its vibratory power whenever sounds of great
intensity are received. It need scarcely be
mentioned that a sound of high pitch can only
be transferred in its true form if the tension of
the drum is increased sufficiently to correspond
to its wave-length. In the second place, it
must be evident that a tense membrane is more
resistant than a flaccid one and cannot, there-
fore, be made to vibrate so easily. For this reason, the tensor tympani
muscle may also be regarded as a protective means against the activa-
tion of the organ of Corti by sounds of unusual intensity. Conse-
quently, its function is very similar to that of the iris which, by the
contraction of its radial fibers, lessens the size of the pupil, thereby
preventing the entrance of a bundle of fight of injurious intensity to
the retina.
The stapedius muscle arises from the inner wall of the tympanum
near the fenestra ovahs. Its tendon passes forward and is inserted
upon the posterior aspect of the neck of the stapes. On contraction
it pulls this bone over in a lateral direction so that the hinder part
of its base is pressed more firmly into the membrane closing this
foramen. In accordance with the degree of its deviation, it increases
the tenseness of this membrane until its vibration is finally prevented
Fig. 387. — Diagram Il-
lustrating THE Action of
THE Stapedius Muscle.
A, state of relaxation;
B, state of contraction; s,
stapes; m-s, muse, sta-
pedius.
THE INTERNAL EAR OR LABYRINTH 771
altogether. The stapedius muscle, therefore, serves the same purposes
as the tensor tympani, i.e., it accommodates the membrane of the fen-
estra ovalis to high sounds, and prevents those of unusual intensity from
reaching the internal ear. The motor fibers of this muscle are derived
from the facial nerve.
Both muscles react in consequence of reflex stimuli which appear
to be derived from the auditory nerve, ^ whence they are transferred
in the medulla to the aforesaid motor paths. These stimuli arise at
the very beginning of the different sounds and subject these membranes
to constant changes. Some persons are capable of contracting the
tensor tympani voluntarily. ^
CHAPTER LXIV
THE INTERNAL EAR OR LABYRINTH
General Structure. — The general cavity of the internal ear, or
osseous labyrinth is hollowed out of the petrous portion of the tem-
poral bone. It consists of three parts, namely, the vestibule, the
semicircular canals and the cochlea. It is lined throughout with tliin
periosteum. This entire space is filled with a lymphatic fluid, called
the perilymph. Suspended in this fluid is a membranous reproduction
of the osseous labyrinth, which in turn is filled with a lymphatic
fluid, called the endolymph. The outer surface of the latter keeps at
varying distances from the wall of the bony cavity. The space be-
tween them is occupied by perilymph and is transected by ligamentous
bands and fibers which hold the membranous labyrinth in place. In
the vestibular part of the osseous labyrinth, this membranous tube
shows two enlargements which are known respectively as the utricle
and saccule. The former is directly continuous with the membranous
tubes of the semicircular canals and the latter, with the membranous
canal of the cochlea.^
It will be brought out later on that the semicircular canals are con-
cerned solely with the sense of equilibrium, while the cochlea mediates
the sense of hearing. For the present, therefore, we must confine our-
selves to a study of the latter structure. The cavity of the internal
ear is separated from that of the tympanum by a bony wall, which is
perforated in two places to form the fenestra ovaUs and the fenestra
rotunda. Both openings are closed by membranes, the outer surfaces
of which lie in contact with air, while their inner surfaces border upon
the perilymph of the labyrinth. It has also been pointed out that the
vibrations in air are eventually converted into vibrations of lymph at
^ Henson, Pfliiger's Archiv, Ixxxvii, 1901, 355.
2 Mangold, Pfliiger's Archiv, cxlix, 1913, 539.
772
THE SENSE OF HEARING
the fenestra ovalis. From here these oscillations spread throughout
the perilymph of the vestibule and pass toward the semicircular canals
as well as toward the cochlea. In most cases, however, they fail
absolutely in activating the sense-organs of equilibrium in the utricle
and ampullae of these canals, because the latter do not lie in the direct
course of these waves, and are not specifically adapted to them. The
cochlea, on the other hand, turns its funnel-shaped basal portion
directly toward the vestibule and into the path of these oscillations.
Besides, this structure gives lodg-
ment to the sense-organ which is
specifically set aside for their recep-
tion.
The Osseous Canal of the
Cochlea. — The central chamber of
the labyrinth, or vestibule, measures
5 mm. in diameter and communicates
anteriorly with the cochlea. The
latter is a cone-shaped structure,
^^^^^^^^ measuring 9 mm. across at its base,
^ NIk^ ^^^^^VEfl^B. ^^^ ^ "^™* ^^^^ ^^^ ^^^^ ^^ ^^^ apex.
15 LLoIIIIIIIn ji^^^^^K iI[T\ m The tip or cupola of the latter is di-
rected outward and slightly forward
V^^^^^^^yMjII^^ and downward. It contains a canal
£ ^^^^Lr/^™^^^\^^^B which is twisted upon itself two and
^^HBHp||^H|^^ one-half times in the manner of the
shell of a snail. This canal measures
Fig. 388.-DIAGRAMMATIC View OF THE ^^^^^ 33 ^^ ^^ j^^^j^^ j^ .^
Internal kjAR. . *p
1. Tympanic cavity; 2, Eustachian largest at its base, where it tueasures
tube; 3, incus; 4, stapes; 5, vestibule of about 2 mm. in diameter. The cen-
the internal ear (perilymph); 6 utricle; ^^^1 ^Ore arOUnd which it is WOUnd,
7, central canal of the cochlea; 8, scala . , , ,. , mi
vestibuli; 9, saccule; 10, endolymphatic IS known aS the modlOluS. ihe
duct between saccule and utricle; 11, latter COnsists of a central Spongy
ampulla of semicircular canal; 12, canalis portion which is pierced by a tube
reuniens; 13, scala tympam; 14, helico- ^ .,, ., . n . ■, r i
trema; 15, fenestra ovalis. • With its VariOUS Collaterals for the
reception of blood-vessels and the
fibers of the cochlear branch of the auditory nerve. A bony plate,
the lamina spiralis, projects from this central mass of bone almost
horizontally into the lumen of the cochlear canal, winding round into
its tip in the manner of a circular staircase. It partially divides the
lumen of this canal into two compartments or scalae; this division be-
ing made complete by a membranous septum which stretches straight
across from the end of the bony lamina to the opposite wall of the
canal. This is. the so-called basilar membrane. Below the latter, we
have the scala tympani and above it, the scala vestibuh. The cochlear
canal as a whole is placed in such a way that its vestibular scala faces
the foramen ovale, while its tympanic scala is directed toward the
foramen rotundum. These tubes communicate with one another
THE INTERNAL EAR OR LABYRINTH
773
through a small orifice in the tip of the cochlea, which is known as
the helicotrema.
8
Fig. 389. — Membranous Labyeinth of the Right Side, Seen from the External
Surface.
1, Utricle; 2, superior semicircular canal; 3, posterior semicircular canal; 4, external
semicircular canal; 5, saccule; 6, endolymphatic canal, with 7 and 7', its two branches,
and 8, its vestibular cul-de-sac; 9, cochlear canal, with 9', its vestibular and 9", its
terminal cul-de-sac; 10, canalis reuniens of Hensen. {American Text-book of Physio-
logy.)
These two scalae, therefore, are separate tubes. The scala vestibuli
ascends from the vestibule into the tip of the cochlea, while the scala
Fig. 390. ■ Fig. 391.
Fig. 390. — Cross-section Through the Cochlea, Showing the Different Windings
OF THE Canals.
M, modiolus, with the branches of the cochlear division of the auditory nerve;
*S, spiral ganglion; h, basilar membrane with the organ of Corti; s-w, scala vestibuli;
s-t, scala tympani; c, central canal.
Fig. 391. — Diagram Illustrating the Vibration in Opposite Directions of the
Membranes Closing the Fenestra Ovalis and Rotunda.
S, stapes; o, fenestra ovalis; r, fenestra rotunda.
tympani descends from here to the fenestra rotunda. Both are
filled with perilymph, and the vibrations set up by the oscillations
774.
THE SENSE OF HEARING
of the stapes are propagated through them in the direction from the
vestibule to the fenestra rotunda. This is of importance, because it
enables the membranes closing the aforesaid foramina, to vibrate in
unison. In other words, an inward movement of the membrane of
mmi^ttS^mMf^^
Fig. 392. — 'Diagram of a Transverse Section of the Cochlea.
Sc.V, scala vestibuli; 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; t.l, lymphatic epithelioid lining of
basilar membrane on the tympanic side; m.b, basilar membrane; Org. C, organ of Corti;
L.t, labium tympanicum; lb, Iimbus;Z/.v, labium vestibulare; m.t, tectorial membrane.
(After Foster.)
the fenestra ovalis gives rise to an outward movement of the mem-
brane of the fenestra rotunda. If no provision had been made for this
interchange of pressure within the internal ear, the membrane of the
r
THE INTERNAL EAR OR LABYRINTH 775
fenestra ovalig could not vibrate properly, because it could not over-
come the high resistance resident in this chamber.
The Membranous Canal of the Cochlea. — It has just been shown
that the osseous canal of the cochlea is bisected by the spiral lamina
and the basilar membrane attached thereto. Directly above the
membranous part of this partition, a second membrane stretches ob-
liquely across the lumen of the vestibular scala which thus cuts off an
angular space, known as the central canal of the cochlea or scala media.
The lower boundary of the latter is formed by the basilar membrane
(lamina basilaris), its outer boundary by the bony wall of the cochlea,
and its upper by the aforesaid membrana vestibularis or membrane of
Reissner. This space is filled with endolymph and forms, there-
fore, the cochlear continuation of the membranous labyrinth. Special
i^^ ;/«^
<^
Fig. 393. — The Organ of Corti in the Guinea Pig. (Nakamura.)
attention, however, should be directed to the colony of modified cells
situated upon the basilar membrane, the free surfaces of which
border upon the endolymph of this tubule. These cells form the organ
of Corti which is rnost directly concerned with the reception of the
sound waves in the form of vibrations of the lymph filling these scalse.
The manner in which this transfer is effected will be more fully dis-
cussed later on.
The Structure of the Organ of Corti. — The basilar membrane
forming the floor of the central canal of the cochlea, gradually increases
in width from the base to the apex of the cochlea. The width of the
osseous lamina, on the other hand, decreases in a corresponding
measure. Thus, Henson^ states that its breadth amounts to only
about 0.041 mm. below, but to 0.495 mm. above. Its total length
measures 33.5 mm. Its substance is formed by a homogeneous ground-
substance containing numerous straight fibers which are suspended
in a radial manner between the tip of the bony lamina and the liga-
1 Archiv fiir Ohrenheilkunde, vi, 1873.
776 THE SENSE OF HEARING
mentous tissue upon the external wall of the cochlear canal. Retzius
has estimated the number of these fibers at 24,000.
The entire cochlear canal is lined by a single layer of cuboidal
cells which also extend across the under surface of the membrane of
Reissner. The body of the latter consists of an extremely thin layer
of connective tissue derived from the periosteal lining of the scala
vestibuli.2 It is to be noted especially that the cells situated upon
the basilar membrane, possess a most peculiar appearance. A single
cross-section of this particular area presents two rod-shaped cells
•nol *■
FiQ. 394, — Diagrammatic View of the Organ or Corti, the Sense Cells, and the
, Accessory Structures of the Membranous Cochlea.
A, inner rods of Corti; B, outer rods of Corti; C, tunnel of Corti; D, basilar mem-
brane; E, single row of inner hair (sense) cells; 6, 6', 6", rows of outer hair (sense) cells;
7, 7', supporting cells of Deiters. The ends of the inner hair cells are seen projecting
through the openings of the reticulate membrane. The terminal arborizations of the
cochlea nerve fibers end around the inner and outer hair cells. {Testut.)-
which are separated at their bases, but come together above in the
manner of the sides of a roof. These cells are usually referred to as
the inner and outer rods of Corti. The triangular space situated in
between this double row of inclined cells, is known as the tunnel of
Corti. Internal to the inner rod of Corti is a single epithelial cell
which sends a brush of short and stiff projections into the endolymph.
On the outer side of the outer rod of Corti are three or four cells which
are slender in shape and also carry hair-like processes.^ They are
supported by the so-called cells of Deiters. External to these hair
^ Das Gehororgan der Wirbeltiere, ii, 1884.
2 Stohr, Anat. Anzeiger, 1907, und Kolmer, Archiv fiir mikr. Anatomie, Ixx,
1907.
3 Scott, Jour, of Anat. und Physiol., 1909, also see: Nakamura, liber die Myeli-
noid-Substanz in den Haarzellen des Cortischen Organes, Berlin, 1914.
THE INTERNAL EAR OR LABYRINTH 777
cells are several tall columnar cells which rapidly decrease in height
until they have attained the simple character of the general lining
of this tubule. Practically the entire surface of the orgp^n of Corti
is covered by a thick fibrillated membrane, the tectorial membrane,
which takes its origin upon the upper surface of the limbus and sweeps
almost transversely through the lumen of this canal.
The Function of the Organ of Corti. — These different rows of cells
are continued spirally into the tip of the scala media. It has been
estimated that there are more than 2500 inner and 13,000 outer hair
cells. Their total number is generally given as at least 16,000. We
have every reason to believe that these hair cells are the elements which
receive the sound waves, this assumption being based principally
upon their general appearance and position. In the second place, it
is noted that the cochlear branch of the auditory nerve ascends through
the modiolus and directs its fibers radially through the spiral lamina
into the organ of Corti. Near the base of the lamina these fibers tra-
verse a ganglion, known as the ganglion spirale. The cells of this
structure are bipolar, their peripheral branches being continued onward
into the basilar membrane where they lose their medullary sheath
and enter the epithelium in the region of the inner hair cells. Some
of these fibers terminate here, while others continue onward and cross
the tunnel of Corti to enter the region of the outer hair cells. In this
region they terminate as fine filaments which invest the lower poles of
the corresponding cells of Deiters.
The fact that the rods of Corti are not present in birds, which
doubtlessly possess a very keen sense of hearing, shows that these
elements are not essential to hearing. The same conclusion may be
drawn from the fact that their number is altogether too small to be
able to receive the large number of sound waves to which we may be
subjected. Retzius, for example, estimates their total number at less
than 10,000, of which 5600 are inner rod cells. This exclusion of the
rods as direct factors in the reception of the sound waves, leaves us free
to localize this function in the hair cells. In accordance with Helm-
holtz, it may then be held that the latter play the part of sympathetic
resonators which are capable of reducing musical sounds into their
components.
The Activation of the Organ of Corti. — In accordance with a sug-
gestion of Hensen, it has been advocated by Helmholtz that the constitu-
ents of the organ of Corti are activated from below by the sympa-
thetic vibrations of the radial fibers imbedded in the basilar membrane.
It is believed in this case that the vibrations of the perilymph in the
scala tympani are transmitted to these fibers and that the latter in
turn stimulate the hair cells above them. This contention harmonizes
with the fact that the basilar membrane contains about 24,000 of
these fibers, and that their length gradually increases from the base to
the tip of the cochlea (135ai to 234^). Thus, the fibers in the base
of the cochlea would be adapted to high notes, and those near the heli-
778 THE SENSE OF HEARING
cotrema to deep notes. In accordance with this view, it must be as-
sumed that each fiber has its own periodicity of vibration and is capable
of analyzing the simple waves of a particular compound wave. The
simultaneous vibration of a number of these fibers would of course
give rise to several sensations which are then fused in consciousness.
No definite statements can be made at the present time regarding
the manner in which the vibrations of these fibers are transferred to
the hair cells and endings of the auditory nerve. ^
Those physiologists who claim that these fibers are not sufficiently
long to serve as eflicient resonators, hold with Max Meyer^ that (a) the
analyzer is the basilar membrane itself, or (b) the vibrations in peri-
lymph are directly transferred to the hair cells through the inter-
vention of the endolymph of the central scala. The first view meets
with the same objections as the resonance theory of Helmholtz. The
second, on the other hand, has several points in its favor, because it
ascribes a perfectly definite function to the peculiar hair-like prolonga-
tions of these cells. It is conceived that these processes float free in
the endolymph of the central canal and are, therefore, in the best pos-
sible position to receive the vibrations set up in this fluid in conse-
quence of the transferred oscillations of the lymph in the adjoining
scala vestibuli. These hairs, therefore, serve the purpose of a battery
of resonators, capable of resolving the compound vibrations into their
simple constituents. In this case, the tectorial membrane is assumed
to play merely the part of a dampener similar to the felt pad upon the
strings of a piano.
In support of the second view Ayers^ asserts that the membrana
tectoria, as seen in ordinary preparations, is an artefact and is nothing
more than a matted mass of hairs which in reality form a waving plume
extending from the surfaces of the hair cells through the endolymph
to be inserted upon the crest of the ridge immediately beside the
internal border of the organ of Corti. These long extended processes
are activated by the vibrations in endolymph and transfer their im-
pulses directly to the cells and adjoining nerve endings.
To make this list complete, it might be mentioned that some
physiologists believe that the resonating organ is the tectorial mem-
brane itself which, however, vibrates only in segments and solely along
its thin margin. 4 Its vibrations are communicated to the hair cells,
the processes of which are in this case regarded as short stubby bristles.
Whichever theory we may feel inclined to accept, it must be evident
that the final analysis of the sound waves is accomplished in the audi-
tory realm of the cerebral cortex. Subsequent to their association
they are projected to the place in the medium from which they appear
1 Baginsky, Virchow's Archiv, xciv, 1883, 65.
2 Zeitschr. fiir Psyc. und Physiol, der Sinnesorgane, xvi, 1898; also see: Ewald,
Pfliiger's Archiv, Ixxvi, 1899, 147, Yoshii, ibid., 1909.
3 Journal of Morphology, 1892.
* Ebner, in KoUicker's Handb. der Gewebelehre, iii, 1902, 958.
THE INTERNAL EAR OR LABYRINTH 779
to have been derived. This localization, however, involves not only
a judgment regarding the intensity of the sounds as individually
perceived by the two ears, but also an analysis of the position of the
head and of the conjugate deviation of the eyes. Naturally, a median
localization of the sound necessitates an equally intense activation of
the two receptors and a lateral localization, an unequal activation.
In the latter case, our judgments as to right and left, are surprisingly
accurate, although we are frequently in error as to whether the sound
has arisen in front or behind us, above or below us. Consequently,
our ears act in the manner of the two eyes during binocular vision,
our judgments regarding the special relationship of objects being
derived from the two visual fields. It seems doubtful, however, that
our judgments regarding the direction and distance of sounds are
much less exact than those pertaining to our visual impressions. Thus,
a ventriloquist plays upon the judgment of other persons by altering
the quality of his vocal sounds in such a way that they imitate the
peculiarities of those sounds which he desires to impart to his hearers.
He thus makes use of perfectly normal mental concepts of sounds to
produce an erroneous impression.
Conduction of Sound Waves by the Cranial Bones. — It has been
pointed out that the organ of Corti is activated by the vibrations in the
neighboring endolymph and perilymph, and that the latter are ordi-
narily the result of the oscillation of the ossicles in consequence of
sound waves. But, conditions may also arise in space which allow of a
direct transfer of these waves to the bones of the cranium and in turn
evoke a vibration of the lymph in the internal ear. Thirdly, it is pos-
sible to produce these vibrations by bringing a resonant body, such as a
tuning fork, in direct contact with one of the cranial bones. If placed
upon the region of the interparietal suture, the localization will be
median in character, for the reason that both ears are now affected in||^^ f%a
an equal measure. If one of the ears is then protected by placing the OvSolO
tip of a finger into the auditory meatus, the sound is immediately
diverted into this ^r, and, if both ears are shielded in this way, again
into the midline of the cranium.^ In explaining this phenomenon,
it must be remembered that the oscillations of the lymph resulting in
consequence of this direct transmission of the sound waves, are also
transferred to the ossicles and to the eardrum. If the ear is now held
shut, the jnitiai Qp^rgy jof, thp ^vihiatioix. in jvinph is pf eyeQledJrom _S C^h 4^
being spent in this way, and hence, must be able to act with greater
intensity upon this particular receptor. In all these cases, however,
the projection is intracranial, as against the extracranial localization
noted whenever the sound waves are permitted to enter in the normal
way through the auditory meatus.
Subjective sensations of sounds, such as ringing in the ears, most
commonly arise in consequence of a local or general hypersensitiveness
of the nervous system. This condition leads to spastic contractions
1 Weber, Archiv f iir Ohrenheilkunde, xviii, 1882, 130.
780 • THE SENSE OF HEARING
of the tensor tympani. Humming or rushing noises most generally
have their origin in circulatory disturbances (hemic murmers). A
common entotic phenomenon is the audibility of the heart beat when
the left side of the head is placed upon a pillow. This position increases
the resonance of the left internal ear in a greater degree than that of
the right.
The Limits of Hearing. Auditory Fatigue. — While inheritance and
training play an important part in determining our range of the appre-
ciation of sounds, it is usually stated that the human ear cannot be
activated by musical tones possessing a lesser vibratory rate than 24 to
30 in a second. Some persons, however, are capable of perceiving
sounds of only 16 vibrations to the second. Below this limit mere
sensations of pressure are produced, although some of these low sounds
may give rise to high overtones which are clearly recognizable. The
upper limit of audibility of musical sounds is generally placed at
40,000 double vibrations in a second. Beyond this point, the notes
give rise to unpleasant sensations rather than to true sounds and can-
not be used in music. At about 60,000 they become inaudible. A
convenient way in which the range of hearing may be tested is to
strike steel rods of varying vibrating frequency (Konig).
It is commonly accepted that rhythmically repeated or long con-
tinued sounds eventually give rise to a condition of auditory fatigue.
In many cases, however, this fatigue is only apparent and is due rather
to inattention. Thus, the ticking of a watch may become inaudible
to us, because other matters temporarily occupy our attention. In-
tense sounds produce a peculiar deafening effect, rather than a true
fatigue.
The Perception of Noises. — Noises form a physical as well as a
physiological entity, because they lack the rhythmic and harmonic
•t^l o« ^character of musical sounds. In spite of this fact, however, they
"^fi^ioj^^ possess a definite pitch, quality and intensity. Helmholtz has advo-
cated the view that they are mediated by a special receptor formed
by the sensory epithelium of the utricle and saccule. Exner,^ on
the other hand, states that they are also received by the organ of
Corti, and that they activate a large number of resonators, in contra-
distinction to the musical sounds which affect only particular ones.
Being a believer in the Helmholtz resonance theory, Exner holds that
^^if^i they stimulate the radial fibers of the basilar jnQn^byane.^
1 Pfliiger's Archiv, xiii, 1876, 228.
SECTION XXII
THE SENSE OF EQUILIBRIUM
CHAPTER LXV
THE SENSE OF POSITION* STATIC SENSE
The Otolithic Cavity. — This organ is usually represented by a
membranous saccule which is placed in the integument in free com-
munication with the outside. Its epithelial Hning is beset with
long hair-Uke processes, the tips of which are weighted with small
concretions of calcium carbonate, known as otohths. Many of
these granules rest free among the hairs. The general structure of
these otocysts has led physiologists to believe
that they are quite unable to oscillate in unison
with the vibrations in the surrounding medium
and cannot, therefore, play a part in the recep-
tion of sounds. For this reason, it is now com-
monly held that they are concerned with equili-
bration and more particularly with the percep-
tion of position than with that of motion; i.e.,
with the ''static" rather than with the "dyna-
mic" sense.
This conclusion has a definite experimental
basis, because if the otolithic material is re-
moved, the animal shows disturbances in its 395— t o
position and movements. Thus, the destruc- u-mic Cavity Showing the
tion of the otocyst in crustaceans gives rise Lining Cells with their
to a tilting of the head toward the side on which h^^^-™ Pbolongations
1 ... 1 ^» r>. ' 'Ml ^^^ "^^^ Otoliths.
this injury has been effected. Quite similarly,
if made to move, this animal invariably moves about in a circle, return-
ing finally to the place from which it started. The same result may
be obtained by cutting the nerves innervating these organs. It
seems, therefore, that the otocyst and otolith should really be named
statocyst and statolith respectively.^ This nomenclature seems to be
indicated the more, because Kreidl,^ has succeeded in varying the
equilibration of the crustacean palemon by changing the contents of
its statocyst. At the time of molting this animal fills its statocystic
cavities with granules of sand to tide it over this particular period. If
1 Von Buddenbrock, Sitzungsber., Akad., Heidelberg, 1911.
2 Sitzungsb., Akad. zu Wien, cii, 1893, 149.
781
782 THE SENSE OF EQUILIBRIUM
it was placed at this time in the vicinity of l&nely pulverized iron, it used
this material instead of the sand, with equally beneficial results. Inas-
much as its otostatic cavities are situated at the base of the antennae
in free communication with the Outside, the gravity of the iron could
be varied by means of magnets. Whenever this was done, the animal
immediately displayed pronounced disturbances in its movements, lead-
ing to a loss of its proper position in space. Very similar disorders have
been observed by Prentiss^ in the larvae of lobsters which had been pre-
vented from obtaining a temporary substitute for their statoUthic ma-
terial by placing them in filtered sea water. Streeter,^ moreover, has
shown that tadpoles do not acquire the power of equilibration until the
sixth day after fertihzation, i.e., not until the auditory vesicles have
made their appearance. The destruction of one of these organs gives
rise to disturbances in its equilibrium which may be rendered even more
pronounced by the removal of both.
The Utricle and Saccule. — While we have seen that the otoHthic
cavity of the invertebrates is not an organ of hearing, it cannot be
denied that it serves as the precursor of the organ of hearing of the
higher vertebrates. The auditory sac, arising as a depression in the
epiblast near the hindbrain, becomes separated from the main tube,
but does not enter into direct communication with the outside. It
gradually develops into the variegated membranous labyrinth, consist-
ing eventually of the central canal of the cochlea, the saccule, utricle,
and the semicircular canals. In the lower vertebrates the cochlea
is absent, the first indication if it being presented by the cysticula of
the bony fish. Kreidl,^ however, beUeves that this organ is still
too rudimentary to react to sounds; instead, he supposes the latter to
be received by the cutaneous sense-organs in consequence of vibrations
set up in the surrounding water. It should be noted, however, that
the fish are in possession of a statolithic sac to which one or more
semicircular canals are attached. The development of the latter
immediately suggests that these animals are also equipped with a
dynamic sense of equilibrium.
Beginning with the terrestrial animals, the cochlea develops more
rapidly, it being present in an elementary form in the amphibia and
reptilia and in its more complete spiral form in birds. In the latter,
the central canal of the cochlea is united with the saccule as well as with
the other endolymphatic spaces. The labyrinth attains a structure
comparable to that of man, only in the higher mammals. Situated
directly within the osseous vestibule, we have two vesicular enlarge-
ments, namely, the saccule and utricle. The former attains a length
of about 3 mm. and a width of 2 mm. It is placed very close to the
orifice of the scala vestibuli of the cochlea. In the direction of the
1 Bull. Mus. of Comp. Zoology, Harvard Univ., xxxvi, 1901.
2 Jour, of Exp. Zoology, iii, 1906, 543.
3 Pfluger's Archiv, Ixiii, 1896, 581. The contrary view is held by Zenneck,
Pfliiger's Archiv, xcv, 1903, 346.
THE SENSE OF POSITION. STATIC SENSE
783
latter it tapers into a narrow duct, measuring 1 mm.
in length and 0.5 mm. in height. It finally connects
with the central canal of the cochlea a short distance
above its expanded lower extremity. The other
pole of the saccule communicates with the utricle
by means of the ductus endolymphaticus. The
utricle is irregular in shape and measures 6-7 mm.
in length and 5 mm. in breadth. It gives origin to
the semicircular canals. Of particular importance
to us at this time is the so-called recessus utriculi,
a blind forward projection from the main cavity
which contains the macula acustica. This area is
formed by auditory epithelium which is beset with
hair-like processes carrying otolithic crystals, and is
innervated by fibers from the auditory nerve. A
similar patch of sensory epithelium is contained in the
saccule.
Three views have been held regarding the func-
tion of the macula utriculi and macula sacculi,
namely (a) that they are the recipients of the sound
waves, (h) that they mediate irregular vibrations or
noises, and (c) that they serve the purpose of stato-
lithic organs. The first contention may be dis-
carded, because it has now been thoroughly estab-
lished that the cochlea is fully capable of taking care
of this function. The second view is based merely
upon assumptions and need not be discussed further. '
By exclusion, therefore, this discussion may be re-
stricted to the view of Brener,^ which holds that
these structures inform us regarding the position of
the head when at rest or when the entire body is en-
gaged in making progressive movements in one direc-
tion or another. It is conceived that the otolithic,
or rather, statolithic crystals evoke stimulations by
means of their weight resting upon the neighboring
hair-like processes. This weight, of course, is not
objective, but is lessened somewhat by the fact that
it is exerted in a medium of endolymph. At any
time when the head is tilted, their lines of gravity
/
\
'rt
7
Fig. 396. — Nerve-endings upon the Intrafusal Muscle-fibebs of a Muscle-spindle
OF THE Rabbit. Moderately Magnified. Methylene-blue Preparation. (Dogiel.)
a, Large medullated fiber coming off from 'spindle' nerve and passing to end in an
annulo-spiral termination on and between the intrafusal fibers; b, fine medullated
fiber coming off from the same stem and dividing. Its branches, c, pass towards the
ends of the muscle-fibers and terminate in a number of small localized arborizations, like
end-plates.
1 Pfliiger's Archiv, Ixviii, 1897, 596.
784 THE SENSE OF EQUILIBRIUM
are shifted, so that the different hairs are mechanically acted upon
with varying force. Furthermore, it should be noted that the maculae
acusticse occupy different planes in space so that they are affected
differently by one and the same position, or progressive movement.
These statolithic receptors supplement the function of the receptors
in the ampullae of the semicircular canals which, as will be shown later,
mediate the sensations of rotatory motion and are, therefore, primarily
concerned with the production of the dynamic sense. In both cases,
these sensations give rise to reflexes which are essential for the main-
tenance of the equilibrium. Obviously, these reflexes initiate first
of all certain muscular movements, which are executed in compensa-
tion for these static and dynamic sensations. In last analysis, how-
ever, the static and dynamic senses are compound in their nature,
because they depend not only upon the sensations derived from the
corresponding sensory structures of the labyrinth, but also upon those
Fig. 397. — Organ of Golgi from Human Tendo Achillis. Chlorid of Gold Prepa-
ration. (Ciaccio.)
m, Muscular fibres; t, tendon-bundles; g, Golgi's organ; n, two nerve-fibres passing
to it.
obtained from the retinae, from the cutaneous receptors, and, as will
be shown later on, from the deep receptors situated in the muscles,
joints and tendons.
It is also to be noted that these organs of equilibrium are thoroughly
protected against all direct influences from without, i.e., their activa-
tion can only be effected by changes arising within the animal itself.
For this reason, the static and dynamic sense-organs are commonly
regarded as belonging to the proprioceptive system of receptors.
Furthermore, since the static and dynamic senses are really compound
senses, because amplified and perfected by sensations received from
other sense-organs, such as the retinae and the cutaneous corpuscles,
their development actually necessitates a harmonious interaction
between different exteroceptors and proprioceptors.
The Muscle Spindles. — It is a well-known fact that the muscles
and tendons as well as the lining of the joints and the deep skin are
THE SENSE OF MOVEMENT. DYNAMIC SENSE 785
supplied with a type of sense-organ, the exclusive function of which
appears to be to give information regarding the position of our Umbs
and body as a whole. The one contained in muscle-tissue, is formed
by one or more muscle fibers which are permeated by lyjnph-spaces
and are enveloped in a sheath which is made up of several layers of
fibrous tissue. The nerve fiber entering this structure, winds spirally
around these fibers and eventually terminates in small platelets upon
their surfaces. In tendinous tissue this sense-organ appears as an
arborization of delicate nerve-filaments upon the surfaces of the in-
dividual strands of tissue. This arrangement enables the fibers of
the muscle to exert a certain pressure upon these nerve-endings, and to
produce impulses which experience has taught us to interpret in terms
of a definite degree of contraction of the muscle or of the position
of the part moved by it. This central association which, as we have
seen, is effected by the cerebellum, constitutes the muscle-sense.
These sensations, however, do not amplify merely the sense of position,
but also that of motion, because the muscles undergo constant changes.
CHAPTER LXVI
THE SENSE OF MOVEMENT— DYNAMIC SENSE
The Semicircular Canals. — The membranous semicircular canal
occupies from one-third to one-fifth of the entire lumen of the osseous
canal. The space intervening between its outer wall and the inner
surface of the bony canal, is filled with perilymph and the suspensory
bands which hold the membranous tube in place (Fig. 388). In cross-
section the latter presents an oval or elliptical outline, and is expanded
into a cavernous space very shortly after it leaves the utricle. At this
particular point it possesses a diameter about twice as long as that
of its remaining portion. This enlargement which is known as the
ampulla^ occupies vepy nearly the entire lumen of the osseous canal
and lies m close contact with the wall of the latter at the convexity
of the semicircle. It gives lodgment to the sensory epithelium mediat-
ing dynamic sensations. The latter are conveyed fom here to the
center by the vestibular branch of the auditory nerve. ^
In cross-section each ampulla presents a transverse prominence
which is known as the crista acustica. This ridge projects far into the
lumen of this passage and is beset with the sensory epithelium. The
latter differs from the flat lining of the remaining portion of the semi-
circular canal in that it consists of elongated columnar cells which are
^ Ewald, Physiol. Untersuchungen iiber das Endorgan des Nerv. Octavus,
Wiesbaden, 1892.
50
786
THE SENSE OF EQUILIBRIUM
surmounted by long tapering processes. These hair-like extensions
measure about 0.03 mm. in length and project straight into the en-
dolymph. Somewhat above the basement membrane these cells termi-
nate in a rounded extremity which lies in relation with the finely
Fig. 398. — Diagrammatic Representation of the Structure of the Ampulla of a
Fish.
The columnar cells of the crista acustica (c) are beset with hair-like prolongations
which float free in the endolymph. N, nerve fibers leading away from ampulla.
subdivided axis cylinders of the vestibular nerve fibers. The space
between the lower poles of these hair-cells and the basement mem-
brane is taken up by the fiber cells of Retzius^ which present themselves
as long filaments showing at one point a nuclear enlargement.
The Relative Position of the Semi-
circular Canals. 2 — The three osseous
semicircular canals take their origin
from the vestibular enlargement of the
labyrinth, while the three membranous
canals arise from the utricle. Since two
of these tubes, namely, the two vertical
ones, become confluent before they
again return to this space, they possess
only five orifices in all. The three
canals of each side are arranged in such
a way that they cover three distinct
planes which lie approximately at right
angles to one another. The external
or horizontal canal measures 15 mm. in
length and traverses a plane at right
angles to the mesial plane of the body
Fig. 399.-FIGURE Showing tUe (Fig. 399^;). It occupies, therefore, a
Position of the Three Semicircular horizontal position when the head is held
fsZidr ^^ ^^"""^^ ""^ ^^ Pigeon. ^^^^^ j^g ampulla is located anteriorly.
The anterior or superior canal is placed
nearly vertical at an angle of 45° to the mesial plane of the body (A).
iBiolog. Untersuchungen, vi; also: Brener, Sitzungsber., Akad. zu Wien,
cxii, 1903.
2 First called attention to by Cyon (1873), Brown (1874), and Mach (1875).
THE SENSE OF MOVEMENT DYNAMIC SENSE
787
Fig. 400. — Diagram to
Show the Position of the
Semicircular Canals To-
It is 19 mm. in length and rises to a higher level than any other part of
the labyrinth, its location being indicated upon the upper surface of the
petrous portion of the temporal bone by an arched prominence. Its
ampulla is situated in front. The posterior or inferior canal (P) is also
placed nearly vertical at an angle of 45° to the mesial plane of the body
but in such a way that it inclines toward the superior canal at a right
angle. It measures 22 mm. in length and its
ampulla Ues at the back part of the vestibule.
A comparison of the planes of these canals
with those of the canals on the opposite side
shows immediately that the left anterior covers
the same plane as the right posterior, and the
right anterior that of the left posterior. It is
evident, therefore, that they supplement one
another. In this connection, attention should
also be called to the fact that the vestibular wTrd ONE^AjiroTHER'
division of the auditory nerve divides into two
branches, namely, into the ramus utriculo-ampullaris and the ramus
sacculo-ampullaris. The former innervates the utricle and ampullae
of the superior and horizontal canals, and the latter, the saccule and
ampulla of the posterior canal.
The Effects of Lesions of the Semicircular Canals. — The first
accurate investigations pertaining to the function of the semicircular
canals, have been made by Flourens*
upon pigeons, these animals having
been selected for this purpose because
their labyrinth is more accessible to
operative procedures than that of
the mammals. It was found first of
all that the destruction of the vesti-
bule and adjoining semicircular canals
does not impair the sense of hearing,
but merely evokes disorders of equili-
bration, which, in accordance with
Goltz,2 are the result of an abolition
of function and not of a loss of stimu-
lation. Thus, it could easily be shown
that the unilateral destruction of the
canals renders the animal unable to
maintain its position. If it is made to
move, it sways and repeatedly tiunbles
The head remains tilted toward the
operated side and is even held in an inverted position. These symp-
toms disappear in the course of three or four weeks so that the animal
1 Compt. rend., lii, 1828; also : Vulpian, Legons, sur la physiol. du syst. nerveux,
Paris, 1866.
2 Pfluger's Archiv, iii, 1870, 172.
Fig. 401. — Abnormal Posture of
Pigeon, in Which the Labyrinth had
BEEN Extirpated on One Side Five
Days Previously. (Ewald.)
toward the side of the injury.
788 THE SENSE OF EQUILIBRIUM
is again able to fly and to walk, although it continues to suffer from a
certain loss of tonus of its muscles, principally of those of the head and
trunk on the side opposite to the injury.
The destruction of the canals on the two sides gives rise at first to
a complete loss of equilibrium, so that the animal can neither walk nor
fly unless supported. It tends to assume a quiet attitude, but when
made to move, executes violent forced and incoherent movements
which may even cause its destruction. Its muscles are abnormally
flaccid and the joints unusually limber. So small a weight as 20
grams attached to its bill or neck, suffices to keep the head perma-
nently in the most abnormal position, and to make it sway in the direc-
tion of the weight. These disorders gradually disappear in the course
of a few weeks. The animal learns to walk again by making use of the
sensations of sight and touch. The muscular weakness, however,
persists and losses of equilibrium may be brought about at any time
later on by bandaging the eyes.
These defects may be localized and restricted to single planes of the
body by destroying only one of these canals. Thus, the loss of, say
the horizontal canal, invariably causes the pigeon to make forced
movements of the head in the horizontal direction, but any unusual
excitation immediately leads to more general rotary movements of the
entire body. The length of time during which these symptoms remain
in evidence, depends upon the location and extent of the lesion; at
all events, it does not suffice to destroy solely the bony canal or to let
the perilymph escape through a fistulous opening. These defects are
quickly compensated for, provided the membranous canal is left intact.
Decided symptoms can only be produced by opening the latter widely
and as close to the ampulla as possible.
The destruction of the labyrinth in amphibia is followed by symp-
toms which are very similar to those just enumerated. Thus, its
removal on one side causes the animal to tilt its head and to move
about in a circle toward the injured side. Moreover, when this animal
is placed upon its back, it experiences great difficulty in righting itself,
and when made to swim, frequently executes rotary movements
toward the operated side. Its musculature exhibits a decided loss of
tonus and precision of action. Disorders of a very similar kind are
exhibited by mammals after the destruction of one or more sets of
semicircular canals.
The Effects of Stimulation of the Semicircular Canals. — Ewald^
has succeeded in rendering certain canals functionally useless by
opening their bony wall with a dentist's burr and temporarily com-
pressing their membranous tube by means of a plug of amalgam, but
the disorders in the plane of this particular canal were evinced only
after the corresponding membranous tube on the opposite had also
1 Physiol. Untersuchungen iiber das Endorgan des Nervus octavus, Wiesbaden,
1892; also: Schrader, Pfliiger's Archiv, xli, 1893, 75.
THE SENSE OF MOVEMENT DYNAMIC SENSE 789
been blocked. Konig and Brener^ have obtained very similar results
by painting the ampulla with cocain so as to paralyze the nerve-
endings. These data serve to contradict the view sometimes advocated,
that the disorders following lesions of the semicircular canals, are phe-
nomena of stimulation rather than of abolition of function (Ausfalls-
erscheinungen) . Besides, of course, we are in possession of the fact
that these disorders are generally lasting in character. ^ Ewald has
also stimulated the membranous canal by pressing upon it with a
bristle inserted through an opening in the bony canal, and by blowing
a current of air upon it through a narrow tube. In another set of
experiments the endolymph was made to circulate by this means first
in one direction and then in the other. In the dog-fish, Lee^ has found
that pressure upon any particular ampulla gives rise to movements
of those fins which this animal ordinarily employs in moving in the
plane of the canal stimulated. Electrical stimulation of the canals
has been resorted to by Brener. It gives rise to the so-called galvano-
tropic reaction, consisting in a deviation of the head toward the anode.
All these procedures have fully confirmed the theory of Brener and
Mach which holds that the specific stimulant of the sensory epithelium
of the ampulla is the movement of the endolymph. Besides, it has
been made evident that these canals evoke movements only along par-
ticular planes of the body.
Labyrinthine Reflexes and Tonus. — The sensations of movement
with which we are concerned at the present time are, of course, passive
in their nature and enable us to form judgments regarding movements
along straight and curved lines. These purely labyrinthine impres-
sions, however, are supplemented by others received from the retinae,
the cutaneous receptors, and the proprioceptors proper. It cannot
surprise us, therefore, to find that this relationship is sometimes re-
versed, so that the labyrinthine sensations become associated with
compensatory reactions of different kinds. Chief among these are
movements of the eyes and head. If a frog is placed upon a board and
is slightly moved around its transverse axis, it raises and lowers its
head against the direction of this movement. In a similar way, if
rotated upon a horizontal disc, it bends its body against the direction
of the rotation. These compensatory reactions cease immediately
if the labyrinth is destroyed or if the nerve fibers leading from it are
cut. Equally pronounced effects may be obtained in the fish,^ birds
and mammals. Since these compensatory movements may also be
evoked in the blind and are, therefore, entirely independent of visual
sensations, their labyrinthine origin cannot be doubted.
As has been pointed out by Purkinje, Ewald and Stein, ^ any
1 Sitzungsber., Akad. zu Wien, cxii, 1887, 1903.
2 Gaglio, Archiv ital. de biologie, xxxi, 1899, 377.
3 Jour, of Physiol., xvii, 1895, 192.
4 Loeb, Pfluger's Archiv, xHx, 1891, 175.
6 Zentralbl. fur Physiol., xiv, 1900, 222.
/790 THE SENSE OF EQUILIBRIUM
unusual rotation, say, around the longitudinal axis of the body, gives
rise to a horizontal nystagmus of the eyes. This phenomenon con-
sists in a slow lateral movement of the eyes in the plane of the rotation
which, however, is soon stopped and superseded by an abrupt return
of the eyes into the midline. This rotation-nystagmus is to be sharply
differentiated from that form of nystagmus which is frequently
exhibited by persons looking out of the window of a railway car. The
former occurs even in the dark and in blind persons, while the latter
does not, and may be suppressed by fixedly gazing into space. A
nystagmus of the entire head is often observed in birds when made to
stand upon a rotating surface. The head is at first turned against the
direction of the rotation and is then made to execute jerky move-
ments around the long axis of the body.
Compensatory movements of the entire body are frequently
noticed after rather excessive rotation. Thus, if we turn around the
longitudinal axis of our body a number of times and then suddenly
stop, it will be found that the objects in space continue to move against
the direction of the rotation, while we ourselves leave our previous
position and sway toward the rotation. It is to be noted, how-
ever, that this compensation is forced upon us reflexly and should not
be mistaken for the ordinary effects of the momentum of the rotation.
In addition, it is easily observed that these compensatory movements
are confined chiefly to the head and trunk and would, in the absence
of corresponding movements of the legs and arms, give rise to a com-
plete loss of equilibrium.
These rotation experiments should be executed with some caution,
because in hypersensitive persons they are prone to produce nausea,
vomiting, muscular weakness, disturbances in vision and slight
cardio-inhibitory effects. For this reason, it is commonly held that
seasickness is caused by an unusual and excessive stimulation of the
static and dynamic sense-organs. A similar complex of symptoms,
aggravated, however, by vertigo, forced movements and a constant
ringing in the ears, is presented by Meniere's disease.^ The latter
seems to have its origin in an inflammatory and hemorrhagic affec-
tion of the semicircular canals and neighboring nerve fibers. It is
also well recognized that the injection of solutions into the tympanic
cavity as a curative means in affections of the middle ear may give
rise to vertigo and nystagmus; in fact, in some persons, loud noises
suffice to induce these symptoms.
The character of the results obtained with deaf persons, differs with
the extent of the lesion. Inasmuch as only about 65 per cent, of these
persons show a lesion of the canals in addition to that of the cochlea,
it cannot surprise us to find that many of them present absolutely
no disorders of their senses of position and movement. The others
have learned in the course of time to compensate for the disturbances
1 Gaz. m^d. de Paris, 1861; also: Frankl-Hochwart, Das Menier^sche Sympto-
men-complex, Wien, 1906.
THE SENSE OF MOVEMENT DYNAMIC SENSE 791
in these sensations and behave normally unless subjected to unusual
conditions. Thus, the tests of James^ have proved 186 among 500
deaf persons to be without vertigo when rotated, and 15 among 25
deaf persons to lose their sense of orientation while diving; Normal
persons, of course, behave very differently; 199 of the 200 examined
displayed vertigo and forced movements.
The general weakness of the musculature following injuries to
the labyrinth, is attributed by Ewald to a loss of the labyrinthine
tonus, mediated by a set of impulses which reflexly keep the mus-
culature in a state of alertness. This effect is obtained through the
intervention of the cerebellum with which the labyrinth is in close
functional relation. Thus, we find that the vestibular fibers of the
auditory nerve terminate in the nucleus of Deiters and the nucleus
of Bechterew, where reflex connections are formed with the cranial
nerves and the different motor centers. Connections are also estab-
lished here with the nucleus fastigius and the cortex of cerebellum.
The semicircular canals, therefore, serve as a sense-organ of the
cerebellum, this central structure enabling the sensations derived
from them, to influence the tonus and behavior of the musculature
and hence, also muscular coordination and the equilibrium.
The Activation of the Hair-cells of the Ampulla. — The first definite
explanation of the action of this receptor has been given by Goltz^
who assumed that the endolymph of these canals rests upon the
sensory epithelium with a certain pressure and that this pressure
changes with the position of the head. But, while he regards them
very distinctly as organs of equilibration, he seems to believe that
they are activated solely by hydrostatic differences. This principle
has been more fully developed by Brener,^ but this investigator
abandons the hydrostatic factor or gravitation almost altogether
and puts in its place a hydrodynamic mechanism. This amphfied
theory which has been materially strengthened by a number of observa-
tions made by Mach and Brown, ^ brings forth the conception that the
hair-cells constitute the peripheral elements of equiUbrium, and that
their activation is accomplished by the changes in the pressure which
the endolymph must suffer whenever the canals are moved. Thus, it is
assumed that the different movements of the head give rise to oscil-
lations of the endolymph which in turn affect the position of the hair-
like processes of the ampullar lining cells. To be sure, the simple
effects of gravity cannot be excluded altogether, but this theory
subordinates the latter completely to those of movement.
If a tumbler is filled with water and is twirled upon a rotating disc,
it will be noted that its walls move first, while the water lags behind,
and exerts a pressure in the opposite direction. If the twirling is
lAmer. Jour, of Otology, 1887; also: Kreidl, Pfluger's Archiv, li, 1892, 119.
2 Pflliger's Archiv, xxx, 1870, 172.
3 Sitzungsb. der Akad. zu Wien, cxii, 1903.
^ Jour, of Anat. and Physiol., viii, 1874, 327.
792
THE SENSE OF EQUILIBRIUM
continued for a brief period of time, a point will be reached when the
walls and the water move with practically the same velocity. Im-
FiG. 402. — Diagrammatic Representation of a Model Illustrating the Deviation
OF THE Hair Processes of the Ampulla.
D, disc rotated by hand; T, circular glass tube filled with water; B, bulbular enlarge-
ment containing a long camel's hair brush, vertically placed.
mediately upon ceasing the rotation, the walls are brought to a stand-
still, while the water continues to move in this direction until it is
finally stopped by the friction. These
phenomena may be illustrated in a more
striking manner with the help of a cir-
cular glass tube filled with water and
enlarged at one point for the reception
of a bundle of soft hairs placed trans-
versely into its lumen (Fig. 402). When
rotated, this primary and secondary
dissociation between the movements of
the walls of the tube and the water are
now made more evident by the devia-
tion of the hairs, first against and then
in the direction of the rotation.
If this hydrodynamical principle
is applied to the semicircular canals,
Fig. 403.— Diagram Illustrat- it must be concluded that the move-
iNG THE Position of the Hair Pro- ment of the head gives rise to a move-
cesses of the Ampulla on Rotation ^^^^ ^f ^^le canals situated in this
of the Canal. . mi- • ^ ^
A, the canal being moved in the Particular plane. To begm with, the
direction of the black arrow, the en- endolymph lags behind the Walls of
T^® the canals, but soon attains the same
speed as the latter. Lastly, it con-
tinues in this direction even after the
canals have ceased to move until its
motion has again been arrested. This
implies that the hair processes are first
turned against the rotation, then vertically into the fluid, and lastly
dolymph at first lags behind,
hairs processes are deviated against
the rotation from a to h. On stop-
ping the rotation of the canal, the
endolymph is carried onward in the
direction of the red arrow deviating
the hair processes from a to c.
THE SENSE OF MOVEMENT — DYNAMIC SENSE 793
in the direction of the rotation. These progressive deviations of the
hairs evoke those sensations which inform us regarding the direction
and extent of the movement executed by us. It should be emphasized,
however, that the endolymph does not move about in a circle through
the entire canal, but undergoes simply the slightest possible oscilla-
tions in the manner just indicated with the help of the preceding
schema. This must necessarily be so, because (a) the internal diameter
of the semicircular canals of man measures only 0.1 mm. (0.04 mm. in
the pigeon), (6) because their course is not absolutely circular, and
(c) because the endolymph possesses a relatively high viscosity.
Naturally, only those hair cells can be affected by a certain gen-
eral movement which lie in this particular plane. It has previously
been mentioned that the semicircular canals act in pairs, i.e., the
anterior of one side is stimulated simultaneously with the posterior
of the opposite side. Both together control movements along vertical
planes. The horizontal canals also act in unison, but are chiefly
concerned with movements along the horizontal plane. Intermediate
movements always stimulate two adjoining pairs of canals but in an
unequal degree. There is this to be remembered, however, that
the primary sensation arises at the beginning, when the movement of
the canal is toward the ampulla and hence, when the pressure of the
endolymph is exerted in the direction from the utricle toward the
other extremity of the canal. Psychically, therefore, all movements
are interpreted correctly, although in a manner opposite to the position
of the hair-like processes. The secondary dynamic effect, producing
the deviation of the hairs at the end of the rotation, does not stimulate
unless excessive. In the latter case, a sensation of rotation is produced
in a direction opposite to the primary.
Naturally, the labyrinthine sensations of movement are augmented
by others to form the s^nso of equihbrium. Chief among these are
the sensations of position, the muscle-sense and the sensations of sight
and touch. Ewald believes that all these unite in regulating the tonus
of the musculature which forms the basis of the stability of our body.
If the body sways toward one side, the stimulation of the hair cells
then ensuing, gives rise to an increase in the tonus of the muscles ordi-
narily counteracting this movement. In this way, the labyrinthine
reflexes are utihzed, together with others, in evoking those compensa-
tory reactions which are directly responsible for our orientation in space.
This point has found substantiation in the experiments of Magnus
and Klijn,^ made upon cats during the condition of decerebrate
rigidity. The muscles of the extremities having been rendered rigid
by the removal of the cerebrum, the mere tilting of the head of the
animal sufl^ced to produce perfectly definite changes in the position
of its limbs. Besides, these compensatory reactions disappeared
immediately after the destruction of both labyrinths.
1 Pfliiger's Archiv, cxlv, 1912, 455.
SECTION XXIII
THE SENSE OF SIGHT
CHAPTER LXVII
PHYSIOLOGICAL OPTICS
The Nature, Cause and Velocity of Light. — The study of the
phenomena connected with hght, and their application, is called optics.
Physiological optics is that subdivision of optics which deals with
these phenomena as appHed in a practical way to our visual mechanism.
In accordance with Aristotle, the universe consists of four mundane
elements, earth, fire, water, air and a fifth submundane, or ether.
This name was applied to this element on account of its ethereal cir-
cular movement and not on account of its "fire.'' At the present
time, of course, we are concerned solely with those ethereal impacts
which give rise to illumination, and particularly with those which
affect the retinae of our eyes, because, as commonly understood, light
is that form of energy which by its action upon this receptor, evokes
the phenomenon of vision. In this group must be placed the ethereal
vibrations forming the spectral colors, namely, vibrations possessing
a rate per second of 482,000,000,000,000 for red light and of 707,000,-
000,000,000 for violet light.
The different sources of light may be divided into natural and artificial. The
most important among the former is the sun. Then follow the fixed stars, nebulae,
comets, meteors, lightning, auroras and lights modified by reflection and refraction,
such as that of the rainbow, clouds, and phosphorescent and fluorescent bodies.
Among the artificial sources might be mentioned the combustions of gas, oil, wood,
coal, etc., and the illumination produced by the electric current and mechanical
impacts. But, since we are dealing in the latter case with certain forms of stored
energy, all these sources of light must have had originally an exherent cause,
presumably the sun.
Regarding the cause of light two theories have been propounded, namely,
the emission or corpuscular theory, generally accredited to Newton, and the undula-
tory theory of Huyghens and Euler. The first assumes that the different luminous
bodies actually discharge certain particles or molecules in straight lines. Conse-
quently, luminous vibrations are really transverse in their direction, while those of
sound are longitudinal. This assumption would lead us to infer that the retina
is stimulated by actual molecules of matter. The second theory holds that all
space is filled with an attenuated medium, called luminiferous ether, which is set
into rapid vibration. This conception would imply that the retina is stimulated
by the vibration of the molecules of the ether, in analogy with the excitation of
the organ of Corti by vibrations or waves occurring in the ordinary atmosphere.
794
PHYSIOLOGICAL OPTICS 795
These vibrations in ether are propagated at an almost inconceivably rapid rate.
If we reckon the distance of the earth from the sun at 91,500,000 miles, the speed
of sunlight may be calculated at 185,500 miles in a second. Thus, it would require
this light about eight minutes to reach the earth, that of Neptune about four
hours, that of Centaurus close to 4 years and that of Sirius 17 years. Light
therefore, travels with a velocity which is 900,000 times greater than that
of sound; moreover, its stimulating power is extremely great, because a flash of
lightning, lasting H > o o o j o o o sec. , suffices to produce a visual sensation. SunHght,
of course, is the strongest light, equalling the power of 5500 candles placed at a
distance of one foot. It is 600,000 as strong as the reflected light of the moon
and 16,000,000,000 as strong as that of Centaurus.
In passing away from its source, light is brought into contact with different
bodies, which tend to hinder its course. Only the most perfect vacuum allows
it to pass with as much freedom as the air. Other media are classified as trans-
parent, translucent and opaque. Transparent media permit of the passage of
white light, as well as of its spectral components, so that any object may be seen
through them in its different colors. Among these might be mentioned the air,
water, glass, the humors of the eye, and others. Translucent bodies allow only a
certain number of the light rays to pass, so that a clear outline of the objects
cannot be obtained. Opaque bodies cannot give rise to visual sensations, because
they prevent the passage of these rays, although permeable to them. The light is
then said to be absorbed, i.e., it is converted into some other form of energy, such
as heat.
Reflection. — ^Luminous bodies are those which emit light, such as
the sun or substances when undergoing combustion. A luminous ray,
therefore, may be defined as the direction of the line in which light is
propagated, and a pencil of light as a collection of rays from the same
source. In this form, it consists of a number of divergent rays, i.e.,
of rays which in passing away from the luminous object, gradually
become more widely separated from one another. A beam of light
includes a large number of light rays showing measurable dimensions.
It embraces divergent, parallel and convergent rays, but thereon vergent
rays are of no use to us under ordinary conditions.
If light is made to pass through a homogeneous medium, such as
air, glass or water, it is propagated onward in a right line, while if an
opaque body is placed in its path, it will be intercepted by it and
be absorbed or reverberated. In the latter case, the light is forced to
change its direction, although allowed to continue onward in the same
medium. To this phenomenon the name of reflection has been given.
Reflecting bodies may be polished or unpolished. The first give rise
to regular and the second to diffused reflection. Thus, if a beam of
light is incident upon a well-polished mirror, the greater part of the
light is reflected in a single direction at a perfectly definite angle;
in fact, the reflection is so precise that it may be said to be governed
by two laws, as follows:
(1) The reflected ray BE is in the plane of the incident ray DB and a normal or
perpendicular AB erected upon the reflecting surface CF at the point of incidence
B of the ray (Fig. 404).
(2) The angle EBA formed by the reflected ray and the perpendicular, equals
the angle DBA made by the incident ray and the perpendicular. In other words,
the angle of reflection is equal to the angle of incidence.
796
THE SENSE OF SIGHT
A beam of light falling upon an unpolished surface suffers a reflec-
tion of its rays in all directions, because inasmuch as the surface is
composed of projecting particles which receive incident rays at all
angles, the reflected rays miist be diffused or scattered in all directions.
Naturally, the intensity of the reflected light is always less than that
of the incident light, because at least some of the original vibrations
are converted into vibrations of the
reflecting surface. Thus, the intensity
of the reflected light really depends
upon, (a) the brilliancy of the source of
light, (6) the perfection of the polish,
(c) the angle of the incident ray, {d)
the character of the reflecting sub-
stance, and (d) the character of the
medium in which the reflection is tak-
ing place.
Fig. 404. — Reflection from
Plane Mirrors.
In accordance with their shape, reflecting
surfaces may be classified as plane, concave,
convex, spherical, parabolic, conical, etc.
The reflection from a plane mirror is illustrated
by Fig. 404. If a ray of light emitted by
point D, meets the surface CF at the angle DBAj the reflected ray forms the angle
EBA. The eye at E then sees the image of D as if it were placed at /, this point
being situated where the prolongation of EB intersects the perpendicular drawn
through D. Hence, the determination of the position and size of images formed
by plane mirrors, resolves itself into a determination of the image points of the
several different luminous points. It will be seen, therefore, that the image is
perceived as being located behind the mirror at a distance equal to that of the
given points.
A
B\
^/'f\
^y^/ \
^y^ f \
^/^ / \
^
y"^ / \
<^^
f A
^^
^^
v,^ \ 1
^v^^ \ 1
^^v^^ N I
^"V.^ ^N /
e
^^^^*^
Fig. 405. — Reflection from a Concave Spherical Mirror if Its Incident Ray is
Parallel.
Spherical mirrors are those possessing the curvature of a sphere,
and are formed, therefore, by the revolution of an arc around the radius
CD. The inner concave and the outer convex surface may of course
be supposed to be made up of an infinite number of plane mirrors.
Reflection may take place from the former as well as from the latter.
Cj the center of the hollow sphere, constitutes the geometrical center
or center oj curvature, while a line drawn through C and D, forms the
PHYSIOLOGICAL OPTICS 797
principal axis of this reflecting surface. Any other Une passing
through C to a different point of the mirror than its middle, consti-
tutes a secondary axis. The perpendicular of each of the small planes
forming this reflecting surface, is the radius of the sphere and each
reflected ray forms with the corresponding radius the same angle as
the incident ray. Thus, all rays parallel to the principal axis {AB and
EH, Fig. 405) are brought to a focus at the principal focus F midway
between C and D. Quite similarly, all rays pursuing a course parallel
to any secondary axis, are brought to a focus in a point lying on this
axis. Hence, if the principal focus F were converted into a luminous
point, the rays emitted from h^re would be reflected back into rays
taking their course parallel to the principal axis.
If the luminous point L is situated upon the principal axis at a distance insuffi-
cient to render the rays emitted by it parallel, then the divergent incident ray LB
(Fig. 406) and the perpendicular BC form the angle LBC. This angle is smaller
than that formed by the parallel ray AB with the corresponding normal BC] and
hence, it may be inferred that the angle of reflection of a divergent ray is smaller
than the angle of reflection of a parallel ray. Consequently, the principal focus
of L must lie in L^ between F and C;i.e., between the center of curvature and the
Fig. 406. — Reflection from a Concave Spherical Mirror if its Incident Ray is
Divergent.
principal focus F. By converting L^ into a luminous point, the rays may in the
same manner be reflected outward into L. The latter, therefore, may be said to
be the conjugate focus of L^. It will then be seen that if the luminous point L is
placed in the center C, the angle of incidence is null and the angle of reflection null.
Consequently, the ray is reflected upon itself so that its focal point coincides with
the luminous point. Lastly, if the luminous point L is situated between the center
of rotation C and the principal focus F, the conjugate focus must be on the other
side of the center and the farther from it, the shorter the distance between L and
the principal focus. These principles find their application in the explanation of
Purkinje's image reflected from the concave anterior surface of the vitreous humor.
The reflection from convex spherical surfaces finds its application in the images
formed upon the anterior surfaces of the cornea and lens. Supposing that the
entering ray pursues a course parallel to the principal axis of the convex mirror,
its reflection from the latter will give to it a divergent course. If the reflected ray
is continued by an imaginary line through the mirror, it will be seen to strike the
principal focus at F which is approximately the center of the radius of curvature
CD of this mirror.
The images formed by rays of light differ with the direction assumed by them
after their reflection. When they converge, as after their reflection by concave
mirrors, they form a real image in front of the mirror and on the same side as the
798
THE SENSE OF SIGHT
object. A real image, therefore, is produced by the reflected rays themselves, and
may be observed with the aid of a screen properly adjusted at their points of inter-
section. Divergent rays, on the other hand, are supposed to be projected directly
through the mirror and are seen as if they proceeded from its other side. In
the latter case, the image has no real existence, but is effected by the prolon-
gations of the reflected rays backward. This is called a virtual image. Obviously,
therefore, a real focus is formed by the reflected rays themselves, while a virtual
focus is formed by their prolongations backward through the mirror.
Refraction. — If a ray of light is made to pass from one medium
into another in a perpendicular direction, it is not deviated from its
course. The contrary result, however, is obtained if it is made to
enter in an oblique direction. To this phenomenon the term of
refraction has been applied. It is to be remembered that not all the
rays of a certain beam of light are refracted, because some of them are
reflected from the surface in accordance with the character of the
medium into which they have been directed. Those that actually
enter the denser medium are refracted, because their velocity of pro-
pagation is now less than it was in the rarer medium. The degree
of refraction differs with the relative densities of the two media.
Supposing that we are dealing with air and water separated by a thin
Fig. 407.
-Diagram Illustkatinq
Refeaction.
Fig. 408. — Diagram Illustrating Refraction.
layer of glass (Fig. 407), it will be found that any ray directed verti-
cally to the surface of the latter (AB), is not deviated from its course
{BC). Any incident ray, however, which strikes the surface of the
water obliquely (DB), is deflected (BE) toward the perpendicular
AC. The angle of incidence ABD^ is then larger than the angle of
refraction CBE, and naturally, this angle becomes the smaller, the
greater the refracting power or density of the second medium. The
ratio between the angle of incidence and the angle of refraction con-
stitutes the index of refraction. When passing in the opposite direc-
tion (Fig. 408), namely from a medium of greater into one of lesser
density or refractive power, the ray BE is bent away from the perpen-
dicular rendering the angle of refraction greater than the angle of
incidence. Thus, taking the index from air to water to be ^ and from
air to glass %, the course of the ray in the opposite direction would
show an index of % and % respectively.
The first law of refraction states that the refracted ray is in the
PHYSIOLOGICAL OPTICS
799
same plane as the incident ray and the perpendicular drawn to the
surface, separating the two media. The second law is that the ratio
which the line of the incident ray bears to the line of the angle of
refraction, is constant for the same two media but different for differ-
ent media. ^
Refractive media may be bounded by:
(a) Two plane surfaces which are parallel to one another. A ray impinging
upon a plate at a right angle, traverses this medium without suffering a change in
Fig. 409. — Diagram Il-
lustrating Refraction by
a Plate-like Body.
Fig. 410. — Diagram Illus-
trating Refraction by Prisms.
its direction. Any other ray DB meeting this surface at an angle, is bent toward
the perpendicular AB on entering, but away from it on leaving the medium. The
emergent ray EF is parallel to the incident ray (Fig. 409).
(6) Two plane surfaces which incline toward one another. At the point of
intersection of these two surfaces is the summit or apex A. Their inclination
constitutes the refractive angle and their right line BC the base. The medium so
outlined is a 'prism (Fig. 410). A ray of light LE impinging upon one of its lateral
surfaces AB, is deflected toward the normal P at E, because it passes into a more
highly refractive medium. It here forms the angle of incidence LEB and the angle
1 ii 3 4 5 6
Fig. 411. — D'ifferent Forms op Convex and Concave Lenses.
of refraction lEF. When meeting with the other surface AC it is again refracted,
the angle of refraction HFK being greater than the angle of incidence EFI] because
it passes from a more highly refractive medium into one of less power. Thus, the
ray is deflected from its course in the direction of the base of the prism. In this
case, the image of L is produced at S, in the prolongation of the emerging ray.
(c) Two surfaces one of which is either curved or plane. The refractive medium
is thus arranged in the form of a lens which in accordance with its shape may be
spherical, cylindrical, elliptical or parabolic. In optics spherical lenses are most
commonly employed and they may be made of crown glass or flint glass. The
former is free from lead and is therefore less refractive than the latter which contains
lead. By combining spherical surfaces either with plane or curved surfaces, six
^ Stated by Snell in 1620, but enunciated by Descartes.
800
THE SENSE OF SIGHT
different kinds of lenses are obtained, namely (a) plano-convex, (6) biconvex,
(c) concavo-convex, (rf) plano-concave, (e) biconcave and (/) concavo-convex
(Fig. 411). The lens in our eye is a double convex or biconvex lens, but we shall
have occasion to refer to the other types of lenses, as well as to prisms and planes
when discussing errors in refraction and their correction.
Refraction by a Biconvex Lens. — A biconvex lens is essentially
the segment formed at the intersection of two spheres drawn upon the
same line with either the same or different radii (Fig. 412). Hence,
Fig. 412.
Fig. 412. — Diagram Illustrating the Formation of
FiQ. 413. — Structure of Biconvex Lens. (From Draper
B C
Fig. 413.
Biconvex Lens.,
' Medical Physics.")
SL line prolonged through the centers of curvature of the two surfaces
of this lens (AB), must form the principal axis of this system. Be-
tween these two centers lies a point C which possesses the property of
permitting rays to pass without refraction, so "that the emergent ray
is parallel to the incident ray. This point constitutes the optical
center of the lens. Any other line passing through this center is a
secondary axis.
The action of a biconvex lens upon the entering rays of light is easily understood
if the lens is imagined to be composed of a number of prisms arranged in the manner
Fig. 414. — Convex Lens Dissected. (From Draper "Medical Physics.")
indicated in Fig. 413. It will be remembered that a prism deflects or deviates the
ray toward its base ; hence, a biconvex lens deflects the entering rays in accordance
with the refractive power of its prismatic constituents. Inasmuch as the central
prisms d, e, etc., have a smaller refracting angle than the outer one / and g, they
must give rise to a lesser deviation. The same holds true of the prismatic elements
situated above the principal axis, and whether in the vertical, horizontal or oblique
meridian of this lens. Their tips are of course directed outward and their bases
inward; and furthermore, the central ray following the line of the principal axis,
is not deflected at all It will be seen, therefore, that a biconvex lens possessing
PHYSIOLOGICAL OPTICS
801
properly centered prisms, converges the previously divergent rays, so that lumi-
nous point A is brought to a precise focus in C upon the principal axis.
In ascertaining the formation of an image by a double convex lens, it must be
remembered that all objects possess numerous luminous points, the rays emitted by
them being collected by the lens into a corresponding number of foci. ' This implies
that under ordinary conditions, the image furnished by a biconvex lens, is real.
Supposing that we are dealing with a biconvex lens of the refractive power of the
lens of our eye, and place an object in front of it at a distance of more than twenty
feet, then the object emits, among others, a large number of rays which pursue a
course parallel to the principal axis of this lens {AB etc.. Fig. 415). All these rays
are converged to very nearly the same focus F upon the principal axis. The dis-
FiG. 415.-
■DiAGRAM Illustrating the Refraction of Parallel Rays by a Biconvex
Lens.
tance LF, is known as the principal focal distance. If the object is now moved
farther away from the lens, the principal focus F moves toward the lens, while if
the object is placed nearer the lens but not close enough to render the rays diver-
gent, the focal point F moves farther backward. Lastly, if F itself is rendered
luminous, the rays emitted from here traverse the lens in the opposite direction
and leave its anterior surface parallel to the principal axis. This is merely a re-
versal of the previous condition in which parallel rays are brought to a focus in F.
If a luminous point L is placed upon the principal axis at a distance greater
than the focal distance of this lens, but not far enough from it to cause its rays to
become parallel, then the rays diverging from it are brought to focus in L\ at a
Fig. 416.
-Diagram Illustrating the Refraction of Divergent Rays by a Biconvex
Lens.
point beyond the principal focus jP (Fig. 416). In case L^ is now rendered lumi-
nous, its rays are brought to a focus in L. For this reason, these points are com-
monly spoken of as conjugate foci. By moving luminous point L nearer to and
farther away from the lens, the focal point L^ may be made to move first farther
away and then nearer to the lens. In the first case, a point will be reached when
the emerging rays finally become so greatly divergent that they cannot be focalized
at all (Fig. 417). This effect appears whenever the luminous point L is situated
nearer the lens than its principal focal distance. In this case, a virtual focus is
formed at L^, at the intersection of the prolongations of the emerging rays.
If rays are directed into this lens which are already convergent, their conver-
gence is simply increased so that their focal point comes to lie nearer the lens than
61
802
THE SENSE OF SIGHT
it would if the rays entering it had been parallel. This is the function of the
cornea. It tends to gather the slightly divergent rays and to render them available
for refraction by the lens. This discussion shows that if an object, even a very
large one, is placed at a sufficient distance from a biconvex lens, a small real and
inverted image of it is formed just outside the principal focus F. The greater the
Fig.
417. — Diagram Illustrating the Refraction of Extremely Divergent Rays by
A Biconvex Lens
distance, the smaller this image. This principle is illustrated by our eye as well as
by the ordinary photographic camera. Quite similarly, one small object placed
upright just outside the principal focal point F oi a, biconvex lens, forms a large
inverted image at a considerable distance in front of the lens. This principle is
illustrated by the projection lantern.
Fig. 418. — Dla.gram Illustrating Formation of an Image by a Biconvex Lens.
In constructing the image of an object AB as formed by a biconvex lens, it must
be remembered that one ray AD emitted by luminous point A, always traverses the
nodal point of the lens N unrefracted and that a second ray AE enters the lens paral-
lel to its principal axis (Fig. 418). The ray AE is then refracted through the focal
point F. The focal point of A lies at the point of intersection of these two hnes.
A
■^
-— ^
c .. •
fT
r>
■-...^
■■■--■*;
^i
Fig. 419. — Diagram Illustrating the Refraction by a Biconcave Lens.
If this construction is now extended to a luminous point B upon the lower end of the
object AB, it will be seen that this one is brought to a focus above. Consequently,
the image of object AB is inverted. In those cases in which the object is placed
between the biconvex lens and its principal focus, only virtual erect images are
formed This principle is made use of in the construction of microscopes and
magnifying
THE GLOBE OF THE EYE 803
Refraction by a Biconcave Lens.— To understand the refraction
by biconcave lenses, imagine the lens to be composed of a number of
prisms, which in cross-section have their apices directed toward the
center or axis of the lens and their bases toward the periphery. If
we remember that the rays entering the incUnation of a prism, are
deflected toward its base, it must be evident that a biconcave lens
renders the rays divergent (Fig. 419). Like the concave mirrors,
these lenses give rise to virtual images. When the incident ray meets
the anterior surface of this lens, it is refracted toward the perpendicular,
CBj but away from it at H. This double refraction also takes place
with every other ray, for example, with DE and hence, there is no real
focus established. The prolongations of these rays intersect in F
which is the principal virtual focus.
CHAPTER LXVIII
THE GLOBE OF THE EYE AND ITS PROTECTIVE
APPENDAGES
The General Structure of the Eyeball. — The eyeball is placed in
the fore part of the orbital cavity and is adjusted in such a way that it
may be activated by almost any ray projected toward it. Its range is
greatly increased by the fact that it may be moved in different direc-
tions by means of muscles attached to its external coat. In the mam-
mals, the visual mechanism consists of two eyeballs and their connec-
tions with the centers for vision in the occipital cortex of the cerebrum.
This implies that these animals are in possession not only of a most
highly developed receptor, but also of the means of forming the best
possible concepts. In this regard they are sharply differentiated from
the lower forms which, although equipped with receptors of sufficient
sensitiveness toward the ethereal impacts, are quite unable to asso-
ciate them properly, because they lack the central organ essential for
this function. Many of the lower forms are able to perceive Hght by
means of their pigment spots and other cutaneous sense-organs,^
but react toward it merely in a reflex way, by displaying phenomena
similar to the heliotropism or phototaxis of the lowest organisms.
In a way, these forms are really in the same position as we would be
if our eyeHds were kept permanently closed, because although still
able to appreciate differences in the intensity of the illumination, we
would then react in accordance with these and no longer depend
upon distinct visual impressions and concepts.
A much more advanced state of development is attained by the
eye of the higher invertebrates. That of the insects is composed of
^ Hesse, Das Sehen der niederen Tiere, Jena, 1908.
804
THE SENSE OF SIGHT
numerous funnel-shaped tubules, through which the rays of light are
refracted by means of a lens-like structure of chitin. This type of eye,
however, is soon abandoned, because already in the cephalopods we
find a single system of curved refracting media. In the vertebrates
the eye is constructed along very similar lines. Retrogressive it
becomes in proteus and sphalax, because these animals live perma-
nently in the dark.
The eye is the organ of space, its purpose being to form images
of external objects upon the retina which are then conveyed into
consciousness. Its general structure and manner of action reminds
Fig. 420. — Diagram of a Horizontal Section Through the Human Eye.
C, cornea; A, anterior cavity; P, posterior cavity; L, lens; J, iris; T, conjunctival sac;
CL, ciliary ligament; CB, ciliary body; CM, ciliary muscle; OS, ora serrata; CS, canal of
Schlemm; R, retina; Ch, choroid; S, sclera; ON, optic nerve; A, retinal artery; B, blind
spot; Y, yellow spot; OA, optical axis; VA, visual axis; H, hyaloid canal.
US of the camera obscura, the box of which is represented by the cor-
neal and sclerotic envelope of the eyeball, its refracting medium by the
aqueous humor, lens and vitreous humor, its diaphragm by the
iris, and its sensitive screen by the retina. Its most essential constitu-
ent is, of course, the retina, while its other structures merely serve the
purpose of adjuncts to effect a proper concentration of the rays of light.
The eyeball is spheroid in shape and is loosely held in the orbital
cavity by a fibrous membrane, known as the capsule of Tenon. Its
anteroposterior diameter measures about 24 mm., and its transverse
and vertical diameters about 22 mm. In longitudinal section it is
seen to be composed of the segments of two spheres, of which the pos-
THE GLOBE OF THE EYE 805
terior occupies five-sixths and the anterior one-sixth of the entire
spheroid. At about the Hne of junction of these segments is placed a
partition consisting of the cihary body, iris and lens. In this way, the
cavity of the eyeball is subdivided into two, known respectively as the
anterior and posterior cavities. The former is filled with aqueous
humor and the latter with vitreous humor. It is also to be noted that
the wall enclosing the former is in part translucent (cornea), whereas
that of the latter is opaque.
The Minute Structure of the Eyeball. — The shell of the eyeball
consists of three layers arranged concentrically as an external, a
middle and an internal coat. The outermost or sclera is made up of
dense, tough, opaque fibrous tissue which is interwoven with elastic
fibers and is distributed longitudinally and transversely around the
eyeball. If the eyelids are widely separated, its anterior zone appears
as the ''white of the eye." In children it has a bluish color, owing
to the fact that it is not sufficiently thick to prevent the dark choroidal
pigment from showing through. It is thickest posteriorly (1.0 mm.)
at the entrance of the optic nerve, and thinnest (0.4 mm.) about 6 mm.
from the cornea. Anterior to this point it is again thickened to give
attachment to the tendons of the recti muscles. The optic nerve and
the retinal blood-vessels pierce the sclera about 2.5 to 3 mm. internal
to the posterior pole of the eyeball and about 1 mm. below the hori-
zontal line uniting its anterior and posterior poles. By virtue of its
firmness, the sclera serves to retain the shape of the eyeball and to
protect its soft internal structures. In this it is aided by the fact that
the hum.ors of the eye are held under a certain pressure which is desig-
nated as the intraocular pressure.
The cornea whicli is really the modified anterior segment of the sclerotic coat,
is transparent and allows the rays of light to enter the interior of the eye. Looked
at from in front, it possesses a nearly circular outline, measuring about 12 mm. in
its transverse and 11 mm. in its vertical diameter. In infants, its central zone
is generally somewhat thicker than its marginal, while in the adult it is somewhat
thinner^ (0.45 to 1.37 mm.). Its curvature is less than that of the sclerotic, but
varies in different persons as well as at different periods of their life; moreover,
its curvature is generally greater in its vertical than in its horizontal meridian.
The substance of the cornea is made up of modified connective tissue which is
continuous with that forming the sclera. Its anterior surface is enveloped by
stratified epithelium which is supported by a structureless membrane, known as
the anterior homogeneous lamella. Its posterior aspect is covered by a simple
layer of endothelial cells situated upon the posterior homogeneous lamella. The
latter is a very resistant membrane, as may be gathered from the fact that it serves
as a barrier to inflammatory processes. In addition, it prevents the absorption
of the aqueous humor through the corneal lymphatic spaces. Close tO the margin
of the cornea, this membrane breaks up into a number of interconnected lamellae
which either serve as attachments to the ciliary muscle or are prolonged backward
into the substance of the iris and sclera. The fissures in between these lamellae
are known as the spaces of Fontana. They communicate freely with the anterior
cavity of the eye as well as with the canal of Schlemm, a circular tube traversing
the substance of the sclera, close to its junction with the cornea. The latter is
1 BUx, Monatsblatt fiir Augenheilkunde, 1872.
806 THE SENSE OF SIGHT
generally regarded as a sinus-like vein which serves as a drainage tube for the
aqueous humor. ^
The cornea is not provided with blood-vessels, excepting along its margin, where
the conjunctival and sclerotic capillaries form superficial and deep networks.
Furthermore, since this structure is also devoid of lymphatics, its nutrition must
be effected by the lymph contained in its connective-tissue spaces. It need scarcely
be emphasized that this arrangement is of great functional importance, because it
enables the rays of light to gain the pupillar aperture without being unduly de-
flected from their course. The nerve fibers of the cornea are derived from the
plexus annularis surrounding its margin. ^ From here these fibers strive radially
into its fibrous substance, where they form secondary plexuses in the anterior
and posterior laminated structures. The fibers of these inner networks are
non-medullated.
The choroid is in firm contact with the internal surface of the sclera. It is dark
brown in color and extends forward to a point very near the cornea where it
terminates in the iris. The latter appears as a transverse fold which is attached
to the eyeball at its circumference, but is otherwise freely suspended in the aqueous
humor in front of the lens. It will be seen, therefore, that this membranous par-
tition divides the anterior cavity of the eyeball into two compartments, called
respectively the anterior and posterior chambers of the eye. The former is bounded
by the cornea and anterior surfaces of the iris and lens, and the latter by the poste-
rior surface of the iris and anterior surface of the lens. Directly behind the
iris, the choroid is folded a number of times into a circular thickening which ex-
tends into the anterior part of the vitreous humor. This structure is known as the
ciliary body and contains the ciliary muscle. Its inner pole gives attachment to
the ciliary ligaments which extend from here to the capsule of the lens. The
function of these minute parts will be more fully discussed later on when studying
the process of accommodation. The choroid consists chiefly of an extensive rami-
fication of blood-vessels held in place by delicate strands of connective tissue.
These vessels are principally derived from the ophthalmic artery and pierce the
sclera externally to the entrance of the optic nerve. They are known as the short
posterior ciliary, the long posterior ciliary, and the anterior ciliary arteries.
The retina, forming the innermost coat of the eye, extends forward to almost
the ciliary body. It terminates in this region in a dentated border, known as the
ora serrata. Externally, its hexagonal pigmented cells He in close contact with
the choroid ; in fact, since these cells most generally remain adherent to the latter,
when the retina is peeled off, they are commonly regarded as a constituent of the
middle coat. It will be shown later on, however, that they are more intimately
related to the retina and should, therefore, be considered as a part of this membrane.
The thickness of the retina diminishes gradually from behind forward, measuring
0.4 mm. at the yellow spot and 0.1 mm. at the ora serrata. When in a perfectly
fresh condition, it exhibits a pink color and appears translucent against the hyaline
external investment of the vitreous humor. Its blood-supply is derived from the
arteria centralis retinae, a branch of the ophthalmic which enters the eyeball to-
gether with the fibers of the optic nerve, and then subdivides in a radial manner
until its terminals reach the ora serrata. The microscopic structure of the retina
will be more fully discussed later on in connection with its function.
The Eyelids. — The closure of the eyelids is effected (a) volitionally
at irregular intervals, (5) involuntarily at rather regular intervals,
(c) reflexly in consequence of the excitation of the trigeminus terminals
innervating the structures in the vicinity of the eyeball, {d) reflexly
on account of the stimulation of the optic nerve by high intensities of
light, and (e) during states of cerebral depression and sleep. The mus-
^ Dogiel, Anat. Anzeiger, 1890.
2 Leber and Gidzecker, Archiv fiir Ophthalm., Ixiv, 1906.
THE GLOBE OF THE EYE 807
cle involved in this process, is the orbicularis palpebranim which de-
rives its innervation from the facial nerve. The closure of the upper
lid is, of course, greatly facilitated by gravity. The opening of the
eyelids is effected by the muse, levator palpebrarum which raises the
upper lid, while the lower lid is carried downward by gravity. The
latter may be depressed still further by the contraction of the muse,
rectus inferior, because the tendon of this muscle and the inferior
tarsus are connected with one another by strands of connective tissue.
This extra depression, however, is only made necessary when objects
in the lower visual fields are to be observed while the head is held erect.
In many fish, amphibia and reptilia, the eye is completely covered
by a transparent skin, while others, such as the sharks, crocodiles
and birds, are in possession of a third lid which moves transversely
across the cornea from its inner angle. This so-called nictitating
membrane is represented in the mammals by the plica semilunaris.
In either case, the eyelids serve primarily as a mechanism of protection
against high intensities of light and impacts of different kinds. Under
ordinary circumstances, their edges are separated by a cleft measuring
about 28 mm. in height. The intervening space is known as the
rima palpebraris. Inasmuch as the size of the eyeball does not vary
very considerably in different individuals, the fact that an eye appears
either large or small, is chiefly dependent upon variations in the height
of this cleft.
The Lacrimal Glands and Their Secretion. — The internal surfaces
of the eyelids are lined with mucous membrane, which is reflected
upon the anterior aspect of the eyeball. This Uning is known as the
conjunctiva and the space between its layers as the conjunctival sac.
The latter is, of course, chiefly potential, because the lids are firmly
appUed to the eyeball and their surfaces are moistened with the se-
cretion of the lacrimal gland. This gland presents a compound
tubuloracemose character, and resembles the serous salivary glands.-^
The cytoplasm of these cells contains two kinds of elements, namely,
small dark granules and large, clear, vacuolar formations which
greatly increase in number during their resting period. If, on the
other hand, the secretory nerve of this gland is stimulated or if lacri-
mation is evoked by means of pilocarpin, these clear bodies disappear,
while the dark granules increase in number. The nerve-fibers inner-
vating this gland, are derived from two sources, namely, from the
lacrimal branch of the ophthalmic (facial) and from the sympathetic.^
This gland occupies the upper and outer extent of the orbital
cavity, while its lower surface rests upon the convexity of the eyeball.
Consequently, its secretion is poured into the outer and upper recess
of the conjunctival sac, whence it is spread by capillarity across the
cornea, moistening its surface as well as that of the opposing conjunc-
1 Noll, Archiv fiir mikr. Anatomie, Iviii, 1901, also: Dobrenil, Dissertation,
Lyons, 1907.
2 Dogiel, Archiv fiir mikr. Anatomie, xliv, 1895.
808
THE SENSE OF SIGHT
tiva. Eventually it is collected in the lacrimal lake, a bay-like ex-
pansion at the inner angle of the eye overlying the plica semilunaris
and the spongy reddish elevation, known as the caruncula lacrymalis.^
We observe here that each lid is slightly raised into a papilla, the
Fig. 421. — Diagrammatic Representation of Alveoli of the Lacrimal Gland.
A, during rest; B, after activity produced by pilocarpin.
apex of which displays the orifice (punctum) of a small carnal, known
as the canaliculus lacrymalis. The purpose of these tubules is to
convey the tears out of the conjunctival sac into the lacrimal sac,
representing the shghtly dilated orbital end of the lacrimal duct.
ZetchfywaZ canaZs ^/^^
TfascU
'SCCC
TftnefjocU/o^foZ
liqcutnJanA
'medUo
Fig. 422.
-Section Showing the Course and Relations of the Nasal Sac and Duct.
{Slightly modified from Merkel.)
The latter is about 5 mm. wide and 15 mm. long, and continues on-
ward in the form of the nasal duct which finally terminates in the
fore-part of the lower meatus of the nose about 30 to 35 mm. behind
the posterior margin of the anterior nasal opening (Fig. 422).
1 Stieda, Archiv fiir mikr. Anatomie, xxxvi, 1890.
THE CORNEA, IRIS AND AQUEOUS HUMOR 809
These channels are Hned with columnar epithelium which becomes
ciUated in places. Their walls are strengthened by muscle tissue which
on contraction tends to enlarge their lumen. This is especially true
of Horner's muscle which envelops the posterior wall of -the lacrimal
sac and which, during the closure of the lids, widens this passage and
aspirates the tears through the dilated punctum. Conversely, the
opening of the hds tends to compress the lacrimal sac so that its con-
tents are forced onward into the nasal duct.-^ At this time the
sphincter-like punctum is closed, while the valve of Hasner guarding
the orifice of the nasal duct, is opened. It should also be mentioned
that the tears are ordinarily prevented from escaping across the edges
of the eyelids by the oily deposits furnished by the Meibomian glands.
The latter are sebaceous in character and are arranged in rows along the
inner margin of each lid. The tears themselves are alkaline in reaction
and are chiefly composed of water (98.1 per cent.). They contain
albumin (0.1 per cent.) mucin, epithelial cells (0.1 per cent.) and salts,
principally sodium chlorid (0.4 to 0.8 per cent.).
CHAPTER LXIX
THE CORNEA, IRIS AND AQUEOUS HUMOR
The Refractive Power of the Cornea. — The cornea of the mam-
malian eye is a perfectly stationary structure possessing a certain
curvature and refractive power. In the birds, on the other hand, it is
set in a cartilaginous ring and its convexity may be altered by muscular
activity. This fact indicates that in these animals it is made to serve
as a powerful adjunct to the lens and thus, is in large part responsible
for the keen sense of vision possessed by them. In the higher mam-
mals, its importance is relatively slight, because its radius of curvature
is only 7.8 mm.,^ but this measurement pertains only to its central
area situated directly in front of the pupil. Its marginal zone is of
practically no optical importance even when the pupillar orifice is
enlarged. It may be concluded, therefore, that the cornea, by virtue
of its convexity, renders the entering rays of light slightly more con-
vergent. In addition, it collects many of the otherwise too divergent
rays, and directs them through the pupillar opening so that they may
still be subjected to the refraction of the lens.
The Aqueous Humor. — It has been stated above that the anterior
cavity of the eyeball consists of the anterior and posterior chambers,
the former being situated in front of the iris and the latter, between
the posterior surface of this partition and the anterior aspect of the
iScimeni, Archiv fiir Physiol., 1892, Suppl. 291.
2 Helmholtz, Physiolog. Optik, Berlin, 1896.
810 THE SENSE OF SIGHT
lens and ciliary body. Many physiologists, however, believe that in
adult life the iris lies in absolute contact with the lens and that the pos-
terior chamber is merely a potential space. The transparent liquid
filling this entire cavity, is known as the aqueous humor. Its quantity
amounts to about 0.4 c.mm. and its specific gravity to 1.0053-1.008,
which is the equivalent of a solution of sodium chlorid of a concen-
tration of rather more than 1.0 per cent.-^ Its osmotic pressure
is somewhat higher than that of the serum of the blood. ^ It may con-
tain a few leukocytes, but only 0.08-0.12 per cent, of protein. This
watery fluid also permeates the interstitial spaces of the gelatinous
substance of the vitreous humor.
If a small manometer is connected with the anterior chamber of the eye by
means of a tubular needle, it will be noted that the aqueous humor is held under a
pressure of about 25 mm. Hg. This pressure is designated as the intraocular
pressure. Its very obvious function is to render the eyeball tense so that its differ-
ent refractive elements are fully unfolded. It need scarcely be emphasized that
any unevenness in the cornea or an unduly relaxed ciHary body and ligament must
greatly impair the usefulness of these structures for refraction. In addition, it
may justly be assumed that the aqueous humor forms the nutritive medium for
the lens, ciliary ligaments, and vitreous humor, because these structures are not
directly supplied with blood. In certain pathological conditions, such as glaucoma,
the intraocular pressure is enormously increased so that the eyeball can scarcely
be indented with the finger. Clinically the tenseness of the eyeball is measured by
means of the ophthalmotonometer. This instrument is pressed against the outer
surface of the eyeball until its plate-like extremity causes a certain flattening at the
point of contact. The pressure necessary to accomplish this end, is indicated by
a tension spring.
A number of observations have been made which prove conclusively
that the aqueous humor is continually renewed. Thus, any operation
requiring an incision through the cornea, most generally leads to a loss
of a considerable portion of this fluid which is again reformed in the
course of a few days. Furthermore, it is possible to drain it off in a
relatively steady stream by inserting a delicate cannula through the
margin of the cornea. Its character is then gradually changed until
it contains as much as 3 or 4 per cent, of proteins and becomes coagula-
ble. It is commonly held that the aqueous humor is secreted by
the epithelium of the ciliary body and its glands. From here it flows
into the anterior recess of the posterior (vitreous) cavity of the
eyeball, whence it finds its way through the clefts in the hgamentum
pectinatum iridis into the angle of the anterior chamber. A portion
of this fluid also escapes through the meshes of the ciliary ligament into
the posterior chamber situated between the iris and the lens, and thence
round the edge of the iris into the anterior chamber. The canal of
Schlemm is the natural drainage tube of this space. A portion of this
fluid also escapes into the lymph spaces of the iris and from here into
the perichoroideal lymphatics. Still another portion is diverted from
the cihary glands into the interstitial spaces of the vitreous humor,
1 Golowin, Archiv fiir Ophthalm., li, 1900.
2 Hamburger, Osmotischer Druck and Jonenlehre, 1904.
I
THE CORNEA, IRIS AND AQUEOUS HUMOR 811
whence it finds its way into the lymphatics accompanying the optic
nerve.
At all events, the offlow balances the production, so that the aque-
ous and vitreous humors are constantly held under a pressure of about
25 mm. Hg. This impHes that these different drainage tubes are
adjusted so as to place a considerable resistance in the path of the
escaping fluid. In spite of this fact, however, it has been estimated
that at least 6 c.mm. of new secretion are required per minute in order
to maintain the pressure at the height just stated; moreover, it has
been found that its quantity may be varied considerably by either
raising or lowering the blood pressure. It cannot be doubted that
this factor plays an important part in all processes of secretion, because
it gives rise to the secretory pressure, but it seems that it is of special
value for the formation of the aqueous humor. This fact suggests
that this fluid finds its origin in large part in transudation.
The Iris. — The circumferential border of the iris is anchored to the
eyeball immediately in front of the ciliary body. At this point it is
continuous with the choroid coat as well as with the cornea through
the Hgamentum pectinatum. In its course through the aqueous
chamber, its posterior surface is brought into close relation with the
cihary body and lens, while its anterior surface is everywhere fully
exposed to the humor filling this cavity. Its inner margin surrounds
an orifice, the pupil, through which the rays of light are enabled to
enter the vitreous chamber. This orifice is nearly circular in shape
and is placed somewhat nearer the nasal side of the eyeball. Under
ordinary conditions its diameter measures about 4 mm., but is subject
to constant changes in consequence of variations in the intensity of the
light and the range of accommodation. A fuller discussion of this
phenomenon will be given in a subsequent paragraph. >
When looked at from in front, the iris measures about 11 mm. across,
its inner margin being held at a distance of about 5 mm. from its cir-
cumference. Its thickness amounts, to about 0.4 mm. Its body is
formed by a stroma, consisting of a delicate framework of connective
tissue, the fibers of which are in large part arranged in a radial direc-
tion. Anteriorly, the latter is lined with cells similar in structure to
those covering the posterior limiting membrane (Descemet) of the
cornea. Posteriorly, it is enveloped by two layers of epithelial cells,
containing black pigment to which the blue color of the iris is due — blue
because transmitted through the stroma. Its different shades of
black, brown and gray, however, are caused by pigment cells which are
scattered through the substance of the stroma. ^
The plain muscle fibers of the iris are arranged either circularly
around the lumen of the pupil or radially to it. The former are most
numerous right next to its margin, where they form a conspicuous
sphincter, about 0.5 mm. in width. The latter form a layer of elon-
1 Retzius, Biolog. Untersuchungen, 1893.
812 THE SENSE OF SIGHT
gated, spindle-shaped cells close to the pigment layer. ^ The blood-
supply of the iris is derived from the long and anterior ciliary arteries,
and its nerve supply from the long and short ciliary nerves. The
origin and function of these nerves will be more fully described in a
later paragraph.
The Function of the Iris. — The action of the iris may be compared
to that of the adjustable diaphragm of an ordinary photographic
camera. As such it possesses two functions, namely, to:
(a) Vary to size of the bundle of light entering the vitreous cavity, (1) during far
and near vision or accommodation, and (2) during the alterations in the intensity
of the light.
(6) Direct the rays of light through the center of the lens which is its most per-
fectly refracting part. Thus, by excluding the margins of lens, it prevents the
occurrence of spherical and chromatic aberration.
It should be evident from the preceding discussion pertaining to
the structure of the iris, that the contraction of its circular muscle
fibers decreases the size of the pupil, while the contraction of its radial
fibers increases it. Thus, we find at times that the margin of the
iris is drawn almost completely over the lens, lessening the diameter
of the pupil to less than 1 mm., and, at other times, that it is pulled
outward until this aperture measures as much as 8 mm. across. The
former change constitutes pupillar constriction, and the latter, pupillar
dilatation. Obviously, these changes either diminish or increase the
number of the light rays entering thie vitreous chamber. A diminution
in their number is mad6 necessary (a) when the intensity of the light
is great, and (b) when the eye is adjusted for a near object. Con-
versely, an increase in their number is required (a) in low intensities of
light, and (6) when the object accommodated for is situated far away
from the eye. Furthermore, inasmuch as these changes are effected
as a result of reflex stimulation, we commonly speak of them as the
light and accommodation reflexes.
The Light Reflex. — If a person is made to look alternately from a
partially darkened surface into a light of moderate intensity, it will
be observed that the pupil becomes small whenever the eye is more
fully illuminated. An intense hght, in fact, decre.ses its size to almost
that of the point of a pin. It is true, however, that this change in the
illumination must be effected rather rapidly, otherwise a decided
alteration in the size of the pupil will not be produced. ^ Moreover,
if the constriction has been continued for a longer time than 3 or 4
minutes, its size gradually increases, owing to an adaptation and
fatigue of the constrictor mechanism. Obviously, the purpose of an-
enlarged pupil is to augment the receptive power of the retina by
permitting as many rays as possible to strike it, while a constricted
pupil serves to protect the retinal elements against an undue and in-
jurious degree of stimulation.
1 Grumert, Arch, fiir Augenheilkunde, xxxvi, 1898.
2 Garten, Pfltiger's Archiv, Ixviii, 1897, 68.
THE CORNEA, IRIS AND AQUEOUS HUMOR 813
In the case of the hght reflex, the stimuh are received upon the
retina, whence they are conveyed over the peripheral optic tract to
the secondary or reflex optic center, situated in the anterior corpora
quadrigemina next to the aqueduct of Sylvius.^ To effect pupillar
constriction they are transferred from here to the oculomotor nerve
and the ciliary ganglion and nerves. Pupillar dilatation, on the other
hand, is accomplished with the aid of the autonomic fibers and hence,
these impulses must be diverted from the secondary optic center into
the sympathetic system proper. Some authors also hold that the
retina gives rise to two kinds of fibers, one group of which has to do
with visual sensations proper and the other solely with the differences
in the intensity of the light. ^ The time which is required for this
reflex response of the iris, has been, estimated at 0.04 to 0.05 second.
In man, as well as in those animals in which the optic fibers decus-
sate in part, the light reflex is bilateral, so that light falling into one
eye also gives rise to a diminution in the size of the pupil of the oppo-
site organ. This is not the case in such animals as the horse, owl and
rabbity in which the crossing is complete.^ Furthermore, it has been
noted that the substance of the iris, and especially in the lower forms,
is extremely sensitive to light. Even small pieces of the iris of the frog
or eel may be made to contract by simply permitting a beam of light to
fall upon them.^ Clinically, the power of reaction of the pupils is
usually tested by shading one eye in such a manner that its pupillar
orifice can be observed beneath the cover. If the shaded eye is then
uncovered, its pupil will be seen to constrict. The other eye also
responds but not so intensely. This implies that the direct reaction
to light is usually more profound than the consensual, as practised in
this test.
From this discussion it may be gathered that the light reflex is
abolished whenever the aforesaid reflex arc is broken at any point of
its course. This calls to our minds the important fact that it is absent
in tabes dorsalis (locomotor ataxia) and general paresis, while the
accommodation reflex is preserved. This phenomenon is known as the
Argyll-Robertson sign. Its explanation is not difficult if it is remem-
bered that the nervous paths required for these two reflexes are totally
different. Thus, the afferent arc in the case of the light reflex is
formed by the optic nerve, whereas that concerned with the accomoda-
tion reflex is formed by the afferent fibers from the muscles of the eye.
Inasmuch as the disease of tabes dorsalis is characterized by a pro-
gressive degeneration of the different spinal roots and tracts, it cannot
surprise us to find that similar changes are finally induced in the optic
path, thereby gradually blocking the impulses from the retina. At
1 Hass, Archiv fiir 4-ugenheilkunde, Ix, 1908, 327.
2 Behr, Archiv fiir Ophthalmologie, Ixxxvi, 1913, 468.
3 Steinach, Pfluger's Archiv, xlvii, 1890, 313.
* Arnold, Physiologic, ii, 1847; also see: Steinach, Pfluger's Archiv, lii, 1892,
495.
d
814 THE SENSE OF SIGHT
this time, the afferent paths having to do with the accommodation
reflex, are still free from these degenerative alterations.
The Accommodation Reflex. — If a person is asked to accommodate
alternately for near and far objects, it will be noted that the size of
his pupil is decreased on near vision and increased on far vision. In
the former instance, the number. of rays entering the eye is diminished,
but not at all sufficiently to impair our power of being able to make
out the finer details of the object. This reduction in the size of the
beam of light is, of course, entirely in keeping with perfect refraction,
because the amount of light projected into the eye from any given ob-
ject, increases inversely as the square of its distance. This implies
that the phenomenon, constituting the accommodation reflex, is an
associated action and is closely interlinked with the muscular efforts
necessary for accommodation. These efforts consist in a convergence
of the eyeballs effected by the contraction of the two internal recti
muscles, and a contraction of the cihary muscles, rendering the lens
more convex. The afferent impulses which give rise to these reactions,
are, of course, chiefly intracerebral in their origin, and do not involve
the optic tract. Consequently, it appears that the constriction of the
pupil on near vision is due to the fact that those motor discharges
from the midbrain which evoke the contraction of the internal recti
and ciliary muscles, overflow and simultaneously activate the neigh-
boring center for the sphincter fibers of the iris.
In sleep the pupils are constricted in spite of the fact that the eyes
are not stimulated by light. This fact may seem to be opposed to
the view just expressed, unless it is remembered that the axes of the
eyeballs are at this time turned inward and upward. Obviously,
therefore, the initial constriction of the pupil during sleep is an associ-
ated movement, akin to that arising on near vision; in other words, the
motor impulses which are required to deviate the eyeballs in the afore-
said direction, also implicate the sphincter muscle of the iris.
The constriction of the pupil during the initial stage of anesthesia
by ether or chloroform may be explained in a very similar way, because
these agents give rise at first to a general excitation of the central ner-
vous system. As soon as this primary effect has weakened, the pupil
retains an intermediate size, but dilates immediately if the narcosis
is deepened or is carried beyond its physiological limit. This danger
point of narcosis may also be determined in other ways, for example,
by noting the intensity of the reflexes and, especially of those which are
usually preserved during sleep and moderate narcosis. The one most
commonly employed for this purpose is the corneal, consisting in a
closure of the eyelids upon mechanical stimulation of the cornea.
Among the agents which constrict the pupil, may be mentioned
opium, and its alkaloid morphin, as well as the alkaloids eserin or
physostigmin and pilocarpin. Among the dilators of the pupil
should be cited the alkaloids of belladonna, namely, atropin and homa-
tropin. A dilatation of the pupil commonly results in consequence
THE CORNEA, IRIS AND AQUEOUS HUMOR
815
of depressions of the nervous centers, as well as in all conditions of ner-
vous exhaustion, deep narcosis and comas. In dyspnea the pupils are
large, but become smaller if this condition is changed into asphyxia.
They are also enlarged by .sensory impulses from the digestive and
sexual organs, as well as by somatic and visceral sensations of pain.
Even the cerebral cortex may influence their size without any apparent
peripheral stimulation. Thus, it has been shown by Haab that if a
I>erson is made to look at a dark wall, while his eyes are illuminated
by a constant hght placed laterally in front of him, a marked constric-
tion of his pupils results whenever his attention is called to the light.
Quite similarly, his pupils may be made to dilate at any time by
drawing his attention to the dark wall. Some persons, indeed, are
able to constrict and to dilate
their pupils by merely calling up
a mental picture of bright and
dark objects.
Spherical Aberration. — In dis-
cussing the focal points formed
by spherical lenses, we have as-
sumed that the rays -emitted by a
luminous object are sharply inter-
sected behind the lens. Strictly
speaking, this is not true, becaus*^
the refraction of a lens diners
somewhat in its different zoi^^s for
the reason that its prismatic con-
stituents are not cen^.ered with
sufficient accuracy/to acVJU per-
fect unison. Tl)^ most perfectly
refracting portion of a lens is its
central area, having an aperture not exceeding 10° to 12°. If the size
of this aperture is increased so that the rays can also traverse its
peripheral segments, these rays will be brought to a focus in front of the
focal point of those refracted through its center (Fig. 423). The in-
tersections of these aberrated rays are called caustics. Obviously,
their presence must render the image indistinct. This condition which
is called spherical aberration, is also present in the lens of our eye, but
is prevented from interfering with the formation of the retinal image
^"/•■'le fact that its peripheral extent is usually covered by the margin
e iris. In this regard, therefore, the latter performs the func-
^ . of a stop, i.e., it cuts off the rays from the circumference of the
' ;3 and allows only the passage of a concentrated central beam.
' liromatic Aberration. — If a b'^^dle of light is projected through a
it will be noted that the rayp versing its central segment appear
5 other side chiefly as whit , while those passing through its I
heral zone are disperse- ir different colored components,
mage then appears surr< ^ a colored margin. This effect*
Fig.
423. — Diagram Illustrating
Spherical Aberration.
The iris being retracted the rays of light
pass through the outer zone of the lens and
are more sharply refracted than those tra-
versing its center.
\
V
\
4
816 THE SENSE OF SI
is to be expected, since light in passing from a rare into a dense medium
suffers a retardation, and this diminution in its velocity affects its
component rays differently, i.e., those at the red end, with long wave-
lengths, are refracted the least and those at the violet end, with short
wave-lengths, the most. Inasmuch as a lens is composed of a series
of prisms — and prisms split the white light in accordance with the
unequal refrangibihty of its simple color components — a spectrum must
result (Fig. 424). Thus, white Hght, when passed through the edge
of a biconvex lens, is dispersed so that "its violet rays are brought
to a focus (7) in front of its red rays {R), while the foci of its orange,
yellow, green, blue and indigo are situated in between these two ex-
treme's. This condition which is called chromatic 'aberration, is also
pre'^eat ini the lens of our eye, but cannot seriously interfere with the
fo^- :ii ; -^f the image, because the iris does not permit the rays of
-\--.
Fig. 424. — Diagram lLi.T7SrE.vriNa Cu<
The iria being retractel, tho rays of white light ni . .
the lens are split into their spectral componentSi Tbi vir.i L -
the leuB than the red. '
light to pass through its more poony iciru-cimg [:•" ■;• on,
By analogy, it may be conc^udeo that the jaydrmiAr . *>-
matically aberrated in '.ages, because the e;%e of it-
to the entering beam of light. 'In artiiicial U n^.
often overcome by combining crown glas^with
as the di^persi ve power of f '
disf)ersion may ih'-rr-
their trial refrai ;
Dollar i in the .... .^ .......,,, id
beini^ le term appa<.; )n of the refractioi
^'i' lecompoBition inu; -
t well-known fact ti at a .ed and vioK
pLi. the same distance m front oi do, the former appears
or f>rorr; ' A ! a * I seems nearer tO m Clearly, this --^ ^
-1 '-• ' j' ^ ; 'r>nse since the rjd rays possess
THE CORNEA, IRIS AND AQUEOUS HUMOR 817
wave-length, a greater effort at accommodation is required in order
to bring them to a precise focal point upon our retina.
Miosis and Mydriasis. — These terms are commonly employed to
indicate that the size of the pupil has been varied by means of drugs or
in consequence of pathological lesions. Miosis signifies pupillar con-
striction, and mydriasis, pupillar dilatation. The first condition is
commonly associated with congestion and traumas of the iris, certain
fevers, pulmonary congestion, and lesions of the sympathetic system.
Among the miotics might be mentioned physostigmin (eserin),
muscarin, and pilocarpin. Their action appears to be due to their
power of stimulating the nerve fibers and corresponding receptor
substance of the constrictor muscle. The mydriatics commonly made
use of, are atropin, homatropin and cocain. The first two act by
paralyzing the endings or receptor substance of the constrictor nerve
fibers.^ Cocain exerts a similar action, but only in larger doses, while
in smaller doses, it stimulates the dilator mechanism. Mydriasis is
also obtained in glaucoma, atrophy of the optic nerve and orbital
diseases. ,
A mydriatic eye must, of course, be shielded against light, because
it is temporarily unable to protect itself. In addition, it should be
remembered that the mydriatics temporarily destroy the mechanism
of accommodation, because they paralyze the ciliary muscle which is
similarly innervated. Near vision, therefore, is practically impossible
at this time. The miotics, on the other hand, also stimulate the ciliary
muscle and kedp the eye in a condition of forced accommodation. In
the latter case, therefore, far vision is practically impossible.
The Innervation of the Iris. — The circular and radial fibers of the
iris receive their nerve supply from the autonomic system, the relay
stations nearest them being the ciliary ganglion and the superior cervi-
cal ganglion. Preganglionically, however, these fibers find their origin
in the cerebrospinal system. As far as the sphincter iridis is con-
cerned, it may be shown that its nerve fibers arise in the midbrain in
the anterior part of the nucleus of the third cranial nerve. They make
use of the third nerve as a highway to reach the ciliary ganglion, whence
Ihey continue onward postganglionically in the short ciliary nerves.
The nerve fibers innervating the dilator mechanism of the iris, sup-
posedly the radial muscle fibers, also arise in the midbrain, but their
place of origin is not definitely known. From here they descend in
the spinal cord, but leave this structure in the eighth cervical and the
first and second thoracic spinal nerves to enter the sympathetic system
by way of the rami albi communicantes. They then ascend to the
superior cervical ganglion by way of the cervical sympathetic nerve
and finally reach the Gasserian ganglion. Distally to this point they
invade the ophthalmic branch of the fifth cranial nerve and its long
c-iliary branch. y
1 Langley, Jour, of Physiol., xxxix, 1909, 235.
52
818
THE SENSE OF SIGHT
On excitation of the trunk of the third nerve, we obtain.a constric-
tion of the pupil, while the stimulation of the sympathetic nerve in
its cervical portion, gives rise to pupillar dilatation. Obviously, there-
fore, the division of the former miist evoke a dilatation of the pupil,
and that of the latter, pupillar constriction. Under normal conditions,
these two mechanisms are tonically set and oppose one another. Con-
sequently, the removal of the constrictor impulses must allow the
dilator impulses to gain the upper hand, while the division of the sym-
pathetic nerve must permit the constrictor influences to exert their fuU-
FiG. 425. — Diagrammatic Representation of the Nerves Governing the PupiLr
(^ After Foster.)
3rve; eg, ciliary ganglion; rh, its short root from ///, motor oculi nerve;
athetic root; rl, its long root from F, ophthalmonasal branch of oph-
1 of fifth nerve ; sc, short ciliary nerves ; Ic, long ciliary nerves.
est power. It appears, therefore, that the constrictor and dilator
muscles of the iris are arranged antagonistically to one another, in
a manner similar to that of the flexor and extensor muscles of the ex-
tremities (Sherrington). Thus, inasmuch as it has been shown that
the contraction of one set of skeletal muscles is usually facilitated by
the inhibition of the other set, it may be assumed that a similar recipro-
cal relationship exists between the muscle fibers of the iris. Certain
\
THE CILIARY BODY AND LENS
819
evidence in support of this reciprocal action has been furnished by-
Anderson. ^ '
In this connection, it should also be mentioned that the oculomotor
and short ciliary nerves innervate the ciliary muscle which is used in
accommodation. For this reason, the excitation of this nerve really
produces a double effect, i.e,, it constricts the pupil and also renders
the lens more convex. Concurrently, its division must be followed not
Gasseriafi ,
Gan^liotu.
OjbhtAaL
Zona ciltaru nerues.
^-. I ^Dilator
Ciliary (^ancUofu Art Ciliary Tierves
Fig. 426. — Schema Showing the Path of the Preganglionic and Postganglionic
Fibers to the Ciliary Muscle and to the Sphincter and Dilator Muscles of the
Iris. {Modified from Schultz.)
only by pupillar dilatation but also by a flattening of the lens, which
change renders it adapted for far vision.
CHAPTER LXX
THE CILIARY BODY AND LENS
The Ciliary Body. — The space beween the ora serrata of the
retina and the base of the iris is occupied by the ciliary processes of
;the choroid, its muscles, ligaments and glands. In this region, the
choroid is considerably thickened, measuring 6 to 7 mm. across. In
cross-section it displays a triangular outline, which is largely taken up
by strands of plain muscle tissue, forming the ciliary muscle. These
fibers are arranged in two ways, namely, longitudinally and transversely
to the long axis of the eyeball. The former arise from the fore-part
of the sclerotic coat close to the cornea, where they are attached to
the ligamentum pectinatum. They pursue a course almost directly
^ Jour, of Physiology, xxx, 1903, 15.
820 THE SENSE OF SIGHT
backward to be inserted in the choroid at and behind the ciliary
process. The circular fibers are most numerous in the base of the
ciliary body, and pursue a course circularly around the aperture in
which the lens is suspended. They are most clearly in evidence in
hypermetropic persons.^
The aperture between the margins of the ciliary body is occupied
by the lens. The latter is invested by a transparent and elastic
capsule, measuring in front 6.5 to 25 /x in thickness. Its substance
is composed of a firm central and softer cortical portion, both of which
appear as hexagonal, prismatic lamellae of homogeneous elastic tissue.
A single layer of cuboidal cells, 2.5 to 10/x in height, forms their outer
investment. It is to be noted especially that the edge of the lens is
not in absolute contact with the margin of the ciliary body, but re-
mains at some distance from it, the intervening space being occupied
by ligamentous bands which extend straight across from its capsule to
the surface of the ciliary body. Furthermore, these ' ligamentous
fibers pursue a peculiar diagonal course, some of them arising upon
the posterior aspect of the ciliary body and terminating upon the
anterior surface of the lens, while others arise upon the anterior surface
of the ciliary body and end upon the posterior surface of the lens. We
shall have occasion to refer to these data again later on, while dis-
cussing the accommodation of the eye for near objects.
The Process of Accommodation in Different Animals. — The pur-
pose of the lens is to bring rays of light to a precise focus upon the
retina. In this function it is aided in a slight measure by the other
refractive media of the eye. But, since objects are situated at different
distances from the eye, some means must be provided by which their
images may be retained upon the retina ; in other words, the eye must
be able to accommodate itself to these varying distances. To ap-
proach this subject in the most logical way, inquiry should first be
made regarding the manner in which the ordinarj^ photographic camera
may be adjusted for far and near objects. Two ways are open to us,
namely, to move the sensitive plate either nearer to or farther away
from the lens, or to move the latter either nearer to or farther away
from the plate. A third method would be to permit the screen as well
as the lens to remain stationary and to adjust the focal distance of
the camera by interposing other lenses of different refractive power.
This procedure, however, is not in common use, because it is less
convenient than the other two.
In the animal kingdom, however, the third method is imitated by
varying the convexity of the lens, while its position, as well as that of
the retina, remains unchanged.
Indeed, the mechanism of accommodation is so diversified among the different
animals that really all of the physical means just enumerated find their prac-
tical application. 2 To begin with, it should be noted that certain species lack
1 Iwanoff, Archiv fur Ophthalmol., xv, 1869, 1.
2 Beer, Wiener klin. Wochenschr., 1898, No. 12.
THE CILIARY BODY AND LENS
821
this power altogether, while others possess it in only a very rudimentary degree.
This is true of the frog, alligator, vipers and certain rodents. Inasmuch as these
animals are chiefly dependent upon near vision and are nocturnal in their habits,
their accommodation is never subjected to wide variations. Furthermore, their
associations are so poorly developed that there is really no necessity for their being
able to discern the exact details of an object, as long as they can' perceive its
simplest movements. They are essentially shadow-animals.
In the cephalopod molluscs, such as sepia, we observe that the thin globe ©f
the eye is strengthened by a transverse ring of cartilage, immediately adjoining an
exceptionally delicate ring of tissue (Fig. 427). The anterior wall to this eye con-
tains bands of meridional muscle fibers which are attached to the cartilaginous ring
(C) and are inserted in the ciliary body. On contraction this muscle pulls the entire
anterior half of the eye backward, in this way bringing the lens nearer the retina.
This movement necessitates, of course, a redistribution of the intraocular pressure
which is made possible by a bulging of the thinned wall of the eyeball directly
behind the cartilaginous ring. It need scarcely be mentioned that this approxi-
mation of the lens to the retina enables this animal to accommodate for far objects.
Fig. 427. — Diagram Il-
lustrating THE Process of
Accommodation in the Eye
OF Sepia.
The anterior half of the
eyeball is drawn toward the
cartilaginous ring C on far
vision.
Fig. 428. — Diagram Illustrating
Process of Accommodation in the
Eye of the Fish.
C, cornea; L, the lens is pulled
toward the retina on far vision by
R, the muse, retractor lentis.
The eyes of the amphibians and many reptiles, such as the snakes, are normally
adjusted for far vision. In these animals accommodation is effected by increasing
the distance between the lens and the retina. This change is accomplished in this
way: As the ciliary muscle contracts, it pulls the sclerotic-corneal junction back-
ward, thereby increasing the pressure in the vitreous cavity. In consequence of
this increase in pressure, the lens is pushed forward into the aqueous cavity and
approaches the cornea. An equalization of the pressure in this chamber is made
possible by a displacement of the aqueous humor into its lateral angle which has
just been enlarged by the retraction of the ciliary body. It is evident that this
removal of the lens from the retina must increase the posterior focal distance
and must accommodate the eye for near objects.
The eyes of the fishes are normally set for near objects (Fig. 428). They are
not in possession of ciliary processes nor of ciliary muscles, and their almost spher-
ical lens is suspended in the visual axis by means of flat bands of connective tissue,
forming the so-called suspensory ligament. The lower and inner pole of the lens
gives attachment to a number of horizontal strands of muscle fibers which on
contraction pull the lens backward, thereby diminishing the distance between it
and the retina. This muscle, known as the retractor lentis, lessens the posterior
focal distance of these eyes and accommodates them for far objects. Consequently,
822 THE SENSE OF SIGHT
the fish's eye may be made extremely myopic by surrounding it with air, while
that of a terrestrial animal may be rendfered hypermetropic by placing it in
water.
The birds are noted for their exceptionally accurate and rapid accommodation.
Their eyes are normally set for distant objects, and their accommodation for near
objects is made possible not by changing the position of the lens, but by increasing
its convexity and hence, its refractive power. The lens is enabled to change
its shape by lessening the tension under which it is ordinarily held. This relaxation
is effected by pulling the sclerotic-corneal junction backward. Inasmuch as the
suspensory ligament of the lens is attached to this area of the eyeball, this retrac-
tion must relax it, thereby permitting the lens to become more convex on account
of its inherent elastic power. A special muscle, known as Crampton's muscle,
controls this retraction. It is also of interest to note that the fibers composing it,
are of the striated variety and are, therefore, under a more direct and exact control
of the higher centers than the ciliary muscle of the mammals. This structural
peculiarity accounts for the rapidity of the accommodation in birds which enables
them to swoop down from great heights to catch their prey. In addition, the birds
of prey possess the power of increasing the convexity of their cornea. A special
muscle is provided for this purpose.
The Accommodation of the Human Eye. — It has been shown by
Helmholtz that the accommodation of the mammaHan eye is effected
by an alteration in the convexity of the lens, chiefly of its anterior
part. Naturally, an increase in its convexity gives rise to an increase
in its refractive power and hence, to an accommodation for near ob-
jects. Two theories have been formed in explanation of this phe-
nomenon, namely:
(a) The greater curvature of the lens on near vision is due to the fact that it is
subjected to a greater tension by the components of the zonula Zinnii.^
(6) The greater convexity of the lens on near vision is caused by the fact that
the tension under which it is ordinarily held is diminished at this time.
The second view is the one commonly accepted to-day. It is
usually designated as the detention theory of Helmholtz. ^ It is
believed that the contraction of the ciliary muscles causes the ciliary
body and adjoining choroid to be pulled forward. In consequence
of this displacement, the ciliary ligaments are loosened, permitting
the lens to bulge forward. Besides, it must be evident from figure
429 that this forward movement of B must give rise to a relaxation es-
pecially of those ligamentous bands which extend between the posterior
surface of the ciliary body {CB) and the anterior marginal zone of the
capsule of the lens (L). As a result of this detention of its peripheral
area, the mass of the entire lens adjusts itself and assumes a more spher-
ical shape. Its anteroposterior diameter is increased thereby.
While it is a matter of common observation that even lenses with
fluid contents tend to assume a spherical outhne,^ it is to be noted that
the lens of the mammalian eye is invested by an elastic capsule.
It is this investment which is chiefly responsible for the aforesaid
^ Schon, Pfliiger's Archiv, lix, 1895, 427; also: Tscherning, Optique physiol-
ogique, Paris, 1897.
2 Physiol. Optik, ii, 136.
3 Schweigger, Archiv fur Augenheilkunde, xxx, 1895, 276.
THE CILIARY BODY AND LENS
823
changes in the lens. We have seen that the ciUary muscle is made up
of meridional and circular fibers. Even a casuaL study of their course
must show that the former are the principal factors concerned in this
detention, but it cannot be denied that the circular fibers are a most
important adjunct, because they fix the base of the ciliary body so
that the longitudinal fibers^ can gain a firmer hold upon this structure
and pull it forward. That a movement of this kind actually takes place
has been proved by Henson and Volker.^ Fine needles were inserted
through different segments of the equatorial region of the eyeball
which, on stimulation of the ciliary body, showed movements indica-
tive of a forward displacement of the choroidea.
Fig. 429. — Diagram Illustrating the Process of Accommodation in the Human Eye.
C, cornea; L, lens; J, iris; CL, ciliary ligament; CB, ciliary body; Ch, choroid; R,
retina; *S, sclera. On near vision the ciliary muscle contracts, drawing the region B
nearer to region A. The tension upon the ciliary ligament being diminished thereby,
the lens assumes a more spherical shape, chiefly in the direction of the cornea. This
change is indicated in red.
Proofs of Accommodation. — When the eye is at rest, it is accom-
modated for far objects. We may convince ourselves of this fact by
suddenly opening the eyelids after they have been held shut for a short
time. We then become conscious of a relaxed vision, i.e., of an accom-
modation for far objects, and also of a distinct effort to direct the eyes
to a near object. During relaxed vision, the suspensory ligaments
are placed under a certain tension, thereby retaining the lens in a
somewhat flattened condition. This may be proved by measuring
the anterior curvature of the lens before and after the excision of the
eye. It is very obvious that a lens freed from its attachments, pos-
sesses a more spherical outline than one still in its normal position.
The increased curvature of the lens, and especially that of its an-
1 Archiv fur Ophthalm., xix, 1873, 156.
824 THE SENSE OF SIGHT
terior portion, leads to a movement of this surface toward the cornea.
This change may be studied in any human eye, if the person under
observation changes his accommodation repeatedly from far to near
objects. The most obvious alteration consists in a forward displace-
ment of the margin of the iris, caused by the forward bulging of the
anterior surface of the lens. The cornea, on the other hand, undergoes
no change whatever. These observations may then be repeated by
actually measuring the curvature of these refracting surfaces on far
and near vision.
Changes in accommodation may also be effected by stimulating the
excised eye electrically. Most commonly we employ for this purpose
the eye of a terrapin, which is adjusted under a
magnifying glass by means of two fine needles in-
serted vertically through its corneal sclerotic junc-
tion. These needles are connected with the
secondary coil of an inductorium (Fig. 430). On
stimulation with single induction shocks, it will
be seen that the iris is pushed far forward into the
aqueous humor, while the anterior portion of the
lens bulges prominently through the pupillar
orifice.
One of the most interesting proofs of accom-
modation has been furnished by Langenbeck.^
It consists in determining the form, size and posi-
tion of the images of a brilliant object reflected
Fig. 430.— Diagram from the different refracting surfaces of the eye.
Illustrating the Th^g jf ^ candle is held at a distance of about 50
Changes in the Lens , , n • r j. r xi. r xi. u j
ON Stimulation of the cm. laterally m front of the eye of the observed
Ciliary Body. person, while the observer places himself at an
A, the eye at rest; angle of 15° to 20° to the visual axis opposite
It^nff^orceiTs'^ct- the candle, three images of this object will be ol>
vexity through the tained, namely,
pupillar orifice, pushing
the iris forward. (a) A bright upright image from the surface of the
cornea,
(6) a large upright but faint image from the anterior surface of the lens, and
(c) a small inverted and faint image from the posterior surface of the lens.
The first is very prominent, while the other two are less distinct, but
can usually be seen without much trouble by properly adjusting the
position of the candle. With this arrangement, the large, faint up-
right image from the anterior surface of the lens, occupies the center
of the pupil, while the faint inverted image from the posterior sur-
face of the lens lies very close to the margin of the pupil opposite the
observer. The relative size and position of these images having been
clearly ascertained, the observed person is asked to accommodate
alternately for near and far objects (Fig. 431). When this is done, it
iRlin. Beitrage zur Chir. und Ophthalm., Gottingen, 1849; also see: Helm-
holtz, Monatsber., Berliner Akad., 1853.
THE CILIARY BODY AND LENS
825
will be found that on near vision the corneal image (a) retains its po-
sition, size and form, while the one reflected from the anterior surface
of the lens (h), becomes smaller in size and more rounded, and moves
toward the corneal image. A very slight diminution in size is also
displayed by the image reflected from the posterior surface- of the lens
Fig. 431. — Reflected Images of a Candle Flame as Seen in the Pupil of an Eye at
Rest and Accommodated for Near Objects. (Williams.)
(c). It need scarcely be mentioned that these changes are associated
with a constriction of the pupil (Descartes, 1637), and that all the
aforesaid alterations are reversed on far vision. Since near vision is
an active muscular process, it is accomplished less speedily than the
accommodation for far objects.
Fig. 432, — Diagram Explaining the Change in the Position of the Image Reflected
FROM THE Anterior Surface of the Crystalline Lens. (Williams, after Bonders.)
The lesson to be derived from this experiment is that the curvature
of the cornea remains absolutely the same, while that of the posterior
surface of the lens suffers only the sUghtest possible alteration. By
far the greatest change takes place at the anterior surface of the lens,
which, on near vision, becomes more convex and therefore forces the
826
THE SENSE OF SIGHT
image closer to the cornea, rendering it at the same time more globular.
These observations may be repeated under more favorable conditions
by making use of a darkened triangular box, known as the phacoscope
(Helmholtz). The eye to be observed is placed in the orifice at A
(Fig. 433) and is directed alternately to a needle situated in orifice B
and to a distant object placed in the prolongation of this visual line.
Orifice C is beset with two prisms which throw a beam of fight into
the observed eye. The observer's eye studies these images through
orifice D. They appear as indicated in Fig. 434.
Another most instructive phenomenon is the so-called wabbling
of the lens,^ which consists in a declination of the lens oii forced near
vision of from 0.28 to 0.3 mm. This
phenomenon clearly proves that ac-
commodation diminishes the tension
under which the lens is held, allow-
ing its weight to force it out of the
central axis of the eyeball. The
direction of this declination depends
3
i
Fig. 433. Fig. 434.
Fig. 433. — Diagram Illustrating Course of the Rays Through the Phacoscope.
A, observed eye; B, opening allowing accommodation for near and far objects;
C, source of light; D, observer's eye. 1, images from cornea; 2, anterior surface of lens;
3, posterior surface of lens.
Fig. 434. — Diagram of Reflected Images as Seen in Phacoscope.
A, during far vision; B, on near vision; 1, image from cornea; 2, image from anterior
surface of the lens; 3, image from posterior surface of the lens.
of course upon the position of the head. Thus, when in the erect
position, near vision would allow the lens to drop downward com-
mensurate with the degree of accommodation. Subjectively we ob-
serve this phenomenon only under unusual conditions, for example,
when endeavoring to form a focus of those shadows which are ordi-
narily produced by opaque bodies floating through the aqueous or
vitreous humor. These particles then appear to execute jerky motions
in space.
In addition, it might be mentioned that the mechanism of accom-
modation may be altered by drugs. The mydriatics atropin, homa-
tropin and cocain paralyze the cihary muscle simultaneously with the
1 Hess, Archiv fur Ophthalm., xliii, 1897, 477.
THE CILIARY BODY AND LENS
827
constrictors of the pupil and retain the eye in a condition adapted for
far vision. Physostigmin, on the other hand, stimulates this muscle
and renders the eye near-sighted. V
Scheiner's Experiment.— An experiment which illustrates the
process of accommodation, as well as the projection of visual impres-
sions, is the one described by Pater Scheiner. Two small holes are
made in a cardboard, the distance between them being less than the
diameter of the pupil. The eye then looks at two pins placed one
behind the other, at a distance of 18 cm. and 60 cm. respectively.
Fig. 435. — Diagram to Illustrate Schehster's Experiment.
The continuous lines indicate the course of the rays from the object for which the
eye is accommodated.
If one pin is focalized sharply, the other appears double. A glance
at Fig. 435 will show why this must be so. Thus if the eye is directed
upon the near pin A , the far pin B is brought to a focus in the vitreous
humor after which the rays again diverge and strike the retina in two
places, C and D. If opening 1 is now blocked, the lower retinal image D
disappears and hence, also the image projected into space on the side
of the block. If the eye is now accommodated for the far pin B, the
near pin A is focalized behind the retina, the still divergent rays
striking the retina in points E and F. It will be seen that blocking
opening 1 will now cut out the upper retinal image E, and hence, the
image projected into the visual field opposite to the block.
The Changes in the Shape and Refractive Power of the Lens. —
The changes in the shape of the lens may be deduced from the following
^ One of the earliest theories pertaining to accommodation proposes that this
process necessitates a lengthening and shortening of the entire eyeball, brought
about- by the pressure of the contracting extrinsic muscles of the eye. By a
process of exclusion, we have shown above that the lens is the essential factor
concerned in accommodation. It would be difficult to disprove the facts brought
forth in support of this view ; moreover, since an accommodation for an object held
at a distance of 15 m., would entail a lengthening of the eyeball of not less than 2
mm., it seems hardly possible that such a change could be brought about by means
of the normally contracting muscles of the eyeball. Electrical stimulation, per-
formed under experimental conditions, might, however, accomplish this end.
This view has recently been resurrected by Bates (New York Med. Jour., ci, 1915).
828 THE SENSE OF SIGHT
ophthalmometric measurements, giving the radius of curvature of the
chief refracting media:
Near vision Far vision
Radius of curv. of cornea 8 mm. 8 mm.
Radius of curv. of ant. surface of lens 10 mm. 6 mm.
Radius of curv. of post, surface of lens 6 mm. 5.5 mm.
The lens of a relaxed eye measures 3.025 to 4.43 mm. in thickness,
average 3.6 mm. On near vision, its anterior surface is carried for-
ward through a distance of 0.36 to 0.44 mm.; hence, it will be seen
that the thickness of the lens, when accommodated for near objects, is
increased by about 0.4 mm., i.e., on the average from 3.6 mm. to 4.0
mm. This implies that its anterior surface is then situated at a dis-
tance of only 3.2 mm. behind the cornea, while this same distance in
the eye at rest measures 3.6 mm. Its posterior surface lies 7.2 mm.
behind the cornea during far vision and retains this position, at least
practically so, during near vision.
This change in the shape of the lens is dependent upon its inherent
elasticity, and especially upon that of its capsular investment. This
property it is permitted to bring into play as soon as the tension under
which it is ordinarily held by the structures of the zonula Zinnii, is
diminished. Since its refractive power is increased thereby, the enter-
ing rays of light must be rendered more convergent. Under ordinary
conditions we express the refractive power of a lens in terms of its
principal focal distance. A lens possessing a focal distance of one
meter, is said to have a refractive power of one diopter (D.). Taking
this value as a unit, a lens with a focal distance of 50 cm. possesses
a refractive power of 2D., one with a focal distance of 10 cm., a re-
fractive power of lOD., and conversely, one with a focal distance of
10 m., a refractive power of O.lD. {]^qD.).
Range of Accommodation. — The ciliary mechanism fulfills the
purpose of bringing any object in space to a precise focus upon the
retina, but, naturally, it cannot simultaneously produce a sharp image
of two objects which are situated at different distances from it. We
can readily convince ourselves of this fact by looking at a distant
object through a network of fine wire held near our eyes. If we
glance at the distant object, the wire network loses its clear contours.
Contrariwise, if we look at the network, the object becomes blurred.
The distant point in space at which an object is still clearly dis-
cernible, is called the far-point or punctum remotum. Quite similarly,
the point nearest the eye at which an object still produces a perfectly
clear impression, is known as the near-point or punctum proximum.
In between these two extremes lies the range of distinct vision, or
range of accommodation. Any object situated beyond the far point
or inside the near point, cannot be brought to a precise focal point
upon the retina and must, therefore, appear blurred.
The Limit of Accommodation of the Normal Eye. — Inasmuch as
the normal or emmetropic eye, when at rest, is adjusted so as to focus
THE CILIARY BODY AND LENS 829
parallel rays coming from the distance, its far point must lie at the
horizon. Consequently, its location must vary with those outside
factors upon which the visibility of objects ordinarily depends. Practi-
cally, however, it has been found that an eye can also perceive objects
without accommodation which are situated at a distance 'of only 6
to 10 m. from it. The deduction to be drawn from this fact is that
even objects situated at this short distance, emit a large number of
parallel rays which the eye is able to intersect upon the retina without
actually increasing its refractive power. In this action, however,
the different refractive media are aided by the material depth of the
receptor. In other words, the rods and cones of the retina upon
which the light impinges, do not form a true plane but possess a certain
depth, allowing us to vary the anterior focal distance in a shght
measure without actually causing the posterior focal point to fall
entirely outside this layer.
If the object is now moved nearer to the eye than the aforesaid
distance, the mechanism of accommodation is immediately brought
into play with the result that the now divergent rays are still brought
to a focus upon the retina.^ The closer the object is made to
approach the cornea, the greater will be this effort at accommodation
until its physiological limit has been reached. As has just been stated,
the nearest point at which the eye is still capable of forming a distinct
image, is called the near point. Beyond this inner limit the rays of
light emitted by an object, are so divergent that they can no longer
be brought to a sharp intersecting point upon the retina. The image
then appears merely as a diffused area of light which fails to give
a proper visual impression.
The determinations of the near-point by means of the ophthal-
mometer have shown that it does not retain a constant position, but
varies not only with age, but also with the general condition of the
body and local defects in refraction. At birth, the lens is rather
spherical in shape; hence, the infant's eye should really be adjusted
for near objects, were it not for the fact that the eyeball is at this time
still too small. In reality, these two factprs are adjusted in such a
way that this eye is somewhat far visioned. Beginning at about the
age of 10 years, the near point recedes gradually with advancing years
^nd more markedly between the fortieth and fiftieth year. This
observation is more fully illustrated by the following figures:
Age
10 years — 7 cm. in front of cornea, equalling 14 D. refr. power
20 years — 10 cm. in front of cofnea, equalling 10 D. refr. power
30 years — 14 cm. in front of cornea, equalling 7 D. refr. power
40 years — 22 cm. in front of cornea, equalling 4.5 D. refr. power
50 years — 40 cm. in front, of cornea, equalling 2.5 D. refr. power
60 years — 100 cm. in front of cornea, equalling 1.0 D. refr. power
^ The term retina is employed here as well as elsewhere, although it is to be
clearly understood that we are actually referring to the sensitive inner layer of the
retina, namely to the rods and cones.
830 THE SENSE OF SIGHT
This gradual restriction of the range of accommodation is generally
explained by saying that the lens loses its elasticity with advancing
years. While this is true, the same may be said regarding the struc-
tures of the zonula Zinnii and the constituents of the ciliary body.
Senescence is a common phenomenon in nature and begins with
infancy, although dimmed at this time by the phenomenon of growth.
Actual disturbances in vision, however, do not arise until the near
point has receded beyond 25 to 30 cm., i.e., until about the forty-fifth
year. At this time, most persons experience certain difficulties
in accurately focusing small print. This condition is designated as
old-sightedness or presbyopia. It indicates that our ciliary mechanism
is no longer capable of rendering the lens sufficiently convex to permit
us to bring near objects to a precise focus upon the retina. Our ac-
commodation for far objects remains of course unimpaired. This
difficulty in refraction may be remedied by the employment of a
biconvex lens of a strength just sufficient to overcome the senile
flatness of the lens.
Late in life the lens frequently undergoes certain retrogressive
changes which lead to an opacity of its substance. When fully
developed, this condition, known as cataract, destroys the vision com-
pletely, because it prevents the rays of fight from entering the fundus
of the eye. The removal of this now useless lens, immediately adjusts
the eye for far vision, because it is then wholly dependent for its re-
fraction upon the cornea and the aqueous and vitreous humors. All
three media together, however, do not equal the refractive power of a
normal lens. An eye of this kind may again be converted into a more
useful organ by placing a biconvex lens of 10 or 11 diopters in front of
it. The same correction must be made for an eye, which has never
been in possession of a lens. This inherited condition is known as
aphakia.
This discussion introduces the question of whether the near point
or far point, as determined for uniocular vision, remains the same
when both eyes are used, as in normal binocular vision. Hess has
proved this to be the case whenever the two visual axes are converged
in a symmetrical manner, but not when we look laterally outward.
The near point of binocular vision is then situated at a somewhat
greater distance from the eyes.
The Innervation of the Ciliary Muscle. — ^Like the sphincter pupillae,
the ciliary muscle derives its motor impulses from the anterior part of
the nucleus of the oculomotor nerve in the midbrain. These pregan-
gfionic fibers are relegated to the cifiary gangfion, where they end in
arborizations around other ceHs. Postgangfionically, these fibers are
continued as elements of the autonomic system and reach their desti-
nation by way of the short, cifiary nerves. This distribution accounts
for the close interaction between the cifiary muscle and the constrictor
of the pupil; near vision, as has been shown above, being associated
with a constriction of the pupil. It also explains the simultaneous con-
THE RETINA 831
vergence of the visual axes of the two eyes on near vision by the recti
interni muscles. All these actions are controlled by a common co-
ordinating center.
It is also of interest to note that the activity of this center is under
the guidance of the will and is, therefore, controlled by the cerebrum.
This must seem peculiar, because the effector, the ciliary muscle, is
composed of smooth muscle tissue. It must be admitted, however,
that these reactions are usually preceded by visual sensations. In
other words, most persons cannot effect these changes in the eyes
unless guided by objects in space. This observation might lead us to
suppose that the act of accommodation is a simple reflex, just because
the motor actions upon which it is based, seem to necessitate certain
sensory impressions. In reality this is not true, because we can easily
learn to accommodate without first directing our eyes to near and far
objects by simply making voHtional efforts in a dark room, or after
our eyes have been shaded. Under ordinary conditions, therefore, the
process of accommodation belongs to the group of the psychical reflexes
or association reflexes. As such, it occupies a position intermediate
between the voluntary responses effected by means of striated muscle,
and the perfectly involuntary reactions accomplished with the help
of smooth muscle.
CHAPTER LXXI
THE RETINA
The General Structure of the Retina. — The retina is a delicate
membrane containing those elements which are absolutely essential
for the reception of the rays of light and for the transfer of the impres-
sions evoked by them to the center of sight in the occipital cortex of
the cerebrum. It occupies the space between the choroid coat and
the hyaloid membrane of the vitreous humor, and extends forward to
near the posterior margin of the ciliary body. It terminates here in
the so-called ora serrata. Its thickness increases gradually from
before backward, namely from 0.1 mm. near the ciliary body to 0.4
mm. upon the posterior expanse of the eyeball.
In cross-section it presents eight distinct layers, namely :
(a) The fiber layer, composed of nerve fibers striving toward their common
point of exit, the porus opticus.
(6) The layer of nerve cells, forming the ganglion nervi optici.
(c) The inner molecular layer (stratum reticulare int.).
(d) The inner nuclear layer, formed by bipolar cells (stratum granularum int.).
(e) The outer molecular layer (stratum reticulare ext.).
(/) The outer nuclear layer (stratum granularum ext.).
(g) The layer of rods and cones.
(A) The layer of hexagonal pigment-cells (stratum nigrum).
832
THE SENSE OF SIGHT
The nerve fibers derived from the different regions of the hemispherically
expanded retina, leave at the optic pore where they pierce the other two coats of the
eyeball and are continued onward as the optic nerve. Inside this point they are
not in possession of a medullary sheath nor of a neurolemma. Most of these fibers
are formed by the axis cylinder processes of the cells of the second layer, but some
also originate in the inner molecular and inner granular layers. The ganglion cells
of the second layer differ greatly in their size and shape, their single unbranched
axones entering the fiber layer. They are especially numerousin the vicinity of the
yellow spot, where they are arranged in three consecutive rows. The inner
molecular layer is granular in its appearance and is made up of the arborescent
(Juter or choroidal surface.
m.Le
. m.L%
Inner or vitreotis surface.
Fig. 436. — Diagrammatic Section of the Human Retina. (Schultze.)
terminations of the processes of the cells constituting the two neighboring layers.
The inner nuclear contains two types of closely packed cells of which the bipolar
type is the most conspicuous. Their inner processes usually extend to the internal
molecular layer within which they terminate in the vicinity of its ganglion cells.
Their outer processes are usually thicker and pursue a more direct course to the
outer molecular layer, where they arborize together with the horizontal cells of the
inner nuclear layer. The outer molecular presents an appearance similar to that
of the inner molecular, but is not quite so thick. The outer nuclear layer consists
of nuclear corpuscles having an oval or elliptical shape. They are known respec-
tively as the rod-granules and cone-granules. The former are the more numerous
and appear as swellings upon the delicate fiber emitted by the rods of the outermost
THE RETINA
833
layer of the retina. The cone-granules are more pyriform in shape, non-striated
and lie in close opposition to the external limiting membrane and the bases of
the cones. Their inner processes are continued into the outer zone of the outer
molecular layer, where they terminate in a prominent varicosity.
The outermost layer of the retina consists of the rods and cones. The former
are elongated cylindrical in shape and measure about 0.06 mm. in length and 0.002
mm. in width. The latter are shorter and thicker and measure 0.035 mm. in
length and 0.006 mm. in breadth. Both present an outer and an inner limb, the
former being imbedded in the neighboring pigment layer. The processes derived
from the inner limbs of the rods, pass into the
nuclei of the outer nuclear layer. A central fiber . i
extends from here into the outer molecular layer, ; ' ■ \
where it ends in a knob-like structure. The pro- ji
cesses from the inner limbs of the cones traverse p
the external nuclear layer and terminate in a broad ** P
expanse in the outer molecular layer. At this point a
connection is made with the bipolar cells of the i\
inner nuclear layer by means of short fibers.^ But, a II
since the retina contains many millions of rods B |' *
and cones, while the optic nerve embraces only ''' ■
about 48,000 nerve fibers, these peripheral axones B ffiK ' ""/
must gradually become confluent. ^ B
The cells of the pigment layer measure 12 to . ^ "^m MMM - k
ISfjL in diameter, but decrease in size near the 8
yellow spot. Their outer surfaces are smooth, m
and while their outer portions are practically free W l^^l-— ?
from pigment, their inner marginal zones are packed ^ " f~
with it and present filamentous prolongations ex- i i«0f j
tending inward along the limbs of the rods and . « i
cones. The former are almost completely sur- \ \| ^
rounded by this pigmentous material. | |j
While we shall have occasion to refer ^ f A f|
to these structural details later on in con- y b
nection with the theories pertaining to 1 %
vision, attention is called to the fact that )
the retina is something more than a simple /
sense organ; in fact, its complex structure «• *
would lead us to believe that it is as truly -^^A^
a subdivision of the brain as is the cerebral
hemisphere itself. For the same reason, it
may be concluded that the optic nerve is ^i^- 437.— I, A Rod; ii, A
not a simple nerve but a true tract of the h^'^'e^tL^aTumi^^^m^m:
cerebrum. In this system the rods and brane. (G. Greeff.)
cones form the receptors, and hence, con-
stitute its neurones of the first order, while the cells composing the
internal granular layer, are its neurones of the second order and those
of the zone of ganglion cell, its neurones of the third order. The latter
convey the impulses to the ventral aspect of the brain by way of the
optic nerve, whence they are relayed to: {a) the cortical center for
vision through the thalamic radiation, (6) the roof of the colliculus
^Ladd and Woodworth., Elements of physiol. Psychology, New York, 1911.
2 Salzer, Sitzangsber., Wiener Akad., Ixxxi, 1880, 3.
53
k
834
THE SENSE OF SIGHT
of the midbrain for purposes of reflex action, and (c) the pulvinar and
lateral geniculate bodies of the region of the thalamus. These connec-
tions convert the optic nerve into a correlation path which is
comparable to the lemniscus system.
The Blind Spot.^ — The retina derives its nerve supply from the
optic nerve which pierces the eyeball in the optic disc or porus opticus.
Beginning at this point, its fibers spread out fan-like across the entire
a V
gcisccnse ^^ n se Jparci^
B
Fig. 438. — Section Through the Place of Entrance of the Optic Nerve (B),
Together with the Ophthalmoscopic View of the Disc (A), to Show the Corre-
sponding Parts of the Two. (Fuchs, after Jaeger.)
cd. Lines of correspondence; 6, depression in center of disc; r, retina; ch, choroid;
si,so, inner and outer parts of the sclerotic coat, s; ct, a ciliary artery cut longitudinally;
a,v, central artery and vein; sd, subdural space; sa, subarachnoid space; du, dural
sheath; ar, arachnoidal sheath of nerve; p, pial sheath; n, nerve-bundles; se, septa
between them.
expanse of this membrane. The circumference of this disc is slightly
elevated, while its center shows a depression from which the blood-
vessels pass radially outward toward the ora serrata. Its diameter
measures about 1.8 mm. When looked at from in front, it appears
as a whitish circle surrounded by a dark ring, the latter indicating the
line where the pigmented choroid begins. Inasmuch as this entire
area is composed solely of nerve fibers, blood-vessels and reticular tissue
1 The blind spot of the eye was discovered by Mariotte in 1668 (M^m., Acad,
de Paris, 1669).
THE RETINA 835
and contains no other retinal element, it is insensitive to light. Nerve
fibers as such cannot be activated by the ethereal impacts of light.
The presence of the blind spot may be demonstrated in several
ways. Bonders, 1 for example, projected the rays of a small flame
alternately upon the entrance of the optic nerve and upon the general
expanse of the retina. The individual received no sensation of light,
when the image was localized upon the former area. Another way
is this: If the left eye is closed, while the right eye gazes steadily at
the crossed lines of Fig. 439, the white circle situated about 8 cm.
to the right of this mark, becomes invisible as soon as the figure is
held at a distance of about 25 cm. from the eye. In other words, the
disappearance of this circle can only take place if the figure is placed
at a distance about 3 times greater than that between the cross and the
circle. If the latter are separated more widely, the figure must be
moved farther away from the eye and vice versa. Furthermore, if the
opposite eye is employed, the figure must be reversed, because the optic
nerve leaves the eyeball on the nasal side of a horizontal line drawn
through the anterior and posterior poles of the eye.
Fig. 439. — Diagram to Demonstrate Presence of Blind Spot in the Visual Field.
Fix the cross with the right eye; bring figure closer to eye until the white dot dis-
appears. (Helmholtz.)
Obviously, therefore, the visual field of each eye must possess an
indifferent area corresponding to the projection of the oj;tic disc into
space. But, this projection does not give rise to a dark patch in space,
nor to a similar impression in consciousness but appears merely as an
area devoid of stimulation, i.e., as a small hole in the visual field with-
out any apparent details. Under ordinary conditions, this defect is
not apparent, because, when gazing at an object, we always deviate
the eye in such a way that the rays of light emitted by it fall upon the
most sensitive part of the retina, which is the yellow spot. Conse-
quently, the blind spot must occupy at this time a place in our indirect
field of vision. In binocular vision, the conditions are even more
favorable, because while an object or part of it, may fall upon the
blind spot of one eye, it cannot also do this in the opposite eye. Hence,
the blank in the field of vision of one eye is always filled in by the
other eye. A similar compensation is effected in the psychic center for
vision.
The size and shape of the blind spot may be mapped out as follows:
Close the left eye and fix the right eye upon a mark upon a sheet of
1 Onderzock., Physiol. Labor., Utrecht, vi, 1852, 134.
836 THE SENSE OF SIGHT
white paper held at a moderate distance vertically in front of it. By
now slowly moving the head of a pin inward along the horizontal
plane of this field, a point will presently be reached when it suddenly
disappears from the view and later On, a second point, when it reappears.
By repeating this procedure along the vertical and oblique planes, the
margins of this indifferent area in space may be mapped out in its
entirety (Fig. 440). By projection it then becomes possible to calcu-
late the position and size of the optic disc. It will be found that ob-
jects of the size of a 5 cent piece may be made to disappear when held
at a distance of about 25 cm., and objects of the size of the head of a
man, when placed at a distance of about 2 m. The shght irregularities
in the contours of this projected figure of the blind spot are due to
the interception of the light rays by the blood-vessels as they cross the
margin of the optic papilla.
Au
Fig. 440. — Form of the Blind Spot. (Helmholtz.)
The Yellow Spot. — About 3.5 mm. or 15 degrees outside the bfind
spot and 1 mm. above the level of a horizontal line drawn through
the posterior pole of the eyeball, lies the most sensitive area of the
retina. It is known as the macula lutea, while its somewhat depressed
center is designated as the fovea centralis. The latter measures about
0.2-0.4 mm. in diameter, and the entire area about 2 mm. Histo-
logically it is noted that the retina of this region is greatly thinned,
retaining in the fovea centralis merely the layer of the rods and cones.
Moreover, it is observed that this particular area is made up exclu-
sively of cones which are much larger than those situated in the out-
lying districts of the retina. They are so closely packed that they give
the appearance of a mosaic of hexagonal prisms (Heine). The fibers
leaving these elements, pursue an oblique course and push the inner
layers of the retina farther toward the circumference of the macula
lutea, so that the cones are more fully exposed to the entering rays
of light. ^ Outside the macula the cones decrease and the rods in-
crease in number. When these histological characteristics are com-
pared with those of the blind spot and those of the outlying districts
of the retina, it must be concluded that the cones are the most im-
portant factor in vision. This inference finds further support in
^ Rochon-Duvigneaud, Archives d'anat. micr,, ix, 1907.
» THE RETINA
837
certain phenomena connected with direct and indirect vision, visual
acuity and the visual sensations produced by shadows.
Direct and Indirect Vision. — Under ordinary conditions, the fixa-
tion of an object is accomphshed by turning our eyes in such a direc-
tion that its central area is brought to a focus upon the fovea centralis
of the yellow spot. The line uniting these two points constitutes the
line of most distinct vision, and is known as the visual axis of the eye.
Thus, in mapping out the details of a certain visual field, we invariably
direct our eyes first to one object or a part thereof, and then to another.
Only that object gives a perfectly clear impression at any one time
which projects its ray of light along the visual line directly into the
vifl.e
m.l.i
Fig. 441. — Diagram of a Section Through the Fovea Centralis. (The outlines of
this figure have been traced from a photograph.) Magnified 350 diameters. (From
a preparation by C. H. Golding-Bird.)
2, Ganglionic layer; 4, inner nuclear; 6, outer nuclear layer, the cone-fibers forming
the so-called external fibrous layer; 7, cones; m.l.e, membrana limitans externa; m.l.i. ^
membrana limitans interna.
fovea. Meanwhile, the other objects of this particular field appear
less distinct, because the rays emitted by them, form too great an
angle with the visual line and fall, therefore, upon the outlying regions
of the retina, where vision is less acute. In reading we invariably
fix one word after another. Quite similarly, it will be noticed that if
we gaze at a single word upon a page, the other words remain indistinct
and the more so, the greater the distance between them and the one
brought to a precise focus upon the fovea. The imaginary lines which
connect the outlying luminous points of an object with the more periph-
eral elements of the retina, constitute secondary visual axes. It will
838 THE SENSE OF SIG^T
be seen, therefore, that the visual appreciation of our external world
is accomplished by direct and indirect vision. The former leads to the
formation of an image in the fovea, and the latter to the formation of
an image upon the more outlying districts of the retina.
This discussion clearly shows that the visual axis and the optical
axis of the eye are two distinct factors. The former is the imaginary
line along which the most distinct vision is obtained, because it con-
nects the object with the most sensitive area of the retina, the fovea
centralis of the yellow spot. The latter is the line of most perfect
refraction, because the different refractive media of the eye are centered
upon it. The most ideal system, of course, is the one in which the
refractive media are adjusted in such a way that their central rays are
brought to a precise focus upon the most sensitive region of the re-
ceptor. This is true of the photographic camera, but not of the
human eye, because the latter frequently shows a divergence of
its visual and optical axes of from 3.5 to 7 degrees.
Visual Acuity. — Another argument in favor of the view that the
cones are the most important element in vision is presented 'by the
close correspondence between the smallest possible image and the
disposition of the cones in the fovea. Salzer^ has shown that 0.01
mm^. of fovea contains 138 cones, and that an illuminated sheet is per-
ceived as such only if each cone is the recipient of at least one ray of
light. This necessitates about 140 rays for each 0.01 mm^. of foveal
surface. In order to obtain a mosaic impression, the different cones
must be invested by a zone of non-stimulated cones. C. DuBois-
Reymond^ has estimated the number of rays then required at 72 per
0.01 mm^. of foveal surface. Thus, a double star is recognized as two
distinct bodies only if the distance between them corresponds to
a visual angle of 60 seconds. Quite similarly, two white lines drawn
across a black surface, are perceived as two lines only if the distance
between them subtends a visual angle of 64 to 73 seconds. At these
angles, the image covers an area of 0.0045 to 0.0055 mm^. of retina and
involves, therefore, two cones of the fovea. These experiments
also show that the visual acuity does not differ greatly within the fovea,
and especially not within the foveola. Outside the fovea, however,
the acuity diminishes very rapidly, and already at a distance of 20
degrees, the Unes of the image must be separated by a distance of
0.035 mm. in order to produce separate impressions.
Guillery has estimated the size of the smallest perceptible image
at 0.0035 mm^., this value being apphcable only to the center of the
fovea, i.e., to the foveola. For this determination he employed a black
dot upon a white background which was gradually moved away from
the eye until it just barely disappeared. When thus just barely
producing a retinal stimulation, the size of the image may be calculated
by correlating its distance from the eyes with its diameter. Inde-
* Dissertation, Berlin, 1881.
2 Zeitschr. fiir Psych, und Physiol, der Sinnesorgane, xii, 1896, 243.
THE RETINA
839
terminations of this kind, it is important to have a uniform and moder-
ate intensity of illumination, because visual discrimination markedly
increases with the light until a certain upper limit has been reached.
Purkinje's Figures. — The fact that the sensory elements of the retina
are deeply seated, is also proved by the phenomenon commonly known
as '^Purkinje's images. "^ It has been pointed out that the blood-
vessels of the retina ramify upon its inner surface, whereas the rods
and cones constitute its outermost layer. Consequently, it might be
supposed that all light entering the eye must cast a shadow of the blood-
vessels upon these sensitive elements. Actually, however, a dis-
turbance of this kind is obviated by the fact that the diameter of even the
largest retinal vessel amounts to only one-sixtK of the thickness of the
retina, while the diameter of the pupil equals
only about one-fifth of the distance between
this orifice and the fundus. Under ordinary
conditions, therefore, the rods and cones are
the recipients of the penumbra of the blood-
vessels, while their umbra falls upon the inner
layers of the retina. Experimentally, how-
ever, we can make use of two or three differ-
ent means to render them visible by throwing
their shadows upon parts of the retina not
ordinarily exposed by them.
If the eye is turned inward and is directed
upon a dull background while the attendant
reflects a beam of light upon the outer sur-
face of the sclera directly behind the cornea,
an arborescent image of the blood-vessels of
the illuminated part of the eyeball will be ob-
tained (Fig. 442). In this case, blood-vessel
B throws a shadow upon the neighboring re-
tina opposite the beam of light AB. If the
latter is then moved one way or another, the image of these vessels is
shifted in the same direction. Naturally, this stimulation at C is
projected into space through the optical axis as apparently having
come from D. This method may also be employed to calculate the
distance between the blood-vessels and the sensory elements of the
retina, the factors necessary for this calculation being the distance of
the background from the eye, the dimensions of the eyeball, the angle
through which the light is moved, and the apparent movement of the
image upon the screen. The values obtained in this way vary be-
tween 0.17 and 0.36 mm. Since it has been determined by histological
measurements that the rods and cones lie at a distance of from 0.2 to
0.3 mm. below the blood-vessels, we have every reason to suppose
that the rays of light are received by these particular constituents of
the retina.
Fig. 442. — Diagram to
Illustrate Purkinje's Fig-
ures.
A, source of light; B,
blood-vessel; C, shadow
thrown by it, which stimu-
lation is projected to D upon
the screen.
1 Beitr. zur Kenntniss des Sehens, Prag, 1819.
840 THE SENSE OF SIGHT
The retinal blood-vessels may also be rendered visible by moving a
candle to and fro in front of the eye while gazing upon a dark back-
ground. In accordance with the foregoing discussion, it will be seen,
however, that the candle must be held well to one side of the visual
line, otherwise the shadows of the vessels cannot be made to fall
upon a lateral zone of the retina which is ordinarily not exposed to
the stimulation by these vessels.
A third method consists in permitting a beam of light to enter
through a pin-hole in a cardboard held directly in front of the cornea.
In this way, sharply defined shadows of the blood-vessels will be thrown
upon the underlying rods and cones, but even now it is necessary to
move the cardboard rapidly to and fro in front of the eye, so that the
shadows are not allowed to rest upon the same area of the retina for
any length of time.
Chemical and Physical Changes in the Retina on Stimulation
by Light. — Having established the fact that the rods and cones are
the elements which are most directly concerned with the transforma-
tion of the light stimulus into a visual impulse, we are now in a posi-
tion to study the manner in which their stimulation is brought about.
The theories pertaining to this subject may be classified as follows:
1. Mechanical imprint theory which holds that the rays of light produce im-
pressions upon the retina, similar to those resulting when the tips of the fingers
are made to impinge upon a layer of gelatin.
2. Thermal theory which proposes that the rays of light traversing the retinal
elements, generate heat.
3. Electrical theory which suggests that the waves of light are transformed into
electrical energy.
4. Chemical imprint theory which holds that the rays of light give rise to chem-
ical reductions, the retina containing the phototropic substances necessary for the
formation of this imprint.
Though in the present state of our knowledge no absolutely con-
vincing proof can be furnished for any one of these conceptions, the
chemical imprint theory is by far the most satisfactory, because we
are in possession of certain evidence tending to support it. In analogy
with the sensitive plate used in photography, it is assumed that the
retina contains a phototropic substance which is dissociated by the
entering rays of light. The question may then be asked, whether such
a substance has actually been isolated. It will be remembered that the
outer poles of the rods and cones are situated upon a layer of pigment
which has its origin in the adjoining hexagonal cells of the choroid-
retinal junction. This pigment possesses a reddish color in amphibia,
and a violet color in fish, owls, sheep, and man.^ For this reason
it is commonly known as visual purple or rhodopsin. In 1876 BolP
made the interesting observation that this formed pigment does not
remain stationary, but moves in and out of the aforesaid cellular
^ H. Miiller, Zeitschr. fiir wissensch. Zoologie, iii, 1851, 234.
2 Sitzungsber,, Akad. der Wissensch., Berlin, 1876.
THE RETINA
841
receptacles along definite channels. It is true, however, that the
latter is chiefly associated with the rods and is absent in the fovea
centraUs which is wholly composed of cones. Since we shall have
occasion to refer to this point again later on, it suffices at this time to
note that a dark adapted eye presents a sharply defined basement
layer of pigment, while a light adapted eye shows a dissemination of
this pigment in between the rods so that their outer poles are thor-
oughly invested by it ^ (Fig. 443). Secondly, it has been observed
by Stort^ that the cones are contractile and move outward under the
influence of light. Thus, the dark adapted eye contains these elements
Fig. 443. — Section of Frog's Retina Showing the Action of Light upon the Pig-
ment-cells, AND upon the Rods and Cones. Highly Magnified, (v. Genderen-Stort.)
A, From a frog which had been kept in the dark for some hours before death, B,
from a frog which had been exposed to light just before being killed. Three pigment-
cells are shown in each section. In A the pigment is collected towards the body of the
cell; in B it extends nearly to the bases of the rods. In A the rods, outer segments,
were colored red (the detached one green) ; in B they had become bleached. In A the
cones, which in the frog are much smaller than the rods, are mostly elongated; in B
they are all contracted.
in a position next to the pigment layer and retracted in between the
neighboring rods, while the light adapted eye shows them in close
relation with the membrana limitans externa.
These changes may be demonstrated very easily in the eyes of
frogs which have been kept for some time in the dark or have been
exposed to strong daylight. After its removal the eye is quickly
bisected equatorially and placed in a fixing solution and subjected to
the ordinary histological processes. In the normal eye, the visual
purple can only be seen in fish, because the layer of the rods and cones
is here situated upon a white tapetum. In man, on the other hand, the
iKiihne, Untersuchungen aus dem physiol. Institut zu Heidelberg, 1878.
2 Onderzoek, Physiol. Labor., Utrecht, ix, 145.
842 THE SENSE OF SIGHT
Ophthalmoscope is of no avail, because the perfectly clear retina
lies here upon the dark background of the choroid. Various other
means, however, are at our disposal to show that this pigment is a
chemical entity serving a particular purpose. Thus, it will be found
that the retina of an eye which has been protected against light for
some time, possesses a purple color, while one which has been exposed
to strong daylight, is entirely colorless. The purple color of the
former soon becomes yellowish and then disappears completely.
This bleaching property of the visual purple enables us to employ the
retina in the manner of a photographic plate, but naturally, the objects
to be taken must show sharp contrasts. Most commonly, we employ
the eye of a rabbit or frog which has been directed for a brief period of
time toward a window, preferably one with many cross-bars. It is
then bisected and immersed in a 4 per cent, solution of alum which
temporarily fixes this inverted image of the window. A retinal
photograph of this kind is known as an optogram (Fig. 444).
1 2
Fig. 444. — Optogram in Eye of Rabbit.
1. The normal appearance of the retina in the rabbit's eye: a, The entrance of the
optic nerve; b, b, a colorless strip of medullated nerve fibers; c, a strip of deeper color
separating the lighter upper from the more heavily pigmented lower portion. 2 shows
the optogram of a window. (Howell.)
It has previously been mentioned that the visual purple is pro-
truded from the pigmental epithelium in the form of delicate processes
which invade the layer of the rods and cones and closely invest the
outer limbs of the former. It cannot surprise us, therefore, to find
that the retina of the light adapted eye is closely adherent to the choroid,
while that of the dark adapted eye may be easily peeled off. Further-
more, a retina which has been bleached, does not regain its original
color unless it is allowed to remain in contact with the pigmented
epithelium. These data clearly prove that the choroidal pigment
serves as the mother-substance of the visual purple, its function
being to supply this sensitive substance to the outer limbs of the rods
as quickly as it is reduced by the light rays.
The visual purple may he extracted from the retina by means of
solutions of bile salts. It will be remembered that the latter possess
the power of quickly abstracting the hemoglobin from the red blood
corpuscles. These actions are very similar, in the present case the
visual pigment being liberated from its combination in the rods. The
THE RETINA 843
solutions thus obtained, contain the visual purple in its original form
and may be bleached by exposing them to light. It does not seem
likely, however, that this reduction gives rise to distinct bodies, such
as have been designated by Kiihne as visual yellow and visual white. ^
A dissolution of this pigment results in alkalies, alcohol, ether, chloro-
form and most acids. It is resistant against ammonia, sodium chlorid,
benzol, fats and oils. Even the different rays of the spectrum affect
it in an unequal measure, red and orange being least destructive
and yellow and green most destructive.
The Function of the Visual Purple. — While it is perfectly obvious
that the visual purple is an unstable pigment which is decomposed by
the ethereal impacts, this fact does not furnish an adequate explana-
tion for the changes resulting in the rods and cones in consequence of
the vibratory energy imparted to them by the ether waves. Neither
is it possible to. recognize in this pigment a substance which is abso-
lutely essential to vision, because it is absent in some animals, such as
the pigeon, hen, certain reptiles, and bats, and remains wholly confined
to the rods. Consequently, since the fovea centralis is composed
exclusively of cones, it is absent from this area which, admittedly,
is the place of most acute vision.
These discrepancies force us to assume that the visual purple
serves merely as a sensitizing substance which is made use of chiefly
in low intensities of light. It is a well-known fact that the sensitiveness
of the fovea decreases in dim light, while that of the peripheral expanse
of the retina increases. In other words, while the cones are employed
in day-vision, the rods are brought into more general use in low inten-
sities of light. In semi-darkness, therefore, we invariably endeavor
to bring the image into the peripheral retinal field by slightly diverging
the eyes, while in daytime we focalize the object direptly upon the
yellow spot. This shows first of all that the cones themselves are
sensitive to light and need no sensitizing substance in ordinary light.
Their acuity, however, decreases steadily with the intensity of the
light, just because they are devoid of this pigment. For this reason,
therefore, the yellow spot becomes practically blind in semi-darkness.
By analogy, it may then be concluded that the greater sensitiveness
of the peripheral zone of the retina in the dark-adapted eye is directly
dependent upon the production of the visual purple and its movement
to the outer segments of the rods. By virtue of this pigment, these
elements are enabled to raise the otherwise inert light rays above the
threshold of stimulation. In this connection, brief reference should
also be made to the view of von Kries,^ according to which the percep-
tion of color is distinctly a function of the cones, while the rods are
regarded merely as playing a- part in the perception of white light of
1 Abellsdorfif and Kottgen, Zeitschr. fiir Psychol, und Physiol, der Sinnesorgane,
xii, 1896.
2 Zeitschr. fiir Phychol. und Physiol, der Sinnesorgane, ix, 1895, 81.
844
THE SENSE OF SIGHT
low intensity. This theory will be more fully discussed later on in
connection with color-vision.
Phosphenes. — It has been emphasized repeatedly that the ade-
quate stimulus for the retina is the light ray, because this receptor
presents the most favorable conditions for the transformation of
this form of energy into nerve impulses.^ In a slight measure,
however, the retina is also accessible to inadequate stimuli in the
form of mechanical and electrical impacts, but the visual impres-
sions then obtained retain the character of very general sensations
of light. These sensations are of course subjective in their quality,
because they are not caused by homologous stimuli of light, but by
stimuli of a heterologous kind. Thus, if the eyelids are closed and
the eyes are turned inward, any pressure
upon the external part of the eyeball, such
as may be exerted with the blunt end of a
pencil, gives rise to luminous sensations,
known as *' phosphenes '^ (Fig. 445). In
this particular case, they appear in the form
of bright yellowish rings, each surrounding
a dark center. It is to be noted especially
that this sensation, although evoked at the
point of pressure, is referred to the opposite
visual field. In other words, any pressure
exerted upon the outer zone of the eyeball
gives rise to a sensation which is projected
into the nasal area of the visual field, be-
cause under ordinary conditions the outer
retina is stimulated by objects situated in
the nasal field. A phosphene of similar
character may be produced by gazing into
a bright light while the eyes are rapidly
Inasmuch as the eyeball is relatively fixed
at the point where the optic nerve leaves it, this abrupt lateral devia-
tion gives rise to a mechanical stimulation of the retinal elements situ-
ated around the edge of the optic disc. In this case, the visual sen-
sation is projected directly outward into the central visual field.
Phosphenes also result in consequence of stagnation at the points of
exit of the vense vorticosae and in consequence of the pulsations of
the retinal arteries. They are most intense in conditions of hyper-
excitability of the general nervous system.
Electrical Variations in the Eye on Vision. — The retina shows a
current of rest or injury as well as a current of action. If an excised eye
is connected with a galvanometer by two non-polarizable electrodes,
one of which is adjusted to the cornea and the other to the end of
the optic nerve, the latter is galvanometrically negative to the former.
1 Klein, Archiv fiir Physiol., 1910, 531. The phenomenon of the phosphenes
has been known since the time of Aristotle.
Fig. 445. — Diagram to Il-
lustrate THE Phenomenon of
Phosphenes.
S, The mechanical stimula-
tion of the coats of the eye ball
at s gives rise to a sensation of
light which is projected to i in
the opposite visual field.
moved from side to side.
THE RETINA 845
This variation is the ordinary current of injury caused by the cutting
of the optic nerve. At this time, however, this nerve is galvanometri-
cally positive to the lateral zones of the fundus of the eyeball.^ Like
all living tissues, the retina also becomes the seat of electrical variations
when stimulated. Thus, the falling of light into a dark-adapted eye
gives rise to an electrical change which may be regarded as analogous
to the current of action of any motor or sensory nerve.^ While the
nature of this response is greatly dependent upon the strength and
duration of the stimulus, and the condition of the eye, it generally
results after a latent period of not more than 0.01 second.^ Its
direction is the same as that of the preexisting current of injury,
provided the electrodes have been applied in the same manner as
before. Consequently, since it passes from the fundus to the cornea
and thus merely intensifies the current of injury, it forms a positive
variation. This is succeeded by a gradual diminution and later on
by a second prolonged increase. Einthoven and Jolly^ who have
analyzed this current with the aid of the string galvanometer,
endeavor to explain its unusual complexity by assuming the occur-
rence in the retina of three distinct processes, called A, B and C.
The first develops more rapidly than the other two and is especially
marked in a light-adapted eye. When this eye is stimulated, it gives
rise to a negative and when darkened, to a positive potential difference.
The second process is less speedily initiated, and leads to a positive
variation on stimulation and a negative difference on darkening.
This process is brought into play with greatest intensity in a dark-
adapted eye, when it is illuminated with a moderate light. The third
process yields the same results as the second, but its speed of develop-
ment is much slower. It is not initiated in a light-adapted eye.
When the non-polarizable electrodes are adjusted to the longitu-
dinal and cut surfaces of the optic nerve itself, a simple negative varia-
tion is obtained, presenting the same characteristics as the ordinary
action current of nerve. Peculiarly enough, however, this variation is
evoked not only when the light is flashed into the eye, but also when
it is withdrawn. Photo-electrical phenomena have also been observed
in plants when alternately darkened and lightened.^
1 Holmgren, Zentralbl. fiir Physiol., xi, 1897.
2 Gotch, Jour, of Physiol., xxxi, 1904, 31.
3 Nagel, Handb. der Physiol., 1905, iii, 103.
4 Quart. Jour, of Exp. Physiol., i, 1908, 373.
^ Waller, Proc. Royal Soc, London, Ixvii, 1900.
846 THE SENSE OF SIGHT
CHAPTER LXXII
THE FORMATION OF THE IMAGE UPON THE RETINA
The Reduced or Schematic Eye. — The eye consists of two parts,
namely, the hemispherically expanded retina with its mosaically ar-
ranged sensory elements and a number of adjuncts which form a
dioptric mechanism for projecting the light rays upon this receptor.
Having previously studied the structure and function of these parts
separately, we are now in a more favorable position to deal with them
collectively and to see how they are capable of forming a real image of
external objects in their correct spatial relationships upon the retinal
surface. This analysis should not be attended by undue difficulties,
because it is based essentially upon the data pertaining to the refrac-
tion by biconvex lenses given in one of the preceding chapters.
The normal or emmetropic eye is constructed in such a way that
the different rays of light are brought to a precise focus upon the retina.
This refraction, however, involves
not only those rays which pursue a
course parallel to its visual axis, but
also those which are projected toward
it in a divergent direction and
would otherwise be lost to it. This
power it exerts by virtue of its ability
to accommodate for near and far
objects. But while the process of
Fig. 446.-DIAGKAM to Illustrate refraction in our eye is essentially
THE Position of the Chief Points of the same as that exhibited by bi-
Refraction in Our Eye. convex lenses, the fact that several
A Cornea; B, anterior surface of ^j ^ j^ ^^ j j^ ^ ^ ^ j^
lens; C, posterior surface of lens. • ^^m ^ * i-
matters more difficult. A biconvex
lens changes the course of the ray in two places, namely, at the point
where the latter enters the denser medium and again where it leaves
it. Upon its passing from the rarer into the denser medium it is
refracted toward the perpendicular, and upon its passing from the
denser into the rarer medium, away from the perpendicular. Our
eye contains a large number of these points of refraction, chief
among which are the anterior surface of the cornea and aqueous humor,
the anterior and posterior surfaces of the lens, together with the an-
terior surface of the vitreous humor (Fig. 446) . In fact, the entering
ray of light first meets with a layer of tears, the refractive power of
which is considerable. Inside the cornea it is not deviated very mate-
rially, because the anterior and posterior surfaces of this medium are
FORMATION OF THE IMAGE UPON THE RETINA 847
practically parallel, while the refractive power of the tears and aqueous
humor are nearly equal. It is strongly deviated, however, at the
anterior and posterior surfaces of the lens, because the refractive
indices of the aqueous and vitreous humors are less than that of the
lens. In general, the refractive power of this entire systeni may be
calculated without difficulty, provided the following factors are open
to analysis:
(a) The indices of refraction of the different media.
(b) The radii of the different curved surfaces.
(c) The distances between them.
Regarding the first factor, the following values have been obtained :^
Air 1.0
Cornea 1 . 3771
Aqueous humor 1 . 3374
r Capsule 1 .3599 ]
Lens \ Ext. layer 1 . 3880 \ 1 .4371
I Body 1.4107]
Vitreous humor. . . : , 1 .3360
It will be seen that the indices of the aqueous and vitreous humors
are practically the same and correspond
to that of water. Furthermore, it will "R
be observed that the total refractive ^
power of the lens (1.4371) is greater /^ j
than that of its different layers, as well / /i'm
as of that of its body. This apparent ~T ^
discrepancy is explained by the fact that V 1
its central substance, when isolated,
possesses a greater curvature than its
entire mass and, therefore, gives rise to a t^ ^^'r t^ t
J. ' . . r • • ^^^- ^'*^ — Diagram to Illus-
Stronger retraction in relation to its trate the Reduced or Schematic
index. Eye.
In order to simplify matters Listing2 ^, imaginary refracting surface;
1 1 • J J.T. i-rt? J. r x- iv, nodal point of this system.
has combined these dmerent refractive
media into a single one possessing a general refractive index of 1.33.
If united in this manner, the entire eye may be regarded as being
composed of a homogeneous substance presenting to the air a single
convex surface with a refractive index of 1.33, and a radius of cur-
vature, of 5.017 mm. (Fig. 447). The principal point of the re-
fracting surface of this reduced or schematic eye lies 2.1 mm. behind
the anterior surface of the cornea, and its nodal point (A^) or optical
center 0.04 mm. in front of the posterior surface of the lens, i.e., 7.3
mm. behind the anterior surface of the cornea. The principal focus
of this imaginary refracting surface lies 22.2 mm. behind the anterior
surface of the cornea of the actual eye. The optical power of this
1 Matthiessen, Pfliiger's Archiv, xxxvi, 1885.
* Wagner's Handworterbuch der Physiol., 1853, iv, 451.
848
THE SENSE OF SIGHT
reduced system is 50.8 diopters, and hence, the focal point of this
eye, when accommodated for a far object and in the position of rest,
Hes precisely upon the retina.
The Formation of the Retinal Image. — In reducing the eye into
this simple form. Listing has followed the mathematical expositions
of Gauss ^ which show that the several media of any refractive system,
whenever centered upon the same optical axis, may be considered as
forming two parallel planes possessing an equal refractive power
(Fig. 448). For practical purposes, these two planes (P) with their
respective nodal points (A^) may be regarded as being coincident, be-
cause the distance between them is actually very small so that the
refracted ray from the first plane is sent into the second still parallel to
the optical axis. In constructing the image of object AB, it must
be remembered that any luminous point upon AB sends out two rays,
one of which passes through the nodal point unrefracted, while the
Fig. 448. — Diagram to Show the Inver- Fig. 449. — Diagram to I llus-
siON OF THE Image by Parallel Refracting trate the Construction Neces-
SURFACES. SARY TO DETERMINE THE LOCATION
AB, object; A^B\ image; A^, nodal point ^^d Size of the Retinal Image.
of two parallel refracting surfaces P; F, focal
point.
other pursues a course parallel to the optical axis of this system and is
then refracted through its focal point F. At the point of intersection
of these two rays (^4. ^) lies the image of luminous point A. If this con-
struction is repeated for luminous point B, it will be seen that the image
of A B is inverted.
The same construction may be followed in the reduced eye (Fig.
449), because we know the center of curvature (n) of its single imaginary
refracting surface {R), in other words, its nodal point through which
all the principal rays may be imagined to enter the eye. These rays
are not deviated from their course, owing to the fact that they strike
the refracting surface at right angles. Consequently, all that is required
for the determination of the position of the image of an object upon the
retina, is to draw straight lines from its different luminous points
through the nodal point n It is evident that the retinal image is
inverted and that its size will be the smaller, the less the distance
of the nodal point from the retina and the greater its distance from the
object. Expressed in terms of the visual angle, it may then be said
^Dioptrische Untersuchungen, Gesellsch. der Wissensch., Gottingen, 1838-1843.
FORMATION OF THE IMAGE UPON THE RETINA 849
that the image becomes the smaller, the less this angle. Obviously,
the latter must vary directly with the size of the object and inversely
as its distance. Thus, if we gaze first at the moon and then at a more
distant but much larger fixed star, the visual angle formed by the rays
from the moon is much larger, because its relative proximity to the
eye more than makes up for its smaller size.
This inversion of the image may be conveniently demonstrated
by observing a landscape upon the ground glass of a photographic
camera. Quite similarly, we may employ the eye of an albino rabbit
which contains no choroidal pigment and in which, therefore, the
image may be seen through the transparent sclerotic coat. The
question may then be asked, why do we not perceive objects upside
down? Our correct interpretation of spatial relationships is gained in
the course of time by experience and in consequence of the association
of various sensory impressions. In other words, our psychic mech-
anism is adjusted in such a way that it conforms absolutely to this in-
version of the image. Consequently, any ray of light striking the
retina below, is invariably regarded as having arisen from a luminous
point situated in the upper visual field. Quite similarly, any stimula-
tion of the upper expanse of the retina is correctly interpreted as
having originated in the lower visual field, and so on.
The fixed character of our spatial associations may be proved in
different ways. Thus, we have previously observed that the mechan-
ical stimulation of the retina gives rise to luminous sensations or phos-
phenes, which are invariably referred to the visual field opposite the
seat of the stimulation. The reason for this is that these elements are
invariably stimulated by rays which are projected along these particu-
lar secondary lines. In localizing these retinal stimuli in space, it
may be imagined that we are guided by the local signs previously
established by them in the visual center. Like the receptors of the
skin, each retinal element may be assumed to be connected with a
particular central neurone which in the course of time has become
adapted to a perfectly definite sensation. Our psychic interpretation,
therefore, corresponds, as it were, to a reversal of the rays of light, i.e.j
the stimulated points upon the retina may be imagined to emit rays
which pass in a straight line through the nodal point and form an
imaginary image in space in accordance with their secondary axes.
Another good illustration of this general fact is obtained whenever
objects are held so close to the eye that the ordinary inverted image
must give way to an erect shadow (Fig. 450). To accomplish this
end, a card with a pin-hole is held at a distance of about 3 cm. in front
of the eye, i.e., within the near point of vision. If a pin is now moved
slowly upward in front of the pupil and as close as possible to the cor-
nea, the pin appears to enter the visual field from above. The same
result is obtained if the object is moved along any other meridian of
the cornea. Since the pin-hole lies inside the near point of this eye,
it is converted into a source of light which widely illuminates the ret-
54
850
THE SENSE OF SIGHT
ina. Inside this circle of light upon the retina lies the shadow of the
pin in its natural position. It appears inverted for the obvious reason
that the retinal elements stimulated by this shadow, are associated in
an inverse manner. Consequently, any shadow falling upon the lower
expanse of the retina, is interpreted as having been produced by an
object situated in the upper visual field.
Fig. 450. — Diagram to Illustrate the Formation and Projection of the Shadow of a
Pin.
A, Pin; /, shadow of it upon lower retina; P, projected as if moving into the visual
line from above.
The Size of the Retinal Image. — The dimensions of the image of
an object upon the retina may readily be ascertained if the size of the
object and its distance from the cornea are known (Fig. 451). Sup-
posing that the object AB is focused upon the retina in A'B'^ then AB
and A'B' really form the bases of two similar triangles, the apices of
which are situated at the nodal point of the lens, while its sides are
formed by the secondary axes AB' and BA\ If C stands for the dis-
tance of the nodal point from A, and D for the distance of this point
from B', then:
AB ^ A'B'
CD
Fig. 451. — Diagram to Show how the Size of the Retinal Image may be Determined.
As has been stated above, the distance of the image from the nodal
point may be reckoned at about 15 mm. Consequently, an object
120 feet in height, placed at a distance of 25 miles, forms an image upon
the retina, the dimension of which is
120 ft. ,, ,^ . 120 ft. ^ _ 1
X 15 mm., I.e. ^^^^ . , ^^ ^. X 15 mm.
25 miles
5280 X 25 ft.
or yTKf) X 15 mm. =
0.013 mm.
FORMATION OF THE IMAGE UPON THE RETINA 851
This image, therefore, would scarcely equal the diameters of two red
corpuscles and would cover about four cones of the fovea centralis.
This same object placed at a distance of one mile (5280 feet), would
give an image measuring 0.341 mm. in height, which corresponds to
about the diameter of the fovea centralis.
The Visual Field. Perimetry. — If our attention is called to an
object, our eyes are always turned in such a way that its central area
is brought to a precise focal point in the foveae centrales. This act
constitutes direct vision. At this very time all other objects in space
fall upon the outlying districts of the retinae and are therefore seen by
indirect vision. Direct vision, therefore, is effected through the visual
axis, connecting the object with the fovea, and indirect vision through
secondary axes which fall upon the more peripheral zones of the retina.
Both eyes together cover a certain extent of the external world which
is known as the visual field, but this entire field is really made up of two,
a right and a left, the nasal spheres of which overlap. From what
has been said above regarding the manner of refraction in our eye, it
must be evident that the retinal image is inverted and that objects
situated in the upper extent of the visual" field, are centered upon the
lower half of the retina, and vice versa. The same is true of objects
situated respectively in the right and left halves of the visual fields,
because they fall upon the opposite side of the retina.
The. configuration of the entire visual field, as well as of that of
each eye, depends chiefly upon the anatomical characteristics of the
margins of the orbital cavity. Centrally, each field is restricted by the
bridge of the nose, above by the orbital arch, and below by the cheeks.
Consequently, each field really presents an irregular oval outline, in-
stead of a circular one which it would possess if the eye were protruded
beyond these restricting boundaries. Its limits may be ascertained by
steadily gazing with one eye upon a mark upon a large cardboard,
placed at a distance of about 25 cm. vertically in front of the cornea.
The visual axis of this eye should strike the cardboard exactly at right
angles. A small object is then moved from without along the vertical,
horizontal and oblique meridians as charted upon the cardboard. A
mark is made each time when the observed person obtains a clear
impression of this object. If these outlying points are then joined
with one another, we obtain the boundaries of the visual field of this
particular eye at the distance of 25 cm.
An instrument commonly made use of for mapping out the visual field is
the perimeter. The one devised by Aubert and Forster^ (Fig. 452), consists of a
hemispherical band of metal fastened to a stand and movable so as to cover the
different meridians of the eye. In front of this arc is placed a support for the chin
of the observed person, his eye being adjusted in such a way that he is able to gaze
horizontally at a white object fastened to the center of this circle (Fig. 452).
A small white disc is then moved slowly from without along this arc until it be-
comes clearly visible. The arc is graduated, allowing the moment of the appear-
ance of this object to be charted (Fig. 453). This procedure is repeated along the
1 Archiv fiir Ophthalmologic, iii, 1857.
852
THE SENSE OF SIGHT
other meridians until the boundaries of the entire visual field have been accurately
mapped out.'^
CUnically this instrument is employed for determining the seat of lesions of the
retina or of the optic tract and visual center. Obviously, any defect of the optic
path must give rise to a retinal area of indifference and hence, to a dark zone within
the visual field. Thus, it will be remembered that unilateral lesions of the occipital
cortex give rise to the condition of hemianopia or half-blindness of the retinae on
the corresponding side. If their right halves have in this way been rendered
functionally useless, the left halves of the visual fields are blotted out. Direct
vision, however, is retained, because each fovea centrahs is connected with both
oooo
Fig. 452. — The Perimeter.
occipital centers. Very similar defects in the visual field follow injuries to the opti-
cal tract or to the retina itself. Thus, the occlusion or rupture of a terminal branch
of the retinal artery most generally leads to a uselessness of a circumscribed patch
of the retina with a corresponding defect in the visual field of this eye. This defect,
however, cannot become apparent unless the corresponding area of the opposite
retina has also been injured. Admittedly, the two retinae act in unison and com-
pensate for minor defects so long as the mjury remains confined to one of them.
This functional reciprocity has already been fully discussed in the paragraphs deal-
ing with the blind spot. It was then found that while a certain number of the rays
1 Peter, Principles and Practice of Perimetry, New York, 1916.
ABNORMALITIES IN THE REFRACTION OF THE EYE
853
emitted by an object, are always projected upon the blind spot of one eye, this
defect is overcome in binocular vision by the fact that the corresponding rays in
the opposite eye are focalized outside this area and are therefore able to produce
a precise and complete impression in consciousness.
Since the sensitiveness of the retina diminishes steadily from center to per-
iphery and also shows certain minor fluctuations in different persons, it cannot
surprise us to find that the visual field frequently possesses marked irregularities.
Furthermore, it must be evident that the luminosity and color of an object have
much to do with its size, because a white disc invariably yields a larger field than
06 L 081 01-^
Fig. 453. — Perimeter Chart to Show the Field of Vision for a Riqht Eye When
Kept in a Fixed Position.
J
one poorly illuminated or colored. Consequently, definite conclusions regarding
abnormalities of the visual field can only be drawn from a perimetric chart
which has been obtained under test conditions.
CHAPTER LXXIII
ABNORMALITIES IN THE REFRACTION OF THE EYE
Constant Optical Defects of the Eye. — In a perfect dioptric system
the media are absolutely transparent. This is not the case in the
human eye, because if a strong beam of light is thrown into its pupil,
the light is diffused by the different luminous points of its refractive
media. In fact, in many instances true opacities may be detected
which are dependent upon the presence of formed elements within the
854 THE SENSE OF SIGHT
vitreous humor. In order to render the latter visible, the eye should
be turned upward upon a uniformly illuminated surface, when they
will place themselves directly in the line of vision, and give rise to a
sensation of beads, strings or patches floating through the visual field.
On account of their almost constant motion, which may be increased
by movements of the head or eyes, they are known as the muscce voli-
tantes. They are said to represent the remains of the embryonic struc-
ture of the vitreous humor, such as cells which have failed to undergo
a complete transformation into vitreous substance. These fleeting
visual sensations belong to the group of the entoptic phenomena, be-
cause they are produced by objects within the eye.
The human eye also shows an imperfect centration of its refractive
media. In the horizontal meridian the optical axis of the cornea
differs from that of the lens by 0.3°, and in the vertical meridian by
as much as 1.3°. Furthermore, attention has already been called to
the fact that the optical axis of the eye does not coincide exactly with
the visual axis. Naturally, the most perfect system would be the one
in which the refractive media are accurately centered upon an axis
which strikes the retina in its most sensitive area.
Reference has already been made to the fact that the crystalline
lens is not free from spherical aberration, the rays passing through
its peripheral zone being converged more than those traversing its
center. It is also open to chromatic aberration, the violet rays being
brought to a focus in a point closer to the lens than the red rays. Like
in all optical instruments, these aberrations are minimized by a stop
in the form of the iris which shuts out its marginal zone. In spite
of this fact, however, we still obtain a slight spherical aberration
which, together with the imperfect centration of the refracting media,
gives rise to a mild degree of astigmatism. Thus, a star or the light
of a lantern is not seen as a round luminous point, but as beset with
radial streamers. Quite similarly, the chromatic aberration still
remaining, frequently amounts to 0.5 mm. as far as the violet and red
rays are concerned. This condition, however, does not interfere
appreciably with the clearness of the retinal image, at least, not with
the impression produced by it in consciousness. Admittedly, the
retina becomes abruptly insensitive toward the rays at the extreme
ends of the spectrum, and is more readily excited by the rays in and
near the yellow. Consequently, the absence of chromatic aberration
in" our eye is due to the fact that the iris prevents refraction through the
peripheral zone of the lens, and secondly, to the physiological and not
to the optical qualities of our eye.
Among these dioptric defects of our eye might also be mentioned
the entoptic phenomena produced by the tears anointing the anterior
surface of the cornea, as well as by the particles of mucus, globules
of fat and dust contained therein. The latter are constantly removed
from in front of the pupil by the movements of the eyelids. Sub-
jective visual impressions atso result in consequence of the heterologous
ABNORMALITIES IN THE REFRACTION OF THE EYE 855
excitation of the retina by strong pulsations of the retinal blood-vessels,
increased intraocular pressure, and venous stagnation caused, for ex-
ample, by the acts of coughing and sneezing.
Inconstant Optical Defects of the Eye. — It is the purpose of the
normal eye to bring rays of light to a sharp intersecting point upon
the retina. An eye which accomplishes this end, is said to be em-
metropic. This condition of normal refraction is designated as
emmetropia. Conversely, any eye which is not capable of producing
a precise focus, is said to be ametropic. This condition of abnormal
refraction is known as ametropia. The causes underlying the latter
may be arranged in the following order:
(a) Imperfect curvature of the cornea, astigmatism.
(6) Diminished elasticity of the lens, presbyopia.
(c) Imperfect shape of the eyeball.
(1) Myopia, the eyeball is too long.
(2) Hypermetropia, the eyeball is too short.
The condition of presbyopia has been fully discussed in one of the pre-
ceding chapters and need not be considered again at this time. Fur-
thermore, while astigmatism is ascribed in this outline to a faulty
curvature of the cornea, we should not lose sight of the fact that this
condition may also be caused by an imperfect curvature of the lens;
in fact, even a so-called normal eye is not entirely free from astigmatism,
due very largely to an improper centration of the constituents of the
lens. Regarding the exciting causes of ametropia no perfectly definite
statements can be made. The shape of the eyeball is inherited together
with other biological characteristics; hence, all these conditions may
be entirely beyond our power of preventing them. This is also true
of those defects which arise later on in life in consequence of retro-
gressive changes, such as infiltrations, alterations in the, intraocular
pressure, and senile weaknesses of the coats of the eyeball. In the
latter case, the eyeball becomes more pliable and adjusts itself more
completely to the shape of the orbital cavity. In spite of this impor-
tant element of inheritance, however, it cannot be denied that these
defects may also be acquired in consequence of an improper mode of
living, and erroneous methods in the use of the eyes. Thus, the
inhabitants in cities are constantly subjected to near work; their hori-
zon being limited in many cases by the walls of the houses on the
opposite side of the street. Besides, their daily work requires strong
convergence of the visual axes which in itself heightens the intraocular
pressure. The contrary picture is presented by the inhabitant of the
open country whose visual impressions are in large part received
from distances greater than 50 m., i.e., from distances which require
no accommodation at all. Civilization imposes upon us many condi-
tions which can only be met by carefully following the most fundamen-
tal rules regarding physiological optics.
Astigmatism. — In accordance with perfect refraction, the cornea
should form a section of a true sphere, but this is not always the case,
856
THE SENSE OF SIGHT
because slight differences between the curvatures of its vertical and
horizontal meridians are not uncommon. Most generally, however,
this defect is overcome functionally, so that an appreciable disturbance
in vision can only result when these differences exceed a certain physio-
logical limit. Astigmatism is classified as regular and irregular, the
former term being applied to it when the meridian of maximal curva-
ture lies at right angles to that of minimal curvature. Accordingly,
irregular astigmatism may be defined as an improper curvature of the
cornea along meridians which do not lie at right angles to each other.
This variety is most commonly produced by an injury and subsequent
formation of a scar in the course of a single meridian; hence, it is re-
stricted to a relatively narrow region of the cornea. We also make use
of the terms ^^with the rule'' and '' against the rule" astigmatism. The
^-^c=:> 6 0
Fig. 454.— Diagram to Illustrate the Cornea of the Rays in "with the Rule"
Astigmatism.
AB, being the plane of greater curvature, its rays are brought to a focus nearer the
lens than those traversing plane CD.
former implies that the cornea is more highly curved along its vertical
meridian, while the latter signifies that its horizontal curvature is
greater than its vertical. Ordinarily, astigmatism is of the regular
variety, presenting itself, therefore, as an excessive curvature along
its vertical plane.
The functional result of these corneal inequalities is not difficult to
understand, if it is remembered that the more convex surface converges
the rays of light more strongly than the less convex and hence,
focalizes them more quickly than the flatter surface. We are dealing
here with planes, i.e., with linear refraction (Fig. 454). Consequently,
an eye which has been rendered ametropic by ''with the rule" astig-
matism, converges those rays of light in a greater degree which traverse
the vertical plane of its cornea {AB). Although the lens receives these
rays in a more convergent form than those which have passed through
the horizontal plane of the cornea (CB), it subjects both lines of light
ABNORMALITIES IN THE REFRACTION OF THE EYE
857
rays to an equal degree of refraction. Accordingly, this eye obtains
first of all an image of those rays which have traversed the more highly
curved vertical meridian of the cornea (AB) and lastly, one of those
rays which have passed through its relatively flat horizontal plane
(CD). The first image (ab) must necessarily be a horizontal line and
the second a vertical line (cd). In between these two images are
Fig. 455. — Astigmatic Chart. (Howell.)
situated first a horizontal ellipse, then a circle and lastly, a vertical
ellipse. The reason for this is that the rays ah again diverge distally
to the horizontal image and henceforth intermingle with the still
convergent rays cd.
To illustrate, let us fill a tall beaker with water, place it upon a table and
project a round beam of light through its central area. The image is a vertical
Figs. 456, 457. — Lines for the Detection of Astigmatism.
line, because the column of water acts in the manner of a cylindrical lens, the great-
est convexity of which is adjusted from side to side. If this beaker is now held
horizontally so that its greatest convexity lies in the vertical plane, the linear
image assumes a horizontal position. The same results may be obtained with a
cylindrical lens. By means of two equally strong cylindrical lenses superimposed
upon another at right angles, these linear lines may be reconverted into a rounded
image.
858
THE SENSE OF SIGHT
The presence of astigmatism may be revealed by looking at a chart
such as is represented in Fig. 455, because an astigmatic eye is unable
simultaneously to obtain a perfectly clear image of lines placed at
right angles to one another. An even more delicate test is presented
by the concentric rings reproduced in Fig. 456. It should be empha-
sized, however, that the oscillating blurring effect which one frequently
obtains while gazing at these charts, is not caused by an astigmatic
condition of the refracting media of the eye, but by slight variations in
the degree of contraction of the ciliary muscle. Such variations must
necessarily give rise to changes in the accommodation.
Fig. 458. — Ophthalmometer. {Hardy.)
An instrument which enables us to determine the direction as well as the degree
of the excessive curvature of the cornea, is the ophthalmometer of Helmholtz (Fig.
458). It is constructed in such a way that the size and shape of the corneal image
of any luminous object may be determined with absolute accuracy. Knowing the
size of this object and its distance from the eye, as well as the size of the corneal
reflection, it is possible to ascertain the radius of curvature of the cornea according
to the equation r=-^^^. In this formula p represents the distance of the object
from the cornea, o, the size of the object, and i, the size of the corneal image. It
need scarcely be mentioned that the reflecting surface and telescope of this instru-
ment may be rotated so as to enable the observer to measure the curvature of the
other planes of the cornea and to compare them with one another. In the modern
ABNORMALITIES IN THE REFRACTION OF THE EYE 859
instruments of this kind the luminous object, or target, is represented by a double
figure possessing a sharp mathematical outline, which in turn is doubled by a prism.
The four images thus obtained are first properly adjusted for a normal cornea.
When transferred upon an abnormally curved cornea, this defect is made apparent
immediately by their displacement toward one another.
The condition of astigmatism may be corrected in one of two ways :
namely (a) by diminishing the refraction along the meridian of greatest
curvature or (6) by increasing the refraction along the meridian of
least curvature. Cylindrical lenses are used for this purpose, the
refracting power of which compensates precisely for the unequal cur-
vature of the cornea. In the former case we employ a lens designated
as minus and, in the latter, one designated as plus.
Myopia. — The condition of myopia or near-sightedness is due either
to an increase in the longitudinal diameter of the eyeball, or to an
excessive refracting power of the lens and other media of the eye. In
most instances, however, it is attributable to the former cause.
The increase in the length of the eyeball may amount to a fraction
of a millimeter or to as much as 3.8 mm. Already with a lengthening
Fig. 459. — Diagram to Illustrate the Refraction in a Myopic Eye.
L, Luminous point focalized in L^ in the vitreous humor. A concave lens L renders
these rays more divergent so that they are made to intersect upon the retina in L^.
of 0.16 mm. the far point is moved to within 200 cm. from the eye, and
with an increase of 3.8 mm. to within 10 cm. The near point is at
this time only 5 to 6 cm. distant. Far objects, therefore, cannot be
brought to a focus upon the retina, unless the eye is equipped with an
artificial lens which exactly compensates for this defect. Thus,
parallel rays emerging from so short a distance as 6 m., actually inter-
sect in the vitreous himaor in front of the retina. Distally to this
point of intersection, the rays again diverge and strike the retina widely
apart as a dispersion circle. It must be evident that this condition
cannot be improved by accommodating more sharply, because any
increase in the convexity of the lens must move the focal point farther
toward the lens, and give rise to an even greater dispersion of the
retinal image. Quite similarly, it may be reasoned that an object
held very close to the eye, is in a much better position, because its
860 THE SENSE OF SIGHT
divergent rays are focalized far behind the lens and may, therefore, fall
precisely upon the retina of the myopic eye.
In order to enable a myopic person to see distant objects clearly,
we must lessen the convergence of the posterior bundle of the rays of
light, i.e., we must force their focal point farther backward until they
reach the retina. How can this be done? By rendering the enter-
ing rays more divergent, so that they impinge upon the lens more
widely separated from one another than formerly. The ordinary
efforts of the ciliary muscle will then suffice to centralize these more
divergent rays precisely upon the retina. Consequently, the condition
of myopia necessitates the use of concave lenses of a diverging power
exactly proportional to the degree of the myopia (Fig. 459).
Hypermetropia. — The condition of hypermetropia or far-sightedness
is due either to a decrease in the longitudinal diameter of the eyeball
or to a diminution in the refracting power of the lens and other media
of the eye. ' The former is the most common cause. A hypermetropic
eye is unable to focalize rays emitted by near objects, because its
refractive mechanism is not sufficiently powerful to converge these
rays in a way to bring them to a sharp intersecting point upon the
retina. Since they are still too widely separated when they strike
this receptor, they cannot give a clear visual impression. In the more
severe cases, this statement also applies to the parallel rays, so that
even distant objects cannot be seen distinctly when the eye is at rest.
It is commonly said, that the focal point in the hypermetropic eye lies
behind the retina, but naturally, this is only a theoretical possibility.
With the increasing hypermetropia, the near point constantly moves
farther away from the eye, sometimes as far as 200 cm., while its far
point lies at an infinite distance.
It will be seen, therefore, that the hypermetropic, as well as the
myopic eye, when at rest, sees distant objects indistinctly. Contrary to
the myopic eye, however, the hypermetropic organ is able to overcome
this difficulty for a time by constantly making extra efforts at accom-
modation. It is evident that any slight shortening of the eyeball
may be compensated for by rendering the lens unusually convex, but
naturally, these hyperefforts must fail to produce the desired result if
the shortening has progressed beyond the limit of accommodation.
Besides, these forceful contractions of the ciliary muscle are generally
followed by a strained feeling, orbital pain, headache, and vertigo.
Slight degrees of hypermetropia, however, may never be noticed for
the reason that the person so affected may readily overcome them
by a somewhat greater contraction of the ciliary muscle. In the
course of time, this muscle then frequently undergoes a compen-
satory hypertrophy.
The condition of hypermetropia may be remedied by forcing the
focal point farther toward the lens; i.e., by rendering the rays of
light emerging from the posterior surface of the lens, more convergent.
How can this end be accomplished? By supplying the lens with
ABNORMALITIES IN THE REFRACTION OF THE EYE
861
convergent rays of light, but since there are no convergent rays or-
dinarily available in space, this direction must first be imparted
to the parallel and divergent xays by means of a convex lens (Fig.
460). The converging power of the lens interposed in front of the
eye, must be proportional to the degree of the hypermetropia.
Keeping these facts clearly in mind, it will be seen that the condi-
tion of presbyopia developed in later years, must improve the vision
of the myopic person, but diminish that of the hypermetropic. Ob-
viously, the gradual flattening of the lens in consequence of the effects
of old age reduces its refractive power and forces the focal point
farther backward. If the eye is hypermetropic, the presbyopia
makes matters worse, because it tends to move the focal point still
farther "behind" the retina. In the myopic eye, on the other hand,
a distinct improvement must result, because the presbyopic lens does
not converge the rays so strongly, and hence, permits their focal
Fig. 460. — Diagram to Illustrate the Refraction in a Hypermetropic Eye.
L, Luminous point focalized in L^ "behind" the retina. A convex lens C renders
these rays more convergent so they are made to intersect upon the retina in L^.
point to move closer to the retina. Conversely, a presbyopic eye may
be greatly benefited by the subsequent development of a myopia,
because the recession of the focal point is then compensated for by a
displacement of the retina in a backward direction. These phenomena
are generally designated as "second sight."
To summarize: An emmetropic eye (Fig. 461, E) brings parallel and
even divergent rays of light to a sharp focus upon the retina, while
a myopic eye {M) focalizes them in front and a hypermetropic eye,
{H) "behind" the retina. In order to render M emmetropic, the
entering rays of light must be diverged by means of a concave lens,
while H can only be made emmetropic by converging them with the
aid of a convex lens.
Simple Methods Used to Determine the Refractive Power of the
Eye. — The acuity of vision may be tested in different rays. Snel-
len's test types consist of a series of letters placed at a distance of 5 m.
from the eye. It has been determined that the smallest object which
a normal eye is capable of distinguishing at this distance, measures
862
THE SENSE OF SIGHT
1.454 mm. and that lines drawn from its two opposite poles through the
nodal point of the lens, subtend an angle of 60 degrees. Consequently,
any other two luminous points separated by a shorter distance than
Fig. 461. — Diagram to Illustrate the Refraction in Emmetropia and Ametropia.
E, Emmetropic eye in which luminous point L is brought to a precise focus upon the
retina, L^; M, myopic eye in which L is focalized in front of the retina, L^; H, hyper-
metropic eye in which L is focalized in L^" behind" the retina. In M, the use of a concave
lens f orces L^ backward upon the retina, L^, correcting the myopia, whereas in H, the
use of a convex lens forces L^ forward upon the retina, L^.
the one just given, are no longer able to produce distinct impressions.
At this distance, the retinal image measures 0.004 mm., which corre-
sponds to a visual angle of 60 seconds. If smaller than this, the two
5ni. "^ — 1^-
Fig. 462. — Dlvgram to Illustrate the Use of Snellen's Test Types.
focal points fail to give separate impressions, because they fall on one
and the same cone. At a distance of 1 m., therefore, an object would
have to possess a dimension of one-fifth of 1.454 mm., or 0.2908 mm.,
ABNORMALITIES IN THE REFRACTION OF THE EYE 863
in order to subtend an angle of 60 seconds. Other letters may then
be constructed for the intervening distances by simply multiplying
the value of 0.2908 mm. by the distance (Fig. 462). This test, there-
fore, consists in determining the smallest retinal image, corresponding
to a visual angle of 60 seconds, which an eye is capable of perceiving.
If a person is unable to recognize this test type when held at its proper
distance, he is first made to look at it through a weak convex lens. If
this improves his vision, he is hypermetropic, because only an eye that
is too short or possesses a subnormal power of refraction, is in a position
properly to focalize convergent rays. He should be given the strong-
est convex lens with which he is able to see clearly, because clear vision
then forces him to relax his accommodation as much as possible. If, on
the other hand, the vision of the patient is more highly impaired by
the interposition of convex glasses, he is myopic and requires spectacles
with concave lenses. In this case, the lenses prescribed for him, should
be the weakest with which he is still able to see clearly, because this
forces him to bring his ciliary mechanism into physiological play. It
is evident that this test should also be made separately for each eye.
Instead of the test letters, ordinary print held at the proper reading
distance, may be used.
The Ophthahnoscopic Method. — The eye is a camera obscura, and
its interior is not open to direct inspection, because the choroid and iris
are pigmented and practically impermeable to light. Even in the
albino, nothing more than a slight ''reflex" sensation of pink is ob-
tained. The fundus of the eye also remains absolutely invisible if we
look through the pupillar orifice, because we must then assume a posi-
tion directly in -front of the head of the observed person. Obviously,
the rays of light are thereby prevented from entering the vitreous
chamber. In some animals, however, the visual axes are more diver-
gent so that the rays can get past the observer's head to illtiminate the
retina.
Whenever light is reflected into an eye, a large part of it is absorbed
by the pigment of the choroid, while a small portion of it is refracted
outward into space in the same direction in which it entered. It
must be evident that if a luminous point in space L is accurately cen-
tered upon the retina in L', this focal point L' remits divergent rays
which are again rendered convergent by the lens to be intersected in L,
Consequently, L and U are conjugate foci. This outward refraction
is made impossible if we adjust our eyes to look into the pupillar orifice
of the patient, because we thereby cut off the supply of light rays and
render the retina non-luminous. In 1851 Helmholtz conceived the
idea of illuminating the eye from a lateral source of light by means of
three mirrors placed at an angle of 56° to the line of light. This instru-
ment which he called the ophthalmoscope (Fig. 463), has been modified
repeatedly, but the principle involved in its construction has remained
the same. In its modern form it consists of a concave silvered mirror
by means of which light is reflected into the patient's eye from a gas-
864
THE SENSE OF SIGHT
lamp adjusted laterally to his head. Since the constriction of the
iris would seriously interfere with this examination, this mechanism
is temporarily paralyzed by means of atropin. Some mirrors are
equipped with a small electric lamp (Dennett's or Marple's modifica-
tion) which enables us to examine the eyes of bedridden patients and
also obviates in a measure the use of atropine.^ In the center of the
Fig. 463. — Loring's Ophthalmoscope, with Tilting Mireok, Complete Disc of
Lenses from — 1 to — 8 and 0 to + 7, and Supplemental Quadrant Containing ±
0.5 AND ± 16 D. This Affords 66 Glasses or Combinations from + 23 to — 24 D.
reflecting mirror is a small opening which is adjusted directly in front
of the pupil of the observer's eye. We may then follow either the
direct or the indirect method of ophthalmoscopic examination.
The Direct Method. — If the eye of the observer is not emmetropic, it should
first be made so by spectacles (Fig. 464). The mirror (w) is held close to the ob-
served eye, so that the rays reflected from it are able to spread out widely upon the
opposing retina {A'B'). The area of the retina so illuminated remits rays (L)
which traverse the dioptric media of this eye and are sent outward into space.
Now, it is evident that thie emmetropic eye remits these rays parallel to the visual
^ Large ophthalmoscopes have been constructed by Gullstrand and others.
The first gives a magnification of 5 to 50 times in monocular and 20 times in
binocular vision. Hertzell illuminates the eye by means of an 80 candle power
electric lamp placed in the patient's mouth (ophthalmodiaphanoscopy).
ABNORMALITIES IN THE REFRACTION OF THE EYE
865
axis, while the myopic and hypermetropic eyes refract them outward in an obUque
direction. Assuming then that the observed person is emmetropic and is accom-
modating for a far object, the parallel rays emitted by his retina must traverse the
central orifice in the mirror and be brought to a precise focus upon the retina of the
observer (L^). The latter thus obtains an erect niagnified image of the retina of the
observed person. A clear image, however, can only be obtained if both eyes are
emmetropic and are accommodated for the distance. Some difficulty may be
experienced at first in relaxing the accommodation, but this may be overcome if
one imagines himself gazing at an object placed far behind the eye of the patient.
A complete relaxation of the eye of the observed person is usually secured by the
administration of atropine, which alkaloid temporarily paralyzes the ciliary
mechanism. It also dilates the pupil, thereby preventing any interference on the
part of the iris with the reflection and refraction of the light.
If the observed eye is myopic, ^ the rays of light emitted by the illuminated area
of its retina, are refracted into space as a convergent beam and cannot, therefore,
be focahzed by the emmetropic and relaxed eye of the observer (Fig. 465). In
0 ■■' P
Fig, 464. — Direct Ophthalmoscopy.
Diagram to illustrate the remittance of the raj^s of light by an emmetropic eye.
O, observer's eye; M, mirror; P, patient's eye; F, the rays FA and FB, illuminate the
retina of P by a diffusion circle A^B^; L, the rays emitted by this luminous point are
brought to a precise focus in L^ of the observer's retina.
order to bring these rays to a precise focus, they must first be rendered less conver-
gent by the interposition of a biconcave lens of sufficient diverging power to over-
come their excessive convergence. If the observed eye is hypermetropic (Fig.
466), the rays emitted by its illuminated retina, are divergent and cannot, there-
fore, enter the pupil of the observer. They may be made to do so, however, by
placing a biconvex lens in front of the orifice in the reflecting mirror. The strength
of the latter should be such that the formerly divergent rays now intersect in the
retina of the relaxed emmetropic eye of the observer.
This method not only allows us to detect errors of refraction, but also to deter-
mine the strength of the lens which must be used by the patient in order to render
him emmetropic. Clearly, the strength and sign of the lens needed by him to
correct his defect, is indicated by the lens which the observer must employ in order
to obtain a clear image of his retina. For reasons stated previously, the weakest
concave lens should be prescribed for myopia and the strongest convex lens for
1 If the observer moves his head and ophthalmoscope from side to side, the
retinal vessels will appear to move in the same direction in the hypermetropic and
in the opposite direction in the myopic eye.
55
866
THE SENSE OF SIGHT
hypermetropia.i Astigmatism may also be detected and corrected in this way.
In order to form an idea regarding the meridians in which the refraction is defect-
ive, we only need to observe the retinal blood-vessels along the horizontal and
Fig. 465. — Direct Ophthalmoscopy.
Diagram to illustrate the remittance of the rays of light by the myopic eye. O,
observer's eye; M, mirror; P, patient's eye; F, the rays FA and FB illuminate the
retina of P by a diffusion circle A'^ B^;L, the rays emitted by this luminous point leave
the eye of P convergently and must therefore be rendered divergent by the interposition
of a concave lens before they can be focalized inL^ by the eye of the observer.
vertical planes of the optic disc (Fig. 438). The latter appears as a nearly round
or slightly oval area varying in color from grayish pink to a more decided red. Its
center is occupied by a light patch marking more exactly the entrance of the
retinal blood-vessels. The circumference of the optic papilla appears as a dark,
Fig. 466. — Direct Ophthalmoscopy.
Diagram to illustrate the remittance of the rays of light by the hypermetropic eye.
O, observer's eye; M, mirror ;P, patient's eye ;F, the raysF^ andFJ5, illuminate the retina
of P by a diffusion circle A^B^; L, the rays emitted by this luminous point leave the eye
of P divergently and must therefore be rendered convergent by the interposition of a
convex lens before they can be focalized inL^ of the eye of the observer.
usually incomplete ring representing the border of the choroid coat. Within this
lies a faint white line, indicative of the brim of the sclerotic coat.
1 If the observer is ametropic and does not employ the necessary glasses during
this examination, he must of course make this additional correction.
ABNORMALITIES IN THE REFRACTION OF THE EYE
867
The Indirect Method. — As the name indicates, indirect ophthalmoscopy con-
sists in the formation of a retinal image in space in front of the observer's eye, the
principle involved being similar to that of the compound microscope (Fig. 467).
The reflecting mirror is held at about an arm's length from the observed eye (30
cm.). A convex lens of about 20 diopters is then placed close to the, latter. Ob-
viously, the purpose of this lens is to gather the rays emerging from the observed
eye and to bring them to a focus between it and the observer's eye. This real
inverted image in space is regarded by the observer through a lens of about 5
diopters inserted in the orifice of the ophthalmoscope. To see this image clearly,
the emmetropic observer must move nearer to or farther away from the patient's
eye until his distance equals the focal distance of this lens, viz. : 20 cm. Errors in
refraction may be detected by moving the objective lens of 20 diopters farther
away from the eye, the image then becoming larger in myopia and smaller in hyper-
metropia. The observer then interposes different concave ( — ) and convex ( + )
lenses until the image becomes perfectly clear.
Fig. 467. — Indirect Ophthalmoscopy.
Diagram to illustrate the remittance of the rays of light by an emmetropic eye.
O, observer's eye; M, mirror; P, patient's eye; F, the rays FA and FB illuminate the
retina of P by a diffusion circle A^B^ (inverted in this case) L, the rays emitted by these
luminous points are converted into a real inverted image in the air at J. The latter is
then focused upon the observer's retina.
Skiascopy or the Shadow Test (Retinoscopy). — This method con-
sists in determining the direction of the movement of the hght in the
pupillar orifice when it is made to move back and forth by rotating
the reflecting mirror around the long axis of the handle supporting
it. It is a matter of common observation that a beam of light reflected
against a wall, moves with the reflecting mirror. A similar phenome-
non occurs in the human eye if the retina is illuminated so that it
can emit hght. Thus, if a beam of hght is thrown into the eye, the
pupil is completely illuminated. If the mirror is now rotated around
its long axis, the pupil is darkened on one side and this shadow moves
either in the same or in the opposite direction to the rotation according
to the position of the observer's eye in the hne of vision of the observed
eye (Fig. 468). If situated exactly at its far point, the pupil remains
either dark or is fully illuminated and does not exhibit a distinct
moving shadow. This point indicates the position of the so-called
Voint oj reversal {A). Retinoscopy, therefore, is a method by means of
which the distance of this point may be accurately determined. Be-
868 THE SENSE OF SIGHT
yond this point (B) an inverted image will be obtained, and the light
in the pupil will appear to move against the rotation of the mirror,
whereas inside A the image (C) is erect, and the light seems to move
with the rotation.
In myopia, the point of reversal lies close to the eye. Con-
sequently, if the observer finds that, on throwing light into the eye,
the light in the pupil is against the rotation, he must be beyond the
point of reversal. He should then approach the observed eye slowly
Fig. 468. — Diagram to Illustrate the Location of the Point of Reversal as Ob-
tained BY THE Shadow Test.
until he finds this movement to be with the rotation. These obser-
vations should be repeated until this point has been accurately local-
ized. The distance between this point and the eye should then be
measured with the ruler, because it represents the focal distance of
the lens necessary to correct the myopia. Thus, if it is possible
to obtain an erect movement at a point 55 cm. from the eye and a
reversed movement at 80 cm., the exact point of reversal will be at
67 cm. The myopia equals in this case 1.50 D.
Fig. 469. — Diagram to Illustrate the Location of the Point of Reversal as Ob-
tained BY THE Shadow Test in the Hypermetropic Eye.
In hypermetropia the rays are emitted divergently and hence, a
point of reversal cannot be present. The observer then finds that the
movement of the light remains with the rotation, no matter how far he
withdraws from the eye. A convex lens should now be interposed to
form a point of reversal at a convenient distance from it, thereby ren-
dering it artifically myopic (Fig. 469). This point of reversal having
been ascertained with the ruler, the degree of myopia represented by it
is then subtracted from the total strength of this lens. The remainder
BINOCULAK VISION 869
corresponds to the power which is required to correct the divergence
of the rays, i.e., the hypermetropia. Thus, if a lens of 5D is employed
and the movement of the light remains with the rotation of the mirror
until a little within a distance of 1 m. but is reversed at a distance of a
little more than 1 m., the point of reversal is at 1 m. Consequently,
ID of the strength of this lens is required to converge the rays,
while 4D of the total 5D have been made use of in overcoming the
divergency of the rays upon their projection from the observed eye.
In this case, the hypermetropia equals 4D.
In astigmatism the same method may be followed, but these
tests must then be repeated for different meridians, i.e., the point
of reversal must be ascertained separately for the horizontal, vertical
and oblique planes.
CHAPTER LXXIV
BINOCULAR VISION
The Movements of the Eyeballs. — The organ of vision consists
of the globe of the eye, measuring nearly an inch from side to side,
slightly less than an inch from above downward and somewhat
more than an inch from before backward. Its volume equals 6.5
cm. and its weight nearly 7 grams. Connected with it externally
are different muscles, nerves and blood-vessels. It is supported by a
quantity of fat and connective tissue, the latter forming a lymphatic
space known as the capsule of Tenon. Within this capsule the eyeball
is made to move by the contraction of a set of muscles, designated as the
ocular muscles. These are the four recti and two oblique muscles.
The former, which are known respectively as the superior, inferior,
external and internal, take their origin from a tendinous ring investing
the optic foramen and sphenoidal fissure. From here they pass
forward along the walls of the orbital cavity and finally perforate
the aforesaid lymphatic space to gain access to the equatorial region
of the eyeball. Closely investing the latter, they finally terminate
in their respective positions about 7 mm. posterior to the margin of
the cornea. The superior oblique muscle arises from a small tendon
upon the inner margin of the optic foramen and, passing forward to
the inner angle of the orbit, terminates in a rounded tendon which
plays in a pulley of fibro-cartilaginous tissue suspended from the
depression in the internal angular process of the frontal bone. From
here this tendon is reflected backward, outward and downward upon
the outer part of the eyeball about midway between its cornea and the
entrance of the optic nerve. The inferior oblique muscle arises from a
depression in the orbital plate of the superior maxillary bone, external
870
THE SENSE OF SIGHT
to the lacrimal groove. From here it passes outward, upward and
backward, and finally ends in a tendinous expansion which is inserted
in the sclera upon the outer part of the eyeball, near to but somewhat
behind the tendon of the superior oblique.
The movements of the eyeball are similar to those of the head of a
long bone within its socket, an unrestricted motion being made im-
possible by several resistances, such as the insertion of the different
muscles, the capsular aponeurosis and the entrance of the optic nerve.
The recti muscles act antagonistic to one another, the range of con-
Ill
Fig. 470, — Diagram Showing the Lines of Insertion of the Ocular Muscles into the
Sclerotic. {Merkel and Kallins.) •
1, Globe from above; II, from the nasal side; III, from below; IV, from the temporal
side, s, rectus superior; i, rectus inferior; m, rectus internus (s. mesialis) ; e, rectus
externus (s. lateralis); os, obliquus superior; oi, obliquus inferior.
traction of one being restricted by the extension of the opposite one.
Their action, however, is unable to pull the eyeball backward owing
to the antagonistic action of the smooth musculature of Tenon's
capsule. In some animals, such as the reptilia and amphibia and
several mammals, a movement of this kind is effected by a special
muscle known as the retractor bulbi.
The globe of the eye does not alter its position in rotating, but is
merely turned around its axes. Thus, if it stated that the eye is moved
upward, reference is had merely to the relative position of its anterior
and posterior poles. While the cornea moves upward, the back of the
eyeball moves downward, and vice versa. Although the axes around
which the eye may be rotated are many, it is customary to recognize
BINOCULAR VISION
871
oi>tsup.
obt. Slip,
r.int
three principal ones, namely, two horizontal and one vertical. All three
traverse the center of rotation at right angles to one another, allowing
the following movements of the eye to be executed: (a) outward or
inward around its vertical axis, giving rise to its average abduction
or adduction, (6) upward or downward around its transverse hori-
zontal axis, and (c) around its sagittal axis connecting its anterior
and posterior poles. The only movements carried on by the contraction
of one muscle, or rather, by the reciprocal action of a single pair of
muscles, are abduction and adduction. The former is accomplished by
the external rectus and the latter, by the internal rectus. Movements
upward or downward necessitate the contraction of at least two
muscles, the former being mediated by
the superior rectus and inferior oblique,
and the latter by the inferior rectus
and superior oblique. When acting
singly, the superior rectus draws the
cornea upward and inward. This ac-
tion is combined with that of the in-
ferior oblique which draws it upward
and outward, but would also, theoret-
ically considered, rotate the eyeball
outward around its sagittal axis. Quite
similarly, the inferior rectus, when
acting alone, pulls the cornea down-
ward, but also adducts it and should
rotate it outward. The superior ob-
lique, on the other hand, deviates the
cornea downward and slightly outward,
but should also turn it inward.
It should be emphasized, however,
that a rotation of the eyeball around Points of Attachment and Lines of
its antero-posterior axis does not take .^S^^ZLS'"" """^ ""'"
place under ordinary conditions,
although the course of these four muscles might warrant us to as-
sume such an action. This point may be proved by first gazing at
the vertical filaments of an electric lamp and then resting the eyes
upon a uniform gray surface. The after-image of these luminous
lines which will then be formed, shows them in their original vertical
position no matter whether the eye be turned upward, downward
or in an oblique direction. Naturally, if the eye were actually
turned around its antero-posterior axis, the after-image of these
filaments should really assume a slanting position. Movements of
the eyeballs around oblique axes require the cooperation of three
muscles, viz.:
(a) Upward and outward; superior rectus, inferior oblique and
external rectus.
r.ext. r.sup, r.int
r.i?tf.
Fig. 471. — Diagram to Show
872
THE SENSE OF SIGHT
(b) Upward and inward; superior rectus, inferior oblique and inter-
nal rectus.
(c) Downward and outward; inferior rectus, superior oblique
and external rectus.
{d) Downward and inward; inferior rectus, superior oblique and
internal rectus.
Binocular Vision. — In man the movements of the eyes are bilateral,
each eye being moved around its center of rotation, situated 13.5 mm.
behind the cornea or 1.3 mm. behind the middle of the eyeball. When
the head is held erect and the eyes are directed to a point at the horizon,
their visual axes are parallel to one another. This constitutes the
primary position. When the eyes are moved directly upward, down-
ward, outward or inward, they occupy secondary positions and when
turned in oblique directions, tertiary positions. The movements of
the two eyes are correlated by a central mass of gray matter,^ the
Fig. 472. — Diagrams to Show Homonymous and Heteronymous Diplopia.
In / the eyes are focused on A; the images of B fall on non-corresponding points,
— that is, on different sides of the foveae, and are seen double, being projected to the
plane of A, giving heteronymous diplopia. In // the eyes are focused on the nearer
point, A, and the farther point, B, forms images on non-corresponding points and
is seen double — homonymous diplopia — the images being projected to the focal
plane A.
anatomical basis for the bilateral character of their innervation being
furnished by the fact that each oculomotor nerve is composed of
fibers derived from both nuclei and that the latter are intimately
connected with one another by commissural fibers. Two chief types
of movements may be recognized, namely :
(a) Movements during which the visual axes of the eyes are kept practically
parallel to one another, no matter whether they are deviated along the vertical
plane of the visual field or laterally outward. Naturally, this parallelism can only
be maintained if the object remains at some distance from the eyes.
(6) Movements during which the visual axes are converged in order to be able
to observe objects near the eyes. This convergence results invariably during near
vision and is therefore accompanied by the contraction of the ciliary muscle.
Converging movements of the eyeballs directed at objects situated
laterally from us, may also be executed, but since these require an
1 Bering's Law of Uniform Innervation, Hermann's Handb. der Physiol., 1879,
III, 343.
BINOCULAR VISION 873
extra effort, they are usually supplemented by movements of the head
as a whole. This furnishes a much simpler means of bringing the
ob j ect into direct opposition with the yellow spots. Furthermore, it will
be noted that the convergence of the eyes necessitates a symmetrical
innervation of the internal recti muscles, while a symmetrical in-
nervation of the external recti is quite superfluous, because we do
not diverge the visual axes during normal vision. In fact, a move-
ment of this kind would give rise to the condition of diplopia or double
vision, for the obvious reason that the rays of light would then be
made to fall upon areas of the retina which are not psychically cor-
related. A condition of diplopia, however, may be established without
much difficulty by exerting a gentle pressure upon one eyeball, so that
it is momentarily forced out of its normal position. Since the retinae
of the two eyes are then activated in dissimilar areas, a double im-
pression in consciousness is the natural consequence.
Diplopia is a common symptom of certain disorders of the nervous
system, leading to disturbances in the coordinated action of the
different orbital muscles. It is true, however, that slight divergencies
are generally compensated for volitionally by simply causing the
weaker muscle to contract more forcibly than it would otherwise, but
naturally, a point will eventually be reached when these extra efforts
cease to produce the desired effect. A condition characterized by a
partial loss of balance of the eye muscles, is designated as heterophoria,
and one characterized by a more complete loss, as strabismus or squint.
In the latter case, the person is quite unable to direct the visual axes
jointly upon the object, but double vision need not result even then,
unless the strabismus is very pronounced or has arisen very suddenly in
consequence of some injury. Most generally, the patient learns by
experience to base his visual associations upon the impressions derived
from the more normal eye, and ignores or suppresses the image from
the non-corresponding area of the opposite retina. Heterophoria,
as well as strabismus, may be mitigated or remedied altogether by the
use of prisms.
This discussion shows that single vision with the two eyes is due to
a fusion of the visual impressions in consciousness, and is largely the
result of experience. Thus, we speak of '^ corresponding points''
upon the retina, although it must be evident that a certain cone in one
retina cannot act in unison with a cone occupying the same position
in the opposite retina. The aforesaid term, therefore, is not indicative
of a histological identity, but of an identity in function. Consequently,
while certain areas in the two retinae may be correlated functionally,
they are not symmetrically placed. This fusion of the visual impres-
sions in consciousness may be illustrated in the following ways:
(a) If the right eye is made to receive a certain impression of red and the left
eye, an identical impression of blue, the result is either a fusion of the two colored
fields (purple) or a struggle of the two fields for supremacy. In the latter case, a
sensation of red alternates with a sensation of blue.
874 THE SENSE OF SlGHT
(6) If the right eye is made to receive a figure composed of horizontal lines and
the left eye one composed of vertical lines, the result is a struggle between these
impressions. Sometimes the former and sometimes the latter gains the upper
hand.
The sum total of the corresponding points in the binocular field
of vision producing a single impression, forms the so-called horopter.^
It differs with every new position of the eyes and may be a
straight or a curved line, a plane or a curved surface.
Visual Judgments. — It has been pointed out repeatedly that our
visual impressions in consciousness are the result of experience. Like
other sense-organs, our eyes are the mere recipients of stimuli which
are moulded into concepts within the cortical realm of vision and these
concepts are acquired gradually by constant repetition. To begin
with, the infant receives these stimuli without being able to interpret
them, because its association areas are as yet incompletely developed.
In the course of a few months, however, it begins to form simple con-
cepts. It follows the course of a moving light with its eyes and also
responds in other ways to stimuli of this kind. A few months later
it has learned to associate objects in space in their proper relations,
irrespective of the fact that the images upon the rods and cones are
inverted.
The adult being, therefore, is guided by the associations thus grad-
ually acquired and does not concern himself with the manner in which
the images are formed in the sense-organ, i.e., the fact that the objects
in space are presented to him inverted he has overcome by experience
and proper psychic interpretation. The visual concepts thus formed
are gradually brought into relation with concepts of a different nature,
so that, for example, the visual concept of a certain object is
subsequently correlated with its taste and odor or with the sound
which it may produce. A similar expansion of our concepts enables
us to form judgments not only regarding the general outline of objects
but also regarding their depth or solidity. Although the most perfect
results are obtained by binocular vision, one eye is quite sufficient to
obtain correct relationships in space, and to rate objects in accordance
with their height, breadth and depth. Obviously, the judgment of
the size of an object is cniefly dependent upon the size of its imag3
upon the retina and hence, upon the angles which its luminous rays
form with the visual angles of the eyes. This requires accommodation
by the ciliary mechanism as well as variations in the position of the
visual axes of the eyes. Since an object at a distance of 5 m. emits
a large number of parallel rays, practically no accommodation is
required. Beyond this point, we must rely chiefly upon the visual
angle, while within this distance, this factor is augmented by the degree
of contraction of the ciliary muscle as well as by that of the orbital
muscles used in converging the visual axes. Lastly, our associations
are based upon certain outside factors, for example, the character
1 Johannes Miiller, Beitr. zur vergl. Physiol, der Sinnesorgane, 1826.
BINOCULAR VISION
875
of the air. Inasmuch as the latter is not entirely transparent, distant
objects cannot be seen so clearly as near objects. In many cases,
this obscuration of the luminous rays of an^ object frequently prompts
us to form an erroneous judgment. Thus, an object dimmed by a
mist ''looms large,'' because we associate indistinct vision with
distance and hence, the sudden relatively large visual image produced
by this near object, leads us to overestimate its actual size.
Concurrently, the size of an object seen in a clear atmosphere, is
L R
Fig. 473. — Right- and Left-eyed Images op Truncated Pyramid. May be Com-
bined TO Produce Solid Image by Relaxing the Accommodation — that is, Gazing to
A Distance Through the Book.
generally under-valued for the reason that distinct vision is
associated with near objects.
The judgments regarding the depth or solidity of objects are formed
in a similar way, i.e., they are based upon several factors, namely:
(a) The difference, in the images formed in the two eyes. Since the eyes are
separated from one another by a certain distance, the right eye sees more of its
right side and the left eye, more of its left side. This difference in the projection
Fig. 474. — Stereoscopic Picture of an Octahedral Crystal. May be Combined
Stereoscopically by Relaxing the Accommodation by the Method of Heteronymous
Diplopia. Hold the Object at a Distance of a Foot or More and Gaze Beyond.
leads to a corresponding difference in the associations. It becomes more pro-
nounced, the nearer the object.
(6) Mathematical perspective. Objects appear in relief and we have learned
to interpret perspective correctly.
(c) Lights and shadows aid our judgment according to their distribution
through the visual field.
\,d) The muscle-sense plays a part in accommodation as well as in the con-
vergence of the visual axes.
(e) Condition of the atmosphere. More distant objects are not so clear as
near objects.
876
THE SENSE OF SIGHT
y.B
The Stereoscope. — The purpose of this instrument is to fuse non-
corresponding images so that they may give rise to a single visual con-
cept possessing solidity. Wheatstone^ accomplished this end by
means of mirrors placed at certain angles to one another, and Brewster^
by means of two prisms. It has been stated above that the images
of a solid object in binocular vision, are somewhat different in the
two eyes, but since they are formed upon corresponding points of the
retinae, they produce a perfectly harmonious relief.
The stereoscope serves to give sohdity to pictures of objects which
would otherwise present only two dimensions, namely those of height
^ and breadth. This fusion of two pic-
tures is effected by permitting each eye
to regard its own field through a curved
prism composed of two half lenses with
convex surfaces, the inner margins of
which are directed inward. A vertical
screen is adjusted between the two
lenses in such a way that the sight of
the left eye is entirely cut off from that
of the right eye (Fig. 475). While the
prisms themselves tend to magnify the
pictures, stereoscopic views are usually
taken with the help of two lenses which
are separated by a distance somewhat
greater than the interocular. Conse-
^''''^%~^^''^^ ^"^ ^i"""'^ quently, the sohdity is in reahty some-
TRATE THE PRINCIPLE OF THE BrEW- ^ '^' iTi •
8TER Stereoscope. what exaggerated. It has been pointed
P and P', the prisms, a, h, and out above that two identical pictures
a, ^, the left- and right-eyed pictures, cannot give a Sensation of rehef, be-
respectively, o, /3, being a point in the 1 ,1 1 • ' c
foreground and a, a, a point in the CaUSe Only the psychlC COmpariSOU of
background. The eyes are converged twO slightly dissimilar images can lead
and focused separately for each point ^^ ^ perception of SOlidity. In Other
as in viewing naturally an object of r i i i i
three dimensions. (Landois.) words, WO have learned by experience
that only those objects can give rise to
this impression which possess solidity. Upon this basis rests the
psychic interpretation of stereoscopic pictures.
Optical Illusions. — It appears, therefore, that seeing is essentially
a process of reasoning in accordance with past experience. This
point is clearly proved by the visual sensations of blind persons whose
sight has been restored in later years by the sudden relief of the condi-
tion causing the blindness. Although these persons have gradually
formed an idea regarding the shape and size of objects by
means of the muscle-sense, they are then quite unable to tell
''which is which," and several days of repeated comparison are required
1 Phil, transactions, 1838.
2 Edinbourgh Phil. Transactions, 1843; also: RoUman, Poggend. Annalen,
1853.
BINOCULAR VISION
877
before they are able to correlate their visual concepts with those pre-
viously established with the help of the muscle-sense. Thus, one person
could not tell which was the. dog and which the cat, concepts formed
solely by the muscle-sense, until he had again felt of the cat's tail and
general contours of its body. In all these cases, the persons made
D B
Fig. 476. — To Illustrate the Illusion of Subdivided Space.
protective movements, because they felt as if the objects were actually
touching their eyes.
While our visual judgment is something quite definite, we are very
prone to form wrong concepts whenever we are subjected to unusual
Fig. 477. — To Illustrate the Over-estimation of Vertical Lines.
conditions, such as may be established by changing the position of our
body as a whole or by altering the configuration of the object. Thus,
a space subdivided by intermediate lines seems larger than one not so
interrupted. Evidently, it requires a somewhat greater muscular
878
THE SENSE OF SIGHT
effort to focalize these lines in succession than if the eyes can sweep
straight across the open field. Quite similarly, if two equally large
squares are subdivided by an equal number of horizontal or vertical
lines, the one subdivided horizontally will appear to be larger from
below upward and the other from side to side (Fig. 476). If we adjust
two lines of equal length at right angles to one another, the vertical
//
V/ ^"^
// \
// \
// ^\
// X
// X
//
//
/
A/ \\
W
\\
\\
\\
\\
w
Y \\
/
/
\
/
//
//
/
/
\
\
\
/
Fig. 478. — Zollner's Lines.
one will seem to be the longer of the two (Fig. 477). This deception
has been explained by assuming that the contraction of the internal
or external oblique muscle, required to visualize the horizontal line,
is effected with a slighter expenditure of energy than that of the
oblique muscles, required to trace the vertical line. In the latter case,
the tendency of the superior rectus to divert the eye inward, must be
Fig. 479.
-Muller-Lyer Figures to Show Illusion in Space Perception. The Lines
A AND B ARE OF THE SaME LeNGTH.
counteracted by the contraction of the inferior oblique which turns
the eye outward.
A very striking illusion may also be produced by placing convergent
and divergent oblique lines upon two parallel lines of the same length.
In the first case, the latter will appear to come together, and in the
second case, to separate more widely. A similar effect may be ob-
COLOR VISION 879
tained with the aid of the so-called Zollner's lines, represented in
Figure 478. This illusion may be explained upon the basis that we
tend to overvalue the size of acute angles. Figure 479 shows two
horizontal lines of the same length which, however, are macje to appear
distinctly unequal by oblique lines affixed to their end-points. Illu-
sions of movement are now extensively employed in cinematographic
pictures. A series of instantaneous photographs having been taken
of a moving object while assuming its successive positions, these pic-
tures may in turn be thrown upon the retina in rapid sucession repro-
ducing the original movement.
CHAPTER LXXV
COLOR VISION
Qualities of Light. — The ethereal vibrations which are capable
of affecting our retinae, have different vibratory qualities. White light,
such as is emitted by the sun, is made up of rays of different wave
lengths or rapidity of vibration. Consequently, if a beam of this light
is made to impinge upon a plane medium of greater density, it is split
into its component rays. Those possessing the more rapid vibratory
rate, are retarded or refracted more sharply than those characterized
by a slow vibration. If the aforesaid medium is arranged in the form
of a prism, this ^'dispersion" or spreading of the different rays will
be even more apparent. We then obtain the so-called prismatic or
solar spectrum (Newton 1657), consisting of seven primary colors,
namely red, orange, yellow, green, blue, indigo and violet. These
colors, however, form a continuous series and gradually shade into
one another. Those which stimulate our retinae vary in their vibra-
tory rate between 392,000,000,000,000 and 757,000,000,000,000 in a
second. In round numbers, therefore, it may be said that we are
subject to rays, the wave lengths of which vary between 400 /zju to
800)Li/x.i Under ordinary conditions, however, we do not recognize
the existence of these rays, because our eyes do not possess the means
of resolving white light into its constituents. Consequently, this
analysis can only be made outside of this receptor, and only when the
retina is subjected to these rays separately, are we in a position to
recognize colors. In this regard, our eyes differ very materially from
the ear, because the latter is equipped with a mechanism for analyzing
sound, i. e., for resolving the compound waves into their simple com-
ponents. It should also be remembered that the spectrum contains
other rays beyond its red and violet ends, and while the latter do not
activate the retinae, they may be made to do so by accessory means.
1 1 MM equals ^oboO ^^-
880 THE SENSE OF SIGHT
Beyond the red we have rays of greater wave length, the so-called heat-
rays, and beyond the violet, rays of smaller wave-length, the so-called
chemical rays. The ultra-violet variety, however, may be raised above
the threshold of stimulation by rendering them fluorescent. This is
true of the Becquerel (radium) and Rontgen rays, the latter causing
a fluorescence of the retina.-^
It will be seen, therefore, that the sensations of color are due to
impacts upon the retina of ether waves of definite length, whether they
be derived from a homogeneous beam or from a mixture of simple lights.
Besides the mere color which is dependent upon the rate of vibration,
these sensations are also modified by the intensity or energy of the
vibrations as well as by the saturation of the primary color. The
intensity of the stimulation gives rise to luminosity or brightness.
Thus, it will be found that the extreme red and violet ends of the spec-
trum are less luminous than the yellow. Furthermore, while we are
able to tell which of two red or green colors is the brighter and are even
able to match them by increasing the intensity of the beam of light,
we fail absolutely when attempting to arrange different colors in strict
accordance with their brightness. These tests, however, may be
greatly varied by changing the illumination. This is shown by the
fact that a colored object appears colorless in low intensities of light,
and that the brightness of the spectrum is then shifted from the yellow
to the green (Purkinje's phenomenon). The saturation of a color is
dependent upon its admixture with white light. Thus, a perfectly
saturated color is one entirely free from ordinary white light, and a
thoroughly colored object, one which reflects specific color rays and no
white rays. Physically, it is not diflScult to establish this condition,
because all we need to do is to restrict the beam of hght to specific
spectral rays. Physiologically, on the other hand, color sensations
are generally not pure, because even monochromatic light appears to
give rise to sensations of white which are thus made to intermingle
with the particular color sensation. In other words, while the physical
saturation of a color may be complete,. the physiological saturation is
generally incomplete.
Color Fusion. — In the same way as white light may be divided into
its components, so may the different spectral colors be reunited into
white light. This can be done very easily by placing suitable lenses
in the path of the colored rays emerging from a prism. It should
also be noted that white hght may be produced by combining only
two, three, four, five, or six of the original seven spectral colors. Any
two colors which give rise to a sensation of white are known as ^^com-
plementary color s.^^
A device most commonly employed to stimulate the retina simul-
taneously with two or more colors is the color-wheel of Maxwell. It
consists of a rotating axis to which may be attached discs of colored
1 Birch-Hirschfeld, Archiv fur Ophthalm., Iviii, 1904, 469.
COLOR VISION 881
pasteboard. The latter are slit radially from periphery to center so
that they may be lapped over each other to expose a larger or smaller
segment of each. Another method is to superimpose different sections
of the spectrum upon a screen by means of a system of lenses or mir-
rors. In either case, this physiological mixing of colors cannot be com-
pared with that employed by the painter. Thus, a blue and yellow
pigment when mixed, give rise to the sensation of green and not of
white, because these two colors combined absorb all the rays excepting
the green, the latter only being reflected into the eye. When used
alone, the formdr appears blue, because it allows only the blue and
some of the green rays to be reflected, while the latter appears yellow
because it absorbs all the rays excepting the yellow. Consequently,
when we mix these colors we obtain a subtraction, the blue pigment
Fig. 480. — Rothe's Rotatory Apparatus for Color Discs. It is so Arranged as to
Give Various Rates of Rotation by Combining the Motions of 1, 2, and 3.
absorbing the red rays which the yellow pigment lets pass, while the
yellow pigment absorbs the blue rays which the blue allows to pass.
Thus, only the green rays are left over.
The colors which may be arranged in a series of pairs to give white
are the following:
Wave-lengths.
Red and greenish blue 656-492
Orange and blue 608-490
Bright yellow and blue 574-482
Yellow and indigo 567-465
Greenish yellow and violet 564-433
The fusion of a pair of colors lying closer together than their com-
plementary colors, yields an intermediate color which becomes more
completely saturated or free from white, the nearer they are to one
another. Thus, the union of red and yellow gives rise to orange,
but the latter is less saturated than the corresponding spectral color.
In the former instances, for example, rays of 656 /xju and 564 /x/x are
56
882 THE SENSE OF SIGHT
mixed, while the spectral orange possesses a wave length of 608 /xyu.
Colors which are more widely separated than the complementary colors,
produce a sensation of purple which is not a spectral color at all but
may be obtained by combining red with violet, the two spectral ex-
tremes. If one or the other of a pair of complementary colors is added
in excess, the resultant sensation is a color similar to the one present
in excess with more white mixed in with it. Supposing that we em-
ploy orange and blue, with the blue present in greater amount than is
necessary to produce white, the result is an unsaturated blue, i.e.,
pale blue.
Visual After-effects. — The fusion of the colors described in the
preceding paragraphs, depends upon the persistance of the individual
stimulations, a second color being thrown upon the retina before the
first sensation has had sufficient time to disappear. This is really true
of all visual impressions, because they invariably last longer than the
stimulus. Everything else remaining equal, these after-images depend
in a large measure upon the intensity of the primary stimulus, i.e.,
upon its strength and duration. Thus, an electric spark generally
leaves a very decided impression in consciousness, because it is intense
although of very brief duration. Quite similarly, if one looks at the
light of a candle, and then closes his eyes, this image persists for ?ome
time thereafter in its natural colors. It then fades away, meanwhile
undergoing certain changes from greenish blue to indigo, violet, rose
and pale orange. But this phenomenon is not restricted to mere
white-black impressions, but also to specific colors. In any case, we
designate them as positive after-images, because they do not change
their original character. Negative after-images, on the other hand, do
not retain their character, but assume colors complementary to those
of the object producing them. White becomes black, red a bluish
green, yellow an indigo blue, and so on. These images are obtained
more frequently than those of the positive kind and may be produced
in the following way. If we gaze intently for a few moments at a red
disc upon a white surface and then at a uniform white background,
an after-image of this disc is obtained which, however, appears green,
while the background assumes a reddish shade. This phenomenon is
usually explained upon the basis of fatigue of the retina toward this
particular color, although it is difficult to reconcile this hypothesis
with all the facts. Nevertheless, it is easy to understand that the
after-image must appear in the complementary color, because the reti-
nal component producing the sensation, say of red, has been considerably
reduced by the exposure, while its greenish-blue element is still present
in normal amounts and is, therefore, still able to produce its character-
istic effect.
Contrast.^— If we place a small white disc upon a larger black field,
the former appears whiter than it would if not contrasted in this way.
Quite similarly, a small black dot adjusted upon a white general field
appears much darker in color than one resting upon a background of
COLOR VISION
883
another quality, and a piece of red paper held against a red background,
does not appear nearly so saturated as one contrasted, say, against
white. A similar contrast niay be obtained by rotating a white disc
containing a certain amount of black, as illustrated in Fi§. 481. On
rotation this disc ought to yield uniform circles of gray, their bright-
ness being least in the center. Instead, each circle presents a darker
outer and lighter inner margin, because the former borders on a zone
darker than itself, while the latter borders upon a zone lighter than
itself.
These phenomena of contrast may also be extended to colors.
Thus, if a piece of gray paper is placed upon a larger green sheet, the
former appears pink or rose-red. The intensity of the latter color may
be increased by covering the whole with a sheet of tissue-paper. It
may also be illustrated by the approximation of colored shadows.
A B
Fig. 481. — A, Black Am) White Disc for Experiment on Contrast; B, Showing the
Result When the Disc A is Set into Rapid Rotation. (Rood.)
This can be done by placing an object of suitable size and shape upon
a white background and illuminating it from one side with day-light
and from the other with gas-light. Two shadows result which are
sharply contrasted against one another. The one thrown by the gas-
lightt appears yellow, while the one produced by the day-light exhibits
a bluish tint, for the reason that it is contrasted against the general
yellowish illumination.
The hypothesis of F^lmholtz which refers contrast to an erroneous
judgment, has been severely criticized by Hering who holds that this
phenomenon is due to the opposing influences of two different regions
of the retina and the visual association areas corresponding to them.
Hering, therefore, ascribes them to the peripheral part of the visual
mechanism and removes from them any purely psychic character.
Evidently, he imagines them to be opposing processes of assimilation
and dissimilation, similar to those occurring during color vision. This
implies that while a dissimilation of a particular substance may be
going on in one part of the retina, a neighboring area may show assim-
ilation. McDougall compares these phenomena of contrast to the
884
THE SENSE OF SIGHT
inhibitor processes going on in the spinal cord during reciprocal inner-
vation. It has been pointed out by Sherrington that the extensor or
stepping reflex may be inhibited by evoking the flexor reflex. In an
analogous manner it is supposed here that the excitation of one part
of the retina prevents similar processes from developing in neighboring
regions or in the neurons innervating them.
The Sensibility of the Retina to Colors. — It will be remembered
that the perimeter is used to map out the visual field for ordinary
objects. It may also be employed for studying the distribution of the
color sense by simply replacing the small white disc by discs of
different colored paper. By bringing the latter into the line of
vision along the different meridians of the eye, it will be found that
the extreme outer zone of the retina is color blind and perceives only
081
Fig. 482. — Perimeter Chart Indicating the Average Fields of Vision for Blue, Red,
AND Green Compared with White (Gray). (Howell.)
objects as such. Somewhat nearer the centel^ of the visual field, we
perceive first blue, then red, and lastly, green. Consequently, the
retina may be divided into three concentric color zones, namely, a
peripheral one for black and white, an intermediate one for yellow and
blue, and a central one for red and green. It is to be noted, however,
that these zones are rarely identical in the retinae of different individu-
als and may even present marked irregularities in one and the same
person. But, many of these variations are referable to differences in
the relative saturation of the colors employed for this test.^ Most
1 Baird, The color sensibility of the peripheral retina, Publ. Carnegie Insti-
tution, No. 29, 1905.
COLOR VISION
885
peculiar abridgments of the color field result in consequence of diseases
of the retina, and optic nerve or of lesions of the visual association area.
Fig. 483. — Perimeter Chart Showing the Highly Restricted Color Fields in the
Left Eye of a Typical Case of So-called Red-green Color Blindness. (Howell.)
Theories of Color Vision. — It has been pointed out above that the
rods and cones are somewhat different in their function. From the
standpoint of color vision it is now commonly believed that the former
Fig. 484. — Diagram to Illustrate the Young-Helmholtz Theory of Color
Vision. Verticals Drawn at any Point of the Spectrum Indicate the Relative
Amount of Stimulation of the Three Substances for that Wave Length of the
Spectrum. (HelmhoUz.)
which alone are present in the zone adjacent to the ora serrata, are
concerned with achromatic vision in low intensities of light, while the
latter are employed for color vision as well as for achromatic vision
in ordinary intensities of light. This conclusion, however, does not
886
THE SENSE OF SIGHT
furnish an adequate explanation for this function, but simply leads to
certain assumptions which have been embodied in the theories now
to be discussed.^ It must be emphasized, however, that the latter are
really mere hypotheses lacking a sound experimental basis. All of
them assume the existence in the retina of certain fundamental sub-
stances which are instrumental in effecting the primary sensations of
color, and the only difference between them really lies in the manner
in which these pigments are distributed.
The Young- Helmholtz theory which was first advocated by Young but has later
on been greatly elaborated by Helmholtz, 2 assumes the presence of three primary
color sensations, designated as red, green and violet (Fig. 484, 1, 2 and 3). These
sensations arise in consequence of the activation of three separate photo-chemical
R 0 Y 6 B V
Fig. 485. — Diagrajm to Illustrate the Herinq Theory of Color Vision.
The curves indicate the relative intensities of stimulation of the three color substances
by different parts of the spectrum. Ordinates above the axis, X-X, indicate catabolic
changes (dissimilation), those below anabolic changes (assimilation). Curve a
represents the conditions for the black-white substance. It is stimulated by all the
rays of the visible spectrum with maximum intensity in the yellow. Curve c represents
the red-green substance, the longer wave lengths causing dissimilation (red), the
shorter ones assimilation (green). Curve b gives the conditions for the yellow- blue
substance. (Foster.)
substances which, on being struck by the rays of light, undergo a decomposition
and generate nerve impulses peculiar to each of them. The red substance is
reduced by the rays of long wave-length, the green substance by rays of medium
wave-length, and the violet substance by rays of short wave-length. When these
chemical elements are excited in an equal measure, the result is the sensation of
white or gray, while no stimulation at all yields black. The other sensations of
color are compound in their nature, i.e., they are dependent upon the joint stimu-
lation of all three substances in different proportions. Thus, yellow is the result
of an excitation of the red and green elements and blue, the result of an activation
of the green and violet substances.
The Hering theory of color vision assumes the presence of four primary sensa-
tions of color, namely, red, yellow, green and blue. These sensations, however, are
supposed to be produced by two groups of photo-chemical substances, namely, red-
1 Calkins, Archiv fiir Physiol., 1902, 244.
2 Handb. der physiol. Optik, Berlin, 1896.
COLOR VISION 887
green and yellow-blue. To these is then added a white-black substance, so that
we have in reality three pairs of recipient elements. Actual sensations of color are
derived from these groups of substances by processes of assimilation and dis-
similation, as follows :
Dissimilation Assimilation
Red-green red green
Yellow-blue yellow blue
White-black white black
Like all other constituents of our body, these substances are first broken down and
then again reformed. They undergo catabolism and anabolism. Thus, if white
light falls upon the retina, the white-black pigment is reduced, this process
giving rise in consciousness to the sensation of white. As soon as this stimulation
ceases, the white-black substance is reformed, setting up in consciousness the sen-
sation of black. But, this recipient is also affected by rays of different wave-lengths
so that the sensations of white and black frequently occur together with those of
the other colors. The yellow-blue and red-green recipient elements, however, are
affected exclusively by rays of their specific wave-lengths.
The Ladd-Franklin theory of color vision ^ assumes that the colorless sensations
of white, gray and black are produced by the excitation of a photo-chemical
substance, designated as gray. While this recipient element is present in the rods
as well as in the cones, only the latter contain it in a form to give rise t6 sensations
of different colors. On exposure to fight this substance is dissociated, the result
being different shades of gray. This is the only reaction possible in the rods, and
hence, these elements give rise exclusively to this particular sensation. In the
coneS; on the other hand, this substance is present in a differentiated form, allow-
ing the development of more complex reactions. The molecules of gray substance
here assume a multiple form so that only certain portions of them are dissociated
by the light. The molecular substance is divided into two parts, one of which is
sensitive to the rays of slow vibration, and the other to those of rapid vibration.
The excitation of the first yields yellow and that of the second blue. The yellow
recipient is again divided into two parts, one of which receives the longest visible
rays (red) and the other the rays giving rise to the spectral green. Thus, the com-
plete dissociation of the red, green and blue recipients produces gray, while the
simultaneous dissociation of the red and green evokes the same sensation as the
dissociation of the entire yellow recipient.
Since this theory necessitates certain new chemical conceptions pertaining to the
differentiation of the molecule, and its complete and partial dissociation, it cannot
be regarded as anything more than a provisional explanation until definite experi-
mental proof has been furnished for these contentions. It is true, however, that
it accounts for certain facts pertaining to color-blindness in a more accurate man-
ner than the two theories mentioned previously. In addition, it furnishes an
explanation for the variations in the visual sensations mediated by the peripheral
zone of the retina.
Color-blindness. — The terms of amblyopia and amaurosis are
employed to indicate an obscurity and loss of sight. In this category
are also placed certain congenital defects of the sense of color which
are present in about 3 per cent, of the eyes examined, but are relatively
rare in woman. In most cases, both eyes are affected and a hereditary
tendency is unmistakable. It also seems that this disorder is more
common among the poorly educated classes.^
1 Psychological Review, 1894, 1896 and 1899.
2 Holmgren, Color Blindness in its Relations to Accidents by Rail and Sea,
Smithsonian Institution Reports, 1878.
888 THE SENSE OF SIGHT
Repeated attempts have been made to harmonize the facts of
color-bhndness with the hypotheses outHned in the preceding para-
graphs. But, inasmuch as this is almost impossible, it seems permis-
sible to adopt a perfectly empirical classification and to state that
one group of color-blind is characterized by an absence of the power
to perceive colors, while the other experiences merely a difficulty
in distinguishing colors. The first possess achromatopsia and the
latter dyschromatopsia, but even the former condition is rarely
complete, excepting in cases of definite pathological changes in the
optic nerve. ^ Consequently, even the achromatopic person is
capable of recognizing one or more fundamental colors. Attention,
however, should be called to the fact that the absence of a particular
color from the spectrum does not imply that perception of its lumi-
nosity has been interfered with. A person may well be able to recognize
the spectrum throughout its entire length and yet be unable to dis-
tinguish more than two colors, say, red and violet.
Upon the basis of the Helmholtz theory, we may divide color-
blindness into blue, green and red-blindness. The most common of
these is the red-blindness, in which the red end of the spectrum is consid-
erably shortened. A person so afflicted confounds Ught red colors with
dark green and cannot see a dark-red square upon a black background.
In fact, the most typical cases show a green-bHndness and are capable
of distinguishing only the yellows and blues. Consequently, the red,
orange yellow, and green appear to them merely as different shades of
yellow, while the green is perceived as gray and the indigo, violet, and
purple seem blue. A person afflicted with green-blindness confounds
light-green with dark red and does not recognize a dark green square
upon a black background, but can perceive a red square upon black.
In many cases, however, they also show a certain interference with
the red end of the spectrum and hence, are really green-red blind,
although they differ from the red-green blind in certain minor par-
ticulars. A person afflicted with blue-blindness, sees only red and
green and confounds blue with green, purple with red, orange with
yellow, and violet with yellow-green. This condition indicates a
shortening of the violet end of the spectrum. Blue-blindness of a
temporary kind may be produced by the ingestion of santonin.
Color-vision is commonly tested by means of a number of skeins
of wool, exhibiting three colors, namely, a pale pure green, a medium
purple, and a vivid red (Holmgren). The person suspected to be
color-blind is asked to match the pale green skein. If red or green
blind, he will recognize this skein as gray with some admixture of
yellow or blue and will match it not only with the green skeins but
also with those possessing a grayish yellow or blue color. If he is
then asked to match the medium purple skein, he will select either
1 Siven and Wendt, Skand. Archiv fiir Physiol., xiv, 1903, 196, and Grunert,
Archiv fiir Ophtbalm., liii, 1903, 132.
COLOR VISION
889
the different purples, the blues and * violets, or only the greens and
grays. In the first instance, this would signify that he is red-blind,
and in the second that he is green-bhnd. If the red-bUnd is then asked
to match the red skein, he will pick out the greens, grays and browns,
possessing a luminosity less than that of the test color, while the greien-
bhnd will select the greens, grays and browns of greater luminosity.
¥
PART VII
SECRETION
SECTION XXIV
THE ** EXTERNAL'' SECRETIONS
CHAPTER LXXVI
THE GROUP OF THE CUTANEOUS SECRETIONS
Classification of the Secretions. — A secretion is a cellular product
which is of further use to the body, while an excretion is a cellular
product which is of no further use to the body. Obviously, this
definition must be held within very general limits, because not all
secretions and excretions are fiuids. It will also be remembered that
the secretions are formed by special colonies of cells which Dresent
themselves as ''externar' and 'in-
ternal" glands. The former possess
a visible duct through which the
secretion escapes, while the latter
do not, and constitute, therefore, the
group of the so-called ductless glands.
Consequently, while the '' external"
secretions are poured upon an open
surface of the body, the internal se- ' ^/
cretions are discharged directly into ^'^'
the blood or lymph stream. For this Fi«- 486.— Diagrammatic Representa-
,^ (. , n TiON OF AN Acinus.
reason, the former most generally r» t^ ^ c ^ n r i v,
,' . ^ -^ D, Duct; S, secretory cells; L, lymph
give rise to local reactions, while the space; C, blood capillaries.
latter are distributed throughout the
body and aid in the promulgation of physiological processes of a more
general and intricate kind. This relatively sharp line of demarcation
already drawn between the '^external" and '^ internal" secretions, may
be elucidated further by briefly noting the histological character of
the glands producing them. The external glands invariably exhibit
a structure which betrays its secretory nature almost immediately,
while that of the internal glands is generally obscure and cannot
readily be associated with secretion.
A secreting mechanism consists essentially of a colony of cells
which are arranged around a central cavity or tube for the reception
891
892 THE EXTERNAL SECRETIONS
of their product. The material required for the formation of the
secretion, is derived from an intricate system of capillaries situated
in the immediate vicinity of their walls. These cells are arranged in
groups forming the so-called acini. By combining many of these acini
we obtain a lobule. Several lobules constitute a lobe and several
lobes the gland as a whole. In general, it may be said that glands
are either tubular or racemose in character and may be either simple
or compound. As an example of a simple tubular gland, we might
mention the sweat glands of the skin or the crypts of Lieberkiihn
of the small intestine; and as an example of a compound tubular gland,
the glands of the pyloric end of the stomach or those of the tongue
or uterus. Simple racemose or alveolar glands are those furnishing
the sebaceous material for the skin, and compound racemose glands
those furnishing the saliva. Some glands, such as the pancreas, are
of a mixed type, combining some of the characteristics of the tubular
with those of the racemose variety. They are called tubulo-racemose
glands.
The Factors Concerned in the Formation of a Secretion. — It was
formerly believed that secretions and excretions are the products of
a process of filtration. It was conceived that the different cells of the
alveoli form a passive membrane, through which the blood plasma
percolates from a place of high pressure to a place of low pressure. Ob-
viously, this mechanism may be represented in a plastic manner
by adjusting a glass funnel lined with filter paper above a beaker.
The solution poured upon this paper takes the place of the blood, because
some of its constituents are forced by pressure through the paper into
the receptacle underneath. In accordance with the pure filtration
theory, the differences in the character of secretions are the result of
variations in the structure and chemical properties of the dialyzing
membrane and not of an active metabolism of its cellular constituents.
Later on this theory was modified by the addition of the factors of
osmosis and diffusion, but even in this case, the epithelium remains
a passive membrane through which these osmotic interchanges between
the blood and the secretion are effected in accordance with ordinary
physical laws.
These factors which have been combined by Ludwig and his pupils,
into the so-called mechanistic theory of secretion, were soon found to
be inadequate, because they failed to explain many of the phenomena
connected with this process. Thus, it was found that the histological
picture of the resting gland is widely different from that of the active
gland, and that in many cases the constituents of the cells could be
traced directly into the ducts. This was followed by the discovery
of distinct secretory nerves, and lastly, by the observation that glandu-
lar processes may also be markedly influenced by chemical means
and frequently furnish a product which is not present in the blood.
All these data were eventually combined into the so-called chemical or
vitalistic theory of secretion, the chief advocate of which was Heidenhain.
GROUP OF THE CUTANEOUS SECRETIONS 893
It is to be emphasized, however, that this chemical theory does not ex-
clude filtration nor osmosis and diffusion as causative factors, but
merely states that these processes are modified by certain intracellular
reactions, the nature of which is as yet not fully understood. Heiden-
hain included the latter under the term of vitalism. It is to be clearly
understood, however, that this term does not refer to metaphysical
phenomena, but simply to a still inexplicable vital activity of the
substance of the cells. This implies that the latter do not act merely
as passive filters, but influence the secretion by their metabolic changes.
Since the internal secretory organs will be more fully described in
a subsequent chapter, the present discussion may be restricted to the
''external" secretions. Several of these have already been alluded to
in the preceding paragraphs, for example, the cerebro-spinal fluid,
the intraocular fluid, the tears and the fatty material of the Meibomian
follicles of the eyelids. There still remain to be considered the sweat,
the milk, the mucous secretion of the buccal and oral glands, as well as
the lymphatic secretions and the very important group of the digestive
juices, formed by the saliva, gastric juice, duodenal juice, bile, pan-
creatic juice and intestinal juice.
The Skin as an Organ of Protection. — The skin consists of the epi-
dermis or cuticle and dermis or cutis vera. The former appears as a
layer of stratified epithelium measuring 0.08 to 0.12 mm. in thickness.
Its deepest layer or rete Malpighii is composed of protoplasmic nucle-
ated cells, possessing a cylindrical shape. The cells of the surface
layer, on the other hand, are hard and horny, non-nucleated, flat-
tened chips which are constantly discharged, their places being taken
by new cells arising from the rete Malpighii. While being gradually
pushed outward, the latter assume the physical and chemical char-
acteristics of the surface cells Pigment cells are found in the deeper
cells of the epidermis as well as in those of the corium; iii the former,
however, the pigment is disseminated while in the latter, it is restricted
to particular cells. From here this pigment is said to migrate into
the more external Malpighian layer, a contention which fully explains
the fact that the skin of a white person, grafted to a negro, presently
becomes thoroughly pigmented.
With the exception of the palms of the hands, soles of the feet,
dorsal surfaces of the last phalanges, glans penis and certain parts of
the labia, the skin is beset with larger and smaller hairs. These ap-
pendages are epidermal growths contained in the skin pits or hair
follicles. The part within the follicles is known as the hair-root.
Physically hairs are characterized by their marked elasticity and co-
hesion, which properties render them capable of supporting a weight
of as much as 60 grams. They are very resistant, because composed
of a pigmented,' horny, fibrous material; and are strongly hygroscopic,
a property which explains the painful sensations generally experienced
in scars during wet weather. The gradual change in the color of the
hairs may be caused either by a diminution in the amount of their pig-
894
THE EXTERNAL SECRETIONS
ment or by the presence of minute air-bubbles within their medulla
and fibrous layer. These bubbles reflect the light very strongly.
The former change is the usual cause of the grayness of the hair in
old age, whereas its sudden turning gray is due principally to the
formation of these vacuoles.
Physiologically, it is of interest to note that the adult human individual pro-
duces about 0.20 gram of hair-substance in the course of a day, but this amount
may be greatly increased by heat, massage, and the cutting of the hair. Attention
has already been called to the fact that numerous smooth muscle cells lie in relation
with the hairs which bridge over the angle formed by the obliquely placed roots
of the latter and the surface of the skin. The contraction of these muscle fibers,
therefore, must lead to an erection of the
hairs and the peculiar reflex phenomenon,
known as "goose flesh." This reaction
most commonly arises in consequence of
local or general stimuli, such as cold, emo-
tions, and irritations within the domain of
the autonomic nervous system. A few
cases, however, have been recorded which
show that the pilo-motor mechanism may
be brought under the control of volition. ^
While the question of whether cats and
other animals are able to erect their hairs
at will, cannot be decided definitely, it
seems that this reaction is not always
wholly reflex but embraces a strong ele-
ment of volition. For the present, how-
ever, it must be placed in the group of the
perception or association reflexes. The
sensitiveness of the hairs which plays so
important a part in the sensations of
touch, is subserved by a ring-like plexus of
nerve fibrils surrounding the hair-follicle.
In the second place, it should be noted
that the contracton of these muscle cells
exerts a certain pressure upon the neigh-
boring sebaceous glands, causing them to
discharge their oily secretion in greater
quantities than before. Moreover, since
the ducts of these glands most commonly
empty directly into the hair-follicles, a means is provided to keep the hairs soft
and pliable. In the third place, it should be remembered that these scattered
muscle cells play an important part in determining the vascularity of the skin,
because their contraction hinders the passive expansion of the capillaries, thereby
keeping the blood in the deeper parts of the body, while their relaxation allows
the superficial capillaries to become injected with blood drawn from other organs
and tissues. Without doubt, these vascular changes possess an important bearing
upon the regulation of the body-temperature, because the relaxation of the cuta-
neous capillaries invariably leads to a greater dissipation of heat, and vice versa.
In this connection brief mention should also be made of the fact that the effect
of cold and warm baths upon the circulation is made possible in part through thesa
muscle cells, and in part through the muscle cells of the arterioles themselves.
The Skin as an Organ of Secretion. — The sebaceous glands are
simple acinous in character and are usually found in close relation with
1 Maxwell, Amer. Jour, of Physiol., vii, 1902, 369.
Fig. 487. — Nerve Terminals Around
THE Root of the Hair Follicle.
M, Medulla; P, papilla; ^.external
root sheath; /, internal root sheath; N,
ramification of the nerve fiber.
GROUP OF THE CUTANEOUS SECRETIONS 895
the roots of the larger hairs. Their ducts open directly into their
sheath. But the other regions of the skin are not free from them; in
fact, many of them contain them in large numbers, their excretory ducts
then opening free upon the surface. ' They are especially numerous
upon the forehead, nose and back; but are absent from the volamanus
and planta pedis. Closely related to these glands are those of the labia
minora, glans penis, and prepuce as well as the ceruminous glands of
the external auditory meatus. The acini of these structures are
packed with polyhedral and flattened cells which divide and gradually
move outward in successive layers, where they disintegrate in the
oily semi-liquid secretion filling the duct. In this way, a fatty ma-
terial is formed which on exposure to the air assumes a cheesy consist-
ency. When the ducts of these glands become blocked, this material
undergoes retrogressive changes and then forms a fertile medium
for the growth of the ordinary pus-microbes.
The exact composition of this secretion is not known. It contains
fats, soaps, cholesterin, albuminous material, remnants of epithelial
cells and inorganic salts. -^ The cerumen or ear-wax contains a
reddish pigment and possesses a bitter-sweet taste. Similar materials
are the smegma prseputii and the fatty and odoriferous secretions of
the anal and uropygal glands of many animals. The sebaceous material
which is generally found upon the skin of the newborn infant, is known
as vernix caseosa.^ Its distribution alone would indicate that it
possesses a manifold function. Thus, it may rightly be concluded that
it serves to lubricate the surface of the skin and to protect the hairs
against drying. Moreover, since it is spread out in an almost continu-
, ous layer across the skin, it aids in retaining the body-heat and plays,
therefore, an important part in regulating the body-temperature.
This fact is clearly recognized by the northern races, such as the Esqui-
maux, because they carefully preserve this secretion and even inten-
sify its action by anointing their bodies with fatty substances. In
the aquatic animals it serves a twofold purpose, because it protects them
against any undue loss of heat and diminishes the friction between
their integument and the water. Lastly, the modified secretions of
the anal, uropygal, and sexual glands of many animals no doubt play
an important part in the production of the sexual reflexes.
The sweat-glands are simple tubular in' character and consist of a
coiled up portion which occupies the deeper layer of the skin, and a
long winding duct which penetrates the corium and epidermis and
eventually terminates in a funnel-shaped enlargement upon its surface.^
They are found in especially large numbers upon the palms of the
hands, the soles of the feet, in the axilla, groin and upon the forehead,
but are absent from the glans penis, prepuce and the margins of the
^ Linser Dissertation, Tubingen, 1904,
2 Zumbusch, Zeitschr., ph. Chemie, LIX, 1909, 506.
3 Rabl (Histology of the Sweat-Glands) in Handb. der Hautkrankheiten,
Wien, 1901.
896
THE EXTERNAL SECRETIONS
lips. Their number has been estimated at two millions^ and their
total secretory surface at 1080 m^ The cells lining the coiled up
extremity of these glands are columnar in shape and possess a gran-
ular cytoplasm. Externally they border upon a dense network of
capillaries.
The sweat is a clear, colorless liquid of low specific gravity (1.004). It consists
of 982 parts of water per 1000 c.c; and contains small quantities of salts, neutral
fats, volatile fatty acids, and traces of proteins and urea. The inorganic salts include
sodium chlorid and small quantities of alkaline
sulphates and phosphates. The latter impart
to it a faint alkaline reaction, although when first
secreted it is prone to be acid, owing to the pres-
ence of a slight amount of sebaceous material.
Profuse sweating, however, may yield other pro-
teins, such as uric acid, creatinin, ethereal sul-
phates, phenol, skatol, and albumin. ^ Conse-
quently, sweating is called for whenever the
activity of the kidneys is temporarily suppressed.
Muscular exercise also tends to augment the urea
content of the sweat, and in addition, gives rise
to an elimination of CO2 which may amount to
as much ^s 20 grams per day. Under normal
conditions, however, the secretion of sweat serves
merely as a means of eliminating water and not
of solid excrements. While this fact may be re-
garded as sufficient reason to classify sweat as an
excretion, the use made of it subsequently in
moistening the surface of the body and in regulat-
ing the body-temperature, may prompt us to con-
sider it as a secretion.
The small quantity of sweat generally
produced, evaporates and leaves non-vola-
tile constituents upon the skin,^ but
naturally, its total quantity differs greatly
with the general condition of the body
and the surroundings. A person dressed
moderately warm may secrete as much
as 2 or 3 liters in a day, although an out-
side temperature which causes the tem-
perature of the skin to rise above 33°C.,
yields a much larger quantity. A part
of this may be removed by evaporation,
while the remainder forming the so-called visible sweat, is absorbed by
the clothing or is lost in mass. Naturally, a moisture-laden atmos-
phere retards the evaporation and tends to produce a much larger
quantity of visible sweat than a dry and warm atmosphere. It should
also be remembered that the secretion of sweat is closely correlated
with that of urine, because copious sweating most generally diminishes
1 Krause, Handb. der Anatomic, 1879.
2 Brieger and Dieselhorst, Deutsch. med. Wochenschr., xxx, 1904, 161.
« Schierbeck, Archiv fiir Anat. und Physiol., 1893, 116.
Fig. 488. — Diagrammatic
Representation of the Skin,
Showing the Location of the
Sweat Glands.
H, Horny layer; L, stratum
lucidum; M, Malpighian layer;
P, corpuscles of Paccini; PL,
papillae of the cutis vera; C,
cutis vera; S, sweat gland; SC,
subcutaneous tissue.
GROUP OF THE CUTANEOUS SECRETIONS 897
the elimination of water by the kidneys, and vice versa. Both of
these processes are related in turn to the intestinal secretions, because
watery stools are invariably associated with a diminished excretion of
water by the. other channels.
The Innervation of the Sweat-Glands. — The sweat-glands are
richly supplied with nerve fibers, some of which are doubtlessly secre-
tory in their nature. They perforate the membrana propria and form
mulberry-like end-organs directly upon the outer surfaces of the cells.
According to Langley,^ those innervating the glands of the cat's
hind limb leave the spinal cord in the first and second lumbar nerves,
enter the sympathetic system and leave it again in the gray rami
of the sixth lumbar to the second sacral nerves. Their chief outpour-
ing takes place in the seventh lumbar and first sacral rami. All of
them enter into the formation of the sciatic plexus. A similar out-
pouring occurs between the fourth and tenth thoracic nerves, the fibers
of which eventually enter the brachial plexus.
The presence of these secretory fibers has been demonstrated by
Goltz^ who stimulated the distal end of the divided sciatic nerve and
observed drops of sweat appearing upon the hairless skin covering the
balls of the feet. This effect may also be evoked after the ligation of
the abdominal aorta as well as after the amputation of the leg, but
naturally, only a very limited amount can then be obtained, because
the cells are no longer able to acquire new secretory material. Under
normal conditions, this nervous mechanism is activated by rises in
the temperature of the atmosphere as well as by increases in the blood-
pressure following muscular activity and increases in the water con-
tent of the body. Furthermore, many factors are constantly at work
which tend to vary the amount and character of this secretion. It is
a well known fact that the skin in fever is dry and that the subsequent
reappearance of the sweat is generally accompanied by a fall in the
body-temperature. In other words, a moist skin is a favorable diagnos-
tic sign, because it facilitates heat-dissipation. Profuse sweating is
frequently associated with dyspnea, nausea and psychic impressions
of terror. Among the drugs which influence the character of this
secretion should be mentioned pilocarpin and atropin. The former
stimulates its flow by acting directly upon the terminals of the secre-
tory nerves, while the latter diminishes it by paralyzing these endings.
Alcohol produces a dry skin and nicotine a moist skin. Cold lessens
the secretion, because it gives rise to a reflex constriction of the cutan-
eous blood-vessels.
The Mammary Glands. — Each fully formed mamma consists of
15 to 20 lobes, which are composed of lobules and the latter in turn of
numerous groups of cells or acini. The smaller ducts emerging from
these eventually unite into a large lactiferous duct which opens
through the nipple. Externally to their point of union the different
1 Jour, of Physiol., xii, 1891, 347.
2 Pfluger's Archiv, xi, 1875, 71.
57
898 THE EXTERNAL SECRETIONS
lobular ducts are enlarged into sinus-like reservoirs, which may be-
come highly distended during the periods of active secretion of this
gland. The orifice of the lactiferous duct is invested by areolar tissue
and smooth muscle fibers, the latter effecting the erection of the nipple
on reflex stimulation. Around its base winds a narrow zone of dark-
tinted skin which is beset with very sensitive papillae and contains
numerous minute secretory glands of the sebaceous type. Although
doubtlessly belonging to the group of the cutaneous glands, it is
difficult to classify the mammae either as modified sweat-glands or
as sebaceous glands. Their alveolar character as well as the fatty
character of their secretion, might prompt us to homologize them with
the latter, but since their secretory cells are short columnar in outline
and are arranged in a single row, they really present a much closer
'•esemblance to the former. Their size, number, and position vary
greatly in different mammals. In man, they are placed one upon
each side of the anterior aspect of the thorax and are copiously supplied
with blood-vessels, lymphatics and nerves.
The histological character of these glands varies considerably
and especially during pregnancy and lactation. When milk is first
formed, the epithelium of the alveoli becomes sharply differentiated
from that of the ducts. While the lining of the latter remains cub-
oidal in shape, that of the former becomes elongated toward the lumen,
and shows a prohferation of the nuclei as well as numerous new granules
and fat-globules. This state is soon followed by one of active secre-
tion. The cells then enlarge still further and project markedly into
the lumen of the acini. Fat-droplets now appear in much greater
numbers, while the granules which during the early secretory period
presented a spherical outline, are now elongated and spiral in shape. -^
A part of the inner segment of each cell then disintegrates, its fragments
being forced into the duct. This fully explains the fact that the early
secretion invariably embraces many epithelial cells which are only
partly transformed, and are, therefore, known as colostrum corpuscles. ^
The places previously occupied by these fragmented cells, are
again taken up by new ones formed by karyokinetic division from
neighboring cells. In many cases, however, the ruptured inner part
of the cell is again closed, whereupon the cytoplasm is slowly reformed.
During pregnancy, the mammae enlarge and become firm and ten-
der to the touch. Their blood-supply then increases enormously, as
is evinced particularly by the formation of prominent plexuses of
veins. The areola investing the base of the nipple, becomes broader
and darker in color and shows very prominent papillae. The nipple
itself increases materially in size. Evidently, these macroscopic
changes find their origin in a gradual proliferation of the secretory
cells and the formation of many new acini. This process of evolution
begins soon after conception and does not cease until shortly after
1 Steinhaus, Archiv fiir Physiol., 1892, 54.
2 Heidenhain, Hermann's Handb. der Physiol., 1883.
GROUP OF THE CUTANEOUS SECRETIONS 899
the birth of the young. The flow of milk, however, does not commence
as a rule until labor has been completed; in fact, in woman it does not
begin until 24 or 48 hours afterward, but its onset may be considerably
hastened by the mechanical stimulation of the mammae. In woman the
duration of the period of lactation varies from a few days to almost a
year, but much depends upon their general condition and the stimuli
to which they have been subjected. Inasmuch as the onset of a new
pregnancy brings this secretion to a close, lactation is frequently made
to continue by artificial means in order to prevent a new conception,
but this practice fails in most instances to have the desired effect.
Lactation having been completed, the glands involute, i.e., they under-
go retrogressive changes which finally lead to the establishment of the
normal histological picture of the resting organ.
The Innervation of the Mammary Glands. — Since the mammary
glands do not seem to be in possession of secretory nerves, we cannot
help being astounded at the close adaptation of the activity of these
organs to the condition of the developing young. Thus, we find that
the mammae begin to grow very shortly after conception and continue
their growth until the birth of the young. With surprising exactitude
the milk pours forth, not to cease until the end of the period lactation,
i.e.y about six to nine months thereafter. The only condition for it
is to remove it regularly — preferably in a normal way by the process
of suckling. Obviously, we are dealing here with a most remarkable
transfer of function, because while the fetus abstracts its nutritive
material directly from the mother's blood with the help of the placenta,
the infant derives its nutritive material entirely from the mammae.
But this change is not at all detrimental to the young, because milk is
a preparation which is accurately adapted to its assimilative and
dissimilative power.
The progressive character of the development of the mammae sug-
gests that it is controlled by some mechanism which in turn is in-
fluenced by the sexual organs. Regarding this point, v/e have
the positive experimental evidence that extracts of corpus luteum of
the ovary and of the developing uterus give rise to an active growth
of the mammae even in non-pregnant animals.^ Secondly, we shall see
later that the internal secretion of the pituitary body possesses a pro-
nounced excitatory influence upon the flow of milk, but while it seems
to have been definitely established that the aquisition of the full
functional power of the mammae is controlled by chemical stimuli of
the type of the hormones, it cannot be denied that a reflex nervous
factor is at work. Thus, it has been found that the stimulation of
sensory nerves is followed by a diminution in the amount of this secre-
tion and that, in woman, the period of lactation may be cut short by
strong emotions, epileptic seizures, and other general functional dis-
turbances. Moreover, this influence may be reciprocal, because the
artificial suppression of this secretion may have deleterious effects upon
1 Lane-Claypon and Starling, Proc. R. Soc, 1906, and Hammond, ibid., 1917.
900 THE EXTERNAL SECRETIONS
the health of the woman. In this connection, it is also of interest to
note that the act of suckling excites tonic contractions of the uterus, a
means commonly employed to cause this organ to assume its former
shape after labor, and especially when this involution is slow and is
associated with hemorrhage. It should also be noted that the secre-
tion of milk is not exclusively a function of the pregnant female,
because many cases are on record of men and boys possessing well
developed and actively secreting mammae. It had also been observed
that virgin bitches may produce milk and that sterile mules may
yield sufficient milk to suckle a foal.
Properties of Milk. — When the mammae first begin to discharge
their secretion, they do not yield pure milk but a peculiar fluid which
is known as colostrum. A few drops of this secretion may usually be
obtained within a short time after the completion of labor by gently
massaging the breasts in the direction of the nipples. Its total amount,
however, is never considerable although it flows more freely later on.
As has been stated above, this material is gradually flushed out of the
ducts, giving way in the course of two or three days to pure milk.
To begin with, the colostrum appears as drops of a watery and usually
very cloudy fluid, possessing a specific gravity of 1.040 to 1.080. In
larger quantities it exhibits an opalescent, yellowish appearance, and
gives rise to a coagulum of similar color. The pigment to which the
latter is due, is contained in its fatty admixtures. When examined
under the microscpoe, it is seen to contain numerous fat-globules and
fragmented cells, among which are many leukocytes which have
migrated and have become loaded with fat-droplets. Colostrum
yields little or no casein but about 3 per cent, of proteins, consisting
of coagulable lactalbumin and lactoglobulin. Moreover, while it con-
tains as much fat as the pure milk secreted subsequently, it embraces
somewhat greater quantities of lactose and salts. Colostrum is na-
ture's laxative, and hence, the infant should be allowed to partake of
it freely.
The milk, following the colostrum, is an opaque fluid, possessing a yellowish
white or bluish white appearance according to its concentration. It possesses a
sweetish taste and a very characteristic odor. Its specific gravity varies between
1.026 and 1.036, the highest values being generally obtained only in well nour-
ished women. It is neutral to litmus, alkaline to lacmoid, and acid to phenol-
phthalein. When examined under the microscope, it is seen to consist of a watery
part, or milk-plasma and numerous fat-globules, or milk-corpuscles. The diameter
of the latter varies between 1/x and 6/x. Here and there we also recognize
fragrtiented epithelial cells, leukocytes and nuclear material. Milk, therefore, is
essentially an emulsion of fat, the opaque appearance of which is due to the diffuse
reflection of the light by these globules. On standing, these droplets of fat rise
to the surface, owing to their lesser specific gravity, and form the cream. By
mechanical agitation the latter may be made to coalesce to form butter. This fact,
that it requires agitation to coalesce the fat-globules, has been the subject of much
study. Thus, it has been shown that the globules in cow's milk are invested
by a mucous-like envelope, which must first be broken up before the fat can run
together. In addition, it has been assumed that the globules in other types of milk
are surrounded by a haptogen membrane which is formed of the proteins of the
GROUP OF THE CUTANEOUS SECRETIONS
901
cell from which they have been derived, but it seems scarcely necessary to make
this assumption, because such an investment might more easily result in conse-
quence of the molecular attraction of the fat for the neighboring protein particles. ^
If milk is boiled, a "skin" is formed upon its surface, which consists of lactal-
bumin, casein and calcium salts. Furthermore, when exposed to the air, milk
undergoes a peculiar fermentation in consequence of the entrance of micro-organ-
isms, chief among which is the bacillus lacticus. Its reaction then changes to sour,
owing to the formation of lactic acid from lactose. Milk may also undergo
plcoholic fermeniation. While this change is not easily effected by means of yeast
cells, it is readily brought about by fungoid growths. The milk-sugar is converted
into glucose and galactose and the latter into alcohol and carbonic acid. In this
way, such preparations as Koumiss and Kephir have been derived. The coagula-
tion of milk is usually brought about by means of rennin, an enzyme contained in
the gastric juice of mammals. The clot, or curd, consists of casein and entangled
fat-droplets, while the fluid residue, or whey, embraces sugar, salts, albumin and a
newly-formed protein called whey-protein.
The Composition of Milk. — The formation of milk depends not
only upon the condition of the mother but also upon that of the infant.
A robust woman, especially a multipara, may yield a large enough
quantity to feed half a dozen infants, but naturally, the true physio-
logical measure is the amount which is required for the wellf are of a
single infant, weighing, say, 3000 to 3500 grams. These requirements
are compiled in the succeeding table :
1 day 20 grams
2 days 75 grams
3 days 168 grams
4 days . . ; 252 grams
5 days 303 grams
6 days 353 grams
7 days 367 grams
2 weeks 472 grams
3 weeks 512 grams
4 weeks 512 grams
5 weeks 577 grams
6 weeks 613 grams
7 weeks 691 grams
Required by infant
A comparison of these data with those now following shows conclu-
sively that the average woman furnishes an ample supply of milk,
and that the quantity secreted increases steadily as demanded by the
growth of the infant, until about the 28th week, when its amount di-
minishes up to the end of the period of lactation.
Secreted by mother
1 day 20 grams
2 days 97 grams
3 days 211 grams
4 days 326 grams
5 days 364 grams
6 days 402 grams
7 days 478 grams
1 week 502 grams
1 Hammarsten, Lehrb. der physiol. Chemie, 1907, und Raudnitz, Ergebn.
der Physiol, ii, 1903.
Secreted by mother
902 THE EXTERNAL SECRETIONS
3-4 weeks 572 grams
5-8 weeks 736 grams
9-12 weeks 797 grams
13-16 weeks 836 grams
17-20 weeks 867 grams
21-24 weeks 944 grams
25-28 weeks 964 grams
29-32 weeks 916 grams
33-36 weeks 909 grams
37 weeks 885 grams
The fats of milk are similar to those contained in adipose tissue. Their propor-
tion may be given as follows: olein, ^^, palmitin, 3^; stearin, 3^ ; butyrin, caproin,
and caprylin, 3^4. In milk-plasma are found various proteins, a carbohydrate,
lactose, inorganic salts and a small amount of lecithin and nitrogenous extractives.
The principal protein is called caseinogen. It belongs to the group of the phos-
phoproteins and may be precipitated by acids, such as acetic acid, or by saturation
with magnesium sulphate, or half-saturation with ammonium sulphate. Rennin
causesit to coagulate with the formation of casein. This process is employed in the
preparation of cheese, the curd consisting of casein and entangled fat-globules.
If this coagulated mass is allowed to stand, milk-serum separates from it. The
latter contains two other proteins, namely, lactalbumin and lactoglobulin. The
carbohydrate is milk-sugar or lactose, a disaccharide of the composition: C12H22O11.
When hydrolized it takes up water and galactose :
Ci2H22Hii + H2O = C6H12O6 + C6H12O6
It may be also be found in the urine of woman during the early days of lactation,
when there is a reabsorption of the lactose owing to an insufficient withdrawal
of the milk. For the same reason, it may enter the urine during and after the period
of weaning. It then gives the ordinary tests for reducing sugar. The salts of
milk consist of calcium phosphate, a small quantity of magnesium phosphate and
the chlorids of sodium and potassium. Especially marked is the richness of
milk in calcium, phosphorus, and magnesium, as compared with the blood-serum.
This is of greatest importance for the growth of the bones, while the growth of the
tissues necessitates potassium rather than sodium. At all events, it is a most
striking fact that these cells are capable of selecting from the fluids of the body
only those salts which are of greatest use to the developing young. This selective
action they also display in the formation of caseinogen and lactose, both of which
do not exist as such in the blood or lymph. It is by means of this concentration of
materials of the proper kind that the rabbit is enabled to double its weight in six
days, the dog in 96 days, and the infant in 108 days.
The practical importance of these brief chemical data becomes
apparent immediately if a substitute must be sought for human milk.^
Although other types of milk are more like human milk, we are then
accustomed to use cow's milk, because it is most easily procured. Its
composition, however, is very unlike that of human milk, as the
following tabulation will show:
Human Cow's
Water 87.16 87.10
Fat 4.28 4.20
Casein 1 .04 3.25
Sugar 7.40 5.00
Ash 0.10 0.52
^ Voltz, in Oppenheimer's Handb. der Biochemie, 1910, iii, 382.
THE LYMPHATIC AND MUCOUS SECRETIONS 903
The most important differences may be briefly summarized as fol-
lows:
(a) Appearance. Cow's milk is white in color and opaque, while human milk
is more translucent and possesses a yellowish or bluish hue in accordance with its
concentration.
(6) Reaction. Cow's milk is acid, while human milk is alkaline,
(c) Specific gravity. Cow's milk: 1.030-1.035; human milk: 1.024-1.035,
{d) Character of the curd. Rennet produces with cow's milk a dense and firm
coagulum which is not easily digested, while human milk yields under the Bame
circumstances a light, flocculent and easily digestible clot.
(e) Histological character. The fat-globules of cow's milk are invested by a
relatively thick albuminous envelope.
(J) Bacteriological character. Human milk is in a practically sterile condition
when withdrawn from the breast.
These differences in the chemical composition and reaction must
first be removed by diluting cow's milk to reduce the casein and by
adding to it cream and milk-sugar, making the whole alkaline in re-
action. The danger of microbic infection of cow's milk may be obvi-
ated by pasteurization, i.e., by subjecting the milk to a temperature of
167-175°F. which sterilizes it, but does not impair its nutritive value.
The following formula may be employed as a sample :
Top milk 5 drams
Water 5 drams
Lime water . . . 1 dram
Sugar of milk . ; . ., 20 grains
But this '^himianized" cow's milk cannot be regarded as a perfect
substitute for natural mother's milk. Undoubtedly, there are also
certain other differences present which the chemist has not detected as
yet. As one of these might be mentioned the qualitative differences
between the caseinogen of different types of milk.
CHAPTER LXXVII
THE LYMPHATIC AND MUCOUS SECRETIONS
The Spleen. — Since this organ possesses the characteristics of
lymphatic tissue and has not been proved to furnish an internal se-
cretion, it may properly be considered under the heading of the lym-
phatic glands. It is, of course, a ductless organ and belongs to the
group of the hemal bodies which are distinguished from the ordinary
lymphatic glands by their red color and by the fact that their sinuses
contain only blood. Histologically it is of importance for us to re-
member that it is enveloped by a capsule of fibrous tissue, containing
elastic fibers and smooth muscle cells. Numerous septa or trabeculse
extend from its inner surface into the interior of the organ which they
904 THE EXTERNAL SECRETIONS
subdivide into compartments containing the spleen pulp. The latter
is dark red or reddish-brown in color and is composed chiefly of cells
embedded in a ground substance of fibers and the prolongations of large
nucleated cells. Some of the latter greatly resemble lymph-corpuscles,
while others contain a pigment which is closely allied to the hemo-
globin of the red blood corpuscles. Scattered through the pulp are
many red corpuscles and the fragments derived from them. The
blood-vessels enter and leave this gland at the hilus and remain at first
confined to the trabeculse. Eventually, however, they terminate in
a network of capillaries in the pulp, their endothelial lining becoming
continuous with that of the rete of the latter. The sheaths of these
minute arteries are beset with rounded bodies, the so-called Malpigh-
ian corpuscles, the structure of which is practically identical with that
of a lymph nodule. The veins also begin as opened tubules. Conse-
quently, it will be seen that the cellular elements of the splenic pulp
are in actual contact with the blood and not with the lymph, as is the
case in other organs. This arrangement enables the blood to be poured
out directly into the interstitial spaces of this organ.
The Function of the Spleen. — Since the removal of this organ is
not followed by serious consequences, the conclusion seems justified
that it does not furnish an internal secretion which is essential to life.
In fact, the symptoms of splenectomy are transient in their nature
and betray themselves in an anemia, a greater cholesterol content
of the blood, and a greater resistance to hemolytic agents. ^ Further-
more, it is possible to transplant this organ into the subcutaneous
tissues, but the growth of these transplants is not assured, unless the
animal is still young and is not in possession of left-over splenic tissue.
In other words, the transplanted portion is more prone to degenerate
if a portion of the spleen has been left in the body or if the animal has
reached a stagie of its life when the function of this organ is no longer
absolutely essential, because its loss may then be more easily compen-
sated for by the other lymphatic tissues. ^ These facts strongly point
toward the presence of a hormone which stimulates the growth of the
transplant.
In the absence of more positive results following the removal of
this organ and in view of its characteristic lymphatic structure, it
may be assumed that it is engaged in the formation of white blood
corpuscles. This assumption is correct, because it has been shown that
the blood of the splenic vein contains large numbers of lymphocytes.
Secondly, it is a well-known fact that the disease, known as leucocy-
themia, in which the number of the white cells is greatly increased, is
invariably associated with an enlargement or hypertrophy of this or-
gan. Large numbers of these cells may then be released from his
organ by causing it to contract by means of an electric current applied
to the neighboring abdominal wall.
1 Karsner and Pearce, Journ. Exp, Med., xvi, 1912, 769.
2 Manely and Marine, Jour. Exp. Med. xxv, 1917, 619.
fc
THE LYMPHATIC AND MUCOUS SECRETIONS 905
It has also been established that in embryonal life the spleen pos-
sesses the function of a hematopoietic organ and that its power of form-
ing corpuscles may be called into play during adult life whenever
required. In fact, it seems to retain this function during the entire life
of some animals, because it embraces cells which display all the charac-
teristics of the hem^toblasts of the bone marrow. In these animals, the
removal of the spleen gives rise to a hypertrophy of the bone marrow.
The spleen is one of the organs in which the red corpuscles of the
blood undergo disintegration. This inference is based upon the fact
that the pulp contains an abundance of these cells in varying stages of
degeneration. This statement, however, is not meant to imply that
this organ is the chief place in which the red corpuscles are destroyed,
nor that their disintegration actually leads to a liberation of their color-
ing material, the hemoglobin. More plausible is the view which holds
that the spleen merely accomplishes the fragmentation of the worn
out corpuscles which are then more fully reduced in the liver. Un-
der pathological conditions, however, its destructive power may be
greatly increased, as is proved by the fact that it then becomes a
depository for iron which can only be derived from the red corpuscles.
Such a condition is developed in the course of the disease, known as
pernicious anemia. It has also been demonstrated that the spleen
aids in the formation of uric acid, because the removal of the kidneys
gives rise to an accumulation of this substance within this organ.
Attention has previously been called to the spongy character of the
pulp of the spleen which enables this organ to accommodate enormous
quantities of blood. With the help of the smooth musculature of its
capsule and trabecule, this blood is again returned into the general
circulation. For this reason, it may be conjectured that this organ
acts as a vascular reservoir or diverticulum for the digestive organs or
the portal circulation. Its smooth musculature is innervated by
fibers which closely invest the splenic arteries and are derived from the
celiac ganghon of the solar plexus. In this way, the spleen is brought
into correlation not only with the other portal organs but also with
the central nervous system. Stimulation of these nerves evokes a
vaso-constrictor reaction which prevents the arterial blood from
entering the spleen, while its venous tubules are emptied. The
division of these nerves, on the other hand, gives rise to an engorge-
ment of this organ and a withdrawal of a considerable quantity of blood
from the general circulation. Of special interest is the fact that these
alterations in its vascularity may also result in consequence of reflex
stimulation; in fact, Roy^ and others state that they appear with
almost rhythmic regularity at the rate of one in about every minute.
Since the mechanical effect of these ordinary wave-like contractions
upon the general circulation cannot be considerable, they must be more
1 Jour, of Physiol., iii, 1881, 203, also Schaefer and Moore, Jour, of Physiol.,
XX, 1896.
906 THE EXTERNAL SECRETIONS
especially concerned with a periodic renewal of the blood filling the
splenic spaces.
The Tonsils. — The faucial tonsils consist of two globular masses
of lymphoid tissue placed in the recesses between the palatal arches.
Although originally developed in two lobes, an upper and a lower, this
demarcation disappears shortly before birth and the entire organ then
appears as a nearly spherical, slightly flattened disc which is attached
to the floor of the tonsillar sinus by a root consisting of tonsillar tissue
and a fibrous investment. The latter, in fact, spreads over its entire at-
tached surface and becomes continuous with the fibrous layer of the
neighboring mucous membrane. A number of membranous septa
extend from its surface into the substance of this organ, subdividing it
into a number of lobules. Its outer surface is covered with epithelium.
The crypts of the tonsil may be single or branched. In the former
case, they retain a rather uniform diameter throughout their course,
while in the latter, their outer portions are much narrower than their
inner. They are directed, as a rule, in a straight line toward the sur-
face and show no contents with the exception of irregular accumula-
tions of cellular debris. Consequently, the capsule of the tonsil with
its trabeculse forms an inverted replica of the epithelium in which
are situated the blind ends of the crypts. A thin layer of lymphoid
tissue surrounds their basal portions, whence it extends outward and
divides the different crypts into several colonies.^
The Function of the Faucial Tonsils. — The tonsils reach their
highest development in the mammals in which they show a steady
growth early in life. They atrophy later on. Regarding their func-
tion we know little, the only definite conclusion beingthat they play the
part of a hematopoietic tissue. This inference seems justified in view
of their lymphoid structure. Many of the lymphocytes produced in
the germinal centers of their follicles find their way through the epithe-
lium into the crypts, where they help in the formation of the cheesy
masses so often found in these ducts. A certain number of them also
enter the general efferent lymphatics of the neck. It is a suggestive
fact that the tonsil attains is greatest activity during the early years
of life, when the body is still growing and is greatly in need of large
numbers of white corpuscles. It will be remembered that the other
lymphoid nodules are at this time similarly active. Consequently, the
tonsils merely participate in a general function and the part played
by them may readily be compensated for by other lymphoid tissues.
These facts tend to show that a mild degree of hypertrophy of the
tonsils is to be expected in early youth and that the removal of these
organs should not be advocated unless their size and condition leads
to such symptoms as impaired breathing, and an interference with the
voice and movability of the palate.
The preceding deduction may be employed as a means of disposing
1 Barnes, The Tonsils, Faucial, Lingual and Pharyngeal, St. Louis, 1914.
THE LYMPHATIC AND MUCOUS SECRETIONS
907
of the assumption that the tonsils give rise to an internal secretion.^
The fact that the now extensively practised enucleation of these organs
does not produce untoward symptoms should be sufficient to prove
this point. Those investigators who nevertheless adhere to the con-
trary contention, must admit that this secretion cannot be specific,
but must be common'to all the lymphoid tissues so that the activity of
the tonsils may be compensated for by other structures. A third con-
tention is that these organs protect the organism against bacterial in-
vasion. This assumption is in accordance with the general conception
that lymphoid nodules act as sieves and catch the infectious particles
in their meshes. While it cannot be denied that the tonsils possess
an influence of this kind, it is also true that they form a relatively
open connection between the cavity of the mouth and the lymphatics
of the neck and may, therefore, rather invite in-
fection than prevent it. In fact, tonsillectomy is
frequently practised to do away with this possible
source and path of infection, and especially if
these organs have been the seat of inflammation
(tonsillitis) and are in part disintegrated. These
cases are usually benefited by tonsillectomy, but
naturally, this is not a sufficient reason to con-
demn the tonsils as perfectly useless organs and
to advocate their removal as soon as they rise
above the margins of the faucial pillars.
The Lingual and Pharyngeal Tonsils. — The
lingual tonsil consists of a variable number of
lymphoid nodules arranged along the base of the
tongue next to the median line. The pharyngeal _
tonsil or adenoid is a similar mass of lymphoid celjTshowing the Ac-
tissue which is suspended from the vault of the cumulation and Dis-
naso-pharynx immediately behind the nasal ^^^^^^ ™^ ^^^^^^
choanse. Smaller depositions are found upon the
posterior and lateral walls of the pharynx. Their histological char-
acter is practically identical with that of the faucial tonsil, and so is
their function.
The Mucous Glands and Their Secretory Product.— A large
number of small glandular bodies are found in the mouth and ahmen-
tary canal which furnish a very viscous and stringy secretion.^ This
quality is imparted to it by a special constituent, the mucin. In
accordance with their distribution, these glands may be classified as
buccal, palatinal and hngual. Their structure is practically identical
with that of a simple tubular gland, possessing large and clear lining
cells. Obviously, the function of this viscous secretion is to lubricate
the mucous surfaces.
A very good illustration of the action of a mucous gland is furnished
1 Massini, Int. Secretion of the Tonsil, New York Med. Jour., 1898, and Scheier,
Berliner Laryngol. Gesellsch., 1903.
Fig. 489. — Goblet
908 THE EXTERNAL SECRETIONS
by the goblet cells with which the epithelial lining of the intestine is
equipped. Scattered among the ordinary reticular cells are some
which undergo constant alterations in their size and shape. Origi-
nally columnar in outline, they are slowly elongated, because their
cytoplasm gradually increases until their free ends project beyond the
general surface of the mucosa. The internal tension having reached
its physiological limit, their inner walls rupture, allowing a large part
of their contents to escape into the intestinal lumen. Being still in
possession of its nucleus, the partially emptied cell forms new material
and closes the defect in its wall. Many of these cells, however, go
to pieces, their places being taken by cells hitherto dormant. The
material which is in this way extruded into the intestinal canal con-
tains large amounts of mucin, the purpose of which is to lubricate the
mucosa. This is of especial value in the large intestine in which the
fecal material becomes partially hardened on account of an absorption
of a considerable portion of its water. In this particular segment of
the alimentary canal, the ordinary goblet cells are augmented by the
modified cells of the crypts of Lieberkiihn. It will be pointed out
later on that these crypts possess a true secretory power only in
the small intestine and become ordinary mucous glands in the large
intestine. .
CHAPTER LXXVIII
THE DIGESTIVE SECRETIONS
A. SALIVA
The Salivary Glands. — Heidenhain recognized two types of glands,
namely, the mucous and the albuminous or serous. Strictly speaking,
this classification is not quite correct, because even the simple mucous
glands of the oral mucosa furnish at least some albuminous material,
while traces of mucin are also found in the albuminous salivary glands.
The first of the digestive secretions is the saliva. It is supplied by the
so-called salivary glands of which there are six in all, namely, two
parotid, two submaxillary and two sublingual glands. Since these
organs are paired, it suffices to state that the first lies above the ramus
of the lower maxillary bone, while the last two occupy positions upon
the floor of the mouth in close proximity to the angle of the jaw. It is
true, however, that the arrangement of these glands differs somewhat
in different animals. In the dog and cat, for example, the sublingual
is wanting entirely, its function being transferred to the so-called retro-
lingual gland which is situated somewhat nearer the angle of the jaw.
In the pig, all three basal glands are present, ^.e., the submaxillary,
retro-lingual and sublingual. Traces of the second are sometimes
found in man, in addition to the three just enumerated.
THE DIGESTIVE SECRETIONS 909
These anatomical variations are associated with very striking
histological differences as well as with differences in the character of
the secretion. Naturally, the saliva obtained from the mouth is
a mixed secretion, because it is derived from three sources, namely:
(a) from Stenson's duct- which drains the parotid gland and opens upon
the inner surface of the cheek opposite the second molar tooth, (6)
from Wharton's duct which conveys the submaxillary secretion into
the groove next to the frenulum of the tongue, and (c) from the ducts
of Rivinus which drain the sublingual gland. The latter are multiple
and may form as many as twenty different tubules. In the dog, one
of them most generally attains a considerable caliber and pursues a
course parallel to Wharton's duct. It is known as the duct of Bartho-
lin. While the chemical characteristics of saliva will be dealt with in
a later chapter, it may be stated at this time that the parotid secretion
is clear serous in character, while that of the sublingual gland is very
viscous and stringy^ The submaxillary furnishes a secretion which
displays intermediate qualities.
The Histological Character of the Salivary Glands. ^^ — Each gland
is made up of lobes and lobules, and each lobule in turn of numerous
groups of tubulo-saccular alveoli or acini. Each acinus consists of
a number of large and rather square cells which surround the inner
extremity of every small duct. The appearance of these so-called
chief cells varies with the character of the secretion. In the fresh
state, those forming the mucous glands, such as the sublingual, con-
tain large granules of mucinogen which is the precursor of mucin.
In the fixed state, on the other hand, these cells appear swollen, the
center of their clear cytoplasm being occupied by a well differentiated
rounded nucleus. In many of these mucous glands, such as the sub-
maxillary of the dog and cat, the different alveoli of chief cells are in-
vested by crescentic groups of marginal cells which stain deeply and
contain no mucinogen. These formations are the demilune cells or
crescents of Gianuzzi. Other glands present a mixed character and
embrace acini composed of mucous cells right beside those made up
of albuminous cells. This is true not only of the submaxillary gland
of man in which the serous cells predominate, but also of the sublingual
gland, in which the mucous cells are more numerous. In the rabbit,
the submaxillary presents the characteristics of a serous gland and the
sublingual those of a mucous gland. It need scarcely be mentioned
that these structural peculiarities are associated with corresponding
differences in the character of the saliva.
Such glands as the parotid, and in part also the submaxillary,
furnish a watery and non-viscid secretion. Their chief cells are filled
with small granules of an albuminous type which constitute the mother-
substance of the active principle of the saliva, called ptyalin. Upon
it depends the digestive power of this secretion. While resting in
the cells these granules are designated as zymogen granules, or ptyaHn-
1 R. Metzner, in Nagel's Handb. der Physiol., Braunschweig, 1907.
910
THE EXTERNAL SECRETIONS
ogen. They remain inactive until discharged into the ducts, when
they are immediately converted into the active enzyme ptyalin.
Histological Changes During Activity. — A most interesting feature
of the activity of glands is that they undergo certain very characteris-
tic changes in their structure. While this is true of the lacrimal,
gastric and pancreatic glands, none exhibit them in a more striking
manner than the salivary glands. They were first studied by Heiden-
hain^ in fixed and stained preparations of the parotid and submaxillary
glands of the rabbit, but have also been observed by Langley ^ and others
in fresh preparations. When resting these cells are large and faintly
outlined against one another by delicate cell walls. Their cytoplasm
is evenly packed with granules which stain deeply with the ordinary
dyes. Near the basement membrane are found their somewhat
irrgular and dark nuclei. Contrary to this picture, a cell which has
been made to secrete for a considerable length of time, is smaller, more
Fig. 490. — Acini of the Submaxillary Gland During Rest (R) and Activity (A).
The Dark Outer Cells Represent the Demilune Cells.
translucent, and contains a rounded nucleus which occupies a position
near its center. Many of these cells, in fact, appear merely as a nar-
row frame of cytoplasm, investing a very prominent rounded nucleus.
The granular material has disappeared from the entire inner part of the
cell and is now arranged in the form of a narrow zone along its margin
next to the duct.
These changes clearly prove that these cells lose a certain part of
their substance in the course of their activity; in fact, Heidenhain
states that many of them disappear altogether, but reform their con-
tents during the subsequent period of rest. Of special interest is
the fact that the active cell gradually discharges its zymogen granules
which, as has been mentioned above, give rise to the enzyme ptyaUn.
Upon the cessation of this stimulation, the stage of dissimilation is
followed immediately by a stage of assimilation during which the
material lost is again replenished. A clear non-granular material
is then seen to invade the basal segment of the cell which is gradually
1 Noll, Ergebn. der Physiol., iv, 1905.
2 Jour, of Physiol., x, 1889, 433.
THE DIGESTIVE SECRETIONS 911
converted into the granular substance so clearly betrayed by the renting
cell. In the mucous cells it has been observed that their large granules
swell up and disappear, probably in consequence of an inhibition of
water which causes the mucinogen to be converted into mucin. The
fact that salivary secretion is associated with such pronounced histolog-
ical changes cannot surprise us, if it is remembered that the submaxil-
lary gland of the dog secretes its own weight as saliva in the course of
five minutes and is able to continue this process for many hours.
The Paralytic Secretion of Saliva. — It has been found by CI.
Bernard (1864) that the division of the chorda tympani innervating
the submaxillary gland, gives rise to a continuous secretion of saliva
which begins about two days after the division and persists for a period
of about two or three weeks. At the end of this time the gland is
mu'ch smaller than the one on the opposite side and exhibits a charac-
teristic picture of degeneration.^ The cells are small and their nuclei
irregular, fragmented and deeply colored. These changes may be
rendered more conspicuous by the simultaneous division of the sympa-
thetic fibers. Obviously, we are dealing here with a trophic disturb-
ance in this gland which finally leads to its exhaustion. In other words,
in the absence of its normal innervation, the local nervous elements
are quite unable to effect an anabolism sufficient to compensate for
the catabolism resulting in consequence of some endogenous stimulus.
The processes of dissimilation finally gain the upper hand and cease
only after the secretory material has been completely exhausted.
The Innervation of the Salivary Glands. — The secretion of saliva
is a reflex act made possible by the existence of definite reflex circuits.
The center controlhng this act is situated in the medulla oblongata,
but its boundaries have not been estabhshed with any degree of defi-
niteness. It is safe to assume, however, that a part of it is formed
by the deep origins of those nerves which participate in the innerva-
tion of the salivary glands, namely by the nuclei of the facial and
glossopharyngeal nerves. Salivation is a function apportioned to the
autonomic system. In last analysis, therefore, the peripheral nerves
controlling this process are autonomic in their character, although
they select typical cerebrospinal paths in gaining access to the center.
On the efferent or motor side, the salivary center is connected with
the different glands by means of two separate sets of fibers, constituting
the so-called cerebral and sympathetic paths. The former reach the
glands by way of one or the other of the cranial nerves, while the latter
first enter the thoracic sympathetic system and then ascend in the
cervical sympathetic nerve. Having attained the superior cervical
ganghon, they follow in the course of the different arteries to their
respective glands.
This arrangement may be studied most conveniently in the dog,
in which animal the cerebral nerve supply of the parotid is derived
* Maximow, Archiv fur mikr. Anat., Iviii, 1901, 1, and Gerhardt and Burton-
Opitz, Pfluger's Archiv, xcvii, 1903, 317.
912
THE EXTERNAL SECRETIONS
from the system of the glossopharyngeal nerve, and that of the sub-
maxillary from the system of the facial nerve. In the first instance,
these fibers become recognizable in the tympanic branch of the glos-
sopharyngeus which is known as the nerve of Jacobson. From here
InfmorTflaxiUan
Ganglioru
Fig. 491. — Schematic Repbesentation of the Course of the Cerebral Fibers to the
Parotid Gland. (Howell.)
they reach the otic ganglion by way of the small superficial petrosal
nerve. Upon their emergence from this autonomic outpost, they
attain the parotid gland by following the highway of the auriculo-
TnferioflPaxiUar)/
Fig. 492.
^rariches
-Schematic Representation of the Course of the Chorda Tympani Nerve
TO THE Submaxillary Gland. {Howell.)
temporal branch of the inferior maxillary division of the fifth cranial
nerve (Fig. 491). The cerebral fibers of the submaxillary gland leave
the facial system in the form of a small nerve, known as the chorda
tympani. After their emergence from the tympanic cavity through
THE DIGESTIVE SECRETIONS 913
the Glaserian fissure, they attach themselves to the Ungual branch of
the fifth cranial nerve. Having followed this highway for a short
distance, they again pursue a separate course along Wharton's duct to
the hilum of this gland. .A small ganglion, known as the submaxillary
ganglion, marks the point where these fibers diverge from the lingual
nerve (Fig. 492). Langley, however, believes that the fibers destined
for the submaxillary gland do not form synapses here, but merely
skirt its border, while those fibers which innervate the sublingual
gland actually terminate in this structure to be continued as secondary
fibers. This ganglion, therefore, should really be called the sublingual
ganglion.
Those fibers, which first enter the sympathetic system, traverse the
thoracic ganglia and become a part of the cervical sympathetic nerve.
They form synapses in the superior cervical ganglion, whence their
postganglionic fibers continue onward along the arteries supplying
the different salivary glands.
On the afferent or sensory side, the salivary center is connected
with a number of external as well as internal receptors. Under or-
dinary conditions, however, the former are of greater value, because a
flow of saliva may be evoked by impressions received from the retina
and olfactory cells as well as by stimuli produced by the food as it
traverses the oral cavity. Thus, it is a matter of common exper-
ience that a flow of saliva may be elicited by the mere smell and sight
of food as well as by psychic stimuli. The opposite effect, in the form
of a dry mouth and parched throat, is incited by fear, embarrassment
and anxiety. Consequently, the salivary center must be connected
reflexly with the olfactory cells, the retina and some of the higher
association centers. Lastly, this center must be in reflex communica-
tion with various general interoceptors, because the feeling of nausea,
visceral pain, and other internal sensations frequently give rise to a
copious flow of saliva.
The Mechanism of Salivary Secretion. — The secretion of saliva
is a reflex act which may be evoked by the stimulation of any one of the
receptors just mentioned. It should not be assumed, however, that
these stimulations affect the different glands in a perfectly uniform
manner, giving rise to a definite quality of saliva under all circum-
stances. The truth seems to be that the quality of the secretion varies
with the quality of the stimulation. Thus, a more specific excitation
of the parotid yields a serous saliva, and a more specific stimulation
of the sublingual a mucous saliva. Such variations are not at all
uncommon, and their occurrence may easily be demonstrated experi-
mentally. Thus, if a fistulous communication is established between
the duct of the submaxillary gland and the outside, a copious flow of
saHva may be produced by the introduction into the mouth of either
a 0.25 per cent, solution of hydrochloric acid or of powdered meat.
On analysis it will then be found that the type of saliva secreted after
the ingestion of meat, contains approximately twice as much solid ma-
ss '
914 THE EXTERNAL SECRETIONS
terial as that obtained with the aid of the acid. What is true of the
submaxillary must also be true of the other glands ; but naturally, these
differences cannot be detected so readily directly within the mouth,
because all three secretions are poured into this common reservoir at
one time. It is also of interest to note that the daily amount of saliva
furnished by each gland exceeds its weight ten or twelve times. The
total production of these glands, therefore, cannot be less than one
liter, this quantity including the small portion which is poured forth
constantly to moisten the surfaces of the mouth as well as those
extra amounts which are produced from time to time in response to
stimulations.
The facts which may be mentioned in explanation of these funda-
mental differences in the saliva, must necessarily be of a very general
kind, because they are based upon the still very obscure microphysical
and microchemical occurrences in cells. Thus, it may be assumed that
the nerves innervating the salivary glands are capable of conveying
impulses of different kinds or that each nerve contains separate sets
of fibers which react specifically to different stimuli.^ This assump-
tion finds substantiation in the fact that the action of the cerebral
(parasympathetic) nerve is quite different from that of the sympa-
thetic nerve. To illustrate, if the chorda tympani is stimulated, it
will be found that the submaxillary gland reddens and becomes
warmer to the touch, because its blood-vessels are markedly dilated. ^
It may then also be observed that the blood returned from this
gland possesses a much brighter color, and that the small vein draining
it pulsates markedly. These pulsations are due to the arterial pulse
which is propagated at this time directly through the dilated and
non-resistant capillaries. Contrariwise, the excitation of the cervical
sympathetic nerve causes this gland to become pale, to decrease in
volume, and to become distinctly cooler to the touch. These changes
unmistakably point to alterations in its blood-supply, the exci ation
of the chorda tympani giving rise to vaso-dilatation and the stimula-
tion of the sympathetic fibers to vaso-constriction.^
Curiously enough, these changes in the vascularity of this gland
are associated with very decided changes in the quantity and quality
of the saliva.^ Very soon after the beginning of the stimulation of
the chorda tympani, Wharton's duct becomes highly distended and
discharges a quantity of saliva four or five times larger than normal.
The secretion itself is very watery and possesses only a slight viscidity.
It contains no more than 1 or 2 per cent, of total solids. If a suffi-
ciently long interval is allowed to separate the successive stimulations,
1 Pawlow, Ergebn. der Physiol., iii, 1905.
2 CI. Bernard, Compt. rend., 1858.
3 These differences may also be recognized by means of the stromuhr or current
measurer. See: Burton-Opitz, Jour, of Physiol., xxx, 1903, 132.
* First observed by Ludwig, Arbeiten aus dem physiol. Institut zu Leipzig,
1851.
THE DIGESTIVE SECRETIONS 915
this experiment may be repeated for many hours without any apparent
decrease in the intensity of the reaction. Contrary to this result, the
excitation of the cervical sympathetic nerve yields only a few drops of
saliva which is characterized by its turbidity and richness in total
sohds (6 per cent.). On the one hand, therefore, we obtain a vaso-
dilatation and copious flow of a very watery saliva and, on the other,
a vaso-constriction and a scanty flow of a very viscous saliva. Very
similar changes may be evoked in the parotid gland; in this case,
however, the excitation of the sympathetic nerve does not yield an
appreciable quantity of secretion, although it produces marked his-
tological changes in the secretory cells.
Regarding the intracellular changes little can be said unless we
confine this discussion to the structural alterations during rest and
activity. Secretion is essentially a transudation of water from the
blood-vessels into the excretory ducts, controlled, of course, by the
constituents of the cell. It is conceivable that the agents most
actively concerned in this process are those granules of the cytoplasm
which take up water, swell and discharge their contents into the ducts.
How this osmotic play may be influenced by impulses brought to
these cells by way of the secretory fibers, is largely a matter of specula-
tion into which we cannot enter at this time. It is certain, however,
that the cell is not merely a pumping mechanism for the flow of water,
but also serves as a generator of organic material which is later on
transferred into the watery medium.^ Obviously, the waves of excita-
tion derived from the chorda tympani, must increase this transudation
as well as rupture the granules, but it is also conceivable that the
aforesaid secretory nerves may innervate different elements of the
gland. While it has been shown that they terminate around the vari-
ous alveoli, forming here delicate arborizations below tl^e basement
membrane, certain evidence has also been presented to prove that the
cerebral autonomic fibers are apportioned to the chief cells and the
sympathetic fibers to the cells of the crescents of Gianuzzi. At least,
this arrangement seems to prevail in the submaxillary gland of the dog.
Upon the basis of Mtiller's Law of the specific nerve energy we might
then assume that these mechanisms react differently to different kinds
of stimulations enacted by the food. In one case, we would obtain a
typical chorda-saliva, and in another, a typical sympathetic-saliva,
or even a mixture of the two.
Barcroft and Piper^ have sought to obtain a measure of the energy
evolved by a secreting gland by ascertaining its respiratory exchange
when resting and when active. Thus, it has been found that the sub-
maxillary gland of the dog consumes 0.25 c.c. of oxygen in a minute and
liberates 0.17 c.c. of carbon dioxid. During this time 6 grams of
gland-tissue furnish about 1.1 calorie of heat. The active organ, on
1 MacuUum introduces the factor of differences in surface-tension, Ergebn. der
Physiol., xi, 1911.
2 Jour, of Physiol., xliv, 1912, 359.
916 THE EXTERNAL SECRETIONS
the other hand, requires 0.86 c.c. of oxygen per minute and yields
6.39 c.c. of carbon dioxid.
It has also been noted that the activity of the salivary glands is ac-
companied by changes in their electrical potential which originate in the
formation of electrolytes and their movements through animal mem-
branes. These differences are similar to those observed in active
muscle and nerve, and may be detected by applying the poles of a gal-
vanometer to the surface and the hilum of the gland. The surface is
then galvanometrically positive. In the case of the submaxillary
gland, the stimulation of the chorda tympani first increases and then
decreases this positivity, which fact signifies that this current pos-
sesses a diphasic character. The one evoked by the stimulation of the
sympathetic nerve, on the other hand, presents itself merely as a
negative variation of the current of rest.
The Action of Drugs upon the Secretion of Saliva. — If atropin is
administered intravenously or is injected into the duct of the sub-
maxillary gland, the stimulation of the chorda tympani soon ceases to
produce its characteristic secretory effect. Meanwhile, however, the
excitation of the sympathetic nerve remains effective and much larger
doses of this alkaloid are required to abolish the flow of this type of
saliva. The vaso-dilator action of the chorda also persists until
additional doses have been administered. This peculiar result sug-
gests that atropin paralyzes the endings of the cerebral autonomic
fibers, but does not affect the secreting cells themselves. Secondly,
it points toward a definite chemical difference between the nervous
elements constituting the cerebral or parasympathetic system and
those forming the sympathetic system proper. Pilocarpin evokes
a copious flow of saliva which is accompanied by vaso-dilatation.
This agent, therefore, possesses an antagonistic action to the preceding
one and stimulates the endings of the cerebral nerve. Ergotoxin para-
lyzes the synnpathetic mechanism, but does not affect the one
controlled by the chorda tympani. This fact, again, speaks for the
previous contention that the cerebral and sympathetic autonomic fibers
differ from one another in their chemical constitution. Adrenalin
evokes a constriction of the blood-vessels which, in some animals, is
soon followed by a vaso-dilatation and a considerable flow of saliva.
Nicotin may be used to abolish the action of the secretory nerves,
but since it does not affect the secreting cells nor the nerve terminals,
it must produce this effect in an indirect way. It is a well-known
fact that it destroys the synapses and hence, may be employed to cause
a functional discontinuity between the preganglionic and postgan-
glionic paths. Thus, if the submaxillary (sublingual) ganglion is
moistened with a solution of this alkaloid, the stimulation of the chorda
tympani centrally to this ganglion ceases to evoke a secretion from the
sublingual gland, because the fibers destined for this organ are relayed
at this point. ^ Moreover, inasmuch as this procedure does not block
^Langley, Proc. R. Soc, London, 1889.
THE DIGESTIVE SECRETIONS 917
the impulses apportioned to the submaxillary gland it may rightly be
concluded that the fibers innervating this organ pass directly through
the aforesaid ganglion without forming new connections.
Facts Disproving the Filtration Theory. — While it cannot be denied
that filtration plays an important part in the secretion of saliva, we are
not warranted in believing that it is the only factor mediating this
process. It has previously been noted that the excitation of the chorda
tympani gives rise to a vaso-dilatation and a copious flow of a very
.watery type of saliva, while the stimulation of the cervical sympathetic
nerve evokes a vaso-constriction and a scanty flow of a very viscous
saliva. While these changes may at first be thought to favor filtration,
they cannot be interpreted in this way if contrasted with such facts
as the following:
(a) We have noted above that the formation of saliva is not wholly
dependent upon the blood-supply, but is more closely related to the
influences of the nervous system.
(6) It has also been pointed out that this secretion may be either
increased or decreased by drugs without altering the pressure existing
in the capillaries of the gland from which the material is taken. ^
(c) Inasmuch as the saUva contains bodies, such as mucin and ptya-
lin, which are not present in the body-fluids, the secreting cells must
possess the specific power of forming them. Carlson states that saliva
also contains a diastase which is present here in smaller amounts than
in the blood.
(d) It has been shown that saliva may also be secreted by the sub-
maxillary glands after its artery has been ligated, and that
(e) The normal gland may be made to secrete against a higher pres-
sure than the capillary pressure.
Under ordinary conditions, the salivary cells derive their secre-
tory material from the blood-capillaries in which the pressure does not
rise above 40 to 60 mm. Hg. They then discharge it into the salivary
duct in which the pressure approximates zero. This arrangement
favors filtration. It can be shown, however, that these cells are also
able to secrete against a pressure which not only exceeds the capillary
pressure, but also that prevaihng in the carotid artery. Thus, if
Wharton's duct is connected with a mercury manometer, and the
chorda tympani is stimulated repeatedly at intervals, it will be found
that the mercury continues to rise until it eventually indicates a pres-
sure at least twice as high as that existing in the capillaries of the sub-
maxillary gland. In fact. Hill and Flack^ have succeeded in obtaining a
salivary pressure of 240 mm. Hg against a blood-pressure of 130 mm. Hg.
Now, if filtration were the only factor concerned in the formation of
saliva, a relationship of this kind could not be successfully estabhshed.
The same conclusion may be derived from the fact that even the
^ Sarmus, Zeitschr. ftir Biologie, Iviii, 1912, 185.
2 Proc. R. Soc. London, Ixxxv, 1912.
918 THE EXTERNAL SECRETIONS
bloodless gland is able to secrete saliva, but since this organ is unable
to acquire new material, the secretion will be scanty in amount.
The General Character of Saliva. — When collected directly from
the mouth, saliva is a transparent, slightly opalescent and slimy
liquid, possessing a moderate viscosity and a specific gravity of 1.002
to 1.006.-^ On standing it becomes cloudy, this change being due to the
deposition of calcium carbonate in consequence of the escape of car-
bonic acid which formerly retained this salt in the form of its bicarbon-
ate. The reaction of saliva is slightly alkaline, but may become
moderately sour during the night and during fevers and digestive
disorders. The reason for this is the diminution in its quantity
which favors the bacterial decomposition of its organic constituents.
Its active principle, ptyalin, ceases to act in a markedly alkaline or
slightly acid medium; in fact, free hydrochloric acid in an amount
equalling a 0.003 per cent, solution suffices to stop its action entirely.
Temperatures of 0° C. and 65° to 70° C. have a similar effect.
The quantity of saliva secreted in a day has been estimated in man at 1 to 2
liters, in horses at 40 liters, and in the large ruminating animals at 60 liters. It
contains 0.5 per cent, of solids, which may be classified as follows:
Organic: Mucin, which gives to it its ropy, mucilaginous character.
Ptyalin, an amylolytic enzyme.
Protein, of the nature of a globulin.
Potassium sulphocyanide.
Inorganic: Sodium chlorid, sodium carbonate.
Calcium phosphate and carbonate, magnesium phosphate and potas-
sium chlorid.
Suspended in the saliva are desquamated epithelial cells, disintegrating leukocytes,
the so-called "salivary corpuscles," gland cells and clumps of mucin. Among the
living organisms might be mentioned a number of saprophytes, such as leptothrix
buccalis, and pathogenic bacteria.
CHAPTER LXXIX
THE DIGESTIVE SECRETIONS (CONTINUED)
B. THE GASTRIC AND PANCREATIC SECRETIONS
The Gastric Glands. — The cavity of the stomach is divided into
a cardiac, fundic and pyloric portion. It is lined throughout by a soft
and thick mucosa which presents a honeycomb appearance owing to
the presence of numerous shallow polygonal depressions. Its unusual
thickness is due very largely to the fact that it is made up of an almost
infinite number of closely packed, long tubular glands which are held
1 Burton-Opitz, Biochem. Bull., 1919; Neilson and Terry, Am. Jour, of Physiol.,
XV, 1906, 406; Tezas, Maly, xxv, 1905.
THE DIGESTIVE SECRETIONS
919
together by slight amounts of reticular tissue. In between these
glands are found columnar goblet cells which secrete mucus. The
former consist of a basement membrane which is covered externally
with epithelium. Toward the gastric surface the enlarged outer
portions of these tubules narrow into a duct which is lined by short
columnar cells. In many cases the latter
^^li^ffiilare mucus-secreting, the same as those
situated directly upon the inner surface of
the mucosa. The epithelium of the outer
portions of these tubules differs somewhat
Fig. 493. Fig. 494.
Fig. 493. — Diagrammatic Representation of a Fundic Gland.
C, Chief cells; P, parietal cells; D, duct of gland; N, neck of gland.
Fig. 494. — Part of Tubule of a Fundus Gland, with the Lumen and Secretory
Canaliculi Stained Black ; the Gland-cells are also Shown.
C, Chief or central cells; p, parietal or oxyntic cells; I, lumen of tubule prolonged
into arborescent canaliculi which penetrate to the parietal cells. (Zimmermann.)
m
m different parts of the stomach, so that we are able to recognize
three distinct types of gastric glands, namely:
(a) The glands of the cardiac end, which are simple tubular or tubulo-racemose
in character and are lined by short columnar cells containing much granular mate-
rial. They are few in number and are found principally in the immediate vicinity
of the esophageal-gastric junction.
(b) The glands of thefundus, which are distributed throughout the remaining
portion of the cardia and the entire fundus. They consist as a rule of three
or four long tubular glands which unite into a short duct. The low columnar
cells lining these ducts gradually pass over into the true secretory cells which are
somewhat polyhedral in shape and are partly filled with granules occupying a posi-
920 THE EXTERNAL SECRETIONS
tion next to the lumen of the duct. These cells line the entire secretory portion of
these glands and are known as central or chief cells. Wedged in between these
and the basement membrane are a number of isolated cells which present a
spheroidal or ovoid shape, and are connected with the main duct by a network
of minute channels situated in between the chief cells. Nearer the duct, these cells
are more abundant and occupy a position in between the chief cells and close to
the lumen (Bensley). These cells are known as the parietal or oxyntic (acid) cells.
(c) The glands of the pyloric end, which are scattered throughout the pyloric
canal, are much longer than those of the fundus and are made up wholly of chief
cells. The latter bear a close resemblance to those composing the fundic glands,
but are not quite so granular. Directly at the pylorus they increase in size, and
become more convoluted and more deeply seated. They are thus gradually
transformed into the glands of Brunner of the submucous layer of the duodenum.
Histological Changes in the Gastric Glands on Secretion. — Accord-
ing to Heidenhain, the chief cells of the inactive glands are large and
clear, save for a certain amount of granular material which is collected
very largely near the duct. During secretion, these granules are dis-
charged into the duct, leaving the outer zones of the cells perfectly
clear. ^ The parietal cells undergo a similar diminution in their size,
but do not exhibit so distinct a clearing of their cytoplasm. Thus, we
are again confronted by the fact that these cells do not merely form a
pumping mechanism for water, but actively concentrate the original
liquid by preformed material.
The Origin of the Active Principles of Gastric Juice. — Heidenhain ^
conceived the idea of isolating a certain portion of the stomach and
giving it an artificial fistulous opening to the outside through which
gastric juice could be obtained separately from its different segments.
This operative procedure has been improved upon by Pawlow^ in
such a way that these gastric pockets need not be deprived of their
normal blood and nerve supply. Upon analysis of these different
samples of gastric juice it was found that the secretion from the pyloric
end is free from hydrochloric acid, but not from pepsin, while that
from a cul-de-sac of the fundus is strongly acid in reaction and contains
much pepsin. Inasmuch as the pyloric glands are made up of chief
cells, while the fundic glands also embrace border cells, it was then
concluded that the pepsin is furnished by the chief cells, and the
hydrochloric acid by the parietal cells.
In support of this hypothesis it has been shown that the esophagus
of the frog is beset with glands which are made up of chief cells and
secrete only pepsin, while the glands of the fundus of the stomach are
composed of ovoidal cells which produce large quantities of acid but
little pepsin. Further light is thrown upon this topic by the fact
that the secretion taken from the pyloric cul-de-sac, does not digest
protein material nor curdle milk unless it is acidified by the addition of
dilute hydrochloric acid. Thus, while these glands secrete pepsin,
this agent remains impotent as long as it is permitted to remain in an
1 Langley, Jour, of Physiol, iii, 1880, 269.
2 Hermann's Handb. der Physiol., 1883.
3 Die Arbeit der Verdauungsdriisen, Wiesbaden, 1898.
THE DIGESTIVE SECRETIONS 921
alkaline medium. Curiously enough, therefore, we are confronted here
by the peculiar functional arrangement that the alkaline product of the
chief cells is acidified almost immediately by the secretion of the parietal
cells, and that the alkaline" juice of the pyloric part of the stomach
must first be mixed with the f undic acid before it can exert its charac-
teristic action.
The genesis of hydrochloric acid has also received attention from
the chemists. Thus, it has been suggested that it is derived from the
chlorids of the blood, but the nature of this decomposition is not known.
The contrary view is that it orginates from the sodium chlorid of the
food upon the surface of the gastric mucosa. The latter view, however,
could be criticized upon the ground that a copious secretion of gastric
juice containing an abundant quantity of hydrochloric acid, may also
be evoked without the introduction of food into the stomach ; for ex-
ample, by the process of sham-feeding, or by allowing an animal to see
or to smell food. More recently, the preceding hypothesis pertaining
to the origin of the hydrochloric acid in the parietal cells has received
additional support in the results of the microchemical tests of Fitz-
gerald ^ and Hammett.2 On injecting a ferrocyanid and a ferric
salt into the circulation of animals, a deposition of Prussian blue was
noted not only in the lumina of the gastric glands bu : also in the cannal-
iculi of the parietal cells and even within the cytoplasm of the latter.
Since this characteristic precipitate was not found in the chief cells
and results only in the presence" of free acid, it was concluded that the
hydrochloric acid orginates in the border cells. Harvey and Bensley^
are at issue with this view, because they state that the parietal cells are
alkaline in their reaction and believe that a deposition of this coloring
material takes place only upon the mucosa of the stomach and in the
orifices of the ducts of the different glands. Without entering in
detail into the technique of the microchemical tests of Hammett, it
may be stated that these later experiments fully confirm the conten-
tion of Heidenhain that the parietal cells secrete the hydrochloric acid.
The gastric glands, therefore, present the same functional picture
as the salivary glands. They are not merely passive filters but living
laboratories in which the contents of the blood and lymph are drawn
upon to yield new and very characteristic vital products. This can
easily be proven by comparing the composition of the gastric secre-
tion with that of the body-fluids. Thus, we obtain in the former such
characteristic bodies as mucin, pepsin, hydrochloric acid, and rennin.
Methods Employed to Obtain Gastric Juice. — The experiments of
the older observers (Spallanzani, 1729-1799) were carried out with
various foods which were sewed in linen bags or enclosed in perforated
capsules of wood. Clean sponges attached to strings have also been
used, the sponges being removed later on and their contents squeezed
1 Proc. R. Soc, London, 1910.
2 Anat. Record, ix, 1915, 21.
3 Biolog. Bull., xxiii, 1912, 225.
922 THE EXTERNAL SECRETIONS
out. These procedures have been displaced in more recent years by
the method of aspirating or siphoning the gastric juice by means of a
long tube of rubber inserted through the esophagus. A number of
cases have also been reported in recent years of persons in whom it
became necessary to establish a free communication between the
gastric cavity and the outside. The first of these has been recorded by
the American frontier physician Beaumont/ the subject being the
Canadian hunter Alexis St. Martin, whose abdominal and gastric walls
had been extensively lacerated by the premature discharge of a gun,
so that even the lung protruded from the wound. In healing, a fis-
tulous communication was formed between the outside and the cavity
of the stomach, but the escape of the gastric contents was prevented by
a flap of mucous membrane which acted as a valve and did not allow
of an unobstructed view of the interior of this organ. Beaumont
determined the time it took to digest meals and found that pork re-
quired a longer period for its digestion than beef. He also noted the
character of the gastric mucosa in health and disease, and obtained
sufficient quantities of pure gastric juice for analysis. The results of
these studies are accepted even to-day as wholly accurate. Further-
more, he introduced various foods through this fistulous opening and
withdrew them again later on to see what changes had taken place in
them.
^ Since the time of Beaumont gastric fistulas have been established
in a number of persons suffering from occlusion of the esophagus in
consequence of erosion by corrosive alkali. Cases of this kind have
been reported by Richet, Sommerfeld and Roder,^ Bickel,^ Umber, ^
Kaznelson,^ and Carlson.^ The subject of the most recent report
was operated upon 16 years ago and has since led a normal life,
offering himself repeatedly for physiological observation. This same
condition may be produced in animals by operative means, the fis-
tulous opening in the abdominal wall being permanently closed by a
silver cannula. The outside cover of the latter is made so that it
can be removed at any time for the purpose of procuring gastric
juice. In this catagory also belong the procedures of Heidenhain
and Pawlow which permit of the resection and isolation of a particular
portion of the stomach and the separate study of its secretion.
Artificial gastric juice may be prepared by extracting macerated
gastric mucosa with dilute hydrochloric acid. This liquid is filtered
and warmed to the temperature of the body whenever required for use.
For coagulated albumin it should have a strength of 0.16 per cent.
Pepsin may be obtained by placing the washed mucosa in alcohol
1 The Physiology of Digestion, 1833.
2 Archiv fur Physiol, 1905.
3 Deutsch. med. Wochenschr., 1906.
* Berliner klin Wochenschr., 1905.
6 Pfliiger's Archiv, xcviii, 1907, 327.
' Am. Jour, of Physiol., xxxi, 1912, 151.
THE DIGESTIVE SECRETIONS 923
for 24 hours, drying it, pulverizing it and extracting it in glycerin for
6 or 7 days. On addition of alcohol to the filtrate, the pepsin is
precipitated, which may then be added to dilute hydrochloric acid.
The Characteristics of Gastric Juice. — When obtained from a
fasting animal, gastric juice is quite clear, odorless, acid in reaction,
and sour to the taste. Its specific gravity varies between 1.002 and
1.006 and its depression of the freezing point between 0.47° and
0.65° C.^ Its quantity may be considerable, large dogs yielding
as much as 1 liter in the course of 3 hours. Human subjects secrete
700 c.c. during a moderate meal and an average total per day of 1500
c.c. As Carlson^ has pointed out, the gastric glands of a healthy
person are never wholly dormant, but secrete continuously in amounts
varying between 2 and 50 c.c. in an hour; the higher figures, however,
are exceptional. Gastric juice contains only 0.3 to 0.6 per cent, of
total solids, as follows:
Acid. 0.46-0.58 per cent.
Chlorin 0 . 49-0 . 62 per cent.
Total solids 0 . 43-0 . 60 per cent.
■ Ash 0.06-0.16 per cent.
If gastric juice is cooled and is allowed to stand, it becomes cloudy and gives rise
to a deposit of finely granular and highly refracting material which appears to
consist of the active principle pepsin. This agent unfolds its action only in an acid
medium which is supplied to it by the hydrochloric add (Prout, 1824). Since the
latter is present in amounts varying, in dogs, between 0.45 and 0.58 per cent, and,
in man, between 0.25 and 0.35 per cent., about 3 grams of hydrochloric acid
must be produced at each meal. In some persons, however, there may be an
achlorhydria or absence of hydrochloric acid, although some peptic digestion may
still be present. A condition of this kind constitutes a diagnostic sign of consider-
able value. It commonly develops in the course of carcinoma of the stomach.
The reverse condition is hyperchlorhydria, which is usually associated with a
hyperpeptic activity and a deficiency in mucus. The cause of this excess in acid
usually lies in a hyperirritability of the nervous system, as well as in lesions produc-
ing a constant stimulation of the gastric mucosa, such as ulcers and growths else-
where in the abdominal cavity.
The acidity of the gastric juice is usually ascertained by means of a test break-
fast. When only a light evening meal is taken, the stomach should be empty
in the morning, i.e., after a period of rest of about 12 hours. The breakfast should
consist of a roll or five crackers or biscuits and a cup of weak tea. A sample of
gastric juice is obtained 45 minutes later by means of the stomach tube. While
the analytical procedures to be followed in this case cannot be described in detail
in a book of this kind, it might be mentioned that the unfiltered juice may be ti-
trated with N/10 NaOH, using phenolphthalein as an indicator. Although the
determination of the free hydrochloric acid may be made with Gtinzberg's or Toper's
reagent, 3 the most accurate procedure is to ascertain the number of hydrogen ions
in the juice in accordance with the gas-chain method.^ The former reagent con-
^ Rosemann, Pfliiger's Archiv, cxviii, 1907. 467, and Sommerfeld, Archiv fiir
Physiol., 1905, 455.
2 Am. Jour, of Physiol., xxxvii, 1915, 50.
3 Zeitschr. fiir physiol. Chemie, xix, 1894, 104 ; also : Christianson, Bioch.
Zeitschr., xlvi, 1912, 24.
^ Panton and Tidy, Analysis of Gastric Contents, Quart. Jour, of Medicine, iv,
1910-1911.
924 THE EXTERNAL SECRETIONS
sists of a mixture of phloroglucin and vanillin dissolved in absolute alcohol, and
the latter of dimethylamino-azo-benzene.
The first amount of hydrochloric acid secreted usually gives a negative reaction
with these reagents, because it is bound by the albuminous bodies to form acid
albuminates. Furthermore, while pure gastric juice contains no lactic acid, this
acid is always present in the gastric contents composed of the pure juice and a
mixture of partly digested food. It arises in consequence of the fermentation of
carbohydrates which are attacked by the bacillus lactici ingested with the food,
and are converted into sugar and lactic acid. Under ordinary conditions, however,
the action of this bacillus is cut short by the hydrochloric acid, because even an
acidity of only 0.07 to 0.08 per cent. HCl absolutely prevents the formation of
lactic acid from dextrose. Consequently, lactic acid must be formed chiefly during
the early stages of gastric digestion or when there is a deficiency in hydrochloric
acid, as during carcinomatous affections of the stomach. But naturally, the acidity
of normal gastric juice is not due to lactic acid, as may be proved by taking this
acid up with ether and applying Uffelmann's test^^to the extract.
Pepsin (Th. Schwann, 1836) is not present in the cells of the gastric glands as
such, but in its inactive form, known as stored pepsin or pepsinogen. ^ The latter,
therefore, may be regarded as the precursor or mother-substance of this ferment
which assumes its active condition only after its escape from the cells and in the
presence of hydrochloric acid. This is proved by the fact that the mucous mem-
brane of the dog or pig, which is alkaline or neutral in reaction, may be extracted
with water and mixed with hydrochloric or some other acid (0.3 percent.) to form
a powerful digestive medium. Contrariwise, gastric mucosa extracted under
glycerin may be kept for some time without any indication of self-digestion or
autolysis. This process, however, sets in immediately if an acid is added to this
extract. Furthermore, Langley^ has shown that pepsin is very sensitive to
alkalies, because when neutralized with sodium hydrate and again acidified, it loses
much of its former potency. An extract of the mucosa, however, may be made
slightly alkaline for a short time without losing its activity on acidification, while
an acid extract cannot be made alkaline without permanently destroying its power.
Another means of showing that the substance contained in the gastric cells is
different from actual pepsin, is furnished by the fact that carbonic anhydrid
gas destroys the action of the pepsinogen contained in a neutral aqueous extract
of frog's esophagus. Contrariwise, if this extract is first acidified and then
neutralized, the passage of carbonic anhydrid through it does not nullify its
power.
Pepsin is a colloidal substance. As such it is not dialyzed through animal
membranes or parchment paper. Regarding its chemical nature we know very
little. Pekelharing3 and Nencki and Lieber* classify it as a protein or protein-
like body of the elementary composition: C, 51.26 per cent., H, 6.74 per cent.,
N, 14.33 per cent., and S, 1.5 per cent. It shoiild be remembered, however, that
this ferment varies in its composition in different animals, because it presents
not only certain differences in the optimum concentration of the acid required to
activate it, but also in its resistance to heat. The question of what becomes of the
pepsin after it has unfolded its ferment-action, cannot be answered with certainty.
The probability is that the largest amount of it is destroyed in the intestine by the
other enzymes or by the bacteria, but a small portion of it may also be absorbed
and enter the blood and urine.
Rennin. — The gastric juice of mammals, as well as aqueous infusions of the
gastric mucosa, possesses the property of curdling milk. This process is essentially
a coagulation during which a soluble protein contained in milk is converted into its
^ Hammarsten, Zeitschr. fiir Physiol. Chemie, xcii, 1914, 121.
2 Jour, of Physiol, vii, 1886, 371.
3 Zeitschr. fiir physiol. Chemie, xxxv, 1902, 8
< Ibid., xxxii, 1901, 261.
THE DIGESTIVE SECRETIONS 925
insoluble form. The active agent concerned in this change is an enzyme, known as
rennin, rennet or chymosin. Like pepsin, this substance is produced by the chief
cells, being stored in them in its inactive form as prorennin or prochymosin.
When passed into the ducts, it assumes its characteristic action of clotting milk,
but only in the presence of calcium and hydrochloric acid. Chemically, .this process
consists in a conversion of the soluble caseinogen of milk into the insoluble casein.
Together with the other proteins, the latter is then subjected to the proteolytic
action of the pepsin.
Rennin, however, is not the only milk-clotting enzyme. Similar bodies are
present in the pancreatic juice, the intestinal juice, the juices of certain fruits, such
as the cocoanut and the pineapple, and in many bacteria. In fact, since the
curdling of ,milk is a common phenomenon of proteolytic processes anywhere in
nature, some authors believe that it is not caused by a specific enzyme but by the
proteolytic ferment itself. Opposed to this view is the less probable one that a
special non-proteolytic coagulating substance is almost universally present in
nature.
This controversy brings up the question pertaining to the possible identity of
rennin and pepsin, which must still be considered as not definitely settled. To be
sure, Hammarsten has shown that pepsin in its pure forrn possesses coagulating
properties, but certain facts are also at hand to prove that rennin and pepsin are
very unlike one another. ^ If it is assumed that the clotting of milk is a general
property of all proteolytic enzymes, the stomach must contain two such agents,
namely pepsin and rennin. The former is a product of the fundi c glands and is
activated only in an acid medium. The latter, on the other hand, is chiefly a
product of the pyloric glands and acts in an acid as well as in a neutral medium.
In this regard, therefore, it is more like the trypsin of the pancreatic juice and the
erepsin of the intestinal secretion. As is usual with many biological properties,
these enzymes are unequally distributed in different animals and undergo changes
in their potency even in the same animal. Thus, we find that rennin is especially
abundant in the stomachs of suckling animals, and that its amount or potency gradu-
ally diminishes in later years and particularly in the carnivora. Its place is then
taken by the pepsin which acts ifl an acid medium at a time when the adult stomach
has acquired a much greater resistance than it possesses shortly after birth.
In addition, gastric juice contains a fat-splitting ferment or lipase which pos-
sesses the property of splitting emulsified neutral fats into glycerin and fatty acids. ^
Such fats are present in milk. The non-emulsified fat, on the other hand, it allows
to traverse the stomach practically unchanged. This lipase exists in the mucosa
in the form of a mother-substance. The fact that it is of much greater importance
in the suckling than in the adult is in accordance with the character of the food
of the young, which consists largely of emulsified fat.
The Resistance of the Stomach to the Gastric Ferments. — Since
the proteolytic ferment pepsin acts in an acid medium, it may seem
strange that the gastric wall is normally exempt from its digestive
power, while a stomach which has been rendered abnormal by inter-
fering with its blood-supply, rapidly undergoes autolytic changes.
This is also true of the excised organ when immersed in its own juice.
A number of theories have been advanced in explanation of these facts,
all of which embody the belief that the lining cells of the stomach are
normally resistant against the gastric juice. Thus, it has been stated
that the surface of the stomach is always covered with a layer of
1 Schmidt-Nielson, Zeitschr. ftir physiol. Chemie, xlviii, 1906, 92; Fuld, Ergebn.
der Physiol., i, 1902; and Pawlow and Pavutschuk, Zeitschr. fiir physik. Chemie,
xlii, 1904, 415.
2 Volhard, Zeitschr. fiir klin. Med., xlii, 1900, 414.
926 THE EXTERNAL SECRETIONS
mucus which acts as a protection for the underlying cells. In prac-
tically all cases of hyperchlorhydria, however, the secretion of mucus
is greatly diminished, without thus creating an especially favorable
condition for the formation of ulcers. Contrariwise, mucus may be
secreted in excessive amounts in the presence of formidable ulcers.
Another theory holds that the aforesaid resistance of the gastric wall
is due to the alkalinity of its constituent cells which tends to neutralize
the gastric juice anointing them. Going a step farther in this direc-
tion, we might say that the cause of the resistance of the gastric
mucosa against digestion lies in the normality of its life processes. The
latter consist in oxidations, and hence, it is evident that the pepsin
immediately exposed to them must be rendered inert by being oxidized.
In this connection it is of interest to note that the cells of the gastric
mucosa possess an intense power of oxidation. This observation
of Lillie^ is in accord with that of Burge,^ proving that pepsin is easily
destroyed by oxidation. Under normal conditions, therefore, a
balance is established between the intracellular oxidations and the
digestive action of the neighboring pepsin. Whenever this balance
is destroyed, the cells are digested with the formation of erosions of
varying size.
These oxidative processes may be disturbed in different ways;
for example, by cutting off the blood supply of a particular area of
the stomach or by depressing the circulatory efficiency of the animal
as a whole. Thus, a local anemia may be established in consequence
of tumors, wounds, stricture of the pylorus and thrombosis; and a
general circulatory deficiency in consequence of hemorrhage, anemia,
poisons and toxins.
The Regulation of the Secretion of Gastric Juice by Hormones
and Vitamines. — In general, it may be said that glands may be made
to secrete in two ways, namely, indirectly by means of chemical agents
contained in the blood, and directly by the stimulation of the nerve
fibers innervating the different cells. Eventually, of course, both types
of stimuli are conveyed to the cells, exciting their cytoplasm at first
hand. Agents which possess this stimulating action, most generally
arise elsewhere in the body and are brought to the gland in the blood-
stream. Thus, it has been found that the pituitary body gives rise
to an internal secretion which increases the flow of milk from the
mammary gland, and that the lining of the duodenum produces an
agent which initiates the flow of pancreatic juice. As far as the stom-
ach is concerned, Edkins^ has shown that the injection into the blood-
stream of broth, dextrin, peptone or acid does not augment the flow
of gastric juice, while an extract of the mucous membrane of the
pylorus invariably acts as a potent secretogogue. It is evident, there-
fore, that the mucosa of the stomach produces a hormone, known
1 Am. Jour, of Physiol., vii, 1902, 413.
2 Ibid., xxxvii, 1915.462. .
3 Jour, of Physiol., xxxiv, 1906, 133.
THE DIGESTIVE SECRETIONS 927
as gastric secretin or gastrin, which is hberated during the process
of gastric digestion and serves as a stimulus to the local glands.
Secondly, it cannot be doubted that food itself contains certain
stimulating substances which upon their absorption exert a definite
synthetic or constructive influence upon all cellular processes. These
accessory bodies are known as vitamines. Practically nothing is
known regarding their chemical nature/ but we divide them as a rule
into two groups, viz. : those soluble in fat which are abundant in but-
ter, ^ and those soluble in water and alcohol which are present in wheat,
maize, cabbage, and in many foods of animal origin.
It must seem strange that an animal fed upon a mixture of pure proteins,
fats, carbohydrates, salts and water, will not thrive, but ceases to develop and pres-
ently exhibits a complex of symptoms indicative of malnutrition. But if this
artificial diet is augmented by some natural food, such as vegetables or milk, the
animal immediately begins to develop normally. Hopkins^ divided a large number
of young rats into two groups, one of which received a diet of caseinogen, fats,
carbohydrates and salts, and the other the same food plus a small ration of fresh
milk. Although the consumption of material was practically the same in both
groups of animals, the former soon ceased growing, while the latter developed
normally. Even man may suffer from these "deficiency-diseases," chief among
which are scurvy, beri-beri, pellagra and rickets. Scurvy, for example, used to be
prevalent upon sailing vessels when fresh meat, vegetables and fruits were unob-
tainable, and when fish formed the almost constant diet. As a means of preventing
this disease, lime or lemon juice was generally given, it being believed that citric
acid and traces of malic acid are essential constituents of food. Scurvy may also
develop in infants fed exclusively on pasteurized milk. All the alarming symptoms
of this disease may be made to disappear in the course of a day or two by the use
of fresh milk or by the addition of orange juice and the white of egg to the former.
Very similar disturbances of nutrition may be incited by the exclusive use
of polished rice. Thus, it has been noted in Japan that Kak-Ka (beri-beri) has
greatly increased since the primitive mill-stones have been displaced by the
modern steel-rollers. In Bengal, on the other hand, where the old methods of
milling are still in use, this disease is practically unknown, although rice forms one
of the chief foods of this country. A similar disease may be evoked in birds by
feeding them only polished rice. This puzzling situation has been cleared up in a
large measure by Funk,^ who has extracted from the polishings, i.e., from the
outer coats of the rice kernel, a basic principle which he calls vitamine. Further-
more, it has been found that if these polishings, or their alcoholic extract, are added
to the rice prepared in the modern way, this food does not produce the aforesaid
disease. After its development, the latter may be quickly remedied by the in-
gestion of unpolished rice or by eating potatoes, fresh vegetables, fruit, milk, meat
and eggs. Yeast is said to contain vitamines in considerable amounts and it is
assumed that the nutritive value of fermented beverages, such as beer, is in large
part due to these bodies. Quite similarly, it is assumed that the value of whole-
meal bread does not depend upon its extra amount of protein but probably upon
its content in vitamines.
It must be concluded, therefore, that the different foods taken into
the stomach contain certain substances which in themselves cannot
be regarded as foods nor as condiments, but which are absolutely
1 McCoUum, Simmonds and Fitz, Am. Jour, of Physiol., Ixi, 1916, 361.
2 Osborne and Mendel, Jour, of Biol. Chem., xxiv, 1916, 37.
3 Jour, of Physiol., xliv, 1912, 425.
4 Ergebn. der Physiol., 1913, 124.
928 THE EXTERNAL SECRETIONS
essential for the maintenance of health and growth. While as yet
chemically unrecognized, their presence has been proved by physiolog-
ical means. They play the part of ^'building stones" in the syntheses
of the developing animal. As such, they act upon the secretory proc-
esses as well as upon the processes of assimilation and dissimilation.
Consequently, they must unfold their function as secretogogues shortly
after their entrance into the digestive tract, and niust also exert a
certain influence upon the activity of the gastric glands. This end
they accomplish (a) by stimulating the cells of the gastric glands
directly, (6) by entering the blood and influencing the secretory ac-
tivity of these glands in an indirect way, and (c) by causing a liberation
of gastric secretin which in turn affects the glandular elements.
The Nervous Control of the Secretion of Gastric Juice. — ^Like
saliva, gastric juice is secreted continuously, but only in amounts suf-
ficient to lubricate the mucous surfaces. At various times, however,
a more copious flow is initiated which finds its origin in stimuli of an
occasional character. The latter embrace (a) chemical agents which
reach the gastric cells either directly from the cavity of the stomach or
indirectly by the blood, and (6) stimuli which act reflexly through
particular reflex circuits. It must be evident, however, that these
reflex arcs need not be situated in the stomach, at least not their
afferent path, or analyzer, because a secretion of gastric juice results
not only in consequence of the entrance of food into the stomach, but
also upon its being taken into the mouth; in fact, even the mere sight
and smell of nutritive substances may serve as an efficient stimulus.
The act of chewing, however, does not serve as a stimulant, nor does
the intake of an indifferent substance not related to food. Conse-
quently, we may say that the secretion of gastric juice is controlled
by nerve impulses of intragastric and extragastric origin produced by
palatable substances.
This statement implies that the afferent side of the reflex circuit
concerned in gastric secretion is diversified, while the efferent side is
not. Relative to the latter, it has been proved that it is contained in
the vagus system, because the division of the ventral and dorsal vagi
below the origins of their pulmonary and cardiac branches abolishes
this reflex, while the stimulation of the distal end of either nerve
is followed by a secretion. In addition, it has been stated that these
nerves contain musculomotor fibers for the stomach.^ The splanchnic
nerves do not seem to be involved in this secretory reaction, because
their division and stimulation remains without effect. We know,
however, that these nerves embrace vasomotor fibers for the stomach
which traverse the ganglia of the solar plexus and reach this organ by
following the highways of the different gastric arteries. Consequently,
since their stimulation must lead to a constriction of the gastric blood-
vessels, they must limit the quantity of the gastric juice, but in an in-
direct way and not as secretory nerves. Now, since their action is
1 Burton-Opitz, Pfiiiger's Archiv, cxxxv, 1910, 205.
THE DIGESTIVE SECRETIONS 929
not inhibito-secretory in its nature, they cannot be considered as
forming a part of an inhibitor mechanism which acts antagonistically
to the vagi nerves. The latter are secretomotors. It seems, therefore,
that the vagi nerves are capable of stimulating as well as of inhibiting
the flow of the gastric juice, and hence, they must form the chief
efferent secretory path between the central nervous system and the
stomach.
In considering the effects of the intragastric stimuli, we are con-
fronted by the statement that the mechanical stimulation of the gastric
mucosa produces only a discharge of mucus and not of gastric juice.
Even water and meat, when introduced through a fistula, give rise
to only a slight flow. The same is true of bread and coagulated white
of egg, and especially if these substances are introduced while the
animal is sleeping. Of particular interest is the long latent period then
intervening between the moment of feeding and the time when the
first drop of gastric juice is obtained. Even in the case of raw meat,
15 to 45 minutes may elapse before the secretion actually begins, but a
somewhat quicker reaction may be evoked by giving these substances
in a semi-digested condition, because the purely nervous excitation
is then augmented by the liberation of chemical bodies in the form of
vitamines and hormones which stimulate the gastric glands either
directly or thrgugh the blood.
A slight secretion of gastric juice is also obtained after the stomach
has been isolated from the central nervous system by the division
of all of its nerves, namely, the vagi and splanchnic nerves and the com-
municating rami of the latter. Consequently, this organ must be in
possession of a local reflex mechanism which under ordinary conditions
is controlled directly by the central nervous system. In other words,
inasmuch as the stomach is a typical autonomic organ, the higher
centers merely alter its activity in accordance with the functional
requirements of other parts of the body. Impulses are relayed to it
which either increase or decrease the flow of gastric juice.
These data tend to show that the direct stimulation of the gastric
receptors is not a very efficient means of evoking a secretion of gastric
juice. Much better results may be obtained by influencing the local
mechanism through a more general mechanism which is capable of
introducing what is termed the psychical element, or appetite. As
long ago as 1852, Bidder and Schmidt observed that a copious secre-
tion of gastric juice may be evoked in a dog with a gastric fistula by
simply allowing him to obtain a visual impression of the food. Some
years later Richet obtained the same results in a boy whose esophagus
had been completely closed by a cicatrix formed in consequence of
an erosion by a strong alkali. Since that time this observation has
been repeated a large number of times both upon human beings with
gastric fistulas as well as upon different mammals with diverticulated
stomachs. Another procedure which has led to valuable results is
930 THE EXTERNAL SECRETIONS
the method of sham-feeding.^ Having established a gastric fistula,
the esophagus is divided in the neck and its two cut ends securely
fastened to the edges of the wound. The animals so changed soon
accommodate themselves to their new conditions and can then be sub-
jected to:
(a) Actual feeding through the distal orifice of esophagus.
(6) Sham-feeding, by allowing them to masticate the food in the
usual way, although it again reaches the outside through the opening
in the neck.
(c) Psychical feeding, in which the animal is merely allowed
to see or to smell the food without actually ingesting it.
The importance of the psychical element in the formation of gas-
tric juice may be proved in various ways.^ Thus, it suffices to allow
the hungry animal to see the food ; moreover, the secretion then ob-
tained is usually more copious than if secreted without the help of
psychic impressions. For example, if two dogs are fed weighed amounts
of meat through fistulas, without their knowledge, a certain quantity
of gastric juice will be secreted by each, but if one of these animals is
now given a sham meal of meat, the amount of protein digested by it
in a given period of time will be five times greater than that digested
by the other animal not psychically stimulated. Those investigators
who have studied the effects of gastric fistulae in hum^n beings, have
made similar observations and maintain that the seeing, smelling and
thinking of palatable food, as well as the leisurely mastication of sapid
substances, give rise to a copious flow of gastric juice. Appetite
is a potent factor in this process and so is the quality of the food. Food
and condiments which the individual liked especially, were more
effective than, say, butter, bread and meat. This fact may serve as
a reason for the ingestion of a palatable dessert, salad, or fruit at the
end of a meal. The purpose of these ''appetizers" is to augment and
to prolong the appetite secretion of gastric juice. ^
The fact to be deduced from these experiments is that the different
kinds of food possess an almost specific stimulating power which en-
ables them to vary not only the quantity of the gastric juice, but also
the length of the period intervening between their ingestion and the
appearance of the secretion. In the case of saliva it is easily observed
that this latent period is short, a fact which is in keeping with func-
tional requirements. Evidently, since the food enters the mouth
quickly and remains here for only a relatively short period, it is
essential that this secretion be produced in the shortest possible
time. In the case of gastric juice an urgency of this kind does not
exist and hence, the latent period may be appreciably prolonged.
1 Pawlow and Schumowa-Simanowskaja, Zentralbl. fiir Physiol., iii, 1889.
2 Bogen, Pfltiger's Archiv, cxvii, 1907.
3 Rabinowitch, Dissertation, Giessen, 1907 (spices); Pinkussohn, Miinch. med.
Wochenschr., 1906 (coffee and cocoa) ; Kast, Archiv fiir Verdauungskr., xii (alcohol) ;
Bickel, Berhner klin. Wochenschr., 1906 (mineral waters).
THE DIGESTIVE SECRETIONS 931
Thus, a meat diet does not give a maximum rate of secretion until the
end of the first or second hour, while a bread diet produces its secretory-
climax during the first hour, and a milk diet during the second and third
hours. Quite similarly, lar^e quantities of oil diminish the secre-
tion considerably, while starch, fat, and white of egg are practically-
inert. It has also been observed that meat-juice is a more efficient
stimulus than bread-juice, while milk-juice occupies in this regard an
intermediate position. Contrariwise, bread-juice contains a more
abundant quantity of ferment than meat-juice. Among the influences
which depress the secretion of gastric juice might be mentioned un-
pleasant emotions, such as anger, and fear. Thus, it has been noted
that dogs with gastric fistulas cease secreting when confronted by a
cat, and we are all well aware of the fact that a clear conscience
and untroubled mind are essential prerequisites for an efficient gastric
digestion.
While it is difficult to combine these facts into a brief story of
events, it may be stated. that the normal secretion of gastric juice is
dependent upon two factors, namely, upon an immediate nervous and
a latent chemical stimulus. The former finds its origin in the exci-
tation of the receptors of the oral cavity as well as of certain extero-
ceptors, such as the retinae and the olfactory cells, and its purpose is
to produce a flow of gastric juice in as short a time as possible after the
ingestion of the food. This gives rise to what has been termed the
appetite secretion. The purpose of the second factor is to maintain
this secretion after it has been initiated. In the latter instance, the
stimulus is of intragastric origin, and is evoked by the vitamines of the
food and the specific hormone, gastrin. The most important reaction
is the first, or appetite secretion, because it serves to establish a diges-
tive medium for those food stuffs which in themselves are very inef-
ficient gastric stimulants. In accordance with this sequence of events,
it may be said that the gastric juice which is secreted in the course of a
meal, consists of two portions, namely, (a) an initial amount which
is poured forth within 5 minutes after the ingestion of the food and
which is due to a reflex stimulation, and (b) a latent amount, the secre-
tion of which follows the chemical stimulation by the food after it has
entered th^ stomach.
The Duodenal Juice. — Beginning at the pylorus, the gastric
glands gradually pass over into the glands of Brunner. The latter are
imbedded in the submucous coat, and appear as branched and con-
voluted tubes, the ducts of which open free upon the mucous surface.
In the carnivora, they occupy an area extending about 3 to 5 cm.
below the pylorus, while in the herbivora they reach to a line about
15 cm. below this point. The secretion furnished by them is known
as the duodenal juice. It is alkaline in reaction, owing to its content
in carbonates, and effervesces strongly when brought in contact with
an acid. Its action as a digestive juice is not important, although it
contains some invertin whi6h inverts Cane-sugar, as well as some
I
932
THE EXTERNAL SECRETIONS
erepsin. Its importance lies rather in the fact that it gives lodgment
to a substance, known as enter okinase,^ which possesses the power of
greatly augmenting the action of the pancreatic juice on proteins. In
the absence of this secretion, following, for example, the resection
of extensive segments of the duodenum, serious digestive disturbances
result; in fact, it is commonly stated that this operation is fatal for
reasons not fully understood. It is supposed, however, that it converts
the inactive trypsinogen into the powerful proteolytic agent- trypsin
A similar activating enzyme has been abstracted from the spleen
(Mendel), but it has not been proved that this organ exerts this par-
ticular function under normal conditions.
The Pancreas. — This gland is tubulo-racemose in its character,
the individual acini being separated from one another by a loose net-
FiG. 495. — Diagram to Show the Position of the Ducts of the Pancreas.
D, Duodenum; P, pancreas; DC, ductus choledochus; DW, ductus Wirsungianus;
DS, ductus Santorini.
work of connective tissue in which are imbedded small groups of
spindle-shaped cells forming the so-called islets of Langerhans. It
will be brought out later on that these cells furnish an internal secre-
tion which has to do with the metabolism of the carbohydrates. For
the present we are concerned solely with the true secretory ^cells of this
organ, forming the typical tubular acini and producing the *' external '*
secretion known as the pancreatic juice. These cells are polyhedral
in shape and exhibit two zones, namely, a clear outer and a granular
inner. Their strongly basophile nuclei occupy a central position
within their cytoplasm.
It will be remembered that this organ forms a narrow band of tissue, the central
portion of which partially envelops the duodenum, while its caput and cauda extend
for some distance into the mesentery. Its principal excretory channel is the pan-
creatic duct or duct of Wirsung, which opens into the duodenum about 10 to 12 cm.
below the sphincter of the pylorus. A smaller duct may also be present, which is
known as the duct of Santorini and drains the head-region of this organ, entering
^ Chepowalnikow, Dissertation, St. Petersburgh, 1899.
THE DIGESTIVE SECRETIONS
933
I
the duodenum separately at a distance of 2 to 3 cm. above the former. ^ In some
animals the duct of Wirsung unites with the common bile duct shortly before its
entrance into the duodenum. This accounts for the fact that tumors, affecting
the head and body of the pancreas, very frequently give rise to a stagnation of the
bile. Thus, a slowly developing j aundice, which is associated with a loss of appetite
and indigestion, but no pain, almost always indicates a carcinoma of the pancreas.
In the dog, the blood-supply of the pancreas is derived from the mesenteric,
pancreatico-duodenal and splenic arteries. The first supplies its head-region,
the second its body, and the third its tail. The venous return is effected by three
channels of which the vena pancreatica is the largest. The latter joins the portal
vein a short distance below thehilum of the liver. A small portion of its blood is
returned by way of the splenic and mesenteric veins, but this also enters the portal
vein. The nerve-fibers innervating this organ arise in the mesenteric and celiac
ganglia of the solar plexus and follow the highways of the aforesaid arteries. Pre-
ganglionically, connection is made with the central nervous system by way of
the vagi and splanchnic nerves.
Histological Changes in the Cells of the Pancreas During Secre-
tion.— In 1856 CI. Bernard observed in fresh preparations of the pan-
FiG. 496. — A Terminal, Lobtj le of the Pancreas of the Rabbit. (Kuhne and Sheridan
Lea.)
A, in resting condition; 5, after active secretion.
creas of the rabbit that two-thirds of the inner zone of its cells are
taken up by a dense granular material which he believed to be the
mother-substance of the active principles of the pancreatic juice.
Later on Kiihne and Lea^ succeeded in showing that the activity of
this gland is associated with a loss of at least a part of this material.
The cells become smaller in size and eventually exhibit a perfectly
clear basal zone. While these changes may be rendered more con-
spicuous by the use of pilocarpin and secretin, their complete develop-
ment frequently necessitates several injections of these drugs until
the flow of pancreatic juice has almost ceased, owing to an exhaustion
of the secretory material. While the normal gland possesses a yellow-
ish-white color, it then becomes transparent, soft, and pink in color.
Methods Employed to Procure Pancreatic Juice. — The best way
in which pancreatic juice may be obtained, is to establish a fistula
^ Opie, Diseases of the Pancreas, London, 1903, and Gegenbaur, Anatomic des
Menschen, Leipzig, 1899.
2 Unters. aus dem physiol. Inst. zu. Heidelberg, 1882.
934
THE EXTERNAL SECRETIONS
between the duct of Wirsung and the outside. CI. Bernard advocated
the use of a lead or silver cannula which he inserted in the orifice of this
duct and secured in the sides of the abdominal wound. A more con-
venient and permanent method has been devised by Heidenhain and
modified by Pawlow. It makes use of the fact that in the dog the
Fig. 497. — Alveoli of Dog's Pancreas, Cells Loaded: Osmic Preparation. (Babkin,
Rvbasckin, and Ssawitsch.)
lower duct is larger than the upper and has a well-defined orifice.
A quadrilateral piece of the intestinal wall immediately surrounding
this orifice is resected and is fastened in the sides of the abdominal
wound. The integrity of the duodenum must of course be reestab-
FiG. 498. — Alveoli of Dog's Pancreas after a Period of Activity Produced by
Application of Acid to Mucous Membrane of Duodenum. (Babkin, Rubasckin, and
Ssawitsch.)
lished before the latter is completely closed. Inasmuch as the pan-
creatic secretion possesses strong proteolytic properties, the external
wound must be kept dry and clean, otherwise erosions and infection
will result. * Furthermore, since the establishment of this fistula
prevents a large portion of the pancreatic juice from entering the
THE DIGESTIVE SECRETIONS 935
intestine, an animal of this kind frequently suffers from indigestion
and metabolic disturbances leading to a loss of weight and severe
general symptoms. But since this disarrangement involves chiefly
the digestion of the proteins, it may be obviated in a measure by the
feeding of abundant quantities of milk to which sodium bicarbonate
has been added.
The Character of the Pancreatic Juice. — It is a clear, watery and
slightly opalescent fluid, possessing a specific gravity of from 1 .007 to
1.009. Moreover, since it contains considerable amounts of phos-
phates and carbonates, and especially those of sodium, its reaction is
strongly alkaline. When its flow is stimulated by means of secretin,
about 30 to 50 c.c. of it may be obtained in the course of an hour and
from 300 to 500 c.c. in a day. Its composition^ is as follows :
Total solids 1 . 6 -1 . 56 per cent.
Total protein 0.5 per cent.
Ash 1.0 -0.96 per cent.
Chlorids 0. 28-0. 29 per cent.
Total nitrogen 0 . 73 per cent.
The organic substances contained in it are enzymes, a small amount of
protein material, and traces of leucine, tyrosine, xanthine, and soaps.
Pancreatic juice contains four enzymes namely:
(a) Trypsin, proteolytic or proteoclastic in its nature (Purkinje and Pappenheim,
1836) . Enterokinase converts trypsinogen into trypsin. Erepsin is present some-
times.
(h) Amylase; amylopsin, amylolytic in its nature (Valentin, 1844).
(c) Lipase; steapsin, fat-splitting, lipolytic or lipoclastic in its nature (CI.
Bernard, 1846), and a
(d) Milk-curdling substance.
The Regulation of the Secretion of Pancreatic Juice. — It is com-
monly held that the pancreas of the carnivora secretes intermittently,
the immediate cause of the secretion being either nervous or chemical
in its nature. In the herbivora, on the other hand, the secretion is
constant, a condition which is in accord with the rather continuous
character of their digestion. If brought about in a reflex way, the
stimuli arise in the forepart of the alimentary canal and are relayed
to the pancreas by way of the vagus nerve which contains secretory
fibers for this organ. The fact that a reflex circuit of this kind exists
seems proven, because the stimulation of the medulla oblongata is
usually followed by a copious flow of pancreatic juice. A similar
effect may be obtained by psychic stimuli as well as by the stimulation
of the central end of the divided lingual nerve . ^ But the early attempts
of Heidenhain to localize the secretory fibers of the pancreas in the
vagus failed completely, because the stimulation of this nerve gives
rise to cardio-inhibition and a fall in blood-pressure which cause the
1 DeZilwa, Jour, of Physiol., xxxi, 1904, 230, and Wolgemuth, Bioch. Zeitschr.,
xxxix, 1912, 321.
2 Pfitiger's Archiv, x, 1875, 606.
936 THE EXTERNAL SECRETIONS
extremely sensitive epithelium of this organ to cease secreting. Later
on Pawlow conceived the idea of permitting the cardiac fibers of the
vagus to degenerate before attempting to test the power of this nerve
upon the pancreas. In all these cases, the stimulation of the distal end
of this nerve, 3 or 4 days after its division, evoked a copious flow of
pancreatic juice, but in spite of the fact that the existence of these
reflex paths has been thoroughly established, no definite statements
can be made at this time regarding the relative importance of the
nervous and chemical stimuli. At all events, the impulses from the
mouth as well as those of psychic origin seem to play a less important
part in the secretion of pancreatic juice than in that of gastric juice.
Inasmuch as a formation of pancreatic juice also takes place
after the pancreas has been completely isolated from the central
nervous system, Popielski^ came to the conclusion that this organ em-
braces a local nervous mechanism which is sufficient for its activity.
The claim was then made by Dolinsky^ and Pawlow that the active
factor involved in this secretion is the acid of the gastric juice which
exerts its peculiar action as soon as the chyme is discharged into the
duodenum. In substantiation of this contention Popielski proved
later on that the injection of an acid into a segment of the duodenum
gives rise to a copious flow of pancreatic juice even after both vagi
nerves and the ramifications of the solar plexus have been cut. This
fact immediately disposed of the contention that the acid stimulates
the duodenal mucosa and thereby sets up certain afferent impulses
which are finally relayed to the pancreas by way of the corresponding
fibers of the vagus system. On repeating these experiments, Bayliss
and Starling^ discovered that a secretion of pancreatic juice also results
if the acid is introduced into a loop of duodenum which had previously
been isolated from the rest of the body by dividing all its nervous
connections. This result showed very clearly that a chemical stimulus
must be at work which affects the pancreatic cells through the blood
stream. In further substantiation of this view these authors found
that an acid, when injected into the portal vein, remains without effect,
while an acid infusion of the mucous membrane of the duodenum, when
neutralized and injected into the same channel, gives rise to a copious
flow of pancreatic juice. These tests were then controlled by the use
of similar extracts of other organs, but none of these yielded positive
results.
The conclusion to be derived from these data is that the activity
of the pancreas is also under the control of a hormone which originates
in the mucosa of the duodenum and upper small intestine. This agent
is called secretin. It should be noted, however, that it is not present
as such in these cells, but is held in them in an inactive form to which
the name of pro-secretin has been given. In consequence of the
1 Centralbl. fiir Physiol., x, 1896, 405, and xix, 1906, 801.
2 Dissertation, St. Petersburgh, 1894.
3 Jour, of Physiol., xxviii, 1902, 325.
THE DIGESTIVE SECRETIONS 937
discharge of the acid gastric contents, this precursor is changed into
the active secretin, which is then conveyed to the pancreas in the blood-
stream'. This organ reacts to it by furnishing an alkaline secretion
which in turn neutralizes the acid chyme, thereby setting, a limit to
the formation of secretin. The succeeding discharge of chyme gives
rise to another stimulation by secretin, and so on until the stomach is
empty. The latter point has been proved by Enriquez and Hallion^
in this way. An anastomosis was formed between the arteries and
veins of two dogs. Cannulas having been inserted in the pancreatic
ducts of both animals, one of them then received an injection of a di-
lute acid into the duodenum. Peculiarly enough, a copious secretion
of pancreatic juice resulted in both animals. This experiment proves
very clearly that secretin is a true chemical messenger and is actively
engaged in the formation of normal pancreatic juice.
Inasmuch as it has been noted that secretin produces at first a
very copious flow, which, however, is soon greatly diminished, ^nd that
a second dose of this agent does not evoke so pronounced an effect as
the first, it may be conjectured that this hormone possesses the func-
tion of exciting the pancreatic secretion in the shortest possible time.
Accordingly, it may then be assumed that it is the purpose of the nerv-
ous mechanism to sustain this secretion as long as required. This
view finds support in the fact that the secretion obtained upon stimula-
tion of the vagus nerve is characterized by a long latent period, and
that the vagus-juice is less watery but contains a larger amount of
organic matter than the secre tin-juice. In analogy with salivary
and gastric secretion, these differences may be explained by assuming
that the nervous and chemical factors just mentioned affect different
constituents of the pancreatic acini, one of them, possibly, stimulating
the cells of the acini proper, and the other the cells nearer the excretory
duct.
The chemical nature of secretin is still unknown. It is not a fer-
ment and may be prepared in the following manner: The mucous
membrane of the duodenum is ground up with sand and boiled with
0.4 per cent, hydrochloric acid. The filtrate contains the secretin.
It is rendered neutral under addition of sodium hydrate. Dale and
Laidlaw^ harden the mucosa in HgCl2, boil it, reject the filtrate and
extract the residue with a 2 per cent, solution of acetic acid, containing
1 per cent, of HgCl2. The filtrate is precipitated by the addition of
NaOH to the neutral point. Secretin is stable in acid solutions, but is
rapidly oxidized in alkaline, and neutral solutions. Its action is not
destroyed by atropin, although this agent paralyzes the secretory
mechanism of the vagus. In this connection, brief reference should
also be made to the fact that a flow of pancreatic juice may be excited
by means of pilocarpin, Witters peptone, and curarin (Popielski).
1 Compt. rend., Iv, 1903, 233.
2 Proc. Physiol. Soc, Jour, of Physiol., xUv, 1912.
938
THE EXTERNAL SECRETIONS
CHAPTER LXXX
THE DIGESTIVE SECRETIONS (CONTINUED)
C. BILE AND INTESTINAL JUICE
The Liver. — The Hver is the largest gland in the body, and is in
origin a tubular gland which, in the course of its development, has lost
much of its original character. It is made up of rounded masses or
lobules which measure about 1.0 mm. in diameter and are composed of
columns of cells radiating from a common center. These cells possess
a spheroidal shape but have in many cases become polygonal on ac-
FiG. 499. — Diagrammatic Representation of the Blood Supply of the Liver Acini.
P, Portal terminal; JV, interlobubar veins; CV, central veins which are eventually
collected in the hepatic vein; HA, hepatic arteriole, the interlobular capillaries of which
empty into the portal terminals; B, biliary capillary which begins as biliary space be-
tween the hepatic cells.
count of their being packed so closely together. Their cytoplasm
contains a rounded and centrally placed nucleus, as well as fatty
particles, and variable amounts of glycogen.
The blood supply of this organ is derived from two sources, namely from the
hepatic artery and the portal vein. The former supplies its reticular network,
i.e., the tissue of the extra- and interlobular spaces, while the latter nourishes the
THE DIGESTIVE SECRETIONS
939
hepatic cells themselves. Eventually the capillaries of the hepatic artery unite
into channels which empty directly into the terminals of the portal vein at the
periphery of each lobule. So united they form the central or intralobular veins,
and these in turn the hepatic veins. This anastomosis between the hepatic arterial
and portal systems accounts for the fact that the secretory power of this organ
cannot be destroyed by the ligation of the aforesaid vein. Under these circum-
stances, the arterial blood finds its way in greater quantity into the portal channels,
thereby compensating in part for the loss of the portal blood. ^
The nerve supply of the liver is derived from the celiac ganglion of the solar
plexus. The individual postganglionic fibers ascend along the hepatic artery
around which they form an intricate plexus. At the hilum of this organ they
ramify extensively, forming here the so-called hepatic plexus. Distally to this
point they follow the branches of the hepatic artery
in order to gain the interior of the different lobes of
this organ.
Of special interest to us at this time is
the fact that the hepatic cells lie in direct
contact with these intralobular capillaries,
and furthermore, since the lining of these
vessels is in many places deficient, the blood
is brought into direct communication with
the contents of these cells. These deficiencies
account for the fact that perfectly intact
red corpuscles may be found inside their
cytoplasm. Here and there along these
vessels we also note the so-called stellate cells
of Kupffer which are large phagocytic bodies
capable of ingesting red cells and other solid
particles contained in the blood. Hence, it
cannot surprise us to find that coloring fluids
injected through the portal vein may be
traced directly into the interior of these cells
where they produce delicate canalicuh or
sinusoids. In this organ, therefore, the
lymph does not play the part of a middle-
man between the blood and the cells.
On the other side of these radial rows of secretory cells are the
biliary spaces and capillaries which convey their characteristic se-
cretion, the bile, into the larger collecting channels. While many his-
tologists state that these delicate tubules arise in secreting vacu-
oles within the cytoplasm of these cells, others claim that they begin
as blind spaces between two adjoining rows of cells. Farther outward
they acquire a lining of columnar epithelium as well as a basement-
membrane and fibrous and smooth muscle tissue. In many animals,
the larger biliary ducts empty into a special reservoir which is known
as the gall-bladder. The liver is also plentifully supplied with lym-
phatics which accompany the capillaries of the portal vein as well
as those of the hepatic artery. These two systems communicate
1 Burton-Opitz, Quart. Jour, of Exp. Physiol., iv, 1911, 93.
Fig. 500. — Diagram to
Illustrate the Relation of
THE Portal Terminals (P)
TO THE Biliary Capillaries
(B). The Arrows Indicate
THE Direction op the Flow.
940 THE EXTERNAL SECRETIONS
with one another at the periphery of the lobule as well as near the
hilum.
The Function of the Liver. — While we are chiefly concerned at
this time with the external secretion of the liver, known as the bile,
it should not be forgotten that this organ performs several other im-
portant functions which may be briefly summarized as follows:
(a) It furnishes an internal secretion which is concerned with the metabolism
of the carbohydrates. Sugar is deposited in the hepatic cells in the form of gly-
cogen, which is later on reconverted into sugar.
(6) It forms those bodies which are subsequently abstracted by the cells of the
kidney and appear in the urine in the shape of urea and allied substances.
(c) It is the principal organ in which the red blood-corpuscles are destroyed.
(d) It plays an important part in the coagulation of the blood, because it gives
rise to anti-coagulating substances.
Fig. 501. — Lfv^er Cells ( ontaim.nc; Clycocen. {Barfurth.)
(e) While its external secretion, the bile, possesses an important digestive
action upon the fats, it is also a natural antiseptic, an excretory medium, and a
stimulant of peristaltic activity.
(/) It is the chief heat-conserving organ in our body, and probably also
' (gr) The principal formant of lymph.
The Characteristics of Bile. — The quantity of bile which is se-
creted by an adult of medium weight in a day, has been estimated at
500 to 1000 c.c. It is not difficult to obtain it, because the establish-
ment of a fistula of the common duct or of the fundus of the gall-
bladder is frequently undertaken to-day for the relief of the symptoms
following the obstruction of these passages by calculi or by malignant
growths affecting the pancreas and neighboring orifices of the duct of
Wirsung and common bile duct. Bile may also be obtained from the
gall-bladder after death, but if removed days later, it may have lost its
normal characteristics altogether. In the dog, Pawlow advises to
establish a biliary fistula by excising the entire segment of duodenum
in the immediate vicinity of the orifice of the common duct, and fasten-
ing it to the edges of the wound in the abdominal wall.
THE DIGESTIVE SECRETIONS 941
Fresh human bile, as well as that of the carnivora, is golden red in color, but
changes into dark green on exposure. Evidently, it must contain a number of
pigments which are rather unstable and are altered by oxidation. The bile of the
herbivora is greenish in color. When fresh, it is very bitter, and has a slimy con-
sistency, due to its content in mucin. The latter pecuHarity, however, is imparted
to it not by the hepatic cells but during its passage into the gall-bladder. This
fact, that bile withdrawn from the hepatic duct and its tributaries is normally
clear, is of some functional importance, because if it were not, its flow might be
greatly retarded. Thus, we find that in extreme cases of biliary catarrh the
larger bile ducts are frequently blocked by mucous plugs, this stagnation of the
bile giving rise to an absorption of its pigments and the complex of symptoms con-
stituting jaundice or icterus. The viscosity of bile is 1.8 times as great as that of
distilled water at 37° C i It is usually neutral or faintly alkaline to litmus. Per-
fectly clear bile possesses a specific gravity of 1.008 to 1.010, while that collected
directly from the gall-bladder may present a value of 1.030 and over.
The bile of all animals contains pigments, salts and cholesterol. In accord-
ance with Hammarsten,2 human bile obtained from a fistula of the hepatic duct
possesses the following composition:
Water 97. 48
Solids 2.52
Bile salts '. 0 . 93
Taurocholate 0 . 30
Glycocholate 0 . 63
Fatty acids 0. 12
Mucin and pigments 0 . 53
Cholesterol 0.06
Lecithin and fat 0 . 02
Soluble salts. 0.81
Insoluble salts 0.02
The bile collected directly from the gall-bladder is more concentrated than
that withdrawn from the hepatic duct. This difference is usually said to be due to
an absorption of its water, but is caused in reality by an ingo of material from the
cells lining the outer biliary passage. In this way mucin, phosphoprotein and some
cholesterol are added to the hepatic bile. It has been shown, however, that the
mucin of the bile of the ox, dog and sheep is not a true mucin, because it does not
yield a carbohydrate group on being boiled with dilute acid, and is rather rich in
phosphorus. It is in reality a representative of the phosphoproteins and seems
to have no other function than that of anointing the surfaces of the biliary chan-
nels and intestines. The mucinoid material in human bile is true mucin.
The amount of bile secreted in a day is estimated at 525 c.c, but since this value
has been obtained from cases of biliary fistula, it cannot serve as anything more
than a general guide. ^ Bile is secreted continuously, but not at a perfectly uniform
rate, because it is produced in smaller amounts during the early morning hours
and in greatest quantity after the noon-day meal.
The Storage of Bile. — In the majority of animals the bile is col-
lected by the hepatic duct which is then united with the cystic duct to
form the common duct, or ductus choledochus. In man, the latter
opens into the duodenum about 10 to 12 cm. below the pylorus, where
it meets the pancreatic duct or duct of Wirsung to form a papillary
prominence. Obviously, this arrangement allows of a thorough mix-
1 Burton-Opitz, Bioch. Bull., iii, 1914, 35.
2 Ergebn. der Physiol., iv, 1905.
3 pfaff and Balch, Jour, of Exp. Med., ii, 1897, 49.
942 THE EXTERNAL SECRETIONS
ing of these secretions. The cystic duct is enlarged peripherally into
a vesicular receptacle, known as the gall-bladder, but this diverticu-
lum is not present in all animals, its place being taken by the biliary
ducts themselves which are then distended into tubular pouches. A
similar enlargement of these ducts results in those human beings who
have had their gall-bladder removed for the relief of malignant and
other affections of this organ. Moreover, it should be noted that
those animals which are not in possession of this storehouse for bile
(horse), show a rather continuous digestive activity and require, there-
fore, a more constant supply of bile.
This is not the case in the carnivora, and hence, the bile is stored in
these animals during the periods intervening between the successive
periods of digestion. Thus, while the hepatic cells furnish a constant
supply of bile, the latter is not conveyed directly into the duodenum,
but is diverted through the cystic duct into the gall-bladder. Its
storage is made possible by the fact that the orifice of the common duct
is guarded by a transverse band of smooth muscle tissue which acts
as a sphincter and prevents its constant escape. Naturally, the con-
tinuous influx of bile from the hepatic duct gives rise to a gradual disten-
tion of the gall-bladder until a stimulation results which relaxes this
sphincter and relieves this organ of its contents. Thus, we are really
in possession of two separate mechanisms, one for the secretion and
one for the storage and expulsion of the bile.
According to Burton-Opitz,^ the gall-bladder is innervated by
fibers derived from the celiac ganglion of the solar plexus which ascend
along the small artery, supplying this organ and neighboring region
of the liver. Their function becomes evident if it is remembered that
the wall of this receptacle is made up in part of smooth muscle tissue
which on contraction lessens its lumen and subjects its contents to
a moderate pressure. The latter, however, rarely exceeds 5.0 mm.
Hg, but evidently, a greater expelling force is not called for, owing
to the fact that practically no resistance need be overcome. The
pressure at the orifice of the common duct is about zero, unless raised
momentarily by peristalsis, so that the only other prerequisite for a
free discharge of the bile is the relaxation of the sphincter. It may
rightly be concluded that the contraction of the gall-bladder coincides
with the relaxation of the latter, although it is not definitely known
how this simultaneous action is brought about. It has been estab-
lished, however, that it takes place shortly after the entrance of
chyme into the duodenum, i.e., generally during the third hour after
a meal, but no clear picture can be drawn of the mechanism involved
in this process. For the present, therefore, it must be regarded as a
reflex evoked in the duodenum, the local nerve paths of which are
contained in the plexus celiacus, plexus hepaticus and plexus gastro-
duodenalis. Preganglionically, the motor fibers of the gall-bladder
1 Am. Jour, of Physiol., xlv, 1917, 62.
THE DIGESTIVE SECRETIONS 943
have been detected in the vagus and greater splanchnic nerves, but
no very convincing data have been obtained.^
The Formation of Bile. — It has been stated above that the bile
is secreted continuously but not at a uniform rate. Naturally, this
variation is dependent upon intermittent stimuli, such as result
whenever the stomach ejects its contents into the duodenum. This
fact suffices to show that the hepatic cells are under the control of a
mechanism which regulates their activity. The latter may be either
nervous or chemical in its nature. Thus, it may be assumed that the
liver is in possession of secretory fibers which arise in the celiac
ganglion and reach this organ by way of the hepatic plexus. But
since a reflex contraction of the gall-bladder and a more copious
flow of bile may also be evoked by the introduction of an acid into the
duodenum, and since these effects may also be obtained after the liver
has been isolated from the central nervous system by the division of
its nerves, it has been concluded that the secretion of bile is also regu-
lated by a specific hormone. Starling recognizes in this chemical
stimulant the secretin of the duodenal mucosa,' his claim being based
upon the fact that the injection of this agent into the blood stream
evokes a copious flow of bile. We shall see later on that secretin
also excites a secretion of intestinal juice, and hence, it may be held
that it serves as the initial stimulus for three of the principal digestive
fluids.
Inasmuch as the hepatic cells derive the material from which they
form the bile from the portal vein, their activities must be adjusted
to a very low secretory pressure. It has been shown by Burton-Opitz^
that the blood arrives in the tributaries of the portal system of the
dog under a pressure of about 12 mm. Hg and enters the hilum of the
liver under a pressure of 9 mm. Hg. In the cat, the pressure encoun-
tered at this point amounts to only 7 mm. Hg. Now, since the pres-
sure in the inferior vena cava opposite the orifices of the hepatic veins
is practically zero, a pressure of about 9 mm. Hg must suffice to drive
the blood through the portal terminals. This is the pressure under
which the hepatic cells perform their secretory function. The blood
of the hepatic artery, on the other hand, arrives at the liver, say,
under a pressure of 100 mm. Hg, which is used up very largely in its
task of overcoming the resistance in the interstitial capillaries. Both
types of blood then traverse the intralobular veins, that of the portal
vein furnishing the secretory material, and that of the hepatic artery
the oxygen.
If the general blood pressure is reduced, the quantity of bile se-
creted is diminished, while its percentage of solids is increased. This
same- effect may be produced by the excitation of the vasoconstrictor
fibers of the liver or by the ligation of several branches of the portal
1 Bainbridge and Dale, Jour, of Physiol., xxxiii, 1905, 138; Doyon, Archives de
Physiol., 1894, and Freese, Bull. Johns Hopkins Univ. Hosp., xvi, 1905.
2 Quart. Jour, of Exp. Physiol, vii, 1913, 57.
944 THE EXTERNAL SECRETIONS
vein. These facts clearly show that the secretion of bile is closely
dependent upon a proper secretory pressure. It should be noted,
however, that the formation of bile takes place in accordance with
the same principles as the formation of other secretions; i.e., it is not
due to filtration alone but also to osmosis, diffusion, and a certain
vital activity on the part of the hepatic cells. To prove this point,
it may be shown that these cells are able to secrete against a higher
pressure than the portal blood pressure. Thus, if a cannula is inserted
in the common duct which in turn is connected with a narrow vertical
glass tube, the bile will rise in this tube until its height equals a pres-
sure considerably above that prevailing in the portal vein at the hilum
of the liver. How rapidly this level will be reached differs with the
general condition of the animal. In a robust cat under ether, prob-
ably 30 to 60 minutes will be required before the pressure in the com-
mon duct will have risen to 15 mm. Hg, which equals twice the pres-
sure ordinarily encountered in the portal vein of this animal. In the
dog, a pressure of 15 to 20 mm. Hg may be established before the
secretion of bile cease's. Clearly, since the hepatic cells are capable
of secreting against a pressure higher than that under which they
obtain their material, filtration cannot be the only factor concerned
in this process.
A very good proof of the secretory power of the hepatic cells is
also furnished by the fact that the constituents of the bile are not brought
to the liver in their complete form but are formed here from their
precursors. Lastly, it is possible to vary the secretion of bile by chem-
ical agents which act in the manner of secretogogues, and stimulate
the cells directly. These bile-driving substances are known as chola-
gogues. While aloes, calomel, peptone and, salicylates may be used
for this purpose, the most powerful agent is the bile itself. Schiff,
however, has shown that if the bile is administered by the mouth or
through an intestinal fistula, a considerable portion of it is absorbed.
Thus, at least a part of the cholagogic action of the constituents of bile
may.be due to the fact that the material absorbed is again made use
of in the formation of new bile. To prove this point Wertheimer^
injected sheep's bile into the mesenteric vein of a dog and was able to
demonstrate the presence of cholohematin in the bile of this animal.
This body occurs normally only in the bile of the sheep.
Icterus. Cholemia. Resorption of Bile. — While it cannot be
doubted that the hepatic cells are capable of secreting against a higher
pressure than that prevailing in the portal vein, this process cannot
be continued indefinitely. The upper limit having been reached,
the secretion ceases and some of the constituents of the stagnated
bile pass over into the circulation. This resorption gives rise to the
condition of icterus or jaundice, which is characterized by a deposition
of the biliary pigments in the tissues of the body, causing a yellow
1 Archive de physiol. norm, et path., 1892, 577; Stadelman, Zeitschr. fiir Biol.,
xvi, 1897, 1; Whipple and Hooper, Am. Jour, of Physiol., xl, 1916, 349.
THE DIGESTIVE SECRETIONS 945
discoloration of the sclera, conjunctiva and mucous surfaces. This
pigmentous material also appears in the urine and finally gives rise
to a reduction in the frequency of the heart and respiration and a
general bodily and mental fatigue.
A condition of this kind may arise in consequence of a catarrhal inflammation
of the larger biliary passages and the formation of mucous plugs, or in consequence
of the escape of a calculus from the gall-bladder which later on becomes firmly
wedged in between this organ and the duodenum. Under these circumstances
the feces assume a grayish color and the consistency of clay, owing to the absence
of bile and the resultant accumulation of much undigested fat. Defecation be-
comes infrequent and labored, owing to the loss of the tonicity of the intestinal
musculature and the solidity of the fecal material. Jaundice may also be
incited by the administration of poisons which, however, do not produce an actual
obstruction of the larger biliary passages. The cause of this non-obstructive type
of icterus is more difficult to explain, unless it is held that the poison gives rise to
an erosion and obliteration of the intralobular channels. This result is quite com-
mon in all conditions producing an excessive destruction of red cells. It is generally
believed that this resorption of bile takes place through the lymphatics and not
through the blood-capillaries, \ because the ligation of the common duct does not
give rise to jaundice if the thoracic duct is obstructed at the same time.
Extirpation of the Liver. — It has previously been shown that the
secretion of bile is dependent upon filtration, diffusion and osmosis,
and a vital activity of the cells. Attention has also been called to the
fact that bile is secreted continuously but not at a uniform rate, be-
cause different stimulations result from time to time which vary its
formation. Chief among these is the chyme which, upon its ejection
into the duodenum, evokes a local reflex and liberates the hormone
secretin. By this means the increased activity of the hepatic cells is
made to coincide precisely with the evacuation of the gall-bladder, so
that both processes occur at about the third hour of digestion and
synchronously with the outpouring of the pancreatic juice. In this
connection it is of interest to note that the digestive products of the
proteins and fats evoke a much more copious flow of bile than the
carbohydrates. It may also be increased by a large intake of water,
and diminished by hunger and emotions.
The Ugation of the portal vein does not stop this secretion alto-
gether, because the hepatic artery is able for a time to compensate
for the loss of the portal blood. But this compensation soon proves
wholly inadequate to sustain life and the animal succimibs to a vas-
cular depression brought about by the engorgement of the portal
circuit. 2 Much better results may be obtained if an artificial com-
munication is first established between the portal vein and the inferior
1 Mendel and Underhill, Am. Jour, of Physiol., xiv, 1905, 252, and Eppinger,
Ziegler's Beitr., xxxi, 1903, 230.
2 The ligation of the portal vein distally to the orifice of the pancreatic vein
does not prove fatal, because the blood of the mesenteric veins then flows into the
splenic vein, whence it reaches the gastric veins and the hilum of the liver by way
of the pancreatic veins. This reversal of the splenic blood stream is made possible
by the enlargement of the small veins upon the pylorus, ordinarily connecting the
pancreatic vein with the gastric veins.
60
946 THE EXTERNAL SECRETIONS
vena cava (Eck fistula) by uniting the edges of a longitudinal incision
in the wall of the former blood-vessel with those of a similar opening
in the latter. ^ In birds, a communication of this kind is normally-
present in the form of a small channel which connects the capillary
expanse of the renal-portal system with the portal vein. Consequently,
the portal vein of these animals may be hgated without causing
serious disturbances. The total removal of the liver, however, even-
tually proves fatal, on account of the loss of the necessary amounts of
bile and other products of the hepatic cells, such as the precursors
of uric acid, salts and pigments. The latter are even more important
than the former in spite of the fact that the loss of bile gives rise to
serious digestive disturbances. The method of partial and total ex-
tirpation of the liver has been made use of more particularly as a
means of showing that the special constituents of the bile are actually
synthetized in this organ and are not brought to it in their complete
form. Naturally, the raw material from which these substances are
derived is the blood pigment, hemoglobin. This can be proved either
by injecting this substance into the bloodstream or by inciting a greater
destruction of the red cells by means of hemolytic agents. It will be
found that the amount of the corresponding constituents of bile is
directly proportional to the destruction of these cells. A similar
reduction of the hemoglobin takes place in those tissues which have
been the seat of an extravasation. As the hematin of these extra-
vasates is slowly converted into bodies similar to the bile-pigments,
the tissues so affected assume different shades of purple, blue and
yellow.
It has already been pointed out that the life of the red blood cor-
puscles is limited and that the *' senile'' ones are gradually removed
from the circulation while they traverse the capillaries of the liver and
spleen. But their destruction cannot be accompanied by a discharge
of their hemoglobin into the blood stream, because this substance is
taken up by the different phagocytic cells, such as the cells of Kupffer
lining the intrahepatic spaces. These cells also possess the power of
engulfing and destroying the red cells in their entirety, a process which
may be more directly studied in the amphibia, because the red cells
of these animals contain a sharply differentiated nucleus. In these
animals, any excessive destruction of their red cells is invariably
followed by an accumulation of a bright green pigment within
these phagocytes, which presents all the characteristics of biliverdin.
A similar deposition of this material takes place in the neighboring
endotheUal hning cells as well as in the hepatic cells themselves. These
accumulations of pigment may be rendered more conspicuous by
staining them with potassium ferrocyanid which colors them blue,
1 Nencki, Pawlow and Zaleski, Archiv fiir Exp. Path., xxxvii, 1896, 26; Carrel
and Guthrie, Compt. rend., 1906, and Bernheim and Voegtlin, Jour, of Pharm.
and Exp. Ther., i, 1909, 463.
THE DIGESTIVE SECRETIONS 947
or with ammonium sulphid which, owing to their content in iron,
colors them dark brown.
Special Constituents of Bile. — The bile contains the sodium
salts of complex amino-acids, such as glycocholic, taurocholic, glyco-
choleic and taurocholeic. The relative proportion of these salts differs
in different animals, glycochoHc acid being more abundant in the bile
of man and herbivora, and taurochoHc acid in that of the carnivora.
They are formed as soon as the liver attains its full functional develop-
ment and do not arise elsewhere in the body. Their detection is
made possible by means of Pettenkofer's reaction, which consists in
adding a few drops of a 10 per cent, solution of cane-sugar and con-
centrated sulphuric acid to the suspected Uquid. If the latter con-
tains bile salts, a violet ring develops at its point of contact with the
reagent. This coloration is due to the formation of an aldehyde-hke
furfurol by the acid from the sugar, and the condensation of this prod-
uct with the bile salts.
The bile salts may be prepared by mixing fresh bile with about 1 per cent, by
weight of animal charcoal. This hquid is evaporated to dryness on the water bath,
and the residue powdered and extracted with water and filtered. The filtrate is
acidified, but contains, in addition to the bile salts, also some cholesterol, mucin,
phosphatides and inorganic salts. Crystallized bile^ is prepared in the same way,
excepting that the dried mixture of charcoal and bile is extracted with boiling ab-
solute alcohol. Since the bile salts are very soluble in alcohol, they are separated
out immediately, leaving the other constituents behind. The alcohol is filtered
and mixed with absolute ether until a precipitate is formed. On cooling, the bile
salts crystallize out, but since they absorb water very readily, they should be kept
in a desiccator. The glycocholic acid may be hydrolyzed by dilute acids and alkalies
and split into glycerin or amino-acetic acid and cholic acid.
C26H43NO6 + H2O = CH2(NH2)COOH + C24H40O5
(Glycocholic acid) (Glycine) (Cholic acid)
In the same way taurocholic acid may be split into taurine, or amino-ethyl-sul-
phonic acid and cholic acid.
C26H45NO7S + H2O = CH3CH(NH2)S02-OH + C24H40O5
(Taurocholic acid) (Taurine) (Cholic acid)
It will be shown later on that the bile salts stimulate peristalsis and serve as
a vehicle for the digestion of the fats. Their function having been completed, a
portion of them is destroyed through the influence of the intestinal microorganisms,
while another portion is again absorbed and returned to the liver by way of the
portal blood stream. The hepatic cells rebuild this material into new bile salts,
thereby greatly reducing their work in synthetizing these salts. A similar ''cir-
culation of the bile" between the intestine and the liver is had in the case of some
of the derivatives of the pigmentous material of the bile.
Cholic or cholalic add is a white, crystalline and very bitter substance which
is almost insoluble in water, but soluble in alcohol. On addition of water it crys-
tallizes from the latter in rhombic pyramids and tetrahedrons. It is closely allied
to cholesterol and may be derived from this substance.
Cholesterol has been found in the bile of almost all animals, but is not present in
considerable amounts in human bile (1.6 in 1000 parts). Since it is insoluble in
water and solutions of salts, it must seem peculiar that it is dissolved by the bile
and may be present here in even greater amounts than normal. This excessive
solvent action of bile is due to its content in bile salts and more particularly to the
^ Platner, Ann. der Chemie und Pharmazie, li, 1844, 105.
948 THE EXTERNAL SECRETIONS
cholic acid radicle of the latter, which unites in some way with the cholesterol and
keeps it in solution. Little is known regarding the origin of this substance. It
may be derived from the food or from the cholesterol of the destroyed red blood
corpuscles. Regarding its place of origin, Naunyn makes the assertion that it is
eliminated chiefly by the lining cells of the gall-bladder, this statement being based
upon the fact that the bile of the latter contains a larger amount of cholesterol than
that of the hepatic duct. But since the relative richness of the bladder-bile in
this substance may be due to the fact that the cholesterol here secreted is not so
easily converted into bile salts, the preceding deduction may not be correct. A
disturbance of these oxidations in consequence of traumatism and inflammation
of the wall of the bladder, or in consequence of general metabolic disorders (meno-
pause), frequently leads to the formation of gall-stones which may at times occupy
every recess of the bladder and also find their way into the large biliary channels.
The constant irritation set up by these concretions tends to excite contractions
of the bladder, which in the course of time mold these masses into many-sided
fragments possessing sharp points and sides. As has just been stated, the chief
constituent of these concretions is cholesterol (20 to 90 per cent.) to which some
desquamated epithelium has been added. ^
The phospholipins of bile present themselves principally in the form of lecithin.
Practically nothing is known regarding their origin and function. In human bile
the lecithin, obtained from the alcohol-soluble material, amounts to 1.7 per cent.,
but varies considerably in accordance with the character of the food ingested.
This fact might lead us to suspect that it is derived from the constituents of the
diet, but it may also be true that it originates from the destroyed red blood cor-
puscles.
The peculiar color of the bile of the carnivora is due to certain pigments of which
bilirubin is the most important. This substance is unstable and is easily oxidized
into a green pigment, known, as biliverdin, which in turn gives rise to a whole series
of bodies, such as the blue biUcyanin. On further reduction it is converted into
urobilin, one of the coloring materials of urine. In the herbivora the chief pigment
is biliverdin, but it seems that the aforesaid pigments are interchangeable. Bili-
ruhin (C32H36N2O6) is an iron-free compound and is derived from the hemoglobin
of the red corpuscles. Consequently, its formation must be dependent upon the
rate of destruction of these cells. Since the bile contains only a trace of iron, it may
be surmised that this element is stored in the liver cells to be made use of sub-
sequently in the formation of new hemoglobin. Bilirubin is prepared from
powdered red gall-stones by dissolving the chalk with hydrochloric acid and extract-
ing the residue successively with chloroform. The pigment crystalUzes from this
solution in beautiful rhombic tables or prisms. Biliverdin (C32H36N4O8) is an
amorphous iron-free body. It may be formed from bilirubin by oxidation and may
be reconverted into this pigment by putrefaction or by the addition of ammonium
sulphid. By reduction with sodium amalgam it is changed into hydrobilirubin,
a substance identical with stereobilin. Similar reductions go on when the bile
pigments reach the intestine, so that they are not recognizable as such in the feces
or urine. The most important derivative of bilirubin is stercorubin or urobilin.
To this body is due the brown color of the feces. In urine it appears as urobiligen,
a colorless substance which is changed into urobilin under the influence of the oxy-
gen of the air. When the bile is prevented from entering the intestine, the urine
does not contain this substance.
The Intestinal Glands. — The mucous membrane of the small
intestine contains numerous goblet cells, similar in structure to those
previously noted in the mucosa of the stomach. Their function is to
discharge mucus which serves to lubricate the surfaces of the intestine
1 Kramer, Jour, of Exp. Med., ix, 1907;Lichtwitz, Arch. klin. Med., xcii,1907,
100, and Bacmeister, Munch, med. Wochenschr.,1908.
THE DIGESTIVE SECRETIONS
949
and to render the feces more slippery. In between the different villi,
however, the mucous membrane is pervaded by simple tubular glands
which are known as the crypts of Lieberktihn. The latter are lined
throughout by a single row of columnar epithelium, among which are
found a few goblet cells. In the crypts of the large intestine, on the
other hand, these mucous cells increase in number and finally displace
the secretory cells altogether. This structural change is in complete
harmony with the fact that the crypts of the large intestine form only
mucus for purposes of lubrication.
The Secretion of the Intestinal Juice or Succus Entericus. — Un-
adulterated intestinal juice may be obtained by means of a fistula.
The method of Thiery (1864) consists
in isolating a loop of intestine by two
transverse cuts made at some distance
from one another.^ The intervening
segment is left in connection with its
normal blood and nerve supply jand
is brought close to the abdominal
wall. Its upper end is then closed
by sutures, while its lower end is
anchored to the sides of the wound
in the abdominal wall. The contin-
uity of the intestine from which this
loop has been obtained is restored
by an end-to-end anastomosis. Vella
advises to fasten both ends of the
isolated loop to the edges of the
wound in the abdominal wall.
Fig. 502. — Diagram to Illustrate
THE Relation Between the Villi and
THE Crypts of Lieberkuhn.
V, Villus; G, goblet cells secreting
mucus; C, crypt of Lieberkuhn; L,
lacteal.
The juice obtained from such isolated
segments of the small intestine is light yellow
in color, opalescent, very watery and strongly
alkaline in reaction. It possesses a specific
gravity of 1.010, and contains 1.07 per cent,
of solids, of which 0.2 per cent, are appor-
tioned to Na-iCOs and 0.58 per cent, to
NaCl. Its small content in proteins is made
up of serum albumin and serum globulin. Its quantity is considerable, a short
segment of intestine furnishing as much as 200 c.c. of juice in the course of a
day. 2 One of the commonest means used to excite its flow is to introduce a rubber
tube through the fistulous opening, but Pawlow states that the character of the
juice is then somewhat different from that obtained without this mechanical
stimulation, one of the points of difference being that it contains no enterokinase.
Its flow may also be increased by dividing the mesenteric plexus, ^ or by produc-
ing hydremic plethora.
In the former case, a copious secretion sets in very shortly after the section of
these nerve fibers and continues for about 24 hours. Clear at first, the fluid soon
becomes cloudy and milky until it assumes the consistency of a thick broth. While
1 Pawlow, Chirurgie des Verdauungskanals, Ergebn. der Physiol., i, 1902.
2 Frouin, Compt. rend., Ivi, 1904, 461.
3 Mendel, Pfliiger's Archiv, Ixiii, 1896, 425.
950 THE EXTERNAL SECRETIONS
we might regard this liquid as a true secretory product of the glands of Lieberkiihii,
it should not be forgotten that a considerable portion of it may be produced by
transudation following the relaxation of the intestinal blood-vessels. In general,
this pnenomenon may be compared to the paralytic secretion of saliva.
The intestinal juice contains several ferments, two of which are proteolytic in
their action. Of these enterokinase has already been mentioned in connection with
the activities of Brunner's glands. The other, which is known as erepsin, is present
in this juice as well as in almost all tissues of the body. Among the ferments
affecting the carbohydrates, may be mentioned invertase which transforms sugar
into glucose and levulose or fructose, and maltase which changes maltose into
glucose. 1 Excepting enterokinase, these ferments have also been regarded as intra-
cellular agents and not as constituents of the juice itself. In this form, they should
exert their action upon the different, foodstuffs while the latter traverse the epitlie-
lial cells on their way to the channels of absorption. This contention is founded
upon the fact that the liquid obtained by extracting the intestinal mucosa forms
a more powerful digestive medium than the intestinal juice itself. In all previous
instances, we have observed that a simple extract of the mucosa is inactive, but may
be activated very readily by giving to it the reaction which it necessitates. Entero-
kinase, on this other hand, is not contained as such in the epithelial lining cells but
only in the form of a precursor which assumes its activity immediately after its
discharge into the general juice of the intestine.
The regulation of this secretion is effected by a nervous as well
as a chemical factor. The former is mediated by the peripheral
expanse of the autonomic system of this particular region of the body,
which presents itself in the form of the plexuses of Meissner and Auer-
bach. These networks of sympathetic fibers are situated beneath the
submucosa. The fact that reflexes play a part in the secretion of
intestinal juice may be gathered from the close dependency of this
process upon extraneous stimuli. ^ Thus, a dog which had not been
fed for a period of about 24 hours showed a flow within 15 minutes
after the ingestion of food ; moreover, this flow reached its maximum
in about 3 hours, i.e., at a time when the pancreatic juice was produced
most copiously. But since the intestinal secretion does not cease
after the intestine has been completely isolated from the central
nervous system by the division of the vagi and sympathetic nerves,
some other agent must be at work, presumably in the form of a se-
cretogogue. Although the nature and place of origin of this hormone
have not been made out with any degree of definiteness, Delezenne
and Frouin^ have proved that the injection of secretin into the blood
stream of animals provided with an intestinal fistula gives rise to
a copious flow of this juice. It seems, therefore, that this chemical
messenger acts simultaneously upon three organs, namely, upon the
pancreas, liver and glands of Lieberkiihn, insuring thereby a concerted
action of these secretions upon the acid gastric chyme. But certain
evidence is also at hand to show that some other chemical agent is
liberated in the lower part of the small intestine, synchronously with
the intestinal juice. The nature of this hormone is not known.
1 Weinland, Zeitschr. fiir biol. Chemie, xlvii, 1905, 279.
2 Bayliss and Starling, Ergebn. der Physiol, 1906.
3 Proc. Soc. Biol., Ivi, 1906, 319.
SECTION XXV
THE INTERNAL SECRETIONS
CHAPTER LXXXI
THE THYROID AND PARATHYROID BODIES* THE THYMUS,
LIVER, AND PANCREAS
General Discussion. ^ — The beginning of the scientific study of the
ductless glands dates from 1849, when Berthold^ showed that the tes-
ticles produce an internal agent which is transferred by them directly
into the blood-stream. He proved his point by removing these organs
from cocks and grafting them upon some other part of the body.
Peculiarly enough, these animals ''remained male in regard to voice,
reproductive instinct, fighting spirit, and growth of comb and wattles.'^
In 1855, Claude Bernard^ gave a more elaborate presentation of this
subject by stating that glands may form a secretion externe by with-
drawing substances from the blood, and also a secretion interne by
passing their products into the blood. He illustrated this conception
by referring especially to the liver which, in addition to its external
secretion, the bile, also furnishes an internal agent which is directly
concerned in the aggregation of glycogen and the formation of sugar.
In 1889, Brown-Sequard, then 72 years of age, announced to the Society
de Biologie de Paris that he had carried out upon himself a series of
experiments with extract of testicle, proving that this therapy ''has
given him much physical strength, an invigoration of cerebral function,
and a good appetite and digestion. " Then followed a period of organo-
therapy during which practically every organ of the body was tested
as to its remedial qualities in diseases supposedly produced by a
deficiency of some internal secretion. Much of this material, however,
is absolutely valueless, because aggrandized for purposes of commercial
exploitation.
Brown-Sequard has added to the conception of Bernard the idea
that certain glands secrete certain specific substances into the blood-
stream, tending to produce a definite correlation of function between
different organs. This interpretation of facts really forms the basis
of a new function. Several years later Schiff compiled additional
^ For references see : Biedl, The Internal Secretory Organs, translated by
Williams, Wood & Co., 1913.
2 Archiv fiir Anat., Physiol, und wissensch. Medizin, 1849, 42.
3 Legons de physiol. exper., Paris, 1855.
951
952 THE INTERNAL SECRETIONS
data pertaining to the effects following the removal of the thyroid
bodies which were based in the main on the clinical observations of
J. L. and A. Reverdin and Kocher on post-operative myxedema.
Somewhat later Glover, Schafer (1895), Cybulski (1895), Biedl (1898)
and Dreyer (1899) studied the action of suprarenal extract upon the
cardio- vascular system. In all these instances, it was shown that our
body contains certain aggregates of cells which possess an altruistic
function, because they supply the organism as a whole with substances
having to do with its general welfare. The medium through which
these organs are able to exert this influence, is the blood or more par-
ticularly the blood plasma.
Classification of the Internal Secretions. — In 1902, Bayliss and
Starling showed that a flow of pancreatic juice may be evoked b}^
means of some agent derived from the mucous membrane of the duo-
denum. To this substance these investigators applied the name of
secretin. At about the same time Starling and Claypon demonstrated
the existence of a similar stimulant in the female generative organs
which induces a growth of the mammary glands. Starling, therefore,
proposed to apply to all these chemical agents or messengers the name
of ''hormone, " from the Greek opy^doi, to stir up or excite. But in-
asmuch as some of these cellular products may also retard a function,
Schafer^ advises to include all of them under the general term of auta-
coid substances, from the Greek olkos, a remedy and auros, natural.
Thus, an autacoid represents any drug-like principle which is produced
in the internal secreting tissues and organs. In accordance with their
action, these substances may then be grouped as hormones or chalones
(Greek x«Xaco, to make slack). The former are excitatory and the
latter inhibitory in their nature.
In most instances these internal agents are as yet wholly unknown
to us chemically, and their presence can only be detected in an experi-
mental way. In some cases, however, they have been isolated, and
have been dealt with as definite chemical entities. Carbon dioxid is a
substance of this kind, because it plays the part of a hormone in stimu-
lating the respiratory center whenever produced in excess. Another
one is adrenalin, a crystalline body obtained from the adrenal glands by
Takamine.2 It constricts the blood-vessels and raises the blood pres-
sure. As a third might be mentioned hydrochloric acid, because it
liberates secretin and as a fourth, idiothyrin which exerts a peculiar
action upon the neuro-muscular mechanism. By far the greatest
number of these autacoids, however, are of unknown composition and
their presence can only be proved physiologically, for example, by in-
jecting the extracts of the tissues in which they are supposed to exist
into the blood-stream.
Starling emphasizes the fact that hormones belong to the crystal-
loids rather than to the colloids. Consequently, they are relatively
^ Intern. Congress of Med., 1913.
2 Therap. Gazette, xvi, 1901, 221.
THE THYROID AND PARATHYROID BODIES
953
stable substances and may be subjected to ordinary degrees of heat
without losing their function, a fact which sharply differentiates them
from the ferments and enzymes. To be sure, both these agents are
cellular products, but while the autacoids are destructible and their
function is restricted to the domain of the body, the enzymes are not
limited in this way. Moreover, they are resistant, and are not changed
during the processes evoked by them.
Any other classification of the autacoids meets with the difficulty
that they act upon specific groups of cells and that the effect produced
by them is usually rather vague in character. Thus, while the action
of adrenin is quite obvious, other internal secretions, for example,
those of the thyroids and thymus, possess a general metabolic function
which it is difficult to analyze. Gley, ^ however, suggests the following
classification :
(a) Nutritive
(6) Harmozones
(Glycose, liver,
Fat, intestinal mucosa,
Albumins of blood, intestinal mucosa and blood.
1. Substances effecting / sugar metabolism, pancreas,
nutritive changes
2. Substances helping
to maintain int. me-
dium
I sugar mobilization, adrenals,
\ antithrombin, liver,
3. Morphogenetic
(c) Hormones
testicles,
ovaries,
thyroid,
hypophysis,
. thymus.
i r^u • 1 / activating the trypsin, spleen,
'"^^"'''^^n catabolic, thyroid,
I ( secretin, duodenum
I Physiological \ adrenin, adrenals,
I galactogogue, placenta.
.js -P, , / Carbon dioxid, muscles and glands,
(d)Parhormones|^^^^ 1-^^^
An inspection of this table must show immediately that this clas-
sification is by no means sufficiently embracing to include all of the
internal secretions in their proper relation to one another and hence,
it may be permissible to arrange them in accordance with their location
rather than their function. In the first place, it is to be noted that
these secretions originate in the so-called endocrine organs (Greek epdov
within, and Kplpo) to separate), including the thyroids, parathyroids,
thymus, duodenum, Hver, pancreas, adrenals, pineal gland, pituitary
body, placenta, choroid plexus, and the testes and ovaries. Every one
of these glands presents at least three of the characteristics ordinarily
assigned to an internal secretory structure, namely: (a) the cells com-
posing them are usually arranged in the form of acini, and embrace a
certain amount of granular and other material from which the secretion
1 The Internal Secretions, translated by Fishberg, Hober, New York, 1917.
954
THE INTERNAL SECRETIONS
may be derived. Furthermore, while not in possession of a true duct,
they lie in close relation with definite efferent and afferent blood-vessels
and lymphatic channels, (6) their product Can be isolated chemically
from their venous blood or lymph, (c) their substance or the blood
or lymph returned from them, may be shown to possess a specific
physiological action, and (d) the removal of the organ is followed by a
loss of a definite function which is absolutely essential to the health
and very existence of the animal.
A. THE THYROID AND PARATHYROID BODIES
Position and Structure of the Thyroid Gland. — In the cat, dog
and man, the thyroid gland (Greek: thyreos, shield) consists of a right
and left lobe which are connected with one another by a bridge or
isthmus of the same tissue extending transversely across the trachea.
These lobes are nearly equal in size, and measure about 5 cm. in length.
Fig. 503. Fio. 504.
Fig. 503. — Diagram Showing the Position of the Thyroid Gland.
TC, thyroid cartilage; TG, thyroid gland; T, Trachea. The parathyroids are indi-
cated in black.
Fig. 504. — Diagrammatic Representation of the Structure of Human Thyroid
Their combined weight amounts to 30 or 40 grams, but these figures
are only approximate, because the vascularity of this organ is subject
to considerable fluctuations. It is generally larger in females, and
increases in size during the menstrual period. During adult life it
shows a proportion to the weight of the body of 1: 1800 and during
infancy a proportion of 1 : 250 ; hence, it is much larger during the latter
period.
The thyroid is developed from an outgrowth of the primitive
pharynx and is, therefore, of hypoplastic origin. It is enveloped by a
layer of dense areolar tissue which also subdivides its substance into
small lobules of irregular size. Its tissue is composed of a large number
THE THYROID AND PARATHYROID BODIES 955
of vesicles which are lined by a single row of cuboidal or columnar epi-
thelium, and contain a peculiar colloid materia . The size and shape
of these vesicles differ, greatly ; some of them attaining a diameter of
1.0 mm. Langendorff states that these acini are made up of two types
of cells, because while some of them appear to have reached adult size
and to be actively secreting, others seem to be held in reserve until
called upon to take the places of those torn away and discharged in the
secretion.
The thyroid is a very vascular organ, receiving 560 c.c. of blood
per 100 grams of substance in the course of a minute.^ Its five supply
channels are the right and left superior and inferior thyroid arteries,
branches of the external carotid, and the thyroidea ima, which ascends
upon the trachea and is a branch of the subclavian arteries. Each
lobe is drained by three collecting channels, namely the superior,
middle and inferior thyroid veins. This gland is also equipped with
an intricate system of lymphatics which, however, do not communi-
cate directly with the colloid vesicles. Its nerve supply is derived
from the superior and inferior laryngeal nerves.
Position and Structure of the Parathyroid Glands. — The parathy-
roids^ usually present themselves as four small rounded masses em-
bedded in the substance of the thyroid. They are oval in shape,
measuring about 6 mm. in length and 3 to 4 mm. in breadth, and their
combined weight rarely exceeds 0.10 gram.^ One pair of them is
usually found near the level of the lower border of the cricoid carti-
lage, between the wall of the esophagus and the lateral mass of the
thyroid, while the second is situated as a rule opposite the third or
fourth ring of the trachea in or near the lower pole of each lobe.*
Accessory parathyroids are encountered at times along the trachea
and even in the cavity of the thorax.
The cells composing these bodies are epithelial in character and
are arranged in palisade-like columns which are connected with one
another by unusually vascular connective tissue. In many cases
this tissue is so well developed that the entire gland appears to be sub-
divided into many smaller lobules. Its parenchyma is made up,
on the one hand, of large polygonal chief cells, the cytoplasm of which
does not stain well, and, on the other, of cells possessing a delicate,
granulated interior which stains intensely with eosin and other acid
dyes. The parathyroids may also contain follicles which are filled
with a colloidal material similar to that occupying the vesicles of the
thyroid.
Extirpation of the Thyroid and Parathyroids. — It was formerly
believed that the thyroid regulates the blood-supply of the brain
1 Tschuewsky, Pfliiger's Archiv, xcvii, 1903, 210.
2 Discovered by Sandstrom, Upsala Lakarefor. Forh., xv, 1880, and described
by Kohn, Archiv fiir mikr. Anat., xlv, 1895.
' Thomson, The Thyroids and parathyroids throughout vertebrates, Phil.
transact., Roy. Soc, 1911.
^ Fischer, Archiv fiir Anat., 1911.
956 THE INTERNAL SECRETIONS
(Cyon), this view being based upon the fact that it is placed directly
in the path of the cerebral vessels and contains at times anastound-
ingly large amount of blood. ^ The latter peculiarity, in particular,
led Tiedemann to assume that it is a blood-forming organ. Its real
nature, however, was not detected until the year 1856, when Schiff^
proved that its total removal induces certain pathological conditions
which invariably prove fatal in the course of three to four weeks. In
spite of these perfectly definite results, the removal of this organ was
resorted to a number of times in subsequent years for the relief of
those serious respiratory difficulties which are usually associated
with goiter. In all these cases, this surgical procedure was followed
by very alarming symptoms which presented themselves chiefly as
disorders in nutrition and a general muscular weakness, tremors and
spasms.^ In 1884, Schiff operated upon a second series of sixty dogs
of which fifty-nine died within three weeks. This study drew renewed
attention to this organ, and spirited efforts were made henceforth to
unravel its function. Thus, it was soon discovered that the serious
symptoms following its total extirpation, could be prevented by per-
mitting a portion of, say, its lower extremity, to remain in the body.^
Likewise, it was shown that the transplantation of the thyroid to some
other part of the body, such as the peritoneal cavity, protects the
animal against the consequences of thyroidectomy. The healing in of
these transplanted segments of the gland proceeds very quickly in
thyroidectomized animals so that their vascularization is practically
completed at the end of the third week. In the normal animal, on
the other hand, these transplants do not grow well and do not attain
this stage in less than eight weeks. ^ Lastly, Vassale^ proved that
the alarming effects of thyroidectomy may also be obviated by the feed-
ing of thyroid substance or the injection of thyroid extract. The
conclusion to be derived from experiments of this kind is that the
thyroid furnishes an agent which is absolutely essential to life.
The Symptoms Following .Th3n'oidectomy. — The effects of ex-
tirpation of the thyroid and parathyroids differ in different animals,
obviously because these structures vary in their size and position. In
the herbivora, for example, the parathyroids generally lie outside
the substance of the thyroid, while other animals are in possession of
accessory parathyroids which are scattered as small globular masses
along the trachea. In the fishes, these bodies are represented by small
patches of tissue of about the size of the head of a pin which are situated
^ Swale Vincent, Ergebn. der Physiol., ix, 1911.
2 Unters. iiber Zuckerbildung, Wiirzburg, 1859. Previous to this time we
have the experiments of Astley Cooper, Rapp and Bardeleben which, however,
led to no definite results.
3 Reverdin (Rev. med. de la Suisse romande, 1882) ; Kocher (Archiv f iir klin.
Chir., 1883), and Billroth (Wiener med. Presse, 1877).
* Eiselberg, Wiener klin, Wochenschr., v, 1892, 81.
6 Salzer, ibid., 1909.
« Neur. Zentralblatt, 1891.
THE THYEOID AND PARATHYROID BODIES 957
along the aorta and along the arches of the gills. If we confine our-
selves, therefore, to the carnivora and include in this discussion the
symptoms caused by the enucleation of the parathyroids, the following
clinical picture is obtained/
The features are swollen and imperfectly outlined, owing to an
edematous condition of the skin which in turn is caused by an accumu-
lation of mucin in the subcutaneous connective tissue. Latier on, the
bloated appearance of the skin is aggravated by a certain roughness
and dryness, which finds its origin in the cessation of the cutaneous
secretions and eventually gives rise to a coarseness and falling out of the
hairs. This infiltration also affects the mucous membranes, and
eventually involves the respiratory passage and conjunctional sacs
(myxedema). The animal loses weight steadily, and finally enters
a condition of pronounced malnutrition, the so-called cachexia thyreo-
priva (strumipriva). But these purely metabolic disturbances which
prove that thyroidectomy renders the animal unfit to utilize its food,
are invariably associated with others, indicating a severe intoxication of
the nervous system. To begin with, it is observed that the muscular
contractions become clonic in their character, then tetanic and lastly,
spastic. This leads to a marked muscular rigidity and contracture,
and finally to a weakness as well as a motor and sensory paralysis of
the entire body. As the anterior and posterior extremities become
weakened and are no longer able to support the trunk, the animal is
forced to assume the position usually occupied by it during sleep. The
muscular tremors are gradually intensified and become more general
in their character, terminating eventually in severe convulsions and
death. Although the higher nerve centers appear to retain their func-
tion for a relatively long period of time, their irritability is gradually
diminished, which renders the animal stupid and very apathetic.
Death usually results in the course of 9 to 12 days.
Cretinism, Mjrxedema and Hyperthyroidism. — Keeping the char-
acter of the symptoms just cited clearly in mind, we are now in a better
position to analyze the clinical pictures of cretinism, myxedema,
hyperthyroidism, exophthalmic goiter, and the conditions forming the
basis of Basedow's disease. In a general way, it may be said that man
is subject either to a diminished or an increased function of the thyroid
gland, or, in other words, to a deficient or an excessive formation of
this internal secretion.
(a) Cretinism or infantilism is due either to an imperfect development of the
thyroid gland or to its atrophy in later years. The infant so afflicted presents a
dwarfed appearance, because the growth of the bones and soft parts has been
checked. The abdomen is large and pendulous, while the legs are poorly formed
and seem scarcely able to support the weight of the trunk. The face presents a
swollen appearance and imperfectly outlined contours. The hair is coarse and
scanty and the skin thick and dry. Mentally, the cretins are far behind children
of the same age, in fact, their intelligence frequently borders upon imbecility and
idiocy. Their movements are clumsy and unsteady. In many instances, this con-
dition of infantile myxedema or cretinism resembles very closely true dwarfism,
958
THE INTERNAL SECRETIONS
and certain types of rachitis fetalis from which it must, therefore, be differentiated.
This cUnical picture may be cleared up in the course of a month or two by the feeding
of thyroid substance or of an extract of thyroid. Growth begins again, the myxe-
dematous symptoms disappear more or less completely, and the infant brightens
up perceptibly from week to week. In our own country myxedematous cretinism
is rather rare, but there are several regions in which it is endemic; for example,
in Italy which reported 13,000 cases in 1883, and in Austria, Savoy, the Pyrenees,
the Himalayas and the Cordilleras. Since these districts are mountainous and
are formed by marine deposit of the Paleozoic, Triassic and Tertiary periods,
cretinism has been etiologically referred to peculiarities of the soil and to the
drinking water derived from these geological strata. That there is some truth in
Fig. 505.-
-Cbetin before (A) and after (B) Treatment with
(Nicholson, in Arch. ofPed., June, 1900.)
's Thyroid.
this explanation is shown by the fact that the introduction of fresh water from
other sources has eradicated this disease in at least some of these districts. More-
over, it is a matter of common experience among these people that the drinking
of water from so-called ''goiter-springs" gives rise to myxedematous symptoms
within a short time, while filtered or boiled water does not.^
(b) Myxedema. — The extirpation or atrophy of the thyroid gland in adults is
soon followed by symptoms such as have just been described. The skin becomes
thickened, swollen and dry and yields mucin when extracted with alkali. The hair
becomes coarse and scanty. There is also present a general fatigue, a mental
apathy, and a tendency to an abnormal deposition of fat. The nitrogen metab-
olism is reduced.
1 Bircher, Zeitschr. fiir exp. Path, und Ther., ix, 1911.
THE THYROID AND PARATHYROID BODIES 959
(c) Hyperthyroidism.^Th.e condition of hyperthyroidism may be produced in
animals either by the continued feeding of thyroid substance or by the intraven-
ous injection of thyroid extract (rabbits). It is usually initiated by frequent at-
tacks of tachycardia to which are added disorders of digestion and metabolism,
such as diarrhea, intestinal hemorrhage, emaciation, polyuria and glycosuria.
A few cases are also on record of persons who have taken excessive amounts of
thyroid for the relief of obesity and other disorders. Thus, one person ingested
in the course of five weeks nearly 1000 tablets of thyroid substance of about 0.3
gram each and developed, in addition to the symptoms just mentioned, an extreme
irritability of the nervous system, psychic exultation, sleeplessness and trembling
of the muscles. 1 This complex of symptoms corresponds almost precisely with
that presented by persons suffering from Basedow's disease or, as it is now more
commonly called, Graves' disease. In 1840, Basedow showed that the combination
Fu;. ~)(H]. -i-lxopa'TllALMIC GoiTER.
The patient shows a goiter of moderate size; great exophthalmos, smooth forehead,
and abnormal expression. (MacCallum.)
of exophthalmos, goiter and tachycardia forms a syndrome of a not infrequent
clinical condition which, in general, is just the reverse of that noted in thyreopriva,
hypothyroidism or diminished thyroid function. The heart is very rapid and
often irregular ; the temperature is usually a degree or two above normal ; the thy-
roid is generally somewhat enlarged; while the eyes, owing to the wide open condi-
tion of the eyelids, are very prominent and staring. To these three fundamental
symptoms, others have been added in the course of more recent years, the combined
clinical picture being that of Graves' disease. Among the secondary conditions
might be mentioned an increased appetite and metabolism, insomnia, restlessness,
intensified sensations, mental excitement accompanied by hallucinations, muscular
tremors, anemia and loss of weight.
The etiological connection of Graves' disease with a hyperactivity of the
^ The therapeutics of preparations containing the active principles of the
internal seoretions, is discussed in Harrower's "Practical Hormone Therapy,"
Hober, New York, 1914.
960 THE INTERNAL SECRETIONS
thyroid and a flooding of the system with an excessive amount of this secretion,
is well illustrated by the fact that the partial extirpation of this organ gives rise to
an almost immediate amelioration of these symptoms. In fact, in many cases
it suffices to reduce the vascularity of this organ by the ligation of one of its arteries.
Kocher states that these operative measures resulted in 76 per cent, of his cases in a
complete cure and in another 14 per cent, in a decided improvement. The mor-
tality which amounts to about 3 per cent., is referable chiefly to erroneous diag-
nosis. Simple hyperthyrosis is characterized by a slight swelling of this gland, i.e.,
by a latent increase in its size and a few of the milder symptoms enumerated above.
It occurs most frequently in young women, and is temporary in its nature.
The Nature of the Active Principle of the Thyroid. — Much un-
certainty still prevails regarding the nature of the active agent
contained in the secretion of this gland, although it seems established
that it is derived from the colloid material of its vesicles. In this connec-
tion, it is of interest to note that a substance has been isolated from
thyroid tissue by Baumann,i to which he has given the name of
iodothyrin or thyroidin. It contains as much as 9.3 per cent, of its
dry weight as iodin. While the action of this substance has not been
definitely ascertained, it seems certain that it is at least closely
associated with the activity of this gland. This is shown by the fact
that it is always present in normal glands and that the minimun amount
of iodin necessary to maintain the usual histological picture of thyroid
tissue, does not fluctuate materially in any given species. Moreover, in
cases of hyperplasia the iodin content is invariably below the minimum
value of 0.1 per cent, of the dried gland; in fact, no demonstrable
quantities of this substance are ever present in extreme conditions of
goiter. Very beneficial results have been obtained with this substance
in the treatment of myxedema and goiter. Hunt^ furnishes the fol-
lowing interesting analyses:
Per cent, of
Thyroid of iodin
Children None
Maltese kid None
Guinea-pig 0 . 05
Dog 0.06
Cat 0.08
Sheep 0.17
Beef 0.25
Hog 0.33
Human 0.23
Human in goiter . 0 . 04
A similar but less complex body has recently been isolated by
KendalP which he calls thyro-oxy-indol or thyroxin and to which he
gives the formula: C11H10O3NI3. It is claimed that this substance
exerts as powerful an influence upon cretinism and myxedema as
desiccated thyroid. Thus, it may be concluded that the active prin-
ciple of this internal secretion is an iodin-containing hormone, the
1 Zeitschr. fiir physiol. Chemie, xxi, 1896, 481.
2 Studies on Thyroid, Bull. Hygienic Lab., Washington, 1909, No. 47.
3 Am. Jour, of Physiol., Proc, xlv, 1918.
THE THYROID AND PARATHYROID BODIES 961
efficacy of which does not depend so much upon the iodin as upon
the character of its combination with other substances. But since
organic iodin complexes, such as iodin-protein, are inactive, the chief
factor to be determined is liow much active iodin-containing material
can actually be liberated from the inactive iodin substance of the
gland.
In order to prove that such an elaboration actually takes place,
Rogoff and Marine^ have followed the method of Gudernatch^ and
have exposed tadpoles to the influence of iodin-free and hydrolized
sheep thyroid, containing varying amounts of available iodin. In
the latter case, their growth was retarded, while their differentiation
took place at a much faster rate. The rapidity and decisiveness with
which these changes are effected, may be employed as a means of
determining the intensity of the evolution of the active iodin-con-
taining substance.
A chemical test of even greater delicacy is the nitrile reaction described by
Hunt. ^ If so little as 0. 1 mg, of dried thyroid substance per gram of body-weight
is fed to a white mouse each day for 10 consecutive days, this animal will survive
as much as 10 times the amount of acetonitrile which would prove fatal to any
other mouse not having received this treatment.
It is also of interest to note that the thyroid possesses marked storative quali-
ties for iodin. Thus, if iodin is administered to animals with actively hyperplas-
tic thyroids, this substance is rapidly stored in this gland and gives rise to definite
histological changes, constituting the so-called colloid goiter. Moreover, the
greatest storative power is possessed by those glands which are most hyperplastic
and contain, to begin with, the smallest amount of iodin. It matters little whether
the iodin is administered at this time intravenously in the form of a salt or is per-
fused through the excised gland.
The Function of the Thyroid and Parathjnroids. — It has been
noted above that the extirpation of the thyroid of carnivorous animals
proves fatal almost without exception, but does not seriously incon-
venience the herbivora. Whatever deviations from this general rule
may have been observed, they are due in all probability to peculiar-
ities in the distribution of the parathyroid bodies. Inasmuch as these
structures were not recognized as an anatomical entity until late dur-
ing the period of thyroid experimentation, many of these symptoms
have undoubtedly been ascribed to the loss of this organ, although
actually caused by the loss of the parathyroids. Besides, since the
latter also appear in the form of accessory masses along the trachea,
they may have escaped detection altogether. It need not surprise us,
therefore, to find that the clinical picture following the removal of the
thyroid and parathyroids, remained incomplete for some time after
the beginning of this kind of experimentation.
Very shortly after the discovery of the parathyroids, Gley and
others proved that the symptoms following the extirpation of the thy-
1 Jour, of Pharm. and Exp. Therapeutics, ix, 1916, 57 and x, 1917, 99.
2 Archiv fur Entwick. Mech. der Organe, xxxv, 1913, 457; also see: Graham,
Jour. Exp. Med., xxiv, 1916, 345.
3 Jour, of Biol. Chem., 1, 1905, 33.
61
962 THE INTERNAL SECRETIONS
roid, are markedly different from those produced by the removal of the
parathyroids. This general fact becomes apparent immediately if
the symptoms enumerated above are subjected to a re-examination.
It will then be noted that they arrange themselves in two groups, one of
which is characterized by disorders of metabolism, such as malnutri-
tion and cachexia, and the other, by defects of nervous function, such
as muscular tremors and tetany. Recent investigations have fully
confirmed this deduction so that it may be regarded as certain that
thyroidectomy gives rise to a state of malnutrition, terminating in the
condition of cachexia thyreopriva, while parathyroidectomy results in
muscular tremors and spasms, forming the clinical picture of tetania
parathyreopriva. Consequently, the combination of these two com-
plexes of symptoms cannot be due to an overlapping of the functions
of these two types of tissue, but must be caused by their simultaneous
destruction or atrophy.
While no definite statements can be made at this time regarding
the manner in which the thyroid exerts its peculiar metabolic action,
it may be surmised that it develops a specific hormone which facilitates
the chemical reductions in other tissues, chief among which is the ner-
vous tissue. First of all, this agent increases the total metabolism,
as is evinced by a greater excretion of nitrogen, carbon dioxid and
phosphoric acid, and a greater consumption of oxygen. Upon this
fact rests the therapeutic value of thyroid feeding in obesity, but since
in this case the difficulty does not lie in the protein metabolism, thyroid
feeding as a remedial measure against adiposity in the absence of an
actual inactivity of the thyroid is a dangerous procedure. It may
produce organic defects of the heart and other pathological lesions. In
this connection it should also be noted that the feeding of animals
with excessive amounts of meat may give rise to goiter and rickets,
and that this outcome may be prevented by the simultaneous ingestion
of milk, bread and bones. No definite explanation can be offered for
the hypertrophy and hyperplasia of the thyroid occurring during the
menstrual period and pregnancy. It cannot be doubted, however,
that it indicates a close functional correlation between the different
endocrine organs, and offers a plausible explanation for the peculiar
metabolic and nervous symptoms exhibited by women during these
periods.
The picture of tetany following the removal of the parathyroids,
is very similar to that obtained in infantile tetany, the convulsions in-
cited by gastro-intestinal disorders, eclampsia, and other conditions.
It consists in a gradually increasing stiffness or rigor of the entire body,
trembling, clonic and tonic spasms of the muscles, as well as a loss of
muscular coordination and strength. The body-temperature rises,
the frequency of the heart and respiration is increased, whereas weight
is lost rapidly. This tetany may be mitigated or even abolished by
the administration of sodium bicarbonate, alkalies, calcium salts ^ or
^ Macallum and Voegtlin, Johns Hopkins Univ. Bull., 1908.
THE THYROID AND PARATHYROID BODIES 963
extracts of parathyroid tissue. While the exact significance of the
symptoms just enumerated is not known, it appears that this tetany
is the outcome of some profound metabohc change resulting in an in-
toxication. In other words, in the absence of this gland certain toxic
substances escape reduction, and finally attack the tissues. This ex-
planation finds substantiation in the experiments of MacuUum,^
which show that bleeding and infusion of saline solution causes the
tetany to disappear, and that the injection of the blood-serum of
animals in tetany produces these symptoms in other animals.
The specific hypothesis suggested by these experiments, is that the
parathyroids possess the power of detoxication by preventing the ac-
cumulation of certain products of metabolism. This conclusion, how-
ever, is not fully justified, because it may also be true that these poisons
are not formed in the normal body and develop only in the absence of
the parathyroids. More recently, Paton^ has brought forth the
hypothesis that this gland regulates the metabolism of guanidin and
thereby exerts a controlMng influence upon the activity of the muscles.
Upon its removal, the guanidin accumulates and gives rise to a fatal
tetany. This contention finds support in the fact that the guanidin
compounds in the blood and urine are markedly increased after
parathyroidectomy and are also present in excessive amounts in the
urine of children suffering from idiopathic tetany. Furthermore, it
is possible to evoke the symptoms of parathyreopriva by the injec-
tion of salts of guanidin.
B. THE THYMUS GLAND
Position and Structure of the Thymus. — This glandular mass is
situated in the anterosuperior recess of the mediastinal space, and
covers the great vessels. By origin it is a bilateral organ, consisting of a
right and left lobe with corresponding prolongations upward. This
division is also in evidence in the adult organ, because although they
overlap, its two portions may be separated from one another without
much difficulty by following the line of the intervening connective
tissue. The size of this organ differs greatly in accordance with the
age of the individual. In infants, for example, its average weight is 12
grams, at puberty 35 grams, at sixty years less than 15 grams, and at
seventy years less than 6 grams. ^ When fully developed, it extends
across the upper portion of the pericardial sac and reaches upward
very nearly to the thyroid gland.
It is invested by a thin capsule of areolar tissue which also divides
its substance into lobules. The different follicles entering into the
formation of the latter, are made up of a central portion or medulla and
1 Jour. Exp. Med., xi, 1909, 118, also: Jour, of Pharm. and Exp. Therap., ii,
1911, 421.
2 Quart. Jour, of Exp. Physiol., x, 1917, 203.
' Hammar, Archiv fiir Anat., 1906.
964 THE INTERNAL SECRETIONS
an external portion or cortex. The medulla presents itself as a coarse
network of connective tissue in which are embedded lymphoid cells
and the concentric corpuscles of Hascall. The latter are of endodermic
origin, and have been formed from an outgrowth of the third pharyngeal
cleft. The former, on the other hand, appear to be of mesodermic ori-
gin. The cortex is made up of a similar reticulum of connective tissue,
the different nodules of which contain numerous lymphoid cells.
Although derived from epithelial tissue, the cortical substance even-
tually acquires the general characteristics of a lymphatic gland, but
this transformation is not complete, because it contains a much larger
amount of nuclear material than the ordinary glands of this type.
The blood-supply of the thymus is derived from the internal mammary,
inferior and superior thyroid, subclavian and carotid arteries.
The Function of the Thymus. — While no absolutely definite
statements can be made at this time regarding the function of this
gland, it is obvious that it exercises a metabolic influence which attains
its greatest importance at about the time of maturation. In support
of this view might be cited the involution of this' organ after puberty,
and secondly, the fact that its removal gives rise to a more rapid
development of the testes. ^ Correspondingly, the removal of the
latter (castration) delays the atrophy of the former. ^ It is surmised
that this close relationship of the aforesaid organs is brought about
wholly by chemical means, because even pieces of the thymus of rab-
bits, when transplanted to other regions of the body, are affected
in precisely the same way by castration and sexual stimulation.^
In accordance with Klose and Vogt^ it has usually been supposed
that the thymus is essential to life and that its complete removal
proves fatal to young animals within a very short time. While these
results have not been substantiated by the work of Pappenheim,
Rowland and Vincent,^ it appears that thymectomy nevertheless
produces certain metabolic disturbances, chief among which are a
retardation of the growth of the bones, mental deterioration, and a
tendency to adiposity. In connection with this point, attention should
be called to the experiments of Gubernatsch which have shown that
the feeding of extract of thymus to young tadpoles stimulates their
growth, but retards their differentiation or metamorphosis. Some
authors, in fact, recognize a condition of hyperthymusism which may
be a compHcating factor in Grave's disease.
C. THE LIVER
The Internal Secretory Power of the Liver. — The carbohydrates
are absorbed in largest part through the intestinal radicles of the portal
1 Paton, Jour, of Physiol., xxxii, 1905, 28, and xlii, 1911, 267.
2 Goodall, Jour, of Physiol., xxxii, 1905, 191, and Pappenheimer, Jour. Exp.
Med., xix, 1914, 319.
3 Marine and Manley, Jour. Lab. Clin. Med., iii, 1917, 48.
* Klinik and Biol, der Thymusdr. Tubingen, 1910.
» Ergebn. der Physiol., 1911.
THE PANCREAS 965
vein. On reaching the liver, some of the glucose, levulose, and galac-
tose is taken up by the hepatic cells, and is deposited here in the form
of a colloidal polysaccharidcj known as glycogen. Consequently, one
of the functions of this organ is to store and to hold in reserve a certain
surplus amount of carbohydrate material until needed by the other
tissues. But, since the muscles contain almost as much glycogen
as the liver, the latter cannot be said to be the only place in which
this substance is deposited. At all events, the liver is constantly
called upon to release some of this glycogen and more particularly
during the periods intervening between meals, when practically no
sugar is absorbed. Lastly, this organ possesses the power of forming
dextrose from protein material and even from many partially oxidized
products of other tissues. This synthesis of glycogen, as well as the
reconversion of this substance into sugar, must be effected by means
of a special intrahepatic principle. Consequently, it may be said
that this organ furnishes an internal secretory product which has to
do with the metabolism of the carbohydrates.
D. THE PANCREAS
The Removal of the Pancreas. — Inasmuch as the general phy-
siological anatomy of the pancreas has been discussed at some length
in connection with its external secretion, it may suffice at this time to
state that this organ also contains numerous colonies of cells which have
been named, after their discoverer, the islands of Langerhans (1869).
These groups of cells are tugged away in between the different acini
and are composed of polygonal cells possessing poorly defined bound-
aries, large round nuclei, and relatively few and small granules. They
are copiously supphed with blood from an interstitial system of cap-
illaries. Bensley^ has proved by the method of intravitam staining
that these structures are permanent and should not be regarded as
developing reserve cells of the acini.
It was CI. Bernard^ who first called attention to the fact that the
occlusion of the duct of Wirsung produces a complete atrophy of the
acini of the pancreas, but does not destroy the islets of Langerhans.
In 1889, Mering and Minkowski^ proved that the total extirpation
of this organ gives rise not only to digestive disorders, owing to the
loss of the pancreatic juice, but also to a complex of symptoms com-
monly associated with the disease, called diabetes mellitus. The
animal shows a hyperglycemia, glycosuria, polyuria, poliphagia, a
loss of weight, an abnormal thirst and hunger, emaciation and muscu-
lar weakness. This disease terminates fatally in the course of two to
four weeks. Contrary to the effect of total extirpation, the removal
^ Harvey Lectures, New York, x, 1915.
2 Sebolew, Virchow's Archiv, clxviii, 1902, 91, and Homans, Journ. of Med.
Research, 1914.
3 Archiv ftir exp. Path, und Pharm., xxi, 1893, 85.
966 THE INTERNAL SECRETIONS
of only a part of this organ does not produce these symptoms, nor do
they appear if a portion of its tissue is transplanted. The latter
procedure usually consists in grafting its processus uncinatus and cor-
responding blood-vessels under the skin of the abdomen. It has also
been established that the ligation of the ducts of the pancreas does not
produce a permanent glycosuria, but only those syraptoms which are
commonly associated with a loss of the pancreatic juice.
The Function of the Internal Secretion of the Pancreas. — The
fact to be derived from the preceding data, is that, in addition to its
digestive juice, the pancreas also produces an internal secretion which
is absolutely essential to the life of the animal. While the evidence is
not absolutely conclusive, it is surmised that this internal secretion
arises in the cells of the islets of Langerhans. This assumption is
strengthened somewhat by the statements of Opie^ and others that
these cells show signs of hyaline degeneration and atrophy in persons
who have died of diabetes mellitus. The correctness of this observa-
tion, however, has recently been questioned. ^ Nothing definite is
known regarding the cause of this disease, although it is supposed that
it develops in consequence of a disturbance of the carbohydrate
metabolism. Regarded from a very general standpoint, the conditions
leading to glycosuria, may be classified under the following headings:
(a) Alimentary; too copious an absorption of sugar is frequently followed by
a temporary excretion of this substance in the urine. This condition is known as
alimentary or physiological glycosuria. It subsides as soon as the body has suc-
ceeded in ridding itself of the excessive amounts of sugar absorbed.
(6) Pancreatic; a disorder in the internal secretory power of the pancreas is the
cause of this form of glycosuria.
(g) Hepatic; the cells of the liver do not exercise their storative functions
properly, and allow too large an amount of sugar to escape into the blood.
(d) Oxidative; the cells of the tissues are unable to oxidize the sugar, because
they lack the agent which is required to accomplish this reduction. The latter
may be conveyed to them from the pancreas or may be a product of their own.
(e) Renal; the cells of the kidney have lost their relative impermeability and
allow the sugar of the blood to pass more readily through them.
Since in the present instance we are solely concerned with the pan-
creatic type of diabetes, this problem may be restricted in the following
way: The pancreas furnishes an active principle, possibly an enzyme,
which aids in the hydrolysis or oxidation of the sugar in the tissues.
In the absence of this agent, this process remains incomplete and
the sugar escapes into the urine. In this case, therefore, the internal
secretion of the pancreas acts in the manner of a hormone, i.e., as
a stimulus to cellular activity. Another view is that the pancreas
furnishes an active principle which regulates the sugar output of the
liver. In the absence of this agent, the cells of the liver convert
their glycogen too rapidly, thereby increasing the sugar content of
the blood and producing a hyperglycemia which is soon followed by a
1 Jour. Exp. Med., v, 1901, 397.
2 Vincent and Thompson, Jour, of Physiol., xxxiv, 1906.
THE ADRENAL BODIES 967
glycosuria. In this case, therefore, the internal secretion of the pan-
creas acts as a chalone, because it checks the activities of the hepatic
cells. The weight of evidence, however, seems to lie with the first
theory which holds that this internal secretion facilitates the reduction
of the sugar by the tissues. Thus, it has been found by Clark that the
perfusion of the pancreas with solutions containing dextrose, causes
this substance to be changed into some form of polysaccharide. On
allowing this condensed dextrose to circulate through the tissues, it
undergoes a further change into a carbohydrate which is easily utilized
by these cells. Thus, it is claimed by Woody att^ that sugar exists
in the blood in some chemical combination which behaves like a
colloid. The substance which combines with dextrose to form this
compound, is closely related to the internal secretion of the pancreas.
The Internal Secretion of the Gastric and Intestinal Mucosa. —
In elaboration of the prelimihary experiments of CI. Bernard,
Popielski, Wertheim and Lepage, it was found by Bayliss and Starling
that the mucous membrane of the duodenum contains a hormone,
known as secretin, which is liberated whenever the reaction of the
adjoining medium is changed to acid. Upon its absorption by the
blood, this agent is carried to the pancreas, liver and intestine, where it
excites a flow of the corresponding secretions. A similar hormone,
called gastrin, has been isolated by Edkins from the mucous mem-
brane of the pylorus. It causes a secretion of gastric juice.
CHAPTER LXXXII
THE ADRENAL BODIES, HYPOPHYSIS, PINEAL GLAND,
TESTES AND OVARIES
E. THE ADRENAL BODIES OR SUPRARENAL CAPSULES
The Position and Structure of the Adrenals. ^ — These glands are
situated in the epigastric region, one on each side of the spine and in
the immediate vicinity of the upper pole of the kidney. They differ
somewhat in their size, shape and position. The right organ is affixed
to the inferior vena cava in close proximity to the orifice of the right
suprarenal vein, while the left organ lies in relation with the left
suprarenal vein, but does not come in actual contact with the cava.^
Their arterial supply is derived from three sources, namely, from the
^ Jour. Am. Med. Assoc, 1915.
2 The suprarenal capsules were first recognized by Bartholomeus Eustachius
Sanctoseverinatus in 1563. An adequate description of them was given by Win-
slow in 1756. Their structural peculiarities have been dealt with by Meckel
(1806), Ecker (1846), Leydig (1851) and Kolliker (1854). '
^ Ferguson, Am. Jour, of Anatomy, v, 1905.
968
THE INTERNAL SECRETIONS
aorta by two or three small branches, and from the phrenic and renal
arteries.^ It is also of importance to remember that each gland
rests upon a ramification of sympathetic fibers which is known as the
suprarenal plexus, and which communicates centrally by way of the
greater and lesser splanchnic nerves (Fig. 226) with the sjrmpathetic
ganglia of the thorax and lumbar region. Peripherally, each supra-
renal plexus is connected with the mesenteric and celiac ganglia of
the solar plexus.
The right gland has a flattened, triangular outline, while the left is crescentic,
its concavity being directed toward the neighboring kidney. In man, each gland
measures about 3 cm. from side to side, 3-5 cm. from above downward and 4-6
mm. in thickness. Their weight varies between 4 and 7 grams, the left one being
Fig. 507. — Diagram to Illustrate the Position or the Adrenal Glands (Rabbit).
K, kidneys; V, ureters; RV, renal veins; RA, renal arteries; JC, inferior vena cava;
A, abdominal aorta; S, adrenal glands; SU, suprarenal veins. In man, the two kidneys
lie very nearly in the same horizontal plane; in fact, the right organ frequently below
the left.
slightly heavier than the right. When cut into, each gland exhibits an outer
cortical and an inner medullary region. The former is divided into compartments
by a fibrous stroma derived from the outer fibrous investment. These spaces are
occupied by numerous columns of intercommunicating cells which are roughly
arranged in the form. of a reticular and glomerular zone. The yellowish globules
(lipoids) contained in these cells, are responsible for the peculiar yellowish-pink
color of the entire gland. The medulla is pervaded by a stroma, enclosing groups
of granular cells, which on treatment with chromic acid acquire a yellowish brown
color. On account of their power of reducing this substance, they are commonly
designated as chromophil or chromaffine cells. We also find here numerous nerve
cells, some smooth muscle tissue, and large venous capillaries supported by fibrous
tissue. These structural differences are in complete agreement with the develop-
ment of this organ, because while the cortex is derived from that part of the
mesoblast which gives rise to the mesonephros, the medulla is formed from an
outgrowth of the sympathetic system. Besides, these two constituents of the
adrenal body remain absolutely separate in some of the lower vertebrates, the
1 Gerard, Jour, de I'anat. et de la physioL, 1913.
THE ADRENAL BODIES
969
medullary substances appearing in them in the form of isolated globular masses
along the course of the spinal nerves. A few separate chromaffine bodies, similar
to or identical with the medulla of the adrenal gland, are also found in almost all
the higher animals.
Removal of the Adrenal Glands.— The function of the suprarenal
glands remained a matter of speculation until 1853, when Thomas
Addison called attention to the fact that the degeneration of these
bodies is associated with a disease
which has since been named after him.
It is almost invariably fatal and is
characterized by a progressive idio-
pathic anemia, digestive disorders,
diarrhea, muscular weakness, tremors,
convulsions, apathy, and a bronzing
of the skin. A few years later Brown-
S^quard^ showed that these symp-
toms also develop in animals after the
complete removal of the adrenals.
Death then results within two or
three days after the operation. These
results were proved to be correct by
Nothnagel,^ Tizzoni,3and others. In
addition, Btilling^ established the fact
that the extirpation of only one of
them does not prove fatal, but is
compensated for by an enlargement
of the opposite organ. The same
favorable results may be obtained by
leaving a piece of one organ in situ
or by transplanting it elsewhere in
the body. Subsequent to the unsuc-
cessful experiments of Canalis (1887)
and Imbort (1899), it was shown by
Haberer^and Stoerk^that these glands
may also be transplanted within the
substance of the kidney, but only if
their blood-supply is not interfered
fefe*!'
with. In like manner, BiedP suc-
FiG. 508. — Vektical Section of
CoKTEx OF Suprarenal of Dog. Mag-
nified ABOUT 150 DIAMETERS.
a, Fibrous capsule; b, zona glo-
merulosa; c, zona fasciculata; d, zona
reticularis. (Bohn and v. Davidoff.)
ceeded in growing them outside the
peritoneum. In all these cases, these transplants first exhibited an
initial retrogression and necrosis which was followed after about five
1 Compt. rend., 1857.
2 Zeitschr. fur klin. Med., i, 1879, 77, and Allg. Med. Zeitschr., 1890.
3 Ziegler's Beitrage, 1889.
* Rev. mM., 1888, and Ziegler's Beitrage, 1905.
^ Wiener, klin. Wochenschr., 1908.
6 Afchiv ftir klin. Chir., 1908.
' Pfliiger's Archiv, Ixvii, 1897.
970 THE INTERNAL SECRETIONS
months by an active proliferation. In this connection, it should also
be mentioned that the results obtained by the feeding of extract of
adrenal gland to animals whose adrenals had been removed, have
not been encouraging. Moreover, in only a few cases has this type
of organotherapy been of any use in relieving the symptoms of Addi-
son's disease.
The General Function of the Adrenal Glands. — While the effects
of total and partial extirpation of the adrenals clearly proved that
these organs furnish an active principle which is absolutely essential
to life, the nature of this internal agent was not revealed until the
time of Oliver and Schafer.^ These investigators made an extract
of this gland and injected it into the venous blood-stream. A rise
in blood-pressure invariably resulted which was correctly referred by
them to a constriction of the blood-vessels. Further experimentation
then showed that this vasoconstrictor agent is a product of the medulla
and not of the cortex of this gland. Nothing definite, however,
could be learned regarding the function of the latter, although it was
surmised that its loss gives rise to a decided muscular weakness (as-
thenia) of the skeletal muscles, coma, and convulsions. The evidence
which has been presented in favor of this view, is chiefly indirect
in its character and is based upon the following data:
(a) The symptoms just cited cannot be mitigated by the repeated or continuous
administration of extracts of the medulla, in the form of epinephrin or adrenalin.
(b) It has been shown by Stewart that the discharge of epinephrin into the
circulation ceases immediately after the removal of one adrenal body and the
denervation of the other. This procedure, however, does not prove fatal to the
animal.
(c) No beneficial results have been obtained so far by treating Addison's
disease with adrenalin which is a product of the medulla.
(d) Those animals which are in possession of "accessory" adrenals in the form
of separate chromaffin-bodies (rabbits), do not die after the removal of the adrenal
glands, and
(e) It has been found that transplanted adrenals exhibit a degeneration of their
medulla and a proliferation of their cortex.
It will be remembered that these animals develop no untoward symp-
toms. Thus, it cannot be doubted that the internal agent of the cor-
tex is different from that of the medulla. While the former furnishes
a still obscure product, the absence of which gives rise to the grave
symptoms mentioned above, the latter gives rise to epinephrin. ^
Epinephrin. — The extract of adrenal gland employed by Ohver and
Schafer,^ was obtained by simply lacerating and pounding the adrenal
tissue in a mortar under a 0.7 per cent, solution of sodium chlorid.^
1 Jour, of Physiol., xxviii, 1895, 230.
2 Vincent, Endocrinology, i, 1917, 140, and Schafer, The Endocrine Organs,
London, 1916.
3 A year later Cybulski and Szymonowicz published the results of a series of
independent experiments of similar nature (Pro. Acad, of Krackau, 1895).
^ In 1856 Vulpian isolated a substance from the adrenal gland which showed
remarkable color reactions (Compt. rend., xliii, 1856).
THE ADRENAL BODIES 971
The filtered extract was then injected intravenously, only a few drops
being required to evoke a marked rise in blood pressure. Some years
later AbeP succeeded in isolating this active agent by extracting the
gland with weak acid and benzoylating it, but the substance, which he
obtained was not the pure active principle but a benzoylated compound
of it. He designated this body as epinephrin. Later on Aldrich^
and Takamine^ obtained its free base, and called it adrenalin. Since
then physiological chemists have determined its constitution as:
HO
H0< > - CH(OH) - CH2NHCH;
It possesses an asymmetric carbon atom and, therefore, may be either
levo- or dextro-rotatory. Both these forms have been prepared syn-
thetically. Stolz and Dakin give its formula as C9H19NO3.
Under normal conditions this agent is transferred from the medul-
lary substances into the suprarenal vein, whence it reaches the
general circulatory system by way of the inferior vena cava. The
active principle thus normally diverted into the blood-stream, is known
as adrenin. It need scarcely be mentioned that we may also em-
ploy the blood of the suprarenal vein in order to produce a rise in
blood pressure, but it should be remembered that adrenin is an unstable
body and decomposes very rapidly. This is the reason why the reac-
tion produced by it cannot be long continued. Even adrenalin is an
unstable and weak base, but is more stable as a dry, free base or as
the hydrochlorid, in which form it may be kept for some time unless
unduly exposed to the light and air. The amount of adrenin present
in the gland may be estimated by colorimetry as well as by the ampli-
tude of the circulatory reaction produced by it, i.e., by physiological
means.* Its free base is extremely potent; as little as 0.000002
gram sufficing to evoke a marked change in the blood pressure. The
suprarenals of human adults contain 1.0 per cent, of adrenin, those of
the cat 0.15 per cent., and those of rabbits, dogs, and monkeys from
0.2 to 0.3 per cent. In this connection, it is also of interest to note
that the parotid gland of the Jamaican toad secretes a similar principle
in amounts equaUing 5.0 per cent.
The Action of Epinephrin upon the Circulation. — The most charac-
teristic action of extracts of the adrenal bodies or of the commercial
preparation adrenalin is a rise in blood pressure and a slowing of the
heart beat. But since these effects are usually obtained by injecting the
diluted adrenalin into the venous blood-stream, a certain time must
elapse before it can reach the arterial system to activate the vasocon-
1 Bull. Johns Hopkins Univ., 1898.
2 Am. Jour, of Physiol., v, 1901, 457.
3 Jour, of Pharm., Ixxiii, 1901, 523.
^ Folin, Cannon and Denis, Jour. Biol. Chem., xiii, 1912, 477; Seidell, ibid.^
XV, 1913, 197, and Steward, Jour. Exp. Med., xiv, 1911, 377.
972 THE INTERNAL SECRETIONS
stricter mechanism. This is also true of adrenin, because inasmuch as
the normal glands discharge their product into the suprarenal veins,
it must first be carried through the heart into the arteries. With a
normally active circulation this requires from 12 to 14 seconds. At
the end of this period of time, the blood pressure rises rather abruptly,
but declines very soon until its normal value has again been estab-
lished. The amplitude of this reaction depends, of course, upon the
potency and quantity of the adrenalin. Upon the heart, this agent
acts in two ways, namely (a) by lessening the frequency of this organ
through vagus-inhibition, and (6) by augmenting its force of con-
traction by a direct influence upon the cardiac musculature. Con-
sequently, the division of the vagi nerves must augment the rise in
blood pressure, because it prevents henceforth the inhibitory dis-
charges of the center from reaching the heart. It should be emphasized,
however, that the adrenalin does not stimulate the cardio-inhibitor
center directly, but in an indirect way through its effect upon the blood
pressure. As has been pointed out in one of the preceding chapters,
a high blood pressure invariably elicits a reflex which slows the heart,
its cause being resident in the distention of the arteries, chiefly of
the root of the aorta.
Regarding the nature of this reaction, it may be stated that the
adrenalin constricts the arteries, and especially the arterioles, thereby
preventing normal amounts of arterial blood from escaping into the
capillaries. Its action, therefore, is to increase the peripheral resistance
by lessening the size of the arterio-capillary outlet. At this point
of the vascular system two elements are present, namely the smooth
muscle cells and the terminals of the vasomotor nerves. Where
then is the point of attack of the adrenalin? Since this rise in blood-
pressure may also be produced after the destruction of the cord and
sympathetic ganglia and even after the completion of secondary
degeneration of the postganglionic fibers, it cannot justly be regarded
as a nervous reaction. Moreover, the evidence so far presented tends
to show that it does not affect the contractile elements of the smooth
muscle cells directly, but some substance interposed between the latter
and the terminals of the nerve. In accordance with Langley and
Elliott, it must be concluded that this structure is the myoneural
junction which is composed of receptor substance, i.e., of a type of
neuroplasm somewhat distinct from ordinary nerve tissue. Adrena-
lin, therefore, acts upon the myoneural connection between the sym-
pathetic nerve fibers and the muscle cells.
At the hand of this fact, it will now be seen that the adrenin dis-
charged by the adrenal bodies, must exercise a similar function. It is
poured out as a rule in insignificant amounts and aids in keeping
the vascular system in a semi-constricted condition i.e., in a state of
tonus. Moreover, in consequence of definite stimuli, larger amounts
may be discharged at any time which actually constrict the blood-
vessels and give rise to a temporary increase in blood pressure. This
THE ADRENAL BODIES 973
statement, however, is not intended to imply that the tonus of the
vascular system depends exclusively upon the presence of adrenin in
the blood-stream. Such an assertion cannot be correct, because the
walls of the blood-vessels are -already tonically set by virtue of the tonic-
ity resident in all living cells, and all the adrenin can do is to vary
their tonus. The fact that adrenin is liberated at a definite rate may
be proved by applying a temporary ligature to the suprarenal vein.
Very shortly after this obstruction to the venous return has been re-
moved, the blood pressure invariably shows an abrupt rise which
indicates that a certain amount of the accumulated adrenin has
reached the general circulatory system. Very similar results may be
obtained by temporarily blocking the inferior vena cava centrally to
the orifices of the suprarenal veins. Whenever the blood is then
allowed to escape from this pocket, the arterial pressure rises, again
proving that this stagnated cava blood has been charged with adrenin.
Under ordinary conditions, however, the amount of this '' spontane-
ously" hberated adrenin. is very small. Thus, Stewart and Rogoff^
estimate it in cats at only 0.001 gram per minute. If this amount is
added to the blood of the general circuits, it will be seen that its con-
centration must be diminished so as to render it practically ineffective.
Actual changes in the circulation, therefore, can only occur when its
discharge is increased by stimulation.
The adrenalin or adrenin introduced into the circulation, is
oxidized very soon after it has performed its temporary excitatory
action. This instability also accounts for its rapid disappearance from
food, so that perfectly enormous doses of it must be administered by
mouth before it can produce its effect upon the blood pressure. Certain
substances, however, have been isolated from the amino-acids by a
process of decarboxylation which, although similar in their composi-
tion to adrenalin, possess a much greater stabihty. Some of these
form the active principle of ergot. Adrenalin applied locally to
open surfaces constricts the blood-vessels and may therefore be em-
ployed as a means to stop excessive hemorrhagic oozing. When added
to solutions of sodium chlorid used for purposes of infusion, it acts
as a vasoconstrictor agent, thereby raising the blood pressure and pro-
ducing a stimulation of the heart by establishing a much greater per-
ipheral resistance than could be obtained with the sodium chlorid
alone.
The Innervation of the Adrenal Bodies. — The activity of the
adrenal glands, at least of their medullary portions, is controlled by
nerve fibers which are derived from the greater splanchnic nerves.
Thus, BiedP and Dreyer^ have shown that the stimulation of this
nerve, or of its distal end, gives rise to a copious discharge of adrenin
which, upon reaching the distant arterial system, constricts these
1 Jour. Exp. Med., xxiv, 1916, 709.
2 Pfluger's Archiv, Ixvii, 1897, 443.
3 Am. Jour, of Physiol., ii, 1899, 283.
974 THE INTERNAL SECRETIONS
blood-vessels and produces a second rise in pressure. Attention has
already been called to the fact that the stimulation of the aforesaid
nerve evokes a rise in the arterial pressure which really consists of two
parts, the first elevation being caused by the direct constriction of the
blood-vessels of the splanchnic organs, and the second by the constric-
tion of the blood-vessels of the general circuits in consequence of the
delayed entrance of adrenin.
The fact that the adrenal bodies may be influenced reflexly, has
given rise to the assumption that this mechanism is held in reserve
to be activated at irregular intervals by afferent stimuh which find
their origin in different parts of the body. Even emotions are said to
give rise to a discharge of adrenin which then evokes the peculiar
vascular reactions and sensations usually experienced during anger and
fright.^ In continuance of this line of thought it is generally believed
that the condition of hypertension, which is developed in nephritis,
is the direct outcome of a continuous liberation of adrenin and that
this agent, owing to its power of mobilizing sugar, must be instrumental
in the production of hyperglycemia and glycosuria. All these and
similar statements, endeavoring to equip the adrenals with emergency
functions of this kind, should be received with scepticism, because
they are still lacking a definite experimental basis. Some writers,
for example, are of the opinion that emotional hyperglycemia may be
produced so easily in animals that it is difficult to ascertain the normal
sugar content of their blood unless precautions are taken to shield
them against excitement. ^ Others, again, hold that a real emotional
glycosuria does not exist. ^ Besides, Stewart and Rogoff^ have not
been able to demonstrate any increase in the percentage of sugar in
the blood of normal cats which could justly be referred to emotional
states. Nor have these authors been able to detect any difference in this
respect between normal cats and cats deprived of their adrenals by
enucleation or nerve-section. Accordingly, it must be concluded that
the mobilization of sugar occurring during experimental hyperglycemia
is not evoked by adrenin, nor is the so-called emotional hyperglycemia
a common phenomenon. This diversity of opinion demands that care
be exercised in attributing to the adrenal bodies an array of functions
which in reality are mere conjectures.
Other Actions of Epinephrin. — Since epinephrin serves more es-
pecially as a stimulant of the sympathetic division of the autonomic
nervous system (Langley), it may be conjectured that its action is a
very general one, involving all the smooth muscle tissue and gland
tissue ordinarily under the control of these elements. Moreover,
since it acts as a general excitant of the sympathetic system, the effect
1 Cannon, Am. Jour, of Psych., xxv, 1914, 256.
2 Schaffer, Jour. Biol. Chem., xix, 1914, 297.
3 Ross and McGuigan, ibid., xxii, 1915, 407.
* Am. Jour, of Physiol., xlvi, 1917, 543.
THE ADRENAL BODIES 975
produced by it may be either an augmentation or an inhibition in
accordance with the structural characteristics of the effector so affected.
This also implies that the reaction thus ensuing, is practically identical
with that induced by the stimulation of the sympathetic fibers them-
selves. As has been stated above, the action of adrenalin is made
possible through the intervention of a special receptor substance.
Thus, Meltzer^ has shown that adrenaUn administered intravenously,
dilates the pupil, while its direct instillation into the conjunctival sac
is not followed by this reaction unless the superior cervical ganglion
has been removed beforehand. This agent may also be employed to
determine the constrictor power of the different blood-vessels. In
illustration of this statement it might be mentioned that its injection
into the cerebral circulation gives a positive reaction, while its injection
into the pulmonary circuit does not. The inference to be derived from
these tests, is that the blood-vessels of the brain are equipped with a
vasomotor mechanism, while those of the lungs are not.
Inasmuch as the smooth muscle tissue of the walls of the intestine
is supplied with inhibitory fibers from the sympathetic division of the
autonomic system, adrenalin must cause a loss of its tonus and a
disappearance of intestinal peristalsis. A similar effect is produced
by it upon the walls of the stomach, gall-bladder and urinary bladder.
In the case of the pregnant uterus of the cat, it gives rise to a contrac-
tion, but to a relaxation in the non-pregnant organ. The vas deferens
and seminal vesicles are contracted, while the plain musculature of the
bronchioles is relaxed. It also possesses a relaxing influence upon the
blood-vessels of cardiac^ and striated muscle tissue.^ It stimulates
the activity of the sahvary and lacrimal glands.
In addition to these effects upon the neuromuscular and neuro-
glandular substance, adrenalin also influences the metabolism of the
different food stuffs, chiefly of the carbohydrates. This deduction is
based upon the fact that its administration gives rise to the condition
of adrenalin-glycosuria, for the obvious reason that it interferes in
some manner with the oxidation of the sugars. Its point of attack,
however, has not been definitely ascertained, although it has been
stated by Underhill and Closson^ that it activates the sympathetic
fibers regulating the formation of dextrose from glycogen. Others,
again, believe that it influences the liver cells directly, causing them
either to discharge a more abundant amount of dextrose or to hinder
them in their storage of glycogen. At all events, adrenalin mobilizes
dextrose, but certainly not by evoking a greater production of sugar
from proteins or fats. Consequently, the condition of adrenalin-
hyperlgycemia and glycosuria cannot be directly related to diabetes
1 Am. Jour, of Physiol., ix, 1903, 252, and ibid., xi, 1904, 28.
2 Gunn, Quart. Jour. Exp. Physiol., vii, 1913, 75.
3 Hoskins, Gunning and Berry, Am. Jour, of Physiol., xli, 1916, 513.
4 Ibid., xvii, 1900, 42.
976
THE INTERNAL. SECRETIONS
mellitus, because the metabolism of the sugars is interfered with in this
disease in a much more extensive manner.^ Since the action of
adrenaUn seems to be concentrated upon the Hver, it cannot surprise
us to find that it also incites a more copious discharge of other products.
Thus, Cannon^ has found that the intravenous injection of this agent
in amounts of 0.0001 mgr. per kilo of body weight (cats) shortens
the coagulation-time of the blood. In addition, it has been shown by-
Cannon and Nice^ as well as by Gruber^ that this procedure is followed
by a temporary improvement in the power of contraction of fatigued
Fig. 509. — Median Sagittal Section through Pituitary of Monkey; Semidiagram-
MATic. {Herring.)
a, Optic chiasma; h, third ventricle; c, g, pars intermedia; d, epithelium of pars
intermedia extending round neck of pars nervosa; e, pars glandularis seu epitheiialis ; /,
intraglandular cleft, lying between pars glandularis (e) and pars intermedia (fir); h,
pars nervosa.
muscles, a change which, owing to the small doses employed, cannot be
due to improved circulatory conditions. More recently, it has been
pointed out by Hartmann and Eraser^ that subminimal doses of this
agent give rise to a vasodilatation. It should be remembered, how-
ever, that these effects have been obtained under experimental con-
ditions and that they do not justify the deduction that they also occur
normally in consequent of the outpouring of var3dng amounts of
adrenin.
1 Lusk and Riche, Arch. Int. Med., xiii, 1914, 673.
2 Am. Jour, of Physiol., xxxiv, 1914, 255.
3 Ibid., xxxii, 1913, 44.
4 Ibid., xxiii, 1914, 335, also: Endocrinology, iii, 1919, 145.
6 Ibid., xliv, 1917, 353.
THE PITUITARY BODY 977
F. THE PITUITARY BODY OR HYPOPHYSIS CEREBRI
Position and Structure of the H3rpophysis. — In human beings this
stru(3ture Hes at the base of the brain directly behind the optic chiasma;
and occupies a niche in the sella turcica of the sphenoid bone. It
appears as a reddish-gray mass of about the size of a pea which is
connected with the ventricular region of the brain by a narrow stalk,
called the infundibulum. The body of this gland consists of two lobes,
aii anterior and a posterior. They are closely approximated, the cleft-
hke space between them being filled with a yellowish fluid. Owing to
the fact that the cells lining this space posteriorly, present several
distinctive structural features and doubtlessly secrete the aforesaid
fluid, they are commonly regarded as forming a special part of the
pituitary which is known as the pars intermedia. Gross anatomically,
however, these cells belong to the posterior lobe.
The two lobes of the hypophysis differ widely from one another in
their structure, development and function. The posterior one is
developed as a hollow outgrowth of that part of the embryonic brain
which later on becomes the third ventricle. While this communica-
tion is obliterated in man, it remains open in certain animals. The
anterior lobe first appears as an extension of the ectoderm of the buccal
cavity. After the obliteration of this prolongation, the epithelium
arranges itself in the form of trabeculse which are invested by a close
network of uncommonly large capillaries, and contain certain cells
which are sharply differentiated from the others by their content in
deeply staining granules of chromophil. Contrary to the general
neuroglia-like character of the posterior lobe, the pars intermedia has
the appearance of ependymal tissue. Herring^ has called attention
to the fact that these cells embrace a material which stains in the form
of globular masses of colloid-like material. From this brief structural
survey it may be gathered that the anterior lobe possesses the character-
istics of a ductless gland which discharges its product directly into the
blood-stream, 2 while the intermediate part discharges its secretion into
the infundibular space and the cerebral ventricles. The structure of
the posterior part, on the other hand, would not lead us to infer that
it possesses a secretory function.
Removal of the Hypophysis. — The experiments of Horsley (1885),
Dastre (1889), and Clay (1891) have shown that the total removal of
the hypophysis is followed by death within a few days, the symptoms
displayed by these animals being similar to those following the extir-
pation of the thyroid or adrenal bodies. Bui since this organ is very
inaccessible, some of these symptoms may not be caused by the loss
of the hypophysis at all, but by injuries to neighboring parts, such as
the tuber cinereum with which its anterior portion lies in close contact.
This possibility, however, does not seem to have played an actual
1 Quart. Jour, of Exp. Physiol., i, 1908, 121.
2 Bell, ibid., xi, 1917, 77.
62
978 THE INTERNAL SECRETIONS
part, because the subsequent experiments of Caselli (1900), Gaglio
(1902), Fischera (1905), Aschner (1912), Biedl (1913), and Gushing/
have given practically identical results. Only a few of the hypophy-
sized animals survived for a longer period than two or three months,
and in these it was impossible to determine whether any of the essential
tissue had been left behind. It was also demonstrated in these animals
that the two lobes of this organ possess different functions, the extirpa-
tion of the anterior one proving fatal immediately, while that of the
posterior one did not produce decisive symptoms for some time there-
after. In the latter case, the animals usually died from some incurrent
condition. Likewise, no immediate symptoms developed after the
partial removal of the anterior lobe, the animals meanwhile acquiring
extensive layers of fat in the omentum and retroperitoneal spaces,
and gradually developing a condition very similar to infantilism.
Pituitrin. — Subsequent to the observation of Oliver and Shafer,^
that the extract of the hypophysis gives rise to a marked increase in
blood pressure, a substance was isolated from the posterior lobe to
which the name of pituitrin or hypophysin has been given. ^ When
injected into the venous blood-stream, this agent raises the arterial
pressure very materially as well as for a considerable period of time.
There is no doubt that this hypertension originates chiefly in a con-
striction of the peripheral blood-vessels, 5,lthough this substance also
seems to strengthen and to slow the heart beats. When compared
with the action of adrenalin, it must be conceded that it produces a
much more lasting although not quite so powerful effect, and that its
action is exerted upon the muscle tissue directly and not upon the
nervous terminals.^
The Function of the Posterior Lobe of the Hjrpophysis. — When
studying the action of extracts of the entire posterior lobe, it must
be remembered that the active principle here involved is a product of
its glandular pars intermedia and not of its n^uroglia-like posterior
portion. When injected intravenously, such extracts cause the smooth
muscle tissue throughout the body to contract, thereby constricting
the arteries and arterioles and raising the arterial pressure. The
same effect is produced upon the urinary bladder and uterus, both these
organs being contracted very powerfully but more so by the first
injection than by the subsequent injections.^ Upon this action is
based the therapeutic value of pituitrin as an agent promoting the
emptying of the pregnant uterus, but its application in obstectrical
practice should be restricted to particular cases. It is a safe agent in
the hands of only the mOst experienced practitioners.
1 The Pituitary Body and Its Disorders, 1912, also see : Houssay, La accion fis.
de los extr. hipofisiarios, Flajban, Buenos Aires, 1918.
2 Jour, of Physiol., xviii, 1895, 23.
3 Engeland and Kutscher, Zeitschr. fiir Biol., Ivii, 1911, 527.
4 Cramer, Quart. Jour. Exp. Physiol., i, 1908, 189.
^ Frankl-Hochwarth and Frohlich, Wiener klin. Wochenschr., 1909.
THE PITUITARY BODY 979
In addition, pituitrin stimulates the flow of certain secretions.
Thus, it has been observed by Ott and Scott ^ that it causes a copious
flow of milk from the mammary glands, if administered to pregnant or
parturient cats and other animals. In woman, it gives rise to a simi-
lar effect which is initiated by a feeling of pressure and discomfort in
the mammae. At the present time, however, it cannot be stated defi-
nitely that it serves as an actual stimulant to the secreting cells, be-
cause its action may be an indirect one, effected by contracting the
smooth muscle cells lining the lactiferous ducts. In addition to its
action as a galactagogue, it exerts a favorable influence upon the for-
mation of the cerebrospinal fluid and urine. In the latter case, it is still
doubtful whether its diuretic influence is due to its power of augment-
ing the circulation or to a stimulating influence upon the renal cells.
The Function of the Anterior Lobe of the Hjrpophysis. — In con-
tradistinction to the posterior lobe, extracts of the anterior lobe pro-
duce no immediate changes when injected into the blood-stream.
Contrariwise, the studies of Pierre Marie^ upon the disease, known as
acromegaly, have proved beyond doubt that the pathogenesis of this
form of gigantism is in some way connected with the hypophysis.
Clinically, acromegaly presents itself as a complex of symptoms
suggesting the presence of a cerebral tumor. The patient, usually
an adult, complains of headache, vertigo, vomiting, failing in intelli-
gence, somnolence, hemianopsia, and progressive amblyopia. The
face becomes distorted, owing to an enlargement of the facial bones and
soft parts; the lips swell; the eyelids thicken, and the lower jaw be-
comes very prominent. The other forms of gigantism appear early in
life and are characterized by an excessive growth of certain bones,
chiefly the long bones and those of the face. In all these cases, it has
been ascertained that the hypophysis is very active, as ig evinced by
its large size and a hyperplasia of the glandular elements of the an-
terior lobe.^ It has also been demonstrated that this gland is rudi-
mentary in true dwarfs.
In correlating these clinical pictures of hyper and hypopituitarism,
it is made obvious by exclusion that the anterior lobe of the hypophysis
produces a hormone which controls the growth of the connective tis-
sues. In the absence of this internal secretion in young animals,
their growth is checked so that they gradually pass over into a condi-
tion of infantilism. Conversely, a hyper-activity on the part of this
gland gives rise to gigantism, general and local. This result may be
produced either directly through the action of this hormone upon the
nervous system, or indirectly through its action upon other internal
glands of the metabolic type, such as the thyroid and thymus. This
^ Therap. Gazette, xxxv, 1911, and Simpson and Hill, Am. Jour, of Physiol,
xxxvi, 1915, 77.
2 Brain, xii, 1890, 59, and Marie and Marinesco, Arch, de m^d. exp. et d'anat.
path., 1891.
^ Benda, Handb. der path. Anat. des Nervensystemes, Berlin, 1904.
980 THE INTERNAL SECRETIONS
conclusion is strengthened materially by the results of organotherapy.
Thus, Robertson 1 has succeeded in isolating a substance which he
calls tethelin. It contains nitrogen and phosphorus and exerts a
stimulating influence upon the growth of mice. Favorable results
have also been obtained by Schafer^ by feeding preparations of the
anterior lobe to young rats. Magnus, Levy and Falta report that the
Fig. 510, — Acromegaly.
This man was an acromegalic giant aged thirty-five, with blindness and large tumor
of the hypophysis. (Cushing.)
administration of extracts of the hypophysis increases the decomposi-
tion of the proteins.
G. THE PINEAL GLAND OR EPIPHYSIS CEREBRI
Position and Function of the Pineal Gland. — ^^In man this structure
lies free between the anterior corpora quadrigemina, its base being
directed forward across the roof of the third ventricle. In early life
it exhibits a glandular appearance and is subdivided by connective
tissue septa into lobules which are made up of pale granular cells.
At about the seventh year it shows signs of involution, its glandular
1 Jour, of Biol. Chem., xxiv, 1916, 397, and Schmidt, Jour. Lab. Clin. Med.,
u, 1917, 719.
2 Quart. Jour, of Exp. Physiol., v, 1912, 203.
THE GENITAL ORGANS 981
elements then being gradually displaced by connective tissue and
glia tissue of a very fibrous type. Hyaline degeneration sets in, lead-
ing to the formation of calcareous concretions of calcium phosphate
and calcium carbonate which constitute the so-called brain-sand.
Virchow first called attention to the fact that the pineal gland is
frequently the seat of cystic growths and gliomas. The clinical picture
presented by persons so afflicted is very similar to that noted in diseases
of the pituitary body, with the exception that sexual infantilism is
absent.^ There may be observed an obesity and cachexia as well as
certain trophic disturbances. Further than this no definite statements
can be made, as is evinced, for example, by the recent papers of Horrp^x^
and McCord.^ The first of these leads us to infer that the removal
of this gland in male guinea-pigs favors the development of the sexual
organs and hastens the sexual maturity and breeding power of the
female. The second paper, on the other hand, informs us that the feed-
ing of pineal gland to young guinea-pigs hastens their sexual maturity
and favors their growth. These series of experiments, therefore, would
lead to believe that hypo and hyperpinealism produce practically
homologous results, and that the extract of this organ acts as a chalone
as well as a hormone. Obviously, further investigation is urgently
needed to clear up this point.
H. THE GENITAL ORGANS
The Function of the Ovaries. — Since the external and internal
secretions of these organs will be dealt with in greater detail in a
later chapter, the present discussion may well be restricted to the
chemical interrelationship existing between these structures and
others. In the first place, it should be noted that the secrptjon of the
ovaries may produce either a local or a general effect. Thus, it is a
well-known fact that castration in women is followed by regressive
changes in their genitals, such as atrophy of the uterus and vagina.
This fact has led to the assumption that the ovaries serve as the trophic
center for these parts, but since the transplantation of these organs or
the grafting of a part of their tissue in other regions of the body does
not allow this condition to be developed, this control must be exercised
by them with the aid of some chemical agent. This deduction is also
justified by a study of the relationship existing between ovulation and
menstruation, because it is entirely probable that the latter process is
initiated by an active principle secreted by the cells forming the corpus
luteum. Lastly, this conclusion is upheld by the disturbing general
symptoms which generally follow in the wake of castration. It is a
matter of common experience that a woman whose ovaries have been
removed for the cure of a tumor or cystic growth, very frequently
^ Deutsche Zeitschr. ftir Nervenheilkunde, 1909.
2 Arch. Int. Med., 1916.
3 Proc, Am. Med. Assoc, June, 1914.
982 THE INTERNAL SECRETIONS
develops well-defined general symptoms of a nervous and metabolic
kind. These disturbances are manifested most typically by vaso-
motor reactions, commonly called ''hot flushes, " sensations of alternat-
ing heat and cold, sweating, vertigo, muscular pains, and headache.
In fact, in severe cases certain psychoneurotic conditions may arise
which finally lead to mental aberrations. The contention that these
symptoms are attributable to the loss of an internal secretion of the
ovaries, is strikingly betrayed by the results of organotherapy. If an
extract of whole ovary is administered to the castrated women, these
symptoms most generally lose their intense character and are shortened
in their duration; in fact, it is not at all uncommon to see them disap-
pear altogether in consequence of this treatment. Moreover, the fact
that extracts of the entire ovary are more beneficial than extracts of
corpus luteum, seems to show that this general metabolic hormone is
not necessarily a product of the corpus luteum or Graafian follicles.
Bouin^ refers this function to the peculiar stroma cells which he
designates as the glande inter stitielle Vovaire.
While these local and general effects following the removal of the
ovaries, are quite definite, it has not been established as yet whether
the active principle of these organs acts directly or indirectly through
the secretions of other ductless glands. It has previously been shown
that the ovary is in functional relation with other endocrine organs,
thus forming a special group which might be named the sexual glands.
It is a well-known fact that Graves disease is very deleterious to preg-
nancy and that operations upon the pelvic organs are prone to intensify
the symptoms of hyperthyroidism. Castration also increases the
weight of the hypophysis, thymus, and adrenal glands.
The Function of the Testes. — It has been known for some time that
the testioles furnish an internal secretion in addition to their external
product, the spermatozoa. Quite aside from the claim of Brown-
S^quard, that extract of testicle possesses an invigorating influence, it
has been shown by Poehl^ that ''spermin" acts as a ''physiological
catalytic" and increases the action of the heart and digestive organs.
Later on Zoth and PregP proved by means of the ergograph that
testicular extract augments the muscular power by as much as 50
per cent, and diminishes muscular fatigue. A more general influence
of the testes upon the general condition of the body is evinced by the'
symptoms following the total removal of these organs. This proce-
dure which is commonly known as castration or spaying, has been
practised upon animals since the earHest times. In the case of the
domestic animals, such as the bulls, stallions, rams and cocks, the in-
variable result is an insufficient development of the sexual organs and
secondary sexual characteristics. Their transformation, however, is
never complete, i.e., castrated males never completely assume the
1 Compt. rend., 1907, 337.
2 Zeitschr. fur kiln. Med., 1894.
3 Pfluger's Archiv, Ixii, 1896, 335.
I
THE GENITAL ORGANS 983
characteristics of the opposite sex. Thus, while the ram lambs may-
develop horns, the further growth of the latter is arrested at an early-
stage. Quite similarly, the castrated cock shows an early withering of
the comb and wattles. The loss of these and other secondary char-
acteristics, however, may be prevented by removing only one testicle
or by grafting one in some other part of the body.
Very similar effects have been noted in human beings. Thus, it
is a well-known clinical fact that castration inhibits the growth of the
prostate and actually incites retrogressive changes in this organ. In
castrated dogs, this atrophy may be greatly retarded by the subcu-
taneous injection of testicular extract. The stories of the East also
tell us that castration, when effected during the prepubescent period,
gives rise to a defective development of the sexual organs which,
however, involves the penis in a lesser degree than the purely glandular
tissues, such as the seminal vesicles and the prostate. This difference
is easily explicable upon the ground that the penis is chiefly composed
of connective tissue. In these individuals, the secondary sexual
characteristics are seldom fully developed, as is shown by the fact that
the pelvis of eunuchs generally retains its infantile character, and that
the amount of axillary and pubic hair is usually very slight. The
child-like soprano character of their voice is referable to an arrested
growth of the larynx. Moreover, they are prone to become phlegmatic
and to develop a heavy panniculus adiposus which smoothens their
contours and gives them a feminine appearance. These observations
may in a large measure be repeated by a study of hermaphroditism in
animals and man, but sexual dimorphism does not always remain
confined to the primary sexual characteristics but may also involve
secondary ones. The "feminine" man and ''mascuHne" woman
are instances of this type of hermaphroditism, showing unisexual
mechanisms but heterologous secondary characteristics.
It cannot be doubted, therefore, that the testes control the develop-
ment of the sexual characteristics. This end they are able to attain
by means of a chemical agent and not by nervous reflexes. In seeking
the place of origin of this hormone, it is of interest to note that the
ligation of the vas deferens, brings about a retrogression of the sper-
matogenetic elements but not of the interstitial cells of these organs.
Contrary to the castrated animals, these animals show perfectly nor-
mal sexual characteristics and instincts.^ Furthermore, Steinach^
has proved that the transplantation of the testes does not destroy
these tendencies and that the transplanted organ exhibits a proUfera-
tion of its interstitial cells and an atrophy of its spermatozoid cells.
In this connection, it is also of interest to note that transplantations
in very young animals may give rise to an almost complete reversion
of the secondary sexual characteristics. Thus, the grafting of an ovary
from a female rat or guinea-pig into a young castrated male of the
1 Tandler, Wiener, klin. Wochenschr., 1908, 1910.
2 Steinach, Pfliiger's Archiv, cxliv, 1912, 71.
984 THE INTERNAL SECRETIONS
same species produced a pseudo-hermaphrodite, which presented primi-
tive male generative organs and female secondary characteristics.
In conclusion, it may therefore be stated that the internal secretion
of the male generative gland is furnished by the interstitial cells of
Leydig. Enclosed in the cytoplasm of these cells we find granules
and peculiar crystals which impart to them the appearance of true
secretory elements. These bodies may be the precursers of this
internal product.
I
i
PART VIII
METABOLISM
SECTION XXVI
DIGESTION
CHAPTER LXXXIII
THE CHEMISTRY OF DIGESTION
General Consideration. — The term of assimilation as originally
employed by the botanists, included all those processes which the
plants must undergo in order to synthetize the inorganic substances
into the organic compound starch. When employed in this general
way, it embraces all those chemical and mechanical processes which
lead to the reduction, absorption and assimilation of the different
foodstuffs by the cells. These stages are followed by cellular dissimi-
lation and excretion. At the present time, all these processes are
generally included under the term of metabohsm which is divided in
turn into a process of building up, or anabolism, and a process of tear-
ing down, or catabohsm, as follows :
C Ingestion
. , T J Digestion
Anabolism < au
Metabolism
Catabolism
j Absorption
I Assimilation
Dissimilation
Excretion
In the lower forms, the process of digestion is completed outside
the cells, enabling them to attain their nutritive material in a fluid
condition ready for assimilation. Beginning with the celenterates,
on the other hand, digestion is chiefly intracellular and hence, the
metabolism of the higher forms requires the presence of special organs,
the purpose of which is to reduce the nutritive material sufficiently
to render it dialyzable through animal membranes, and assimilable
by the cells. But since the food must be reduced mechanically as well
as chemically, two types of organs must really be present which sever-
ally accomplish these ends. In most instances, however, the mechan-
•985 .
986 DIGESTION
ical and chemical mechanisms are combined in such a way that both
kinds of reductions may be had within the confines of the same organ.
Obviously, the histological elements more directly concerned with them,
are the striated and smooth muscle cells and the gland cells.
The food ^ade use of by the higher animals, is heterogeneous m
its character, consisting of inorganic and organic principles, and a
certain amount of non-digestible and non-nutritive material, such as
connective tissue and the cellulose of the plants. The predigestive
procedures which man employs in preparing his food, cannot materially
alter this condition, because only very few non-assimilable mate-
rials can be made available thereby. This is true of the process
of cooking as well as of that of maceration. All that can be accom-
phshed by these means is to free the nutritive principles from their
non-digestible investments, and to increase the solvent action of the dif-
ferent digestive juices, so that they may be more readily reduced, chemi-
cally as well as mechanically. Nutritive material is consumed in the
form of food, consisting of different foodstuffs. Consequently, a
food is a mixture of nutritive substances, whereas a foodstuff is a
single nutritive substance. The latter are grouped as water, salts,
carbohydrate, fat, and protein, and may be arranged as nitrogenous
and non-nitrogenous substances, as follows:
Organic Inorganic
I —I
Nitrogenous Non-nitrogenous (Non-nitrogenous)
I , ! 1 1^1
Proteins Fats Carbohydrates Salts Water
Obviously, the purpose of food is to replenish the material which
nas been used up by the cells during their oxidations in furnishing the
energy upon which the bodily machine is run. Were this waste to con-
tinue without being balanced by an adequate intake, the animal
would soon have to discontinue its activities. Moreover, since food
as exemphfied by meat, potatoes, milk, bread, etc., is invariably
made up of several foodstuffs, it will be seen that our diet usually
consists of several of the proximate principles just mentioned. In
fact, no diet can be regarded as adequate for man which does not em-
brace all the different foodstuffs, mixed in proper proportion, to burden
the body with only a minimum of labor.
Water, salts and some carbohydrates, such as dextrose, are capable
of traversing the intestinal epitheUum in their original form, whereas
the indiffusible colloidal carbohydrates, such as starch and dextrin,
must first be converted into soluble and diffusible sugar. This is
also true of the fats which must first be changed into glycerin and fatty
acids, and the natural proteins which must first be converted into dif-
fusible peptones and simpler compounds. As stated above, digestion
does not end here, but in addition imparts to the now diffusible end-
products of the different foodstuffs ^ form which will enable the cells
THE CHEMISTRY OF DIGESTION 987
of the tissues to utilize them. For this reason, the disaccharides, such
as cane-sugar, maltose, and lactose, are first converted into mono-
saccharides, such as dextrose, levulose, and galactose, while the pro-
tein molecule is split up into amino-acids.
Ferments. — The word ferment was formerly applied to living
organisms such as the yeast cells, which during their conversion
of sugar into carbonic acid and alcohol, cause the liquid to boil up
(f ervere), owing to the evolution of this gas. For similar reasons this
entire process was designated as fermentation. In recent years,
however, many similar substances have been found in animal and vege-
table cells, so that the term of ferment is now applied to all those com-
plex organic bodies which are capable of inciting a chemical reaction
without they themselves undergoing a quantitative or qualitative alter-
ation. Hence, any fermentation must derive the energy evolved in
the course of this process from the substances concerned in it and not
from the activating agent. Besides, no direct relationship can exist
between the amount of the ferment and the intensity of the reaction.
This imphes that even the most minute amounts of ferment are capable
of inducting chemical changes in proportionately much larger quan-
tities of reducible material, and that the addition of more ferment can
only serve to quicken the reaction, and not to alter its character. A
chemical change of this kind is known as a catalysis, while the agent
producing it is designated as a catalyzer or catalyst. The sub-
stance acted upon by the catalyzer is termed the substrate. There
are, of course, many other catalytic agents besides the ferments.
Thus, potassium chromate may act as the catalyzer for the oxidation
of hydriodic acid by bromic acid or spongy platinum, and may cause
the spontaneous combustion of hydrogen peroxide into water and
oxygen.
Until comparatively recently, ferments have been classified as
organized and unorganized, or as hving and dead. Among the former
might be mentioned the yeast plant or saccharomycetes, and a large
number of bacteria, and among the latter, the different active princi-
ples of the digestive juices, such as ptyalin, pepsin, trypsin, and others.
On the one hand, therefore, we have living cells possessing a distinct
organization, and, on the other, dead sustances, which in most
instances have not been satisfactorily isolated and are known to be
present solely from the reactions incited by them. While this classifica-
tion is easily understood, it is no longer tenable, because it has been
shown that the yeast cell and allied hving entities may be made to
give up their ferments by chemical means without that the latter
lose their power of inciting fermentation. In other words, it is not at
all essential to the action of the ferment that it be carried by hving
matter, and hence, it must be considered merely as a product of cellular
metabolism. Consequently, it is really as '^ unorganized" as the
enzyme of the cells of the salivary glands or any other (Buchner
1897), and hence, the terms of ferment and enzyme are now synonymous
988 DIGESTION
in their meaning. The distinction commonly made between them
at the present time, is based upon their place of action. Thus, we may
speak of an intracellular or endo-enzyme, when it acts in the cells in
which it originated, and of an extracellular or exo-enzyme, when it
acts outside its mother-cell. There is every reason to believe that
the action of yeast is due to the intracellular behavior of its endo-
enzyme (zymase), while, for example, saliva owes its chemical power
to its extracellular exo-enzyme, ptyalin.^
The Nature of Ferments. — Since ferments are not destroyed in
the course of the processes incited by them, the medium must contain
them even after the reaction has ceased. In the cells themselves
they are held in an inactive form which is somewhat different from that
of the active derivative. But, the fact that ferments are never pres-
ent in abundant amounts is not the only difficulty met with in isolat-
ing them in a sufficiently pure state to determine their chemical nature.
Many of them are very unstable and are rendered inert at 80°C.,
and all of them are colloidal or semi-colloidal in their nature and not
easily diffusible. While this peculiarity enables them to adhere to
other colloidal material as well as to precipitates, it does not materially
facilitate their isolation, because the attempt of separating them most
generally diminishes their power of producing their characteristic
reaction, and hence, destroys practically the only means of detecting
their presence and identity.
Since ferments are formed from Uving matter, they have been
considered as belonging to the class of the proteins. But, inasmuch
as their separation from these substances cannot be effected with
certainty, the fact that many of them give the characteristic reactions
of proteins cannot serve as a means of identifying them, because these
positive results may be due to the protein material which is still
adherent to them. Consequently, it must suffice at this time to desig-
nate them as^ organic substances which are derived from proteins
and possess a colloidal nature.
Classification of Ferments. — Ferments are almost universally
present in nature. So great is their number, that the present discus-
sion must be restricted to those which take a more direct part in the
economy of the animal body. Moreover, since we know more about
digestion than we do about the processes of cellular assimilation, any
enumeration of this kind must be characterized by a preponderance
of the digestive enzymes. This fact is largely responsible for the cus-
tom of arranging them in accordance with the character of the reaction
produced by them, as follows:
1 Since these topics are exhaustively dealt with in Mathews' and Hammarsten's
Textbooks of Physiological Chemistry, I shall discuss these purely chemical data as
briefly as possible. More complete references will also be found in Oppenheimer's
Handb. der Biochemie, 1910, and "Die Fermente and ihre Wirkungen," 1903;
Vernon's "Intracellular Enzymes," 1908; Euler's "General Chem. of the Enzymes"
(transl. by Pope) 1912, and Bayliss, "The Nature of Enzyme Action," 1908.
THE CHEMISTRY OF DIGESTION
989
(a) Proteolytic or protein-splitting enzymes, such as pepsin, give rise to a
hydrolytic cleavage of the protein molecule.
(6) Lipolytic or fat-splitting enzymes, such as steapsin, cause a hydrolytic
cleavage of the fat molecule.
(c) Amylolytic or starch-splitting enzymes, such as ptyalin, produce a hydro-
lytic cleavage of the starch molecule.
(d) Inverting enzymes, such as maltase, split the disaccharides into monosac-
charides and the latter into simpler molecules.
(e) Oxidizing enzymes, such as the oxidases of the tissues, which aid in internal
respiration.
(/) Coagulating enzymes, such as rennin, which change soluble into insoluble
proteins.
(g) Diaminizing enzymes, such as alanin, which split off an NH2 group from an
amino-acid as ammonia.
In the following table are included some of the ferments with which
we are chiefly concerned at the present time, it being the custom
to designate them by the name of the substance upon which they act
and to affix the letters, ase. This suggestion (Duclaux) has been fol-
lowed in most instances, the only exceptions being those enzymes which
have been recognized for a long time, such as ptyalin, pepsin and trypsin.
Ferment
Place of action
Character of action
Ptyalin
Saliva
Starch — maltose
Amylopsin
Pancreatic juice
Starch — maltose
Glycogenase
Liver and muscles
Glycogen — dextrose
Amylolytic
Invertase
Small intestine
Cane-sugar — dextrose
and
Maltase
Saliva and small intestine
Maltose — dextrose
inverting
Lactase
Lactic acid
Small intestine
Lactose — dextrose and galactose
ferment
Intestine
Glucose — lactic acid
Steapsin
Pancreatic juice
Neutral fats — fatty acids and
Lipolytic
Lipase
Liver, etc.
glycerin
Neutral fats — fatty acids and
glycerin
Pepsin
Gastric juice
Proteins — peptones and amino-
acids
Trypsin
Pancreatic juice
Proteins — peptones and amino-
Proteolytic
acids
Erepsin
Small intestine
Proteoses — amino-acids
Nuclease
Pancreas, spleen, thymus, etc.
Nucleic acid — purin bases
Enterokinase
Small intestine
Trypsinogen — trypsin
Guanase
Thymus, adrenals and pancreas
Guanin — xanthin
Deaminizing
Adenase
Deaminase
Spleen, pancreas and liver
Tissues
. Adenin — hypoxanthin
Arginase
Liver and spleen
A m i n o-acids — oxyacids
arginin — urea
Oxidase
Lungs, liver and tissues
Oxidizes organic substances
Catalase
Tissues
Decomposes hydrogen peroxide
Reductase
Tissues
Causes deoxidation
Although still incomplete, this enumeration proves very clearly
that almost every reaction necessitates the presence of a particular
enzyme. There can be only one reason for this, namely, that they are
specific in their action and cannot be employed interchangingly to
produce one and the same result. Thus, ptyalin changes starch into
maltose, but does not affect the fats and proteins, nor even the other
carbohydrates. Quite similarly, given a number of closely allied
990 DIGESTION
substances, such as the disaccharides, it will be found that they re-
quire several enzymes to convert them into the monosaccharides.
Maltose has its own specific enzyme maltase, and lactose a similarly
specific enzyme lactase. We also note that a single secretion, such as
the pancreatic juice, may harbor a number of ferments, which act sepa-
rately upon different foodstuffs. To be sure, this specificity is also
displayed by other catalyzers, but not quite so definitely as by the
enzymes. Thus, it is a well-known fact that the oxidation of hydriodic
acid by bromic acid may be effected by means of potassium bichromate
but not by iodic acid. Quite similarly, the oxidation of potassium
iodid by potassium persulphate may be quickened by copper salts,
but not the oxidation of sulphur dioxid by potassium persulphate.
In many cases, these ferments exist within the cell in an inactive
form and do not unfold their characteristic properties until they have
been discharged into the secretory medium. This antecedent body
is known as the proferment or zymogen, and is usually stored in the
form of granules. Its activation may be accomplished by inorganic
or organic means. In the former instance the intermediary substance
is known as an activator and the latter as a kinase.'^
The Manner of Action of the Ferments. — Catalysis is a common
phenomenon in nature and many chemical means and substances may
be employed to bring it about. Thus, the disaccharides may be made
to undergo hydrolysis into the monosaccharides by simply heating
them under pressure to 110°C., and cane-sugar may be inverted into
dextrose and levulose by the addition of a weak acid. Either means
serves to accelerate the reaction, which otherwise would not take place
at all or only with extreme slowness. It is for this reason that cata-
lyzers have been compared to the oil by means of which machinery may
be made to run smoothly, i.e., while they do not initiate a certain proc-
ess, they are in a position to vary its velocity. Consequently, the
essential difference between ordinary catalyzing agents and ferments
lies in the fact that the latter effect catalysis much more rapidly at
moderate temperatures and impart to it a more specific character. In
analogy with ordinary catalyzing agents the ferments may cause:
(a) Hydrolysis. — This change involves a taking up of water and a conversion of
the substance into simpler molecules. As an example of this process might be
mentioned the decomposition of the disaccharides, such as maltose, into monosac-
charides, one molecule of water being taken up and two molecules of the latter
substance being produced. The conversion of fats into fatty acids and glycerin
requires three molecules of water. The reverse process is dehydration. As an
example of this kind might be mentioned the building up of the amino-acids into
polypeptides and the complex proteins of the cells.
(h) Deamination. — Many tissues possess the power of splitting off an NH2
group from amino-acid as ammonia and replacing it by H or OH. The reverse
process is continuously going on in plants which synthetize proteins from ammonia
and a carbohydrate. Some evidence is also at hand to show that this reversion
may be effected by animals.
(c) Decarboxylation. — This process involves the loss of a molecule of carbon di-
^ Samuely, Handb. der Biochemie, 1908.
THE CHEMISTRY OF DIGESTION 991
oxide from amino-acids and their conversion into the corresponding amine. This
change is commonly produced by bacterial action, but may also take place normally
as a step in the oxidation of the carbon atoms in the carbohydrates and long chain
fatty acids.
(d) Oxidation and i2e6Z^^cfion.—=-This process consists in the successive- conversion
of substances into CO2 and water under an evolution of energy which is much greater
than that derived from the changes enumerated previously.
One of the important deductions to be derived from this tabulation
is that catalyzers and especially ferments, not only accelerate decompo-
sitions, but are also instrumental in reforming the original substance
from its simple end-products. This phenomenon which is known as
reversibility, was first shown to take place by Croft HilP in two experi-
ments with sucrose and invertase. An especially good example of such
a reversible action has been furnished by Kastle and Loevenhart.^
By employing the simple ester ethyl-butyrate, they were able to prove
that lipase not only hydrolyzes this substance into ethyl-alcohol and
butyric acid, but also synthetizes these products of hydrolysis into
ethyl-butyrate and water. It appears, therefore, that one and the
same enzyme may serve not only to split a foodstuff into its simple
constituents, but also to reconstruct the latter into a more complex
substance while they traverse the lining of the intestine or enter the
tissues. Some investigators assert that this reversibility is something
more than a mere establishment of an equilibrium and conforms closely
to a true synthesis (Bertrand).
It is also to be noted that ferments act best at an optimum tempera-
ture of 40° to 50°C. While this is true of all catalyzers, ferments seem
to have a more restricted sphere, low and high temperatures being
detrimental to them. At 60° to 80°C., they lose their power, and are
destroyed absolutely at 100°C. It is also apparent that the action of
catalyzing agents increases with their surface. An analogous process
is presented by the condensation of a gas upon a solid surface or by the
combination of hydrogen and oxygen by means of finely- subdivided
platinum. In addition, it has been assumed that the unusual power
of ferments is due to their ability of forming certain intermediate
products which, although they do not energize the reaction itself,
serve as a means of attaining the end-stage of the catalysis more
rapidly. As a last factor influencing ferment action might be men-
tioned the number of ferment-molecules involved. Thus, it has been
found that the degree of the change effected in a given period of time,
is proportional to the amount of the ferment engaged in this process,
and is in a measure independent of the concentration of the substra-
tum. It should be remembered, however, that ferments act in infin-
itesimally small quantities, and that an abundant supply of them is
rather deleterious to the reaction. The reason for this diminution in
the effectiveness of a ferment, when present in large amounts, is not
1 Brit. Med. Jour., 1903, also Mathews and Glenn, Jour. Biol. Chem., ix, 1911,
29.
2 Am. Jour, of Physiol., vi, 1902, 331.
992 DIGESTION
easily understood, unless it is assumed that the enzyme then destroys
itself in part by autolysis. But this retardation does not take place
under all circumstances, because certain fermentations which have
come to a standstill owing to the large amounts of ferment present,
may again be brought under way by diluting the mixture or by remov-
ing the products formed in the course of the reaction.
This ''self -inhibition" is closely allied to the inhibition of ferment
action by outside means. ^ Thus, it is a well-known fact that these proc-
esses may be greatly retarded and abolished by strong acids, alkalies,
alcohol, iodin, potassium cyanide, formaldehyde, and the salts of the
heavy metals. In many instances, the cells of the different tissues
produce a substance which is called anti-enzyme. For example, if
an enzyme is injected into the blood-stream, certain cells are stimu-
lated to produce an anti-enzyme of a specific kind, so that the serum of
this blood may be mixed with the original enzyme with the result that
the latter is then quite unable to unfold its characteristic action.
As to the manner in which enzymes increase the velocity of the re-
action to which they are specifically assigned, few positive statements
can be made. In the first place, it may be assumed that the ferment is
combined with the substrate in a loose manner — fitted to it as a key in
its corresponding lock.^ This simile, no doubt, calls to our minds the
interaction between the antigen and the immune bodies, as explained
by the side chain theory of Ehrlich. In the second place, it is evi-
dent that the ferment is finally removed from the sphere of its action
and enters the end-products. This brings the catalysis to an end.
These reactions, however, are different from those taking place between
various inorganic substances, because the latter are chiefly interac-
tions between electrolytes. Thus, the molecules of sodium chlorid
are broken up into their cations Na which are charged positively and
move toward the cathode or negative pole, and their anions CI which
are negative and move toward the anode or positive pole. Since the
organic foodstuffs, namely, the proteins, carbohydrates and fats, are
not electrolytes, their reactions cannot be regarded as analogous to
these almost instantaneous ionic movements. They take place more
slowly and are in reality molecular interactions. When only one.
substance is being transformed, it constitutes a unimolecular reaction.
As an example of this kind might be mentioned the conversion of
starch into sugar. The velocity of the reaction is measured in this
case in terms of substance transformed, i.e.y in gram-molecules per
liter in the unit-time of one minute. But, as the amount of substance
acted upon is gradually diminished, the velocity of the reaction must
also be reduced in a proportionate measure. In those cases in which
two substances are changed simultaneously, as occurs in the decompo-
sition of esters under the influence of an alkali, a bimolecular reaction
1 Porter, Quart. Jour, of Exp. Physiol., iii, 1910, 375.
2 Emil Fischer, Zeitschr. fiir physiol. Chemie, 1898.
THE CHEMISTRY OF DIGESTION 993
takes place. The velocity of the reaction is then proportional to the
square of the amount of the substance.
The Function of Saliva. — Saliva possesses a two-fold action, namely,
a physical one and a chemical one. It moistens the mucous surfaces
of the mouth as well as the food, thereby facilitating its mastication and
deglutition. In addition, it acts as a solvent allowing sapid substances
to excite sensations of taste, and as a cleaning agent of the oral cavity.
The former is of special importance, because it serves to evoke those
stimuli which give rise to the psychic secretion of gastric juice and a
certain satisfaction in eating. These are its only functions in those
animals, such as the horse, sheep, ox and dog, in which a true digestive
ferment is not present.^ The substance more particularly concerned
in this purely mechanical process is mucin. In man and some of the
herbivora, however, it also possesses a moderate chemical action by
virtue of its enzyme ptyalin. This ferment acts exclusively upon
starch, converting it into maltose through several intermediary stages,
such as soluble starch or erythro-dextrin which gives a red color with
iodin, and achroo-dextrin which gives no color with iodin. But since
ptyalin does not attack cellulose, it is imperative that the starch be
well cooked beforehand so as to destroy its capsular investments.
Moreover, while the warmth of the mouth causes the starch to be re-
duced very rapidly, a considerable portion of even the boiled starch
invariably escapes salivary digestion, because mastication is usually
practised in a hasty and careless manner. The solid starch which is
ingested in farinaceous foods, bread, and biscuits, is only slightly
affected by the saliva and- practically no hydrolysis is instituted by
this secretion.
Ptyalin is most effective at 37°C. and in a neutral or weak acid
medium, but a slightly alkaline medium is not unfavorable to its
activity. Inasmuch as its action is destroyed by such small amounts
of acid as 0.003 per cent. HCl, it might be supposed that it must lose
its effectiveness as soon as it enters the stomach. This is not the case,
because the freshly swallowed food forms a coherent mass which is not
easily penetrated by the gastric juice, and besides, some time must
elapse before a sufficient quantity of the latter has been secreted to fill
the relatively inactive cardiac end of the stomach. During the interim,
the ptyalin continues its reductions and it is safe to say that from 30 to
40 minutes must elapse before its action is stopped completely. Mean-
while, the largest part of the available starch has been hydrolyzed and,
while a certain proportion of unreduced starch may escape salivary
digestion, it is later on subjected to the action of the amylopsin of the
pancreatic juice. Unboiled starch, on the other hand, escapes even
this powerful diastatic ferment and enters the feces unutilized.
The Function of Gastric Juice. — The action of the gastric juice
is due partly to its acid and partly to the combined action of its acid
and ferments. It may be said that :
iKuss, Ref. Maly, 1898, Zebrowski, Pfliiger's Archiv, ex, 1905, 105, and
Palmer, Am. Jour, of Physiol., xli, 1916, 483.
63
994 DIGESTION
(a) It is Antiseptic— Whenever carbohydrates are ingested, a certain number
of micro-organisms are also taken in. These give rise to fermentations, in the
course of which considerable quantities of lactic acid may be produced. The
subsequent outpouring of hydrochloric acid destroys many of these organisms,
as well as others of pathogenic character, but some of them always escape into the
intestine (bac. acidi lactici), where they find a more suitable medium for their
growth. •
(5) It Inverts Sucrose into Glucose and Fructose. — This action is not due to the
presence of an invertase in this juice, but to the hydrochloric acid and such invert-
ing enzymes as may be present in the food ingested: ^
(c) It contains a fat-splitting enzyme or lipase. Its action in this regard is two-
fold, because the hydrochloric-pepsin combination dissolves the protein constitu-
ents and investments of the fat-cells, and allows the fat to escape and to coalesce.
In addition, a small quantity of lipase is present which splits the emulsified fat
into glycerol and fatty acids, but naturally, the hydrolysis going on in this organ
is insignificant when compared with that effected in the intestine by the pan-
creatic juice. The origin of this lipase is somewhat in doubt; some claim that
it is regurgitated with the contents of the small intestine and some, that it is an
actual product of the gastric mucosa. It is of much greater importance to the
suckling thair to the adult.
(d) It Curdles Milk. — This property of gastric juice is due to its ferment
rennin or chymosin^ which, as has been mentioned above, appears to be formed
separately from the pepsin, ^ It initiates a two-fold process, namely, the conversion
of caseinogen into casein, and the combination of the altered casein with the
soluble calcium salts to form a curd.'* This action is greatly accelerated by the
hydrochloric acid which in itself is capable of precipitating caseinogen, but this acid
is by no means an indispensable factor as is provided by the fact that the curdling of
milk also takes place in a neutral or alkaline medium, but not after the milk has
been boiled. Moreover, the curd produced by rennin in the presence of calcium
salts, exhibits certain properties which are quite different from those exhibited by
the acid precipitate. At all events, the newly formed casein is subjected later on
to the action of pepsin in the same way as other proteins. It seems, however,
that the curdling of milk takes place before much acid has been secreted ; in fact,
milk is not an effective stimulant for the secretion of hydrochloric acid, and is used,
therefore, to allay hyperchlorhydria. To the suckling, the curd is of profound
importance, because it tends to retain this important nutritive material for a longer
time in the stomach so that it may undergo thorough digestion.^
(e) It contains a proteolytic enzyme. This is its most important property. The
combination of pepsin and hydrochloric acid converts the proteins of the food into
peptones, but does not change their constituent polypeptides into their ultimate
cleavage products, the amino-acids. This change is effected by hydrolysis, the
first stage being the formation of acid meta-protein, and the next step, the forma-
tion of proteoses, such as albumoses, globuloses, vitelloses, etc., as follows:
Protein
Acid meta-protein
[p . I Proteo-proteose
Propeptone or proteose nma y | Hetero-proteose
[ Secondary, Deutero-proteose
Peptone or polypeptides
^ Widdicombe, Jour, of Physiol., xxviii, 1902, 175.
^ Hammersten, Maly's Jahresb., 1872.
3 Porter, Jour, of Physiol., xlii, 1911, 389.
4 Van Slyke, New York Med. Jour., 1909, Proc, Soc. Exp. Biol, and Med.,
1911.
6 Gmelin, Pfliiger's Archiv, ciii, 1904, 618.
THE CHEMISTRY OF DIGESTION
995
Proteoses and peptones are classified in accordance with their physical character-
istics, such as their solubility and salting out. In the following table a native
protein albumin is contrasted in this respect with its peptic end-products :
Action of
Heat
Alcohol
Nitric
acid
Ammonium
sulphate
Copper
sulphate
Diffusi-
bility
Albumin
Coagula-
tion
Precipita-
tion and
c o a g u 1 a-
tion.
Precipita-
tion in the
cold ; not
easily dis-
solved on
heating
Precipita-
tion after
complete
saturation
Violet
color
None
Proteo-
ses
No coagula-
tion
Precipita-
tion, but
no coagula-
tion
Precipita-
tion in the
cold ; easily
dissolved
on heating
Precipita-
tion after
saturation
Rose red
color
Slight
Peptones
No coagula-
tion
Precipita-
tion but no
coagulation
No precipi-
tation
No precipi-
tation
Rose red
color
Readily
Upon the constituents of connective tissue and other allied protein substances,
the pepsin-hydrochloric acid combination acts as follows:
(a) Collagen, a constituent of bone and white fibrous and areolar tissue, is
converted into gelatin, gelatoses and gelatin-peptones. Since these tissues con-
tain much fat, this foodstuff is separated from its investments.
(6) Elastin, a constituent of elastic tissue, is not acted upon under ordinary
conditions.
(c) Mucin, a constituent of the ground-substance of connective tissue, is con-
verted into peptone-like substances.
(d) Nucleo-proteins are changed into a protein portion and a nuclein portion.
The former is then converted into proteoses and peptones, whereas the latter is
precipitated in an insoluble form. On phospho-proteins it acts in a somewhat simi-
lar manner.
The Function of Pancreatic Juice. — This secretion plays an even
more important part in digestion than the gastric juice, because it
contains several powerful enzymes. Its function may be summarized
as follows:
(a) Proteolytic. — This property is imparted to it by its enzyme trypsin which
differs materially from pepsin, because it gives rise to a more rapid as well as more
thorough catalysis. To begin with, it is to be noted that trypsin acts in an alka-
line medium, whereas pepsin acts in an acid medium. Moreover, while the former
produces the same initial conversions of the protein molecule as the latter, it does
not stop here but reduces the peptones still further into their constituent amino-
acids, such as leucine, tyrosine, alanine, aspartic acid, glutamic acid, arginine,
tryptophane, and others. It is also to be observed that this conversion is effected
so rapidly that the formation of the primary proteoses can scarcely be detected,
while the secondary derivatives come into prominence almost immediately. In
place of acid-metaprotein, however, we now obtain alkaline-metaprotein. In
addition, a reduction of elastin takes place which is not effected at all by the gastric
996 DIGESTION
juice. When the peptone stage has been passed, the biuret reaction is no longer
obtained. Regarding the degree of alkahnity existing in the duodenum much
uncertainty prevails. While pancreatic juice is a strongly alkaline secretion,
owing to its content in sodium carbonate, it must be remembered that the alkalin-
ity of this medium must be changed repeatedly by the entrance of the fresh acid
chyme. Its reaction may then become neutral, but the action of trypsin cannot
be unfavorably affected by a condition of this kind, because most effective artificial
media are usually made by dissolving commercial trypsin in only 0.2 to 0.3 per cent,
of sodium carbonate. It is true, however, that larger amounts of this enzyme
require a larger amount of this salt. It has been pointed out above that the con-
version of trypsinogen into trypsin necessitates the presence of enterokinase or cal-
cium salts. 1 It is also said that erepsin-may be present at times in pancreatic juice,
because when inactivated, this secretion may digest casein but not other proteins.
(6) Amylolyiic. — Pancreatic juice contains an amylase, known as amylopsin,
which hydrolyses the starches more rapidly than ptyalin. Even unboiled starch
is affected by it under formation of erythro-dextrin and maltose. In a nearly
neutral mediupi this disaccharide is converted further into the monosaccharide
dextrose or glucose. This additional hydrolysis is dependent upon the presence
of a second ferment, maltase.
(c) Lipolytic.^ — The powerful fat-splitting enzyme of pancreatic juice is
called steapsin. It changes neutral fats, such as the triglycerides of palmitic,
stearic and oleic acids, into the corresponding fatty acids. Since this medium pos-
sesses an alkaline reaction, these fatty acids unite with the alkaline bases to form
soaps which then appear as films upon the outer surfaces of the fat-globules and
prevent them from coalescing. These emulsions assume a more stable character
in the. presence of proteins, and colloids.
(d) Milk-curdling.^ — Pancreatic juice also possesses the power of clotting
milk, but this action may not be due to the presence of a special enzyme. It differs
in its character from that of rennin.
The Function of Bile. — The velocity with which lipolysis takes
place in the small intestine, is considerably increased by the presence
of bile, the active agent concerned in this process being the bile salts.
These act in two ways, namely by their solvent action on fatty acids
and soaps and secondly, by their property of diminishing the surface
tension between the fat and the water. This enables the intestinal
juices to enter into closer relation with the globules of fat. Con-
sequently, the digestive value of bile lies in its adjuvant power of
furnishing a more appropriate medium for the interaction between the
steapsin and the fatty acids than the pancreatic juice alone could
possibly constitute. In some animals, it also contains a weak amyloly-
tic enzyme.
Bile also serves as a vehicle for the fats during their absorption.
This statement implies that the end-products of lipolysis traverse
the intestinal epithelium not merely in an emulsified form, but as fatty
acids or soaps and glycerin. This gives rise to a " circulation of the
bile, " because some of the biliary substances are again absorbed and
made use of later on in the manner just indicated.
While the bile salts possess mild antiseptic qualities, the bile itself
^ Schepowalnikow, Dissertation, St. Petersburgh, 1899, and Bayliss and Star-
hng, Jour, of Physiol., xxviii, 1902, 375.
2 Connstein, Ergebn. der Physiol., iii, 1904.
^ Kiihne Verh., med. Verein, Heidelberg, iii, 1881.
THE CHEMISTRY OF DIGESTION 997
has no definite influence of this kind. In other words, the fact that it
diminishes putrefaction in the intestine, is due chiefly to its power of
hastening the absorption of those substances which are most likely
to give rise to these processes. Bile is to a certain extent fexcretory.
In addition, it aids in neutralizing the acid chyme and in precipitat-
ing its unpeptonized protein. This renders the chyme more viscid
and retards its progress through the intestine, thereby augmenting
absorption.
The Function of the Intestinal Juice. — The principal action of the
intestinal secretion is exerted upon the carbohydrates. Its invertase
changes cane-sugar into glucose and levulose or fructose, whereas its
maltase^ transforms maltose into glucose. ^ A special enzyme, called
lactase, 3 is abundantly present in young animals for the purpose of
converting milk-sugar into galactose and glucose. The ferment
enterokinase (Pawlow) which activates trypsinogen, is widely distrib-
uted through the intestine. A similar body is erepsin^ which increases
the hydrolysis of the first products of the proteolysis and rapidly changes
albumoses and peptones into amino- and diamino-acids. Moreover,
since a great deal of fat may be split up in the small intestine
even in the absence of both bile and pancreatic juice, it is assumed that
it contains a lipase of relatively feeble power. The sodium carbonate,
in which it is rather rich, must, of course, aid in the formation of soaps
from the fatty acids.
This fact brings up the important point that the secretions in the
intestine form a suitable medium for the growth of bacteria, contrary
to the gastric juice which by virtue of its acidity attenuates micro-
organisms. Some of them, however, reach the intestine in spite of
the gastric juice and produce here certain enzymes, the actions of
which are very similar to those of the ferments normally contained
in the local secretions. In some instances, these putrefactive organ-
isms also give rise to more specific reactions, as follows:
(a) On Carbohydrates. — The most important reaction is the lactic acid fermenta-
tion which is chiefly responsible for the formation of intestinal gases. It usually
takes place in two stages which may be represented by the following two equations :
CizHazOn + H2O = 4C3H6O3
(Lactose) (Lactic acid)
4C3H6O3 = 2C4H8O2 + 4CO2 + 4H2
(Lactic acid) (Butyric acid)
Vegetable food increases this fermentation, the cellulose being split into carbonic
acid and urethane.
(6) On Fats. — Some bacteria possess a lipolytic action and are capable of pro-
ducing lower acids, such as valeric and butyric. It cannot surprise us, therefoi^,
1 Rosenbloom, Conn. Biolog. Chem., xiv, 1913, 241, and Hammarsten,
Ergebn. der Physiol., 1905.
2 Rohmann, Pfliiger's Archiv, xH, 1887, 424.
3 Halliburton, Textb. of Chem. Path, and Physiol., 1891.
^ Cohnhein, Zeitschr. fiir phys. Chemie, xxxvi, 1902, 13, and Vernon, Jour, of
Physiol, xxxii, 1904, 32.
)\f(.-i , V
998 DIGESTION
to find that the contents of the lower small intestine may become acid, in fact, this
acidity may on occasions invade higher segments without, however, materially
impairing pancreatic digestion. The latter, as we have seen, does not require an
especially high alkalinity.
(c) On Proteins. — Some bacteria are capable of splitting proteins into amino-
acids, liberating during this process such substa^nces as indol (CsHtN), scatol
(C9H9N), and phenol (CeHeO). These animo-acids are further reduced by them
into their corresponding amine bases by the process of decarboxylation which con-
sists in removing carbon dioxid from their carboxyl (COOH) group. In this way,
leucine may be converted into its base iso-amylamine, as follows :
g^^^CHCHaCHNHz-COOH = ggjNcHCHzCHa-NHa + CO2
This base, and especially the oxyphenylethylamine derived from
tyramine, possesses a pressor action similar to that of adrenalin.
The former substance is a constituent of ergot. It is also of interest
to note that the enzymes of fungi, such as those affecting grasses and
fruits, are capable of decarboxylizing some of these bases. In spite
of the formation of the aforesaid acids, however, the contents of the
large intestine become alkaline. This change is due to the fact that
some of the bacteria generate ammonia which again neutralizes the
organic acids.
CHAPTER LXXXIV
THE MECHANICS OF DIGESTION
A. MASTICATION AND DEGLUTITION
General Consideration. — In those animals in which digestion is
chiefly intracellular, the chemical processes necessitate a mechanical
manipulation of the food which purposes to effect its reduction into
smaller masses and its steady onward movement, so that it may be
successively subjected to the different secretions. Leaving out of
consideration the celenterata, in which the digestive and vascular
systems are still incompletely separated, as well as the echinodermata,
in which this separation is complete, it may be said that the arth-
ropoda are the first to present an alimentary canal which shows
definite variations in its caliber, corresponding to the stomach, and
small and large intestines of the higher animals. Glandular organs
are placed along this canal which seem to be homologous with the
salivary glands and the liver-pancreas of the higher forms. Possibly
the simplest alimentary system among the vertebrates is presented
by the fishes. It consists of a stomach, the glands of which furnish
an acid proteolytic secretion, and a fully differentiated intestine with
a series of digestive fluids possessing different actions.
The alimentary canal of birds exhibits several peculiarities, such as
THE MECHANICS OF DIGESTION 999
the crop and the double stomach. The former appears as an enlarge-
ment of the proximal segment of the esophagus, and serves as a
reservoir for the food, performing a function similar to that of the oral
pockets of the squirrels and" allied animals. Besides, this pro-stomach
furnishes a secretion which institutes a swelling of the kernels and a
destruction of their cellulose investments. Of special interest is the
fact that this organ also secretes a milk-like fluid which serves as food
for the young during the first two or three weeks of their life. It
contains a considerable amount of fat which is derived from the des-
quamated and degenerated epithelial lining. The stomach of these
animals consists of two segments, namely, a glandular pro-ventriculus,
and a muscular ventriculus. The former furnishes an acid secretion
rich in pepsin, whereas the latter reduces the food into smaller frag-
ments. In this function it is aided very materially by the solid sub-
stances, such as granules of sand, which these animals are in the
habit of ingesting with their food.
The alimentary canal of the mammals presents as its two principal
characteristics the division of the stomach into two or four cavities,
and the varying length and caliber of the small and large intestines.
The carnivora are characterized by a preponderance of the small
intestine, and the herbivora by a preponderance of the large intestine.
Some of the mammals, such as the rodents and cetacese, are in possession
of a stomach consisting of two pouches, while that of the ruminating
animals consists of four compartments. In the latter, the esophagus
terminates in a vestibular enlargement which communicates with the
first and second gastric cavities. The food enters chiefly the first
cavity, where it is iAtei mingled with older material and is in part
forced into the second compartment. After 30 to 70 minutes (cow),
small amounts of the now somewhat softened material are projected
into the mouth to be remasticated. Most of this material is finally
converted into a liquid mass which upon being reswallowed is directed
into a muscular furrow through which it attains the third and fourth
cavities. Its still unreduced portion is retained in the first compart-
ment to be remasticated if necessary at the rate of 6 to 8 times in the
course of 24 hours, each act of mastication lasting from 45 to 60 min-
utes. Liquids, on the other hand, may enter all four compartments
simultaneously. The capacity of the cow's stomach varies between
160 and 230 liters, four-fifths of which are apportioned to the first
two chambers.
The alimentary canal contains secretory as well as muscular ele-
ments which are held together by varying amounts of connective tissue.
Its length varies considerably in different animals, being shortest in
the carnivora and longest in the herbivora. In general, the ratio
between its length and that of the entire body is, in man, as 1 : 5 or 1 : 6;
in the dog, as 1:6; in the cat, as 1 : 4; in the cow, as 1 :20, and in the
sheep, as 1 :27. The mucous membrane lining th^ digestive tract
presents a surprisingly large surface to the simplified foodstuffs.
1000 DIGESTION
Thus, it has been ascertained that the mucosa of the dog, if spread out
in a single layer, covers more than one-half of the body-surface.
In man, the muscular stratum of the alimentary canal is made up of
smooth muscle tissue which is arranged in two layers, an outer longi-
tudinal and an inner circular. This arrangement is departed from in
the mouth, pharynx and stomach, where oblique fibers are added;
moreover, the mouth, pharynx, upper part of the esophagus, and end
of the rectum, contain numerous strands of striated muscle. Inter-
nally, the circular layer of smooth muscle tissue lies in relation with
areolar tissue, containing blood-vessels, lymphatics and nerves. It
forms the submucous coat. This in turn is clad with epithelium,
constituting the continuous mucous lining of the entire digestive tract.
Externally, the longitudinal layer of smooth muscle tissue is enveloped
by a thin serous layer, the peritoneum. The mechanical processes
associated with digestion, are mastication, deglutition, and the churn-
ing movements of the stomach, small intestine and large intestine.
Mastication. — The articulation between the mandible and max-
illary bone is classified as a double condyloid joint. Owing to the
looseness and strength of its capsular ligament, the articular surfaces
of these bones may be moved freely upon one another, allowing the
mandible to execute three types of movements which may be classi-
fied as (a) depression and elevation, (h) projection and retraction, and
(c) deviation from side to side. Its raising is effected by the combined
contraction of the temporal, masseter, and internal pterygoid muscles,
and its depression by gravity and the action of the digastric muscle
in conjunction with the mylohyoid and geniohyoid. At this time,
the hyoid bone is fixed by the contraction of the'omohyoid and sterno-
hyoid muscles. When both external pterygoids contract simulta-
neously, the jaw is protruded. The opposite movement is effected by
the internal pterygoids. The contraction of only one set of these
antagonistic muscles gives rise to a deviation of the jaw toward one
side or the other.
The grinding motions of mastication consist chiefly in a lowering
and raising and a lateral deviation of the jaw, the food being kept
between the molar teeth by the action of the tongue, the orbicularis
oris and the buccinators. The action of these parts is controlled by a
reflex center which is situated in the medulla oblongata and includes
the nuclei of the motor nerves innervating the aforesaid muscles,
namely, those of the trigeminal, facial and hypoglossal nerves. On
the afferent side, this center is connected with different receptors, and
particularly with the spindles of the muscles concerned in this act.
By this means, the force and character of the movements of the jaw are
reflexly regulated. The closure of the lips and depression of the tongue
and jaw during inspiration may give rise to a negative pressure in the
oral cavity, approximating 25 to 50 cm. H2O.
The importance of mastication differs in different animals. In
the carnivora, the food is rapidly projected through the mouth and is
THE MECHANICS OF DIGESTION 1001
swallowed in rather large masses, whereas in the herbivora, and especially
in the ruminating mammals, it is slowly reduced into the smallest
possible fragments. The omnivora, such as man, occupy an interme-
diate position in this regard. These differences are associated with
definite peculiarities in the shape and structure of the parts concerned
in mastication. Thus, we find that the teeth of the carnivora are
well adapted to catch the food, while those of the ruminants present all
the characteristics of grinders. In man, the incisors are to hold and
to divide the food, whereas the canines divide it, and the bicuspids
and molars macerate it. The development of these parts proceeds
in the same manner as that of the hairs. A continuous thickening of
the epithelium takes place along the gums which grows into the corium
of the mucosa and forms the dental germ or dental lamina. Further
thickenings and growths give rise to the special dental germ from which
the milk teeth are developed. Each germ contains a vascular papilla
and is eventually separated from the general mucous membrane by a
vascular septum, which is known as the dental sac. The papilla is
finally transformed into the dentine and pulp of the growing tooth,
while its enamel is deposited upon this core by the epithelial cells of the
dental germ. Later on, as the tooth grows outward, its root is formed
which is then covered with cement.
In man, the teeth appear in two sets, a temporary one and a permanent one.
The first consists of the so-called milk teeth. They are twenty in number and appear
between the 5th and 30th month. Their time of appearance, however, varies
considerably, being subject to family characteristics, and the condition of the child.
The first to appear are the two central incisors below (5th to 9th month), next the
four upper central teeth (8th to 12th month) ; then the other two lower central
teeth and the four front double teeth (12th to 18th month). The four incisors follow
next (18th to 24th month), the upper being known as the "eye teeth" and the
lower as the "stomach teeth." The four back double teeth which complete the
first set, break through between the 24th and 30th month. Every one of the
milk teeth is replaced in the course of time by a permanent tooth. This change
begins at about the 7th year and proceeds in about the same sequence as the
formation of the temporary set. In addition, each maxilla acquires six new teeth,
three on each side. These are the permanent molars. The last of these, or wis-
dom teeth, appear about the 20th year, but have been known to be delayed until
the 30th year and later. The permanent set, therefore, consists of thirty-two
teeth.
Deglutition. — In brief, the process of mastication consists in a
mechanical reduction and anointment of the food which eventually
leads to the formation of the holus. This rounded pulpy mass of food
is then projected into the stomach by the process of deglutition or
swallowing. In general, it may be said that the onward movement of
the food through the alimentary canal is effected by peristaltic motion,
but the gross character of this muscular activity differs somewhat in
the different segments of this channel. The act of deglutition is
divided into three stages. The first is oral in its character and termi-
nates with the passage of the bolus through the pillars of the fauces.
The second concerns the constituents of the pharynx and ends with
1002 DIGESTION
the entrance of the food into the upper extremity of the esophagus.
The third is restricted to the esophagus and terminates with the
arrival of the food in the cardiac end of the stomach. It is also to be
noted that the first is effected by striated muscle, and constitutes, there-
fore, a voluntary act, whereas the last two are due almost wholly to
the contraction of smooth muscle tissue and are, therefore, involuntary
or reflex in their nature. In spite of these functional differences, how-
ever, deglutition is a continuous act and no pauses occur between its
successive phases. Further, the initiation of the first invariably means
the completion of the third, although some persons may acquire a
limited volitional control over the second.
Immediately before the beginning of the first stage, the process of
mastication is suspended. Respiration is arrested after a slight con-
traction of the diaphragm, constituting the so-called *' respiration of
swallowing." The lips are closed and the maxillae closely approxi-
mated. The tip of the tongue is then elevated and pressed against the
the inner aspect of the upper gum. The muscles effecting this move-
ment are the inner longitudinal strands of the tongue which are con-
trolled by the hypoglossal nerve. This elevation then progressively
involves the entire tongue from before backward, forcing the bolus in the
same direction through the fauces. This movement brings into play the
muse, mylohyoideus (nerv. trigeminus) which raises the hyoid bone,
as well as the muse, styloglossus, muse, palatoglossus and, in an in-
direct manner, also the muse, stylohyoid (nerv. facialis). The latter
elevate the back of the tongue, so that its inherent muscle strands may
progressively obstruct the posterior extent of the oral cavity.
As soon as the bolus has been forced through the fauces, it is
brought under the control of the three sphincters of the pharynx which
direct it into the upper extremity of the esophagus. This process
necessitates a temporary obstruction of the nasal and laryngeal
cavities. The closure of the first is brought about by the simultaneous
contraction of the levator palati and palato-pharyngeus muscles, the
uvula being at this time forced in contact with the posterior pillars, and
the latter in turn with the upper posterior wall of the pharynx. The
closure of the epiglottidean orifice necessitates the elevation of the
hyoid bone and an upward and forward movement of the larynx. The
former is brought about by the contraction of the geniohyoid, anterior
belly of the digastric and mylohyoid, and the latter, by the contraction
of the thyrohyoid. At this time, the back of the tongue is pulled
backward by the contraction of the styloglossus, thereby forcing the
epiglottis downward across the laryngeal orifice. A still firmer
closure of this passage is effected by the contraction of the reflector
epiglottis and aryepiglotticus, as well as by the constriction of the
glottis itself. Stuart and McCormick,^ however, have shown that the
removal of the epiglottis does not seriously interfere with the act of
^ Jour, of Anat. and Physiol., 1892; also: Kanthak and Anderson, Jour, of
Physiol., xiv, 1893, 154.
THE MECHANICS OF" DIGESTION 1003
swallowing, because the backward movement of the tongue and upward
deviation of the larynx usually suffice to prevent an ingress of food
into the respiratory passage.
At about the level of the closed epiglottidean orifice, the bolus is
brought under the influence of the middle and inferior constrictors of
the pharynx, the successive contractions of which force it into the
upper segment of the esophagus. It has been shown by Kronecker
and Falk^ that fluids pass more rapidly and usually do not require a
concerted action of the parts just enumerated; in fact, the movements
of the back of the tongue generally suffice to direct them through the
relaxed upper segment of the esophagus into its lower portion. It is
for this reason that some persons, under abolition of the pharyngeal
reflexes, are able to pour considerable quantities of water almost
directly into the cardia. This also explains the fact that the erosions
produced by the hasty intake of corrosive fluids, are usually most
severe in the lower esophagus.
It has been shown by Cannon and Moser^ that the progression of
semi-solid food through the esophagus takes place much more leisurely,
and is effected by peristaltic waves which proceed from above down-
ward. It will be remembered that the smooth musculature of this
membranous tube is arranged in two layers, namely, as an inner
circular and an outer longitudinal coat. A peristaltic wave, however,
does not consist solely of a contraction of the circular fibers, but pre-
sents itself in all instances as a progressive wave of constriction which
is anteceded by a wave of relaxation, the bolus being driven ahead of
the contracting band of muscle tissue in the direction of least resistance.
But since the upper and even the middle segments of the esophagus
contain a few strands of striated muscle tissue, it cannot surprise us to
find that the progress of the bolus is more rapid above than in the vi-
cinity of the cardia. According to Schreiber,^ the entire act of peristal-
sis for semi-solid food consumes about 6 seconds, about one-half of
this period being occupied by the passage of the bolus through the lower
segment of the esophagus.
A very appreciable retardation also results at the cardiac sphincter
which guards the gastric orifice of the esophagus. This circular
ring of smooth muscle tissue relaxes only under the gradually increas-
ing force of the newly arrived bolus. Obviously, this mechanism pre-
vents the sudden ingress of the food into the stomach as well as its
immediate projection into the fundic portion of this organ. ^ On
listening over the region of the cardia when fluid is taken, two sounds
are heard, the first of which is produced by its sudden projection
1 Archiv fiir Anat. und Physiol., 1880, 296.
2 Am. Jour, of Physiol., i, 1899, 435, and Eykmann, Pfluger's Archiv, xcix,
1903, 513.
3 Archiv fiir exp. Path, und Pharm., xlvi, 1901, 414.
^ Beaumont's observations upon Alexis St. Martin, also Hertz, Guy's Hosp.
Rep., London, 1907.
1004 DIGESTION
through the esophagus, and the second, by its gurgUng through the
cardiac orifice.
Nervous Control of Deglutition. — The act of swallowing involves
the voluntary mechanisms of the mouth and pharynx, and the invol-
untary mechanism of the esophagus. Consequently, deglutition may
be treated as a reflex act which is evoked by the projection of the bolus
against the mucosa of the fauces and pharynx, regions which are in-
nervated, on the one hand, by the trigeminus and, on the other, by the
glossopharyngeus. Besides these normal ''pace-makers," this passage
also includes several other areas which upon mechanical stimulation
give rise to deglutition. ^ The afferent channels involved in this reflex
lie in the second division of the trigeminus, the glossopharyngeus
and the pharyngeal branches of the superior laryngeus, whereas the
center occupies a place in the upper part of the medulla oblongata.
The motor fibers are contained in the hypoglossal, facial, trigeminus,
and vagus nerves.
This enumeration shows very clearly that the parts involved in
deglutition, are arranged segmentally, but the sensory and motor
nerves controlling them, are coordinated in so precise a manner that
no interruption can possibly result in the orderly progression of the
wave of contraction. Thus, Meltzer^ has shown that the peristaltic
wave does not require an integrity of the muscular tube so long as the
nervous mechanisms have not been interfered with, while Mosso^
has proved that a ligature applied to the esophagus, does not block
this wave, provided the reflex circuits have not been broken. An
even more striking proof of the successive involvement of the different
segments of this membranous tube has been furnished by Mikulicz.
It concerns a man whose esophagus had been resected in part for the
removal of a carcinomatous growth. The lower segment of this tube
was made to open through a wound in the neck, the purpose of this
arrangement being to allow the food to reach the stomach in the normal
way. It was found, however, that its introduction through this open-
ing did not incite peristalsis, whereas it was moved onward immedi-
ately if the act of swallowing was instigated in the normal way by
the corresponding movements of the mouth parts.
An interval of at least 1.0 second must intervene between the suc-
cessive acts of swallowing, otherwise certain inhibitor influences will
arise which effectively block the succeeding peristalsis. This
inhibition is said to be under the control of the glossopharyngeus,
because it is a well-known fact that the normal pace-maker of deglu-
tition is represented by the nucleus of this nerve. Evidently, this
refraction allows each act of deglutition to be completed before the
beginning of the next, although it may happen at times that new food
reaches the cardiac sphincter before the material swallowed previ-
1 Kahn, Archiv fiir Physiol., 1903, Suppl., 386.
2 Brit. Med. Jour., 1906.
2 Moleschott's Untersuchungen, 1876.
THE MECHANICS OF DIGESTION
1005
ously, has had sufficient time to escape into the stomach. This inter-
ference invariably gives rise to painful sensations and regurgitation
of the food. -
It should also be noted that the afferent impulses which determine
the activity of the center of deglutition, cause a stoppage of the respir-
atory movements. This is important, because an inspiratory motion
occurring during deglutition, might draw the food into the respiratory
passage, whereas an expiration occurring at this time, might force it
into the nasal cavity. The fact that this inhibition of respiration is
effected with the help of the glossopharyngeal nerve, may be proved
by stimulating the fauces and neighboring regions of the pharynx,
either mechanically or electrically. We have previously seen that
an analagous reaction may be produced by the excitation of the
mucous membrane hning the
nasal (trigeminus) and laryngeal
cavities (sup. laryngeal nerve).
Thus, it cannot surprise lis to find
that the introduction of a
stomach-tube gives rise to an
almost immediate inhibition of
respiration which persists even
after a severe cyanosis has* been
established. Repeated attempts
at swallowing, however, will tem-
porarily remove the inhibition
and allow the subject to replenish
the oxygen content of his blood.
A close reflex relationship also
exists between the center of deg-
lutition and the cardiac center,
as is evinced by the fact that the
act of swallowing increases the sphincter antri pylori; PS, pyloric sphine
rate of the heart. t^r; V, valvulae conniventes.
Fig. 511. — Diagrammatic Representation
OF THE Stomach.
C, Cardiac end; F, fundus; P, pylorus;
D, duodenum; CS, cardiac sphincter; *S^,
B. THE MOVEMENTS OF THE STOMACH
The Movements of the Fundus and Pylorus. — The muscular
coat of the stomach consists essentially of an outer longitudinal and an
inner circular layer. To these are added in certain areas of this organ
an inner layer of obliquely placed muscle strands which serve to
strengthen its wall along its anterior and posterior surfaces below the
cardia. The layer of circular strands is the heaviest of all and is of great-
est functional importance. At the pyloric and esophageal poles of the
stomach it suddenly increases in thickness, forming here the so-called
pyloric and cardiac sphincters. A third band of circular fibers invests
the stomach at the junction between its fundic and pyloric portions,
i.e., about 7 to 10 cm. above the pylorus. It is known as the sphincter
1006 DIGESTION
antri pylori and corresponds to the point of origin of the peristaltic
movements of the pyloric end of this organ. It is also of interest to
note that this muscular band is more highly constricted in some
persons than in others, giving rise to the so-called hour-glass stomach.
While this condition may be inherited, it is more commonly caused by
excitations of the gastric mucosa, such as may arise in consequence of
erosions and ulcers. The outer longitudinal layer continues at the
cardia with the longitudinal fibers of the esophagus, and is heaviest
along the greater and lesser curvatures of the stomach. At the pylo-
rus it passes over into the longitudinal layer of muscle tissue of the
duodenum.
Anatomically, therefore, the stomach may be divided into two
compartments, namely, into its pyloric portion or antrum pylori,
comprising about one-fifth of the entire organ, and its much larger
fundic portion and cardiac recess. This division also possesses a
correct physiological basis, because the antrum pylori is infinitely
more active than the fundus, so much so, in fact, that the latter is
commonly regarded as the reservoir of the former. A more thorough
study of these movements may be made with the help of the following
methods :
(a) Observation of the manner in. which th^ gastric contents are discKarged
through a duodenal fistula. ^
(6) Introduction of a small rubber bag into the cavity of the stomach which is
connected with a recording tambour. 2
(c) Inspection of the interior of the stomach through a fistulous opening
(Beaumont).
{d) Observation of the stomach through a wound in the abdominal wall, a
piece of mica being inserted in tHe opening to protect the stomach against external
stimuli,
(e) Observation of the excised stomach under proper conditions of moisture
and temperature. 3
(/) Observation of the stomach by means of the Rontgen-rays after the inges-
tion of food containing subnitrate of bismuth.^
The empty stomach is small in size, but its walls cannot collapse,
because a thin layer of frothy material remains interposed between
them. This froth consists of mucus and a few cubic centimeters of
gastric juice. At this time, the intragastric pressure is zero. The
entrance of food then separates its walls more widely but chiefly those
of the cardia, because the newly swallowed material collects at first di-
rectly below the esophageal orifice. Here it may remain in a rela-
tively undisturbed condition for nearly an hour, salivary digestion
going on unhindredly during the interim. This fact is wiell illustrated
by the experiments of Griitzner,^ who fed rats successively with semi-
1 Hirsch, Zentralbl. klin. Med., 1892.
2 Ducceshi, Arch. itil. de Biol., xxvii, 1897, 61.
3 Hofmeister and Stutz, Archiv fiir Exp. Path, und Pharm., xx, 1885, 1.
* Roux and Balthasard, Compt. rend., 1897, and Cannon, Am. Jour, of Physiol.
i, 1898, 359, and xii, 1904, 387.
^ Pfliiger's Archiv, cvi, 1905, 463.
I
r
THE MECHANICS OF DIGESTION 1007
solid food of different color and found it later on arranged in concentric
strata in the vicinity of the esophageal orifice. The material ingested
first was pushed downward and outward toward the gastric wall,
while that eaten last, occupied the central extent of this space. This
slow whirling about of the food serves to bring its different portions
into more intimate contact with the walls of the fundus and, therefore,
also with the gastric juice. Eventually, when even its innermost mass
has been completely acidified, the action of the ptyalin ceases, while that
of the pepsin begins. As far as the mechanical function of the fundus
is concerned, it may therefore be said that this gastric segment acts
merely as a reservoir for the digestive tract. Considerable amounts of
food may be stored in it which are then
fed, hopper-like, to the pyloric mill for
mechanical and chemical reduction.
This function does not require an un-
usual muscular activity, because gravity
and the pressure exerted by the food as
it slowly oozes through the relaxed car
diac sphincter, no doubt suffice to force
it toward the sphincter antri pylori.
Later on in the course of gastric diges-
tion, its walls contract more forcibly in Fig. 6I2.— Section of Frozen
1 , , -A. 1 J J. Stomach OF Rat During Digestion
order to empty its more dependent por- ^^ g^^^ ^^ Stratification of
tions, a regurgitation of the food being Food Given at Different Times.
prevented at this time by the closure of iGrutzner.)
the cardiac sphincter. But the pressure
present in this compartment at the height of digestion, rarely exceeds
6 to 8 cm. of water. ^
The mechanical conditions existing in the pyloric end of the
stomach, differ widely from those just described. Food having been
received, a band-like constriction appears at the sphincter antri
pylori which gradually increases in depth until the fundus has been
completely shut off from the pylorus. This circular constriction then
moves slowly toward the pyloric sphincter, where it arrives about 20
seconds later. Some time before it disappears another one develops
and progresses in the same direction. In this way, a number of peri-
staltic waves are produced which force the food toward the pylorus,
whence it recoils along the wall toward its starting point. As many
as three of these waves may be observed at one time. Thus, one may
just be disappearing at the pylorus, while another is still at some dis-
tance from it, and a third is just forming at the antrum. Although the
intensity and frequency of these waves vary with the time of gastric
digestion, they usually recur at intervals of about 10 seconds (cat)
and invariably proceed from the fundus toward the pylorus. Anti-
peristaltic movements occur only under pathological conditions.
iKelling, Zeitschr. fiir Biol., xliv, 1903, 161; and Schlippe, Deutsch. Arch,
klin. Med., Ixxvii, 1903, 450.
1008
DIGESTION
In man these movements may be studied with the help of the Ront-
gen-rays, the person to be examined having previously ingested a mix-
ture of koumiss and subnitrate of bismuth. Most commonly, these
Fig. 513. — Rokntgen Cinematograms of the Human Stomach. {Kastle, Rieder, and
Rosenthal.)
examinations are made in the standing position, so as to be able to
note the lower boundary of the stomach, and to be able to determine
i
THE MECHANICS OF DIGESTION 1009
whether this organ possesses a muscular power sufficient to force its
contents through the pyloric orifice. Obviously, the latter is situated
at this time somewhat above the level of the general cavity of the py-
lorus. Moreover, when standing erect, the stomach assumes more
nearly the shape of a suspended stocking and allows the gases to escape
very freely, whereas, when lying down, the esophageal orifice assumes
a position somewhat below the level of the general gastric cavity and
entraps any gases that may have been formed.
The Evacuation of the Gastric Contents. — The purpose of the peri-
staltic movements of the stomach is to mix the food with the gastric
juice, and to reduce it eventually into a liquid which is known as
the chyme. In this form, the gastric contents are then ejected through
the relaxed pyloric orifice into the duodenum. The muscular activity
which is required to accomplish this end is somewhat different from
that previously noted in the course of the formation of the chyme.
It consists essentially in a contraction of the horizontal and oblique
layers of muscle tissue which employ the cardia as a fixed point and
raise the fundus above the general level of the pylorus. Meanwhile,
the pylorus continues its peristaltic activity, and forces its contents to-
ward the pyloric orifice. Naturally, the chyme cannot escape as long
as this sphincter remains closed and must in this event be whirled
back along the sides of the gastric wall.
Two reasons may be assigned for the continued closure of this
sphincter, namely: (a) the gastric contents still contain solid masses
which exert a mechanical influence upon the mucosa of this region,
and (6) the gastric contents have not as yet been sufficiently acidified.^
Contrariwise, if the gastric contents have been thoroughly liquefied
and acidified, these mechanical and chemical stimulations cease and
allow the sphincter to relax. The chyme is then ejected into the duo-
denum, being here thrown against the upper surfaces of the valvulae
conni ventes which extend as transverse flaps partially across the lumen
of this passage. The presence of acid in the duodenum then effects
the closure of the pyloric orifice. Thus, the ejection of chyme is im-
mediately followed by a constriction of the sphincter until the acid
liquid in the duodenum has again been neutralized. The ejection of
chyme is then repeated. Consequently, it may be concluded that the
opening and closing of the pyloric sphincter is dependent upon the
physical condition of the gastric juice as well as upon the relative de-
grees of acidity in the cavities of the stomach and duodenum. Conse-
quently, the evacuation of the stomach is not a continuous act, but
takes place at intervals until its cavity has been completely emptied.
The nervous mechanism concerned in this reflex act, lies in the domain
of the plexus gastro-duodenalis.
The Time of Evacuation of the Gastric Contents. — The preceding
discussion must show immediately that the time of evacuation of the
gastric contents is subject to considerable variations which depend
1 Hirsch, Zentralbl. fiir innere Med., 1901.
1010
DIGESTION
not only upon the force and frequency of the peristalsis, but also upon
the character of the food ingested. Thus, Cannon^ has shown that the
carbohydrates begin to leave the stomach soon after their ingestion
and require only about one-half the time necessary for the complete
digestion of the proteins. Fats, when ingested alone, remain in the
stomach for a long time. Quite similarly, the simultaneous intake of
different foodstuffs markedly interferes with the evacuation of those
which otherwise escape very rapidly. Accordingly, if protein is fed
before the carbohydrates, the latter are retarded, whereas fat tends to
hinder the progress of both. In general, however, it may be said that
a moderate meal, consisting of all foodstuffs, should be out of the
stomach after four hours, and its ejection should begin within an hour
after its ingestion. The first portion of this chyme, therefore, may
have arrived at the iliocecal valve before its last portion has trav-
Fig. 514. — Shadows of the Human Stomach Obtained with the Aid of the Rontgen
Rays 15 Minutes, 1 Hour, and 4 Hours after Ingestion of the Bismuth Meal.
ersed the pyloric orifice. These facts imply that a stomach which
still contains material at the end of five hours, either lacks tonicity or
is unable to discharge on account of some obstruction, possibly a
pyloric stricture. Water and isotonic salt solutions are passed into the
duodenum very rapidly. Hypertonic? solutions and other drinks,
such as coffee and tea, require a somewhat longer time.^ As far as
the intake of moderately large quantities of water during meals is
concerned it may be stated in general that it serves the purpose of
hastening the formation of chyme, although it may also tend to dilute
the gastric juice to such an extent that its digestive power is unduly
diminished. In view of the results of Carlson, however, showing that
very abundant amounts of hydrochloric acid and pepsin are held in
reserve, the latter possibihty is rather remote, and should be taken
into consideration only when a hypochlorhydria is present.
Gastro-enterostomy. — The operation of gastro-enterostomy con-
sists in uniting the lower duodenum directly with the stomach distally
to its sphincter antri pylori. Physiologically, it is of importance to
1 Am. Jour, of Physiol., xii, 1904, 387.
« Arch, fur Exp. Path, und Pharm., lii, 1905, 370, and Miiller, Zeitschr. fiir
diat. und phys. Ther., viii, 1905.
THE MECHANICS OF DIGESTION 1011
remember that unless the fistulous communication is yery large, the
food will nevertheless pass through the pylorus. Consequently, the
pyloric obstruction must be rather complete before the fistula can
serve its purpose. Secondly, it has been observed in animals that
some of the material which has left the stomach by way of the pylorus
again enters this organ through the fistulous communication. Thirdly,
the outpouring of the acid gastric juice into intestinal segments which
are normally not directly exposed to it, may lead to erosions and ulcera-
tions of the mucosa, and especially if the blood- or nerve-supply have
in any way been interfered with during the operation. Consequently,
such a communication should not be established in the absence of
organic disease of the pylorus.
Vomiting. — The act of vomiting is a complex reflex in which
different muscles take part and which is usually preceded by a sensa-
tion of nausea, a reflex secretion of saliva, and other symptoms of a
more general character. In the suckling it consists essentially of a
contraction of the musculature of the stomach and a relaxation of the
esophagus and presents, therefore, the simplest possible details. In
the adult, on the other hand, other factors are brought into play,
chief among which is the abdominal press. The latter consists in a
spasmodic contraction of the abdominal muscles, inclusive of the
diaphragm, following a short inspiration and closure of the glottis.
It is apparent, however, that in the adult the stomach plays a rather
subordinate part, as is evinced by the fact that the retching movements
occurring at the beginning of the act of vomiting, which are wholly
of gastric origin, are altogether too weak to eject the gastric contents.
Moreover, it has been shown by Gianuzzi that this act cannot be
evoked in curarized animals, because this agent paralyzes the muscles
of the abdomen. In addition, it has been proved by Magendie that
vomiting also results in animals whose stomach has been replaced
by a bladder filled with water.
During the act of vomiting the peristalsis is abolished, although
intense movements of this kind may take place shortly beforehand.
Irregular retching motions then result which, however, do not seem to
be antiperistaltic in their character. The essential factor concerned
in vomiting, is the production of a high intragastric pressure, which,
as we have just seen, is the direct result of the contraction of the
abdominal muscles and smooth musculature of the stomach. The
pylorus is tightly closed at this time, while the cardiac sphincter and
esophagus are relaxed.^ An eructation of gas frequently precedes
this act, in fact, many animals such as the dog hasten its occurrence by
distending the stomach with freshly swallowed air. Vomiting also
necessitates a forward movement of the hyoid bone and larynx,
as well as a projection of the mandible. Both measures serve to
straighten the channel of ejection. Although the nasal cavity is
partly protected against the ingress of vomited material by the con-
1 Openchowski, Archiv fur Physiol., 1889, 552.
1012 DIGESTION
traction of the.upper constrictor and the approximation of the pharyn-
geal wall and pillars of the fauces, the force of the ejection is sometimes
so great that this hindrance is overcome.
The act of vomiting is controlled by a special center situated in the
medulla oblongata. On the efferent side, it is connected with the
different muscles mentioned previously and, on the afferent side, with
various local and general receptors. Thus, it is a well-known fact that
the sight and smell of offensive food or objects may serve as ade-
quate exciting causes, and that it may also be evoked by the mechanical
stimulation of the fauces and pharynx, as well as by irritations of the
gastric and intestinal mucosa. Even extragastric stimuli in the form
of abdominal tumors and the gradually enlarging uterus of pregnancy
may instigate it. Apomorphin produces its characteristic effect by
a direct stimulation of the vomiting center.
The Innervation of the Gastric Musculature. — The stomach is
wholly under the control of the autonomic nervous system, the distal-
most fibers of which are expanded between its circular and longitudinal
layers of muscle tissue into the plexuses of Meissner and Auerbach.
This organ, therefore, is well equipped with a local reflex mechanism
which is destined to. regulate its various motor activities. Thus, it
has been ascertained that the excised stomach, if kept under proper
conditions of moisture and temperature, may be made to contract
upon local stimulation, and may even show a spontaneous activity.
Under normal conditions, this peripheral sympathetic mechanism
is connected with the central nervous system by way of the two vagi
and splanchnic nerves. The former terminate in the vicinity of the
cardia in two ramifications which are known as the ventral and dorsal
gastric plexuses. From here fibers pass over to the left suprarenal
plexus of the splanchnic system, as well as to the neighboring region
of the lesser curvature. At the present time, however, no evidence
is at hand to show that these plexuses also send fibers directly to the
greater curvature or to the region of the pylorus. The latter seem to
derive their innervation from the celiac ganglion of the solar plexus
by way of the celiac and splenic plexuses.
It can no longer be doubted that the vagi nerves embrace musculo-
motor nerves for this organ. This is proved by the fact that their
stimulation above the diaphragm evokes well marked contractions
which involve chiefly its pyloric segment and possess all the charac-
teristics of regular peristaltic waves. While it is commonly stated
that the splanchnic nerves exert an inhibitory influence upon the
movements of this organ, it cannot be said that this view possesses a
satisfactory experimental basis. Inasmuch as these nerves contain
powerful vasoconstrictors, the relaxing effect sometimes observed
upon their stimulation, may in reality be caused by a diminution in
the gastric blood-supply.^ Since the musculo-motor function of the
vagi nerves has been well established, it may be said that their nuclei,
1 Burton-Opitz, Pfliiger's Archiv, xxxv, 1910, 205.
THE MECHANICS OF DIGESTION 1013
in conjunction with some additional ganglion cells, form a center which
regulates the activity of the intragastric reflex mechanism. This
medullary center is connected with different afferent channels through
which sensory impulses are enabled to reach it. They are here con-
verted into motor impulses and relayed to the intragastric plexuses.
Thus, Wertheimer^ has shown that the stimulation of the central end
of the sciatic nerve gives rise to a reflex inhibition of the gastric move-
ments. Accelleratory and inhibitory effects may also be produced
by psychic influences, such as dehght, anxiety, anger and fright.
C. THE MOVEMENTS OF THE INTESTINES
The Movements of the Small Intestine. — Since the entrance of air
into the abdominal cavity, the evaporation of the serous fluid and
the lowering of the temperature generally induce a refractory state
in this organ, various precautions must be taken in order to avoid
this motor disturbance. Thus, it has been advocated to insert an oval
piece of glass or mica in the incision in the abdominal wall, or to open
the peritoneal cavity in a bath of warmed saline solution. In rabbits
it is possible to thin the abdominal wall in such a degree that the ab-
dominal organs may be inspected without actually opening this cavity.
These methods have been supplemented at an early date by graphic
procedures, consisting in fastening a soft rubber bulb to the surfacie of
the abdomen or in inserting it directly into the intestinal canal. Air
transmission being employed in both these cases, the recording tambour
accurately registers the displacements of the air from the bulb.
Another means which is now extensively used, is the fluoroscope which
allows us to follow the food in its course through the aUmentary canal
by virtue of the fact that subnitrate of bismuth when mixed with
the ingesta, does not allow the Rontgen rays to pass. Lastly, it is
possible to study excised segments of intestine under proper conditions
of moisture and temperature. They may then be connected with
recording levers and pneumographs. A special piece of apparatus of
this kind is the enterograph.
The arrangement of the musculature of the small intestine is
simple; an outer, relatively thin coat of horizontal muscle fibers Hes
in relation with an inner circular coat. It should be noted, however,
that the structure of its different segments is not absolutely uniform,
but shows certain variations with regard to the thickness of the
muscle tissue. Thus, it will be found that the jejunum is large in
caliber and very muscular, while the ileum is narrow and possesses
much thinner walls. Similar differences are encountered in the dif-
ferent segments of the duodenum.
The movements occurring in the intestine, consist of peristaltic
and pendular motions. Obviously, the contraction of the circular
^ Arch, de physiol., norm, et path., 1892, also, Doyon, ibid., 1895.
1014 DIGESTION
fibers must constrict its lumen, whereas the contraction of the longi-
tudinal fibers must render that particular segment more bulky and
enlarge its capacity. Ordinarily, however, these two movements are
combined into what is known as the peristaltic wave, which consists of
a zone of constriction and an anteceding zone of relaxation. These
peristaltic waves may proceed either from above downward or from
below upward. The former constitute the regular peristaltic waves
and the latter, the antiperistaltic waves. We shall see later that anti-
peristalsis is the chief movement of the beginning portion of the large
intestine, while regular peristalsis is the principal movement of the
small intestine. Antiperistalsis is observed here only under abnormal
conditions. A second type of movement executed usually by the small
intestine, is the so-called pendular motion. It consists of alternate
constrictions and relaxations of neighboring segments of the gut, which
are repeated with a definite regularity or rhythm.
Fig. 515. — Diagram to Show the Effect of the Rhythmical Constricting Move-
ments OF the Small Intestine upon the Contained Food.
A string of food (1) is divided suddenly into a series of segments (2); each of the
latter is again divided and the process is repeated a number of times (3 and 4) . Even-
tually a peristaltic wave sweeps these segments forward a certain distance and gathers
them again into a long string , as in (1). The process of segmentation is then repeated
as described above. (Cannon.)
When the chyme is ejected into the duodenum, it is forced against
the upper surfaces of the valvulae conniventes which stretch across the
lumen of the sub pyloric canal in the form of incomplete transverse
partitions. In consequence of this initial impediment to its rapid
onward flow, the chyme is collected in a single mass well above the
orifices of the bihary and pancreatic ducts. Now begins its subdivision
into smaller portions by the pendular or rhythmic movements. A
comprehensive study of these has been made by Griitzner^ who was
able to analyze them by mixing insoluble substances, such as nitrate
of bismuth, with the ingesta. More recently, Cannon^ has studied
them with the help of the Rontgen rays. Constrictions appear here
and there which spHt the formerly large mass into numerous smaller
ones. Moreover, these constrictions appear in a perfectly regular order
so that the original mass is divided first into two, then into four, then
into eight, and more. These smaller portions are then reunited into
1 Pfiiiger's Archiv, Ixxi, 1898.
2 Am. Jour, of Physiol., i, 1898, and vi, 1902.
THE MECHANICS OF DIGESTION 1015
larger ones. This rhythmic play continues for some time at the rate
of 20 to 30 in a minute (cat) until the chyme has been thoroughly mixed
with the intestinal secretions, ^ and naturally, the cessation of these
alternate constrictions and' relaxations must leave the now rather
liquid material again reunited into a single mass. A regular peristaltic
wave then sweeps it onward into a lower segment of the small intestine,
where the pendular movements are repeated with the same result.
While this mechanical and chemical reduction of the food is continued
far into the ileum, the material already reduced is absorbed; in fact,
absorption begins very soon after the entrance of the chyme into the
duodenum and reaches its height in the jejunum and upper ileum. In
the lower ileum, on the other hand, most of the assimilable material
has already been removed, but naturally, much depends upon the
character of the ingesta, and the tonicity of the intestinal musculature.
It should also be noted that the peristalsis and pendular motion
undoubtedly facilitate absorption in a mechanical way, because they
tend to increase the flow of the lymph and blood. Secondly, they tend
to bring the individual villi into a more intimate relation with the
intestinal contents. As far as the regular peristaltic wave is concerned,
it should be mentioned that it occurs in two forms, namely, as a slowly
advancing contraction (2 to 3 cm. per sec.) which again disappears at
a distance of about 5 cm. from its place of origin, and as a more rapid
contraction which may cover a distance of 10 to 15 cm. and more.
The former, therefore, remains more localized and serves to disseminate
the material so that it may be acted upon later on by the pendular
motions. The latter, on the other hand, serves to remove the com-
pletely digested material into more distant segments situated nearer
the ileocecal valve. No definite statements can be made regarding the
degree of pressure which may be developed by these waves, but since
the fecal material is in a liquid state, it may be surmised that the energy
required to move it is very slight. This deduction is upheld by the
experiments of Cash^ which show that a weight of 5 to 8 gm. applied
to the surface of the intestines, sufB.ces to block the progress of the
feces.
Antiperistaltic movements occur in the small intestine only under
abnormal conditions, such as may arise in consequence of obstructions
by foreign bodies and tumors, or as a result of an invagination or
kinking of the entire gut. If the lesion is a high one, the fecal mate-
rial is often forced into the stomach, whence it is expelled by the proc-
ess of vomiting.
The Nervous Control of the Intestinal Movements. — While these
peristaltic movements may be evoked almost anywhere along the intes-
tine, they begin as a rule high up in the duodenum, and hence, it would
not be incorrect to speak of a *' pace-maker" of peristalsis. In all
these instances, the stimulations are local in their character and may
1 Magnus, Pfliiger's Archiv, cxi, 1906, 152.
2 Proc. R. Soc, London, 1887.
1016 DIGESTION
be brought to bear either upon the muscle tissue or upon the nervous
tissue. The early experiments of Bayliss and Starling^ have led
strength to the first view, which is embodied in the so-called myogenic
theory of the origin of peristalsis, because it could be shown that the
application of nicotine does not destroy these movements. The
experiments of Cohnheim^ and Magnus,^ on the other hand, favor the
neurogenic theory, which holds that the nervous tissue is the recipient
element. Thus, it was found that isolated segments exhibited these
movements even after the removal of their mucosa and submucosa,
and that the separation of the inner and outer coats of muscle tissue
destroyed them only in that layer which was disconnected from the
plexus of Auerbach. In addition, Yanase^ has shown that the intes-
tines of the embryo rabbit and human fetus do not begin to move
until the aforesaid nervous elements have made their appearance.
While this controversy seems to favor the neurogenic theory, it
may be best to confine ourselves for the present to the statement that
the peristaltic movements result in consequence of the stimulation of
the intestine by the fecal material and that they may arise in any one
of its different segments. The result is a diphasic wave, consisting of a
zone of constriction which is anteceded by a zone or relaxation. Con-
sequently, the peristaltic movement represents a true reflex response
which is made possible by the coordinated action of the local nervous
mechanism. The latter may in turn be influenced by afferent impulses
arising in other parts of the body, because it is a matter of common
experience that emotions or sensory impressions of different kinds
may inhibit or accelerate the activity of the intestinal musculature.
These impulses, in all probability, descend through the vagus system
and terminate in the mesenteric ganglion of the solar plexus, whence
they are relayed to the intra-intestinal mechanism by way of the mes-
enteric plexus. Regarding the latter, it has been proved by Burton-
Opitz^ that it contains efferent as well as afferent fibers for the
intestine. The fact that the vagus nerve constitutes the preganglionic
path of these musculomotor impulses seems definitely proved, because
its stimulation evokes strong contractions of the intestine. The claim
that the splanchnic nerve is the musculo-inhibitor nerve of the intes-
tine, need not be discussed at length, because it lacks a satisfactory
experimental basis. As has been stated above, the flaccidity of parts
ensuing in consequence of the stimulation of this nerve, may be due to
its vasoconstrictor action and the anemia resulting therefrom. To
summarize : (a) the intestine is in possession of a local nervous mech-
anism which renders it relatively independent of the central nervous
system, (6) systemic reflexes are made possible by the communications
1 Jour, of Physiol., xxvi, 1901, 125.
2 Zeitschr. fiir Biol., xxxii, 1899.
3 Ergebn. der Physiol., 1908.
4 Pfluger's Archiv, cxix, 1907, 451.
6 Ibid., cxxxv, 1910, 245.
THE MECHANICS OF DIGESTION
1017
existing between this sympathetic ramification and cetitral parts by
way of the mesenteric ganghon of the solar plexus and the vagi nerves,
and (c) the successive segments of the intestine are enabled to act in
unison, because the plexus 'of Meissner and Auerbach is arranged in
the form of successive reflex circuits which are correlated with one
another.
The last contention is based upon the experimental evidence that
peristaltic waves may be incited almost anywhere along the intestine
which then progress in a downward direction through its successive seg-
ments. Additional light has been thrown upon this question by Mall
who has resected and reversed certain segments of the small intestine so
that their formerly lower ends became their upper. At autopsy, these
animals invariably exhibited a fusiform distention of the intestine above
the line of the upper suture and an accumulation of fecal material
which in many cases had resulted in necrosis, perforation, and peri-
tonitis. It is evident, therefore, that this in-
version of an intestinal loop causes the regular
peristalsis to cease at the upper line of
sutures. Moreover, if an oval ball of wood
is inserted into the upper end of one of these
inverted segments, it is again expelled
through the same opening, whereas its inser-
tion through the lower orifice gives rise to a
peristaltic wave which moves it in the direc-
tion of the stomach. The question of
whether the intestinal movements of man
can at all be compared with those of other
animals, may be answered in the positive;
in fact, Carvallo, as well as Ktipferli^ state
that they are identical.
The Movements of the Large Intestine.
— The function of the large intestine is so
widely different from that of the small intes-
tine that these two parts may almost be
considered as separate organs. In the car-
nivora the process of digestion and absorption is practically completed at
the ileocecal valve, while in the herbivora these processes continue
in all their intensity distally to this point. The omnivora occupy an
intermediate position, but since the human large intestine is relatively
long and possesses a capacious cecal vestibule and peculiarly indented
colon, it more nearly resembles that of the herbivorous animals.
The ileocecal valve is a sphincter formed of a heavy band of muscle
tissue and two membranous flaps which are unequal in size and do not
close firmly. The fact that the contents of the cecum may be forced
back into the ileum with great ease, shows that it does not form a very
efficient sphincter. At the same time, it must be admitted that it
1 Zeitschr. ftir Rontgenkunde, xiv, 1912.
Fig. 516. — Diagram to
Show the Position of the
Ileocecal Valve.
J, Ileum; C, cecum; A,
orifice of the proc. vermi-
formis; AC, ascending colon;
H, haustrum.
1018 DIGESTION
impedes the progress of the contents of the ileum sufficiently, so that
the latter can advance into the cecum only in larger masses and under
a slight increase in pressure effected by the periodic peristaltic move-
ments of the ileum.
The large intestine may be divided into four parts, namely, the
cecum with its vermiform appendix, and the ascending (proximal),
transverse (intermediate), and descending (distal) portions of the
colon. The movements observed here are very similar to those pre-
viously noted in the upper gut, i.e., they consist of peristaltic and pen-
dular motions. It is to be emphasized, however, that the latter are
now of little importance, whereas the antiperistaltic movements are
even more prominent than the peristaltic.^ It is also obvious that
the large intestine is much more quiescent than the small intestine, a
Fig. 517. — Shadows of the Human Large Intestine Obtained by Means of the
RONTGEN Rays.
I, Entrance of the contents of the ileum into the cecum and colon. II, the material
has progressed through the transverse colon as far as the splenic flexure, some has
escaped into rectum. Ill, the large intestine outlined by means of a solution of sub-
nitrate of bismuth injected through the rectum.
fact which is in perfect agreement with the time required by the food
to traverse this channel. To illustrate, while the human stomach and
small intestine which measure about 7 m. in length, retain the food for
only about 7 to 9 hours, the large intestine which is only 1.5 m. in
length, cannot be passed in a much briefer time than 20 hours. Con-
sequently, the passage of the food from the mouth to the anus occu-
pies in all from 25 to 30 hours. An active alimentary canal, therefore,
would evacuate its contents once in about every 24 hours.
On entering the ascending colon, the chyme incites antiperistaltic
waves which force it into the cecum. A regular peristaltic wave
then moves it upward toward the hepatic flexure, whence it is again
thrown back into the cecum by the antiperistalsis. These back and
forth movements continue for some time until the contents have lost
most of their water and gradually escape in a semisolid state into the
transverse colon. It is to be noted especially that these antiperistaltic
motions do not oppose the regular waves, but alternate with them and
1 Jacobi, Archiv fiir exp. Path, und Pharm., xxvii, 1890.
THE MECHANICS OF DIGESTION 1019
give rise to a harmonious back and forth motion of the feces. Further-
more, since the proximal colon is subdivided into successive recesses
by incomplete transverse partitions, a whirlpool effect is produced
which carries the contents from haustrum to haustrum. It is for this
reason that the movements in the proximal colon and cecum are often
designated as haustral churning.
Gradually as the water is absorbed, the fecal material assumes
a more solid consistency and escapes into the transverse colon, whereas
its more fluid portion is forced back into the cecum. Eventually,
however, all of it is lodged in the transverse colon and is held here
until forced into the rectum by long and forceful peristaltic waves.
This segment, therefore, plays the part of a storehouse and hence, it
cannot surprise us to find that any retardation of the feces must
result in a loss of an excessive quantity of water and a firm lodgment
of these masses in the haustrse. Its gradually increasing weight then
gives rise to a sagging which causes the hepatic flexure to assume a
much lower level than the splenic flexure. This condition is not at
all uncommon and is responsible for the peculiar outline of this part
of the intestine when observed with the Rontgen rays. It then dis-
plays the contours of a snake when assuming the position of striking.
The descending colon and rectum are usually empty and are filled only
a short time before the beginning of the act of defecation.^ This
filling of the rectum is accomplished by two or three powerful long
peristaltic waves which begin in the transverse colon and slowly trav-
erse the descending colon, forcing the feces into the rectal receptacle.
They are usually accompanied by noises which have been designated by
Kussmaul as the ''tormina intestinorum.'' In accordance with Scharz, ^
it may be concluded that these waves are the direct cause of defecation,
because they force a certain amount of fecal material into the rectum
which then serves as the initial stimulus to the receptors initiating this
process.
Cannon^ divides the large intestine into two parts, the first of
which includes the very active cecum and ascending colon and the
second, the relatively inactive transverse and descending colons.
This line of demarcation transects it distally to the hepatic flexure.
Furthermore, Elliott and Barclay-Smith^ have shown that the intense
antiperistaltic movements of the upper large intestine are present in
a great variety of animals, and are especially prominent in the her-
bivora in which the cecum plays the part of a large thin-waUed
reservoir for the food while undergoing bacterial decomposition.
Defecation. — The distal portion of the colon leads into the sigmoid
flexure and rectum. Under normal conditions, the latter receives
1 Roith, Anat. Hefte, 1902, and Reider, Fortschr. auf dem Geb. der Rontgen-
strahlen, 1912.
2 Munchener med. Wochenschr., 1911.
3 Am. Jour, of Physiol., xxix,.1911, 238.
* Jour, of Physiol., xxxi, 1904, 272.
1020
DIGESTION
fecal material very shortly after arising, because the food which has
found lodgment in the transverse colon during the preceding night,
is then aided by gravity and a renewed irritability of the receptors
in exciting those long peristaltic waves which finally move it into the
vicinity of the anal orifice. The gradually increasing mass of rectal
contents finally stimulates the mucosa in a mechanical manner and
evokes those muscular responses which are required for its expulsion.
If the feeling of fulness experienced at this time, is neglected, the walls
of the rectum relax more fully, so that a much greater excitation will
be required to make them contract again. In man. Hertz ^ has shown
Sy/npafhr/i'c Trunk
G«inalioh itteseHlin cum uiferti
Branches to Colo
Fig. 518. — Schema to Show the Innervation of the Rectum and Internal Sphinc-
ter OF the Anus, and the Formation of the Hypogastric Plexus. {After Frankl-
Hochwart and Frohlich.)
that the intrarectal pressure may rise to 30 and 40 mm. Hg. before the
act of defecation is actually initiated.
While defecation is a reflex phenomenon, it also embraces a definite
voluntary factor. The former consists in peristaltic contractions of
the rectum and the inhibition of the internal sphincter, whereas the
latter comprises the relaxation of the external sphincter and the activa-
tion of the abdominal press. Under normal conditions, these refiexes
may be counteracted if necessary, by volition, but only until the sen-
sory stimuli become so powerful that they are able to overcome the
volitional efforts. The reflex center for defecation is situated in
the lumbar segment of the spinal cord, whence efferent and afferent
1 Guy's Hosp. Rep., 1907.
¥
I
THE MECHANICS OF DIGESTION 1021
nerve fibers pass to the musculature of the rectum and the internal and
external sphincters. By means of these channels, this center is
brought into functional relation with different local receptors which
may either augment or inhibit its activity. In the latter case, the
sphincters are relaxed. It is connected with the cerebrum by means
of different afferent and efferent paths, so that volition, emotions, and
various sensory impulses, may be brought to bear upon it.
The powerful band of smooth muscle tissue forming the internal
sphincter, receives its motor supply from the hypogastric plexus by way
of the nervus erigens, and its inhibitory supply from the same source
by way of hypogastric nerve. These nerves also embrace sensory
fibers from the same region, as well as sensory and motor fibers for
the rectum. When severed, the excitation of the central end of the
nervus erigens gives rise to an inhibitory effect which is made possible
with the help of the hypogastric nerve. Quite similarly, the stimula-
tion of the central end of the divided hypogastric nerve produces
motor results through the intervention of the nervus erigens.^ The
external sphincter is composed of striated muscle tissue and is inner-
vated by the nervi hemorrhoidals inferiores which are derived from
the nervus pudendus and sacral spinal nerves. This muscle acts in
unison with the levator ani and other perineal muscles, and aids in
restoring the everted mucous membrane of the anus after the completion
of defecation.
1 Frankl-Hochwart and Frohlich, Pfliiger's Archiv, Ixxxi, 1900, 420.
SECTION XXVII
ABSORPTION
CHAPTER LXXXV
THE ABSORPTION OF THE REDUCED FOODSTUFFS FROM
THE ALIMENTARY CANAL
General Discussion. — The term absorption refers more particu-
larly to the process by means of which the simplified foodstuffs are
transferred from the lumen of the alimentary canal into the absorbing
channels, i.e,, into the blood-capillaries or the lacteals. It is to be
remembered, however, that certain animals also take in materials
through their skin, and that absorption from the different body-cavi-
ties is a common phenomenon. If we confine ourselves at this time
to the foodstuffs, it is to be noted first of all that water, salts, and the
simple sugars are dialyzable without digestion, whereas others must
be changed so as to be able to pass through the intestinal epithelium.
This brings in a definite element of time; digestion and absorption
going on side by side, because certain substances begin to pass into the
body long before the chemical and mechanical reductions of all the
different foodstuffs have actually been completed. Moreover, while
some of the digested material may be taken up in the mouth, stomach,
and large intestine, by far the largest amount is absorbed in the small
intestine.
In endeavoring to obtain an idea regarding the factors concerned
in absorption, we find first of all that they are resident in a layer of
epithelial cells, which, physiologically considered, really form a part
of the external envelope of the body. Through these the simplified
foodstuffs must pass in order to gain access to the fluids of the body.
Until not so many years ago it was believed that the forces by means of
which this transfer is effected, consist of filtration, diffusion, and
osmosis. In the course of time, however, it has become evident that
many of these phenomena cannot be explained upon this basis
and hence, physiologists finally took recourse to a purely vitalistic
hypothesis. As emphasized repeatedly on previous occasions, it is for
us to accept an intermediate view which not only acknowledges the
above physical principles, but also recognizes the occurrence of certain
intracellular processes, regarding which our knowledge is as yet ex-
1022
THE ABSORPTION OF THE REDUCED FOODSTUFFS
1023
tremely imperfect. The latter consist in microphysical and micro-
chemical reactions and not in phenomena which might more rightly
find a place in metaphysics. While the work in molecular physics,
such as that of DeVries, Van't Hoff and Fischer, has gone f9,r to clear
up the nature of these processes, it must be admitted that our explana-
tions are still based upon generalities.
Diffusion, Osmosis, Dialysis. — The term diffusion is applied to
the spreading about or scattering of molecules through media allowing
this movement. Thus, if a solution of a salt is placed in a receptacle
and a layer of water is carefully allowed to run over it, it will be found
after a time that a certain number of the mole-
cules of the salt have entered the overlying
water and have established a medium of uniform
composition throughout. This spreading out
also takes place if two solutions of different
salts are brought into contact with one another.
A uniform mixture is the final result. Next we
proceed to interpose between the solution and
the water an animal membrane, such as a
piece of intestine, urinary bladder, swim-
bladder, or an artificial membrane made by
allowing ferrocyanide of potassium to come in
contact with cupric sulphate in an unglazed
piece of porcelain. The result of this interac-
tion is a layer of ferrocyanide of copper.^ Such
membranes may be absolutely impermeable,
completely permeable, or partially permeable
to water and its constituents. The first allows
no diffusion at all, whereas the second permits
it to occur freely in both directions. This
narrows this discussion down to membranes of
semi-permeable character, namely, to those
Fig. 519. — A Simple
Osmometer.
The receptacle contains
water, and the cell a solu-
,.,,, „ -.1 £ xrii tion of magnesium sul-
which allow a free mtercnange ot water but not phate. As the molecules
of the dissolved substances. Consequently, if of water are drawn through
the water and the salt solution are separated SLet'^ih'e'Tvei^^of'^'the
by a membrane of this kind, the molecules of Mgs64 solution rises.
water will gradually pass through its pores into
the solution. This phenomenon is called osmosis. Quite similarly,
we may fill a thistle tube with a solution of magnesium sulphate,
close its large orifice with an animal membrane, and place it in water
so that the level of the latter corresponds precisely with that of the
said solution. Water then passes into the thistle tube, causing the
level of the magnesium sulphate solution to rise until its height indicates
a considerable back pressure against the membrane. This pressure
1 Morse and Frazer, Am. Chem. Jour., xxxiv, 1905, 1, also Hedin, Pfliiger's
Archiv, Ixxviii, 1899, 205, Hober, ibid., Ixxi, 1898, 624, and Denis, Am. Jour, of
Physiol., xvii, 1906, 35.
1024
ABSORPTION
which is known as the osmotic pressure, is responsible for the passage
C'puUing") of the molecules of water through the pores of the mem-
brane. In general, it may be said that the osmotic pressure of a solu-
tion is proportional to its molecular concentration, i.e., to the number
of molecules of the dissolved substance in a given volume of the solu-
tion. This fact implies that it differs with the character of the solu-
tions employed. Its force, however, is considerable at all times.
Thus, it has been determined that a 1.0 per cent, solution of cane-
sugar at 0°C. exerts a pressure of 493 mm. Hg. Regarding its origin
little is known, but it is commonly believed that it is due to the
Fig. 520. — Dialyser, Consisting of a Tube of Parchment Paper Immersed ina Ves-
sel THROUGH Which a Constant Stream of Sterile Distilled Water can be Passed.
{Wrobleski.)
kinetic energy of the moving molecules. The greater their attraction,
the greater this pressure.
While such simple arrangements as have just been described,
actually exist in our body, the most common interchanges take place
between crystalloids and colloids. The process of transferring these
substances through an animal membrane interposed between the
solution containing them and the water, is known as dialysis. In
this case, the crystalloids traverse the membrane and enter the water,
while the colloids do not. But since the membranes in our body are
only approximately semi-permeable, they allow water to go through
THE ABSORPTION OF THE REDUCED FOODSTUFFS 1025
with ease and besides, also the substances in solution. The latter, how-
ever, pass with much greater difficulty. For this reason, the osmotic
flow of water to the side of the crystalloid is associated with a passage
of the molecules of the latter into the water on the other side of the
membrane. These counter streams eventually lead to an equalization
of the concentration of the fluids on the two sides of the membrane,
as well as to an equalization of the osmotic pressure and a cessation of
the osmosis. Only diffusion then continues in both directions.
The osmotic pressure of a solution may be calculated by ascertain-
ing the amount of the substance present in it and the degree of the
dissociation of its electrolytes. A much simpler method is to deter-
mine its freezing point, because the freezing point of water is lowered
by substances held in solution, and the degree of lowering is propor-
tional to the molecules and ions present in it. A comparison of the
osmotic pressures of different solutions may be made by noting their
influence upon certain vegetable and animal cells. ^ Thus, if erythro-
cytes are brought in contact with the solution to be tested, they either
swell, or shrink, or remain normal. Inasmuch as these cells are ordi-
narily contained in blood plasma, this medium must be isotonic to
them, i.e., it must possess the same osmotic pressure as the red cor-
puscles. No osmotic interchanges then take place. It may, therefore,
be reasoned that any solution in which they retain their normal size
and shape, is isosmotic or isotonic to them as well as to the blood
plasma, A hyperosmotic or hypertonic solution is one possessing
a greater osmotic pressure, and a hyposmotic or hypotonic solution, one
possessing a slighter osmotic pressure than these cells or the blood-
serum. In the first instance, these cells will lose water and shrink
and in the latter, acquire water and swell up.^
Electroljrtes. — The law of osmosis as previously stated, is prac-
tically identical with the law of Boyle pertaining to the diffusion of
gases. The latter states that the pressure of a gas is proportional to
its density, i.e., to the number of the molecules in a given volume of
the gas. Like the osmotic pressure, the gaseous pressure remains pro-
portional to the absolute temperature and the sum of the partial
pressures of the constituents of the mixture. A slight discrepancy be-
tween gas pressure and osmotic pressure, however, is produced by
the fact that the molecules of many substances, when in solution, are
dissociated into two or more parts which are designated as ions. These
ions are charged electrically and may be made to arrange themselves
in accordance with their potential by passing an electrical current
through the solution. Thus, it will be found that sodium chlorid
gives rise to Na ions and CI ions, the former being positive and the
latter negative. If an electrical current is now passed in a definite
direction through this solution, these ions migrate until a perfect
^ McClendon, Physical Chemistry and Vital Phenomena, 1917, and Bayliss,
Principles of Gen. Physiology, 1915.
2 Overton, Nagel's Handb. der Physiologic, 1907.
65
1026 ABSORPTION
electrical series has been established by the alternate position of plus
and minus elements. Water, on the other hand, is not easily dissoci-
ated and hence, cannot serve as a good conductor of electricity. The
same is true of sugar. Upon these differences is based the division
of substances into electrolytes and non-electrolytes. Now, since an
ion plays the same part in the production of osmotic pressure as a
molecule, it will be seen that a solution of an electrolyte must exert
a proportionally greater osmotic pressure, because it contains a greater
number of particles consisting, on the one hand, of molecules and, on
the other, of ions.
The Diffusion of the Proteins. — Conditions in our body are
complicated still further by the fact that its different fluids do not
contain solely crystalloids, but also other substances, such as proteins.
The latter are practically indiffusible through animal membranes,
although most of them are soluble in water, weak salt solutions, and
dilute acids and alkalies. Moreover, they form compounds with
metallic salts, acids or alkalies and, when in solution or pseudo-solution,
can be converted into an insoluble form by various simple means,
such as changes in the reaction and temperature, shaking, and the
addition of neutral salts. By reason of their indiffusibility, they may
be separated from the diffusible crystalloid substances by dialyzers,
such as vegetable parchment. This separation, however, cannot be
accomplished without difficulty.
Considerable progress has been made in this direction more recently by the
work of J. Loeb.i It has been shown that while non-ionized gelatin may exist in
gelatin solutions on both sides of the isoelectric point (which equals an hydrogen
ion concentration of CH = 2.10"^ or pH = 4.7), gelatin when it ionizes, can only
exist as an anion on the less acid side of its isoelectric point (pPH>4.7) and as a
cation only on the more acid side of its isoelectric point (pH>4.7). At the iso-
electric point gelatin can dissociate practically neither as anion nor cation.
On the acid side of the isoelectric point amphoteric electrolytes can only com-
bine with the anions of neutral salts, on the less acid side of their isoelectric point
with cations; and at the isoelectric point neither with the anion nor cation of a
neutrat salt. It has also been shown that the isoelectric point of an amphoteric
electrolyte is not only a point where the physical properties of an ampholyte ex-
perience a sharp drop and become a minimum, but that it is also a turning point
for the mode of chemical reactions of the ampholyte. It is suggested by Loeb
that this chemical influence of the isoelectric point upon life phenomena over-
shadows its physical influence.
Surface-tension. — Another factor which no doubt plays a part
in absorption is surface-tension. Its action may be illustrated by
placing a drop of water upon an oily surface or by suspending a globule
of oil in a fluid with which it does not readily mix. In either case,
there is a tendency on the part of the drop to assume a spherical out-
line. This is brought about by the fact that its surface-layer is under
a certain tension which tends to give to the whole as small a surface as
possible, and naturally, the force here at work is cohesion, i.e., a
mutual attraction between its constituent molecules. Supposing
that we single out a molecule in its interior, it will be found that this
1 Jour, of Gen. Physiol., i, 1918, 39.
THE ABSORPTION OF THE REDUCED FOODSTUFFS 1027
unit is acted upon from all sides by the neighboring molecules, and that
this action is equal in all four directions. At the surface, on the other
hand, conditions are different, because here the molecules are not
counterbalanced by a tension resting upon their external surfaces.
Hence, they are pulled inward. Now, it will be seen that if the drop is
surrounded by some fluid, its surface-molecules must be acted upon by
the molecules of the medium, depending, of course, upon the nature of
the latter. Obviously, this now uneven balance must give a different
shape to the drop as a whole. The surface-tension may also be
altered by changes in temperature, because heat tends to separate
the different molecules from one another and to counteract their
power of attraction. Cold, on the other hand, increases the surface-
tension, because it brings the molecules closer together by removing
from them the kinetic energy necessary for expansion. A third means
by which the surface-tension may be altered, is the electrical current.^
Adsorption. — The phenomenon of adsorption may be illustrated
by exposing a solid substance in powdered form to a solution of some
kind. The dissolved substance then accumulates upon the surfaces
of the sohd particles and leaves the solution, thereby lessening the
concentration of the latter. This property is well displayed by the
colloids to which the proteins, with the exception of the peptones, be-
long. Consequently, since our body contains very extensive surfaces
which lie in relation, on the one hand, with the body-fluids and, on
the other, with nutritive material, most favorable conditions are
estabUshed for the occurrence of this phenomenon.^
A, ABSORPTION FROM THE INTESTINAL CANAL
The Absorption of Water. — Water and the ordinary soluble salts
are absorbed unchanged, but the quantity which actually finds its
way into the body, depends upon the intake and how greatly the
system is in need of it. Since water is lost constantly, because it
serves as a medium for our secretions and excretions, correspondingly
large quantities of it must be consumed in order to make up for this
loss. In a way, therefore, it may be said that the body is in water-
equilibrium, and it makes little difference whether a man takes in one
liter or six, because any superfluity is soon compensated for by a
greater discharge, chiefly through the kidneys. Quite similarly, any
scarcity is equaUzed by a corresponding reduction in the quantity of
the secretions and excretions. In the latter case, however, a physio-
logical limit is soon reached, at which the phenomenon of tissue-thirst
arises as a means of safety. The body also possesses the power of
guarding itself against too large an intake, because unusually large
1 Macallum, Ergebn. der Physiol., xi, 1911, 598; also: Traube, Pfliiger's Archiv,
cv, 1904, 559.
^Hofmann, Zentralbl. fiir Physiol., xxiv, 1910, 805; Robertson, Jour. Biol.
Chem., iv, 1908, 35; and Van Slyke, ibid., iv, 1908, 259.
1028 ABSORPTION
quantities of water give rise to mechanical reflexes, nausea, irritations
of the gastric and intestinal mucosa, and certain symptoms associated
with hydremic plethora.
One of the reasons for the relative ease with which the system may
be surcharged with water is that the alimentary surface is not suffi-
ciently resistant to counteract and to prevent osmosis. Moreover,
while the excessive intake of water may eventually cause the feces
in the large intestine to become watery, this channel offers a certain
resistance to its escape which it avoids by passing through the epithe-
lium. At least, this is the tendency in most persons. Thus, it is a matter
of common experience that constipation is usually associated with a
disinclination to take much water, and as much as 3 to 5 liters may be
absorbed, before the feces actually assume a fluid consistency. The
absorption of water is most intense in the small intestine, but some of
it also passes over into the cecum, because in this segment the fluid
ileac contents are gradually changed into the semi-solid feces. Under
normal conditions the stomach does not allow an appreciable quantity
of water to pass through, although slight amounts of peptones, sugar,
and certain drugs may be absorbed from its cavity. ^ It is for this
reason that stenosis of the pylorus and dilatation of the stomach are
usually accompanied by tissue-thirst, which cannot be relieved by
drinking. As -far as the channel of absorption is concerned, it has
been observed that the introduction of salt solutions into the small
intestine does not increase the flow of lymph from the thoracic duct,
whereas large quantities of water frequently bring about a dilution
of the portal blood. It is probable, therefore, that these foodstuffs
pass directly into the blood-stream and not into the lacteals and lym-
phatic system.
The osmotic interchanges between the intestinal contents and the
blood, may be illustrated in the following manner. A section of the
small intestine of an etherized mammal is drawn through a wound in
the abdominal wall. Two loops of equal size are then marked off
by three ligatures. Into one of these a quantity of normal saline
solution is injected which thoroughly distends its walls. Into the
other, a few drops of a concentrated solution of magnesium sulphate
are injected. Having replaced these loops in their proper place in
the abdominal cavity, the animal is allowed to rest for about one hour.
At the end of this time, it will be found that the loop containing the
saline solution, is now practically empty, while the formerly perfectly
flabby loop containing the magnesium sulphate, is highly distended.
This experiment clearly shows that the saline solution acts as a hypo-
tonic solution, and the magnesium sulphate solution as a hypertonic
solution. In the former case, water is removed from the intestinal
canal, and in the latter, from the blood. This is the picture of saline
catharsis, because the introduction of such solutions as citrate of mag-
1 Moritz, Zeitschr. fur Biol., xlii, 1901, 565.
THE ABSORPTION OF THE REDUCED FOODSTUFFS 1029
nesium, epsom salt, and others, causes large quantities of water to be
poured into the intestinal canal which eventually excite peristalsis.
Other cathartics, such as cascara sagrada, act by stimulating the peris-
talsis without rendering the- feces especially watery, and still others,
such as the inert oils, by lubricating the intestinal surfaces as well as
the feces.
While the experiment just described, lays special emphasis upon
osmosis, it may be shown that this factor is by no means the only
one concerned in absorption. Thus, it will be remembered that the
villi of the small intestine are supplied with capillaries in which the
pressure cannot be less than 30 or 40 mm. Hg. Evidently, absorption
takes place against this pressure. It has also been shown that if a
certain quantity of the animal's own blood-serum is introduced into
the intestine, its water and salts will be absorbed, while its proteins
are left behind. Some time later, however, all of this serum is taken
up and this in spite of the fact that the fluids on the two sides of the
intestinal epithelium are practically identical. These and other
experiments that might still be mentioned, prove very conclusively
that the lining cells of the intestine are able to intervene in this process
by virtue of certain forces which originate during their metabolism.
This implies that the different substances do not simply pass through
the pores in this membrane, but actually interact with the solvent as
well as with the cytoplasm of these cells.
The Absorption of the Carbohydrates. — Since only the mono-
saccharides are readily dialyzable, the polysaccharides must first be
converted into their simplest form. We have seen that this process
involves a constant hydrolysis which is effected by the enzymes
mentioned previously. In the intestine, therefore, we have such
substances as dextrose, levulose or fructose, and galactose.,
The first is present in largest amounts and is easily diffusible and
reduced by the tissue cells. Such disaccharides as cane-sugar, milk-
sugar, and maltose, are also soluble and diffusible, but cannot be con-
verted directly into glycogen, nor can they be fully utilized by the
tissue-cells. The small percentage of them actually made available
to the latter, has previously been acted upon by the maltase of which a
small amount is present in the body-fluids. The difference in the
diffusibility of these sugars is also shown by the fact that as small
an amount as 100 grm. of glucose when introduced into the intestine,
may give rise to glycosuria, while as much as 300 grm. of cane-sugar
may be ingested before the aforesaid symptom is produced. Lactose is
absorbed with even greater difficulty and hence, this sugar must pass
into the feces whenever lactase is present in insuflicient amounts.
The absorption of the simple sugars is effected chiefly in the small
intestine, and the chief channel of absorption is the portal vein and
not the lymphatic system.^
1 Munk, Archiv fiir Physiol., 1890, 376.
1030 iABSOBPTION
The Absorption of the Fats. — In the upper small intestine the fats
appear as glycerin and fatty acids, while in its lower segments
some of these fatty acids have been combined with alkalies to form
soaps. This implies that the neutral fat ingested is hydrolyzed by the
gastric, pancreatic and intestinal juices, the end-products of this
lipolysis being the substances just mentioned. We know that the
alkaline soaps are soluble in water, while those of calcium and mag-
nesium are soluble in bile. This is also true of the free fatty acids.
Herein really lies the importance of bile as an aid to pancreatic diges-
tion; i.e., while it does not dissolve neutral fat, it possesses a power-
ful solvent action upon fatty acids and soaps and even upon the
otherwise insoluble soaps. From this statement it may be gathered
that this secretion is a prerequisite of the normal absorption of fat,
because in its absence more than half of this foodstuff is lost to the
body and escapes into the feces. It cannot surprise us to find that
the accumulation of these masses of unutihzed fat also seriously in-
terferes with the digestion and absorption of the other foodstuffs.
Similar conditions result in the absence of the pancreatic juice, but
it seems that the loss of this secretion may be compensated for in a
large measure by the secretions still remaining as well as by the
activity of micro-organisms.^
In its journey through the epithelial cells this material is then
synthetized into neutral body-fat. The soaps are split, while the fatty
acids thus liberated, are united with glycerin to form neutral fat
under elimination of water. This fat is then diverted into the lacteals
of the different villi, whence it reaches the mesenteric lymphatics and
eventually the thoracic duct and venous circulation. It is true, how-
ever, that only about 60 per cent, of the 95 per cent, of the fat usually
absorbed, can be accounted for in this way, whereas the other 40 per
cent, must be transferred into the portal radicles directly or be burned
up during their passage through the intestinal epithelium. In support
of the former view might be mentioned the fact that from 32 to 48 per
cent, of the fat enters the system in spite of the ligation of the thoracic
duct. Obviously, this absorption can only take place through the
portal terminals. As far as the time is concerned during which this
transfer is accomplished, it might be stated that in the dog from 9 to
21 per cent, of the fat is absorbed within 3 to 4 hours, 21 to 46 per
cent, in 7 hours, and the remaining portion in 18 hours.
At the height of absorption even the distalmost Ijonphatics are
sharply outlined against the dark red background of the intestine
by their milky white contents. Even the blood presents an oily
appearance, owing to its admixture with chyle, and if a sample of this
blood is allowed to clot, the serum derived therefrom exhibits a white
color, and fat globules gradually collect upon its surface. This cannot
surprise us, because fat absorption is both abundant as well as rapid,
^Leathes, "The Fats," Monographs in Bioch., Longmans, Green & Co., 1912,
and Dakin, "Oxidations and Reductions in the Animal Body," ibid., 1912.
THE ABSORPTION OF THE REDUCED FOODSTUFFS
1031
as much as 12 grams of fat being absorbed by a dog of medium weight
in the course of one hour. Histologically, it is of interest to note that
the fat globules may be traced in their journey through the epithelial
lining by virtue of the power of the unsaturated fatty acids, to reduce
osmic acid. When stained in this way they appear as dark granules
of varying size within the cytoplasm of the different cells. It should
be remembered, however, that this stain does not furnish a means of
determining the actual amount of fat present within these cells, be-
cause only the free fatty acids are rendered visible thereby. On leav-
ing these cells the fat globules enter the tributaries of the lacteals.^
There is no reason to believe that they are transported into these
channels by the leukocytes, as has
been supposed by Schafer and
others. The histological picture
just briefly described, has led many
observers to conclude that the fat
globules traverse the intestinal epi-
thelium in their original form.
This view constitutes the so-called
mechanistic theory of fat absorption.
As we have seen, the evidence now
at hand shows that the fat is broken
down and is reconstructed into
neutral fat before it leaves the lining
cells. This fact forms the basis of
the chemical theory of fat absorption.
The Absorption of the Proteins.
— The proteins of the food are re-
tained in the small intestine in the
form of peptones and their amino-
acid derivatives. The latter trav-
erse the intestinal epithelium and
are eventually converted into the
proteins of the body. We know this to be true, because amino-acids
may be isolated from the blood, and because animals may be kept in
nitrogen-equilibrium by feeding them with completely predigested
protein mixtures. It has also been observed that the introduction
of foreign proteins and even of peptones into the circulation, gives
rise to severe symptoms and may even result in the death of the
animal. In other words, the direct introduction into the blood-stream
of substances which are otherwise chemically indistinguishable from
the digested proteins is usually followed by the development of anaphy-
lactic reactions. These same substances given by mouth, are per-
fectly harmless. It appears, therefore, that the proteins cannot be
absorbed as such from the intestine, but must first be reduced into
1 Whitehead, Am. Jour, of Physiol., xxv, 1910, 28, and Mendel, ihid., xxiv,
1909, 493.
Fig. 521. — Section through the
Lining Cells of the Intestine (Rat) at
Different Periods after the Ingestion
OF Fat.
1032 ABSORPTION
their amino-acids, from which the proteins of the body are then re-
constructed. It is also evident that these products of protein diges-
tion enter the portal radicles, because the composition of the lymph
obtained from the thoracic duct, is not appreciably altered during pro-
tein absorption. Moreover, it has been shown that the ligation of
this collecting channel does not interfere with the intake of proteins as
determined by the output of urea.^
These facts have led to the establishment of the hypothesis that
the amino-acids are reconstructed into the proteins of the blood while
they traverse the intestinal lining. But since this view is based upon
negative evidence, and is contradicted by the presence of amino-acids
in the blood, it cannot be retained in its original form. Instead, it
must be concluded that a true synthesis of the amino-acids by the
intestinal lining cells does not take place and that these bodies enter
the blood directly. From this medium they are then picked up by
the different cells either to replace the protein material which the latter
have lost, or to be excreted directly. ^ The acceptance of this view
makes it necessary for us to discard the assumption that the white
blood corpuscles play a part in the transfer of these bodies from the
lining cells into the blood-stream (Schafer). Consequently, it may be
concluded that the increase in the number of leukocytes after meals is
caused in all probability by changes in the circulation.
The difficulties encountered in endeavoring to prove the presence
of amino-acids in the blood, are dependent upon the fact that their
absorption is effected very slowly and that they are diluted after that
by large quantities of blood, and carried with greatest speed to the
tissues. Consequently, they do not remain in the blood for any
length of time, but are quickly acted upon by the tissue-cells; An
additional difficulty is presented by the fact that their chemical isola-
tion is seriously hampered by the presence in the blood of a large quan-
tity of coagulable proteins.
In accordance with the above view, the amino-acids must be re-
garded as mere building stones which may be brought together selec-
tively to form the body-proteins. This is also true of the amino-acids
constituting the proteins of the food, because the differences which they
show are really due to the manner in which their molecules are com-
bined. As soon as the protein material has been split by the ac-
tion of the successive proteolytic enzymes, their amino constituents arc
again united in the organism in accordance with the peculiar require-
ments of the tissue-cells. In this way, a large number of perfectly new
combinations may be produced. It must also be considered as an
established fact that the intestinal cells possess the power of splitting
the amino groups from those polypeptides which have been swept
into them. This deduction is based upon the fact that the intestinal
iFolin and Denig, Jour. Biol. Chem.,xi, 1912, 493.
2 Paton and Goodall, Jour, of Physiol., xxxiii, 1915, 20, also Burian and Schur,
Wiener, klin. Wochenschr., 1897.
THE ABSORPTION OF THE REDUCED FOODSTUFFS 1033
mucosa contains more ammonia than any other tissue, and that the
blood of the mesenteric veins contains from 6 to 10 times as much
ammonia as that of other veins.
In man practically all the proteins are taken in as insoluble com-
pounds, or are rendered so by the process of cooking. Their absorp-
tion, therefore, necessitates their first being brought into solution and
this end is attained by hydration and the action of the different pro-
teolytic enzymes. Certain evidence is also at hand to show that a
certain proportion of the protein may be absorbed before it has ac-
tually reached its final stage of cleavage. Thus, it has been mentioned
above that the proteins of blood-serum are eventually taken up; in
fact, Friedlander states that as much as 21 per cent, of white of egg
may be absorbed by washed small intestine in the course of three
hours. Syntonin and casein, on the other hand, are not absorbed.
Furthermore, patients fed per rectum with protein material, are capa-
ble of absorbing a considerable portion of it, although proteolytic
enzymes are not present in this segment of the intestine. It is also a
matter of common experience that certain persons may develop an idio-
syncrasy or anaphylaxis against the proteins of milk and white of egg,
which is due in all probability to the absorption of protein in its more
complex form. We are justified, however, in concluding that, under
perfectly normal conditions, the absorption of only partially reduced
protein is the exception.
Besides the increase in the number of the leukocjrtes, it has been
noted by Renter that the cells of the villi become swollen when protein
absorption is going on. Furthermore, their cytoplasm does not stain
deeply at this time, owing, in all probability, to the accumulation of
a hyaline coagulable material.
B. ABSORPTION FROM THE CAVITIES OF THE BODY
Absorption from the Peritoneal Cavity. — In the intestine, the body-
fluids are separated from the liquefied foodstuffs by a layer of colum-
nar epithelium which owing to its depth, is capable of influencing
diffusion in an active manner. The body-cavities, on the other hand,
are lined with only a thin sheet of endothelial cells, and hence, we
might expect in this case a preponderance of the physical forces.
While these functional differences no doubt exist, the fact still remains
that the endothelial cells are by no means perfectly passive entities.
We have really come to this conclusion on previous occasions, while
discussing the part played by the glomerulus in the formation of urine
and the function of the endothelium of the blood capillaries in the pro-
duction of lymph. As far as the lining of the pleural and peritoneal
cavities is concerned, it has been noted repeatedly that pleural and
ascitic effusions may be reabsorbed in the course of time, provided
the cause leading to these extravasations has ceased being active.
1034 ABSORPTION
This is also true of blood-serum and isotonic salt solutions when intro-
duced into these spaces.
In general, it may be said that the endothelium acts in the same man-
ner as other animal membranes. Thus, it has been shown by Roth^
that the introduction of hypotonic salt solutions into the peritoneal
cavity leads to a rapid absorption of its water until it has become isos-
motic with the blood. Eventually, all of the solution disappears from
this cavity. A hypertonic salt solution, on the other hand, first draws
water from the blood until an isosmotic condition has been established.
The fluid as a whole then begins to pass over into the system. It is
difficult to explain these phenomena unless we assume with Reckling-
hausen^ that the peritoneal cavity stands in direct communication
with the lymphatic system by means of minute defects or stomata
which are situated between the individual endothelial plates. Thus,
while the ordinary laws of diffusion would play the most important
part to begin with, the final escape of the fluid would occur through
these openings. This explanation has much in its favor and especi-
ally since this absorption is proportional to the pressure under which
the fluid is injected into the cavity. But inasmuch as the aforesaid
stomata have not been definitely recognized by histologists. Starling^
has supposed that the absorption from these cavities is dependent upon
the fact that the proteins of the blood are indiffusible and exert, there-
fore, a considerable osmotic pressure upon the neighboring salt solu-
tion. This explanation is strengthened by the fact that the absorbed
material enters the blood and not the lymph, because the ligation
of the thoracic duct does not impede this process. Obviously, this
subject is still in a decidedly theoretical state and we cannot do much
else at the present time than to consider it in the same light as the for-
mation of the lymph, ^.e., we must suppose, and rightly so, that the
purely physical factors of diffusion and osmosis are modified by the
metabolic activity of the endothelial cells.
Absorption Through the Skin. — It has been stated in one of the
preceding chapters that the skin excretes carbon dioxid, water, salts
and at times also urea.^ To what extent the skin may also be regarded
as an organ of absorption has not been definitely ascertained, although
it may be assumed that this function must differ in different animals.
Concerning the skin of man it has been established that it possesses
practically no absorbing power under ordinary conditions, whereas
that of the frogs and eels (not the fish) absorbs oxygen as well as water,
alcohol, and possibly also salts and other substances.^
1 Engelmann's Archiv., 1899.
2 Virchow's Archiv, xxvi, 72; also: Meltzer, Jour, of Physiol., xxii, 1898, 196.
3 Jour, of Physiol., xviii, 1895, 106.
4 Schierbeck, Archiv fiir Physiol., 1893, and Taylor, Jour. Biol. Chem., ix, 1911,
21.
5 Berg, Dissertation, Dorpat, 1868, Bohr. Skand. Archiv fiir Physiol., x, 1900,
88, and Maxwell, Am. Jour, of Physiol., xxxii, 1913, 286.
THE ABSORPTION OF THE REDUCED FOODSTUFFS 1035
C. THE FORMATION OF THE FECES ^
Character of the Feces. — ^The feces are alkaline in their reaction,
and contain the indigestible constituents of the food plus a very small
proportion of nutritive material which has escaped digestion, epithelial
cells, pigment, mucin, and countless bacteria. The products of bac-
terial decomposition, include indol and scatol to which their disagree-
able odor is due, and also certain gases, such as NH4, CO2, H, Nand
H2S. A small quantity of fecal material is also excreted during
periods of starvation, as well as from isolated loops of intestine. In the
latter case, however, it consists solely of desquamated epithelium,
intestinal juice, and bacteria; simulating, therefore, the meconium of
the new-born child which embraces solely concentrated bile and cast-
off epithelium. The character of the feces of a normal adult depends
in a large measure upon the type of the food ingested. They contain
elastic fibers, and the remnants of the connective tissues, spiral ves-
sels of plants, and vegetable residue in the form of cellulose. When
no vegetables have been ingested, about 65 to 75 per cent, of the feces
consist of water, while their dry residue contains about 7 per cent, of
nitrogenous material. Their non-nitrogenous portion is composed
of about 11 to 12 per cent, of ash and 12 to 18 per cent, of substances
soluble in ether, as well as of sterobilin and other bile residues. The
ethereal extract embraces fatty acids, cholesterol, a small amount
of lecithin, and neutral fat. The proteins consist of mucin and nucleo-
protein, derived from the epithelial cells and the countless numbers of
bacteria. The ash embodies chiefly calcium phosphate and small
amounts of iron and magnesium.
Very different conditions are met with if " the diet contains large
amounts of cellulose, because this material escapes from the small
intestine unchanged and may carry other substances with it. In
the large intestine, it is first acted upon in a slight measure by bacteria
before it actually becomes a constituent of the feces. Thus, Voit has
shown that as much as 42 per cent, of the nitrogen of the food of vege-
tarians may be lost to the system, obviously because the digestive
juices cannot penetrate its cellulose investments. Only about 85 per
cent, of the dry substance of green vegetables is available for absorp-
tion, and only 80 per cent, of carrots and turnips. But naturally, the
vegetable proteins as such are as digestible as the animal proteins,
and their complete utilization requires merely maceration and cooking
to free them from the cellulose. In the herbivora, of course, condi-
tions are quite different, because in them the beginning portion of the
large intestine is set aside especially for the digestion by fermentation
of these particular types of foods. This material may remain here
for two or three days, while it undergoes slow reduction and absorption.
Botulism. — Excessive protein putrefaction in the intestine may
give rise to a complex of symptoms, consisting of constipation, vertigo,
diplopia, hemianopia, difficulty in swallowing, weakness, and cardiac
1036 ABSORPTION
irregularities. In most instances, these symptoms are attributable to
an unusual inactivity on the part of the large intestine or to the
ingestion of smoked and canned meat and other foods. It is said
that these toxins are derived from processes instigated by the Bacillus
botulinus, an anaerobe which is easily destroyed by the cooking of the
food.
The Formation of the Feces. — Even at the height of digestion the
small intestine is not distended with food, but contains merely froth
and semi-solid masses of mucous material which are never large enough
to separate its walls very widely. Hence, the name of jejunum or
''empty gut." This peculiar condition finds its origin in the periodic
entrance of chyme and its relatively rapid distribution through a large
stretch of intestine. At the ileocecal valve a certain quantity of its
water has already been abstracted from this material, although enough
of it is left behind to give to the contents of the cecum the consistency
of a thick broth. The regular and antiperistaltic movements of this
segment, together with those of the ascending colon, then allow sufi&-
cient time for most of this water to be absorbed, so that the transverse
colon receives this material in a more compact and dry form. Ob-
viously, any retardation of the feces must tend to increase this
absorption of water, permitting them to become more firmly lodged
in the haustral spaces, whence they are dislodged only with difficulty.
In extreme cases of constipation even the descending colon may be-
come blocked with these impacted masses, which then set up disturb-
ing reflexes by virtue of their irritating action upon the intestinal
mucosa and neighboring abdominal organs.
While it is not my intention to enter into a lengthy discussion of
the causes and effects of intestinal stasis and constipation, it might be
mentioned that the ingestion of food containing a larger proportion
of vegetables may obviate this difficulty, because it tends to shorten
the time consumed in the passage of the food through the intestine.
This result it accomplishes first by virtue of its greater content in
water, and secondly, by means of its stimulating influence upon peri-
stalsis. Consequently, the indigestible cellulose of the food is not with-
out value, because it increases the bulk of the feces and sets up certain
mechanical reactions, which lead to a quicker evacuation of the large
intestine. This point is more fully illustrated by the fact that an
ordinary mixed diet gives rise to a daily output of feces consisting of
about 100 grm. of water and 35 grm. of solids, whereas a vegetable
diet yields 260 grm. of water and 75 grm. of solids.
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1037
CHAPTER LXXXVI
THE HISTORY OF THE DIFFERENT FOODSTUFFS
IN THE BODY
General Discussion. — The process of alimentation having been
completed by the absorption of the foodstuffs, the latter circulate in
the blood and are then acted upon by the cells of the different tissues.
One of two things may now happen to them, namely, they may be
taken up to form an intricate part of the tissue-substance or may be
burned up immediately and excreted. Eventually, of course, even
the first portion must again be discharged by the cells into the cir-
culating media, because activity entails a constant loss of substance.
As far as excretion is concerned, it is, therefore, quite immaterial
whether a given foodstuff first becomes an actual part of a cell or does
not, because both portions are finally turned into waste products.
Clearly, every living entity attains at a particular time of its life a
mature size which it retains for some time by properly balancing its
outgo in waste material by an adequate ingo of nutritive substances.
Meanwhile its physiological destiny is to produce energy in its various
forms, simulating a steam engine which converts its fuel into waste
under an evolution of energy. In order to satisfy its wants; to retain
its weight; and to enable it to yield energy, the living substance re-
quires fresh air, drink and food. Only when each of these three
things is supplied to it can it continue incessantly to oxidize and to
produce work. Thus, each cell may be said to be in a state of un-
stable equilibrium which favors the building up processes during its
period of growth and the tearing down processes during its period
of decline.
While cellular anabolism and catabolism in this general form is
not difficult to understand, it is true that we are not as yet in a satis-
factory position to follow the different foodstuffs in their journey
through the body with exactness. The reason for this lies in the
extreme complexity and invisibility of the intracellular processes.
Regarded in a general way, it may be said that the body consists of
64 per cent, of water, 16 per cent, of proteins, 14 per cent, of fat, 5 per
cent, of salt, and 1 per cent, of carbohydrates. Among its constituents
might be mentioned carbon, nitrogen, hydrogen, oxygen, sulphur, phos-
phorus, fluorin, chlorin, iodin, sodium, potassium, calcium, silicon,
magnesium, lithium, iron, and at times also traces of manganese, copper
and lead. Excepting oxygen, nitrogen and hydrogen, these elements
1038 ABSORPTION
are usually united into compounds, forming (a) the mineral or inorganic
constituents, and (6) the organic constituents of our body. Physiolog-
ical chemistry concerns itself chiefly with the latter which present
themselves as carbohydrates, fats and proteins. So far, however,
chemical analyses have not succeeded in establishing anything further
regarding the *'life history '^ of these substances than what might be
termed a balance sheet between their ingo and outgo. This need not
surprise us, because even the simplest determinations frequently
necessitate difficult analytical procedures. In general, it may be said
that our knowledge regarding the sum total of the changes which the
foodstuffs undergo in our body (metabolism) has been derived from
determinations of:
(o) the quantity and quality of food ingested,
(6) the quantity and quality of the material excreted,
(c) the weight of the animal before and after the experiment, and
(d) the energy evolved by the animal in the form of work and heat,
while in the calorimeter.
THE METABOLISM OF THE CARBOHYDRATES
The Formation of Glycogen. — The animal derives its carbohydrates
in the main from vegetable carbohydrates which upon digestion
yield three monosaccharides, namely, glucose, fructose and galactose.
About 500 grm. of carbohydrate are ordinarily ingested in the course
of a day. Our body, however, is normally unable to synthetize this
foodstuff, differing in this regard very sharply from the plants, which
are able with the help of the chlorophyll to form a simple carbo-
hydrate, probably formic aldehyde, from carbon dioxid and water.
By condensation this simple substance is then changed into sugar, and
eventually into starch. Since the aforesaid sugars are easily inter-
convertible, the tissues may form whatever type of sugar they need.
This is true, for example, of lactose, a constituent of the secretion of
the mammary glands, and of the galactosides of nervous tissue. Since
lactose is a compound of glucose and galactose, it requires only a very
slight intermolecular rearrangement to produce this substance. In
other words, there is sufficient evidence at hand to show that one type
of sugar may be transformed into another either by the cells of all
the tissues or only by those of certain tissues.
It has been ascertained by CI. Bernard (1853) that the sugar ab-
sorbed is not passed directly into the circulation, because the amount
of reducing sugar present in the blood retains the almost constant
value of 0.1 to 0.15 per cent, even at the height of digestion. In
between the successive periods of absorption the percentage of this
substance in the blood of the portal vein is about the same as that of
the blood in the systemic channels, whereas during absorption the
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1039
sugar-content of the former is markedly raised.^ These facts imme-
diately suggest that some barrier is interposed which prevents the newly
absorbed sugar from entering the general circulation. This conclusion
is also upheld by the fact that extracts of the livers of animals which
had been killed some time beforehand, contained a large quantity of
reducing sugar, while those of washed livers exhibited an opalescence
which was proved to be caused by the presence of a polysaccharide,
known as glycogen (CgHioOsn)- When an extract of this kind is treated
with alcohol, it yields an abundant precipitate which, may be con-
verted into sugar by hydrolysis with a mineral acid. This conversion
also takes place in pieces of liver which have been allowed to stand for
some time, so that their yield of glycogen gradually becomes less,
while their content in glucose increases. In either case, this glyco-
genolysis proves that the hepatic cells must contain some enzyme
which is capable of effecting this transformation. The name of
glycogenase has been applied to it.
After an abundant intake of carbohydrates glycogen may be
present in the liver in as large amounts as 12 per cent, of the weight
of the fresh organ. It is demonstrable here in the form of hyalin
chips which give a characteristic port-wine color with iodin; more-
over, a liver of this kind is large, soft and easily injured. But while
the chief source of glycogen is the assimilable carbohydrate material
of the food, namely, glucose, fructose, galactose and mannose, it may
also be formed from proteins or the products of their decomposition.
Whether this conversion takes place under normal conditions cannot
be stated with certainty, althotigh it is known that a starving animal
may employ this means to retain a certain store of sugar. Thus,
it will be found that the liver of an animal during starvation contains
only a very small amount of glycogen, whereas its blood sugar, al-
though less than normal, has not disappeared altogether. This rem-
nant of liver-glycogen, however, may be removed without difficulty
by supplementing the starvation wifh muscular work. Inasmuch as
no carbohydrates are ingested during this period, and inasmuch as
the glycogen of the liver and muscles has been used up, it is evident
that some sugar, or a substance similar to it, must have been formed
from the proteins. This deduction seems justified, because no evi-
dence has been presented as yet to show that glycogen may also be
derived from the fats. Further, if an animal whose store in glycogen
has been exhausted, is fed with washed fibrin, caseinogen, or even
amino-acids, the liver will be found to have acquired glycogen. This
substance also quickly disappears if the starving animal is thrown into
convulsions by means of strychnin. If these spasms are stopped
later on by the administration of chloral, a certain amount of glycogen
is again found in the liver, derived in all probabiHty from the tissue
proteins.
1 McLeoud and Fulk, Am. Jour, of Physiol., xlii, 1917, 193, and Dakin, Oxida-
tion and reduction in the animal body, Monogr. in Biochem., 1912.
1040 ABSORPTION
Our search for the possible source of this glycogen leads us first
of all to mucin, which yields a considerable amount of carbohydrate,
but this substance does not play a significant part in metabolism.
Contrariwise, it has been proved that casein, which does not contain a
carbohydrate radicle, may be made to yield sugar when fed to animals
suffering from phloridzin glycosuria. Similar tests with different
amino-acids have given positive and negative results, although their
composition does not vary very considerably. Two of these, however,
have been proved to yield sugar, namely, alamin and aspartic acid.
In the former instance this conversion is not difficult chemically, be-
cause the substitution of HO in its molecule for NH2 gives lactic acid,
from which sugar may be obtained without much difficulty. Quite
similarly, if aspartic acid loses carbon dioxid, it is transformed into
lactic acid. Another substance, the conversion of which into carbo-
hydrate does not seem improbable, is glycerol. It may be concluded,
therefore, that the body possesses the power of forming its sugar from
the aforesaid substances, and possibly also -from other amino-acids,
although the chemistry of their conversion is not so obvious as in
the cases just cited. Under ordinary circumstances, however, the
body derives its glycogen directly from the carbohydrates of the food.
The Utilization of Sugar. — In the cells of the liver a twofold
process is going on, namely, a conversion of the sugar into glycogen,
and a reconversion of this polysaccharide into circulating sugar under
the influence of an enzyme. We have seen that this circulating sugar
is changed in the pancreas into a form (colloid) which is more acceptable
to the tissue cells, i.e., one which they can burn up more readily than
ordinary glucose. Consequently, the glycogen of the liver serves as
a reserve material which is deposited here temporarily as an inert
polysaccharide. But the liver is not the only storehouse of sugar,
because it is also found in abundant amounts in the muscle tissue.
The difference between these two stores seems to be one of availability,
because if a muscle is suddenly cdUed upon to do extra work, it cannot
await the transfer of sugar from the liver. It is for this reason that
rapidly growing tissues invariably contain much glycogen which they
make use of in the course of their subsequent development. Thus,
while sugar is normally released by the liver into the blood stream,
the outlying depots are there for the purpose of serving the more im-
mediate needs of the body.
It is a well-known fact that every contraction of muscle, whether
in the body or outside of it, consumes glucose. Thus, the normally
contracting heart necessitates about 4 mgr. of this substance per gram
of tissue in the course of 1 hour.^ Now, since the muscle tissue
forms about 42 per cent, of the body weight, its requirements in sugar
must be considerable. Moreover, since our body contains only 1.0
per cent, of carbohydrates, it will be seen that this foodstuff, contrary
1 Starling and Knowlton, Jour, of Physiol., xlv, 1912, 146.
i
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1041
to the proteins, does not serve as a permanent building stone, but
merely as a temporary acquisition which is destined to yield energy.
Work and heat are derived in largest amounts from the muscles,
and we have seen that their contractions require the presence of glyco-
gen and sugar, and that each gram. of sugar furnishes as much as four
calories of the latter form of energy. Considering the preponderating
mass of muscle-tissue and the high heat-value of sugar, it may, therefore,
be concluded that the oxidation of this substance constitutes a safety
mechanism by means of which the body is enabled to protect its real
building stones, the proteins. Fat plays a similar role, but we shall
see later on that it occupies an intermediate position and serves merely
as an accessory means of safeguarding the protein substratum of the
body. Thus, an animal may be retained in nitrogen-equilibrium if it
continues to ingest a small amount of protein material to make up its
ordinary loss in tissue-proteins, and if it continues to take in a suffi-
cient quantity of carbohydrates (or fats) to make up for the energy
requirements of the body. Inasmuch as the carbohydrates merely
play the part of oxidizing. substances and sparers of the tissue-proteins,
it will be seen that they alone cannot keep the body in nitrogen-
equilibrium. Consequently, an animal fed exclusively on carbohy-
drate food must eventually lose its tissue-proteins, and starve to death
in spite of its abundant intake of carbohydrates. On the other hand,
if an animal is in nitrogen-equilibrium to begin with, the abundant inges-
tion of carbohydrates first gives rise to a storage of glycogen and subse-
quently to a synthesis of the superfluous sugar into fat. The latter is
held in reserve as an accessory substance to be employed for future
oxidations. This ''carbohydrate-fat" differs somewhat in its consist-
ency from the ordinary tissue-fat.
The final product of the oxidation of sugar is carbon dioxid and
water, and its principal excretory channel the lungs. Thus, we find
that the increased output of energy which accompanies muscular
exercise is characterized by a greater outgo of carbon dioxid and a
greater consumption of oxygen. This respiratory change immediately
suggests an increased metabolism of the carbohydrates and fats. But,
while the final stage of the oxidation of the carbohydrates is quite evi-
dent, much diversity of opinion prevails regarding the intermediary
transformations of this foodstuff. The initial change is a hydrolytic
cleavage which liberates some chemical energy, and the final stage an
oxidation and evolution of that large amount of energy, which after
all is the purpose of the reduction of this foodstuff. As an interme-
diary stage is usually mentioned the production of lactic acid, through
the preliminary formation of glyceric aldehyde and methylglyoxal.
It has been shown that lactic acid is present in the body chiefly as the
dextro-rotatory variety or sarcolactic acid, and as the optically inactive
variety. Whether all of this lactic acid is derived from the sugars is
still in doubt, although it must be admitted that this is its principal
source.
66
1042 ABSORPTION
The Regulation of the Sugar Supply of the Body. — The sugar con-
tent of the blood of the general circulatory system is determined by
two factors, namely, by the production of glucose by the liver (glyco-
genolysis), and by the consumption of this substance by the tissues
(glycolysis). Both these processes are in turn dependent upon an
adequate conversion of the absorbed sugar into glycogen (glycogenesis).
Consequently, it may be said that the sugar content of the body is
the result of an interaction between these three factors, and that such
conditions as hyperglycemia and glycosuria are the outcome of a dis-
turbance in any one or several of these processes.^ Under normal
conditions, a harmonious interaction between these factors may be
brought about through the nervous system or through chemical agents
contained in the blood stream. Regarding the nervous control we
have the positive evidence of CI. Bernard that a puncture of the floor
of the fourth ventricle (rabbits) is usually followed by an excessive
secretion of urine, containing abnormally large amounts of sugar
(glycosuria). This has led to the assumption that the aforesaid ac-
tivities are under the control of a special center which is often referred
to as the glycogenic or diabetic center.
It has been shown that the stimulation of either the greater splanch-
nic nerves or the hepatic plexus gives rise to glycosuria, the claim
being made that these nerves are concerned with the storage and con-
version of glycogen by the cells of the liver. It is held further that
this regulation is under the control of a hormone secreted by the
adrenal glands, but the evidence so far presented in support of this
contention, is not at all convincing. In spite of this fact, however, it
cannot be doubted that glycosuria is frequently associated with mental
excitement. Furthermore, the disease of diabetes mellitus usually
affects persons with neurotic tendencies or those who are under a
constant and severe mental strain, or whose work demands much
mental concentration and exactitude. ^ At present, however, no
facts are at hand to show that diabetes mellitus finds its initial cause
in an outpouring of adrenin in consequence of too frequently repeated
emotions, such as anger, fear and fright.^
The control of the formation and consumption of the sugars by
hormones may be discussed at this time in a very brief manner, because
this subject matter has already been dealt with in a preceding chap-
ter. McLeod^ states that this regulation may arise in consequence of
(a) the concentration of the glucose in the blood, (6) the presence in
the blood of the products of decomposition of the glucose, and (c) the
action of some internal secretion. In accordance with this investi-
gator, the first possibility is based upon the law of mass action, in
1 McLeod, Physiol, and Biochem. in Modern Medicine, C. V. Mosby, St. Louis,
1918; and Hewlett, Monogr. Med., Appleton and Co., 1917.
2 Cannon, Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co.,
1915.
3 Allen, Glycosuria and Diabetes, Boston, 1913; also: Von Noorden, Metabolism
and Pract. Medicine, Chicago, 1907.
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1043
agreement with which the conversion of the glucose into glycogen, as
well as the conversion of the latter into the former substance, is
determined by the amounts of glucose in the blood available for pur-
poses of oxidation. It cannot be doubted that this process- is actually
at work, but obviously, the fact that it takes place does not offer an
explanation for the manner in which it is accomplished. The second
PQSsibility finds its basis in the fact that such products as lactic acid
and carbon dioxid are circulating in the blood and change the hydro-
gen ion concentration of the blood, thereby exciting a glycogenolysis.
The third possibility, that this regulation is effected by means of a hor-
mone secreted by some ductless gland, possesses a sound experimental
basis. Chief among these internal secretory organs is the pancreas,
then follow the adrenals, parathyroids and pituitary.
We have previously noted that the hyperglycemia and glycosuria,
following the removal of the pancreas, are due to the loss of an internal
agent which makes the sugar immediately available for oxidation by
the tissue cells. The other glands, in all probability, act in an indirect
way through the nervous system, increasing glycogenolysis. These
two conditions, therefore, would give rise to the so-called pancreatic
and hepatic types of glycosuria. The temporary alimentary type is,
of course, dependent upon an increased absorption of sugar and an
overburdening of the system with this substance. A fourth method of
producing glycosuria has been discovered by Mering.^ It has been
used extensively by Lusk,^ and consists in the administration of a
glucoside, known as phloridzin, which is derived from the bark of the
roots of the apple, cherry and pear trees. It produces a glycosuria
in spite of the fact that the sugar content of the blood may be below
normal. This shows that this type of glycosuria must be due pri-
marily to a leakage of the sugar through the kidneys in consequence of
an injurious action of this substance upon the renal epithelium. Phlor-
idzin-glycosuria, therefore, is a type of renal glycosuria. The tempo-
rary glycosuria which may be developed in consequence of nervous
excitement is in all probability to be classified as a disorder of glyco-
genesis and glycogenolysis.
It will now be seen that the condition of acidosis cannot be attrib-
uted exclusively to a disarrangement of the carbohydrate metabolism,
because the bodies causing this disturbance are aceto-acetic and jS-
oxybutyric acid, which are the oxidation products of acetone and the
fatty acids. When these substances accumulate in the course of dia-
betes mellitus, the condition is known as ketosis. It appears to be due
to the fact that the fats cannot be burned up thoroughly unless their
combustion is stimulated by the heat derived from oxidizing sugar.
In the absence of this heat, the fats are imperfectly reduced. Conse-
1 Verhandl. des Kongr. fiir inn. Medizin, vi, 1887, and Zeitschr. fur klin.
Med., 1889.
2 Zeitschr. fur Biol., xlii, 1904, 31.
1044 ABSORPTION
quently, ketosis is caused by an imperfect balance between the metab-
olism of the fats and carbohydrates.^
A term frequently met with in the Hterature upon carbohydrate
metabolism is the D:N ratio. We have seen that the absolute with-
drawal of carbohydrate from a diabetic animal does not prevent the
excretion of sugar in its urine. Since this dextrose is not derived
from the fats, it must be synthetized from the proteins. Minkowski
and Lusk^ have shown that a dog in complete glucose intolerance may
form as much as 60 grm. of glucose. Now, inasmuch as 100 grm.
of proteins yield about 16 grm. of nitrogen in the urine, the ratio of
dextrose to nitrogen would be 60 : 16 = 3.7. Lusk states that a D :N
ratio varying between 3.3 and 3.7 is a fatal ratio, because it proves
that a person kept on a diet which is free from carbohydrate, cannot
consume sugar.
THE METABOLISM OF THE FATS
The Source of the Body Fat. — The neutral fats formed by a resyn-
thesis of the fatty acid and glycerin in the lining cells of the intestine,
find their way into the lacteals, whence they reach the blood stream
by way of the thoracic duct. But since the fat content of the blood
of the portal vein is invariably higher than that of the external jugular,
it is claimed by some investigators that a slight amount of fat also
enters the intestinal capillaries directly. As far as the systemic blood
is concerned, it has been found that its content in fat (0.7 per cent.)
remains tolerably constant, provided only moderate amounts of fat
are ingested. The intake of larger quantities of fat, on the other hand,
invariably raises its percentage, which reaches its maximal value about
6 hours after a meal and then gradually declines to the twelfth hour.
But since even the intravenous injection of oil emulsions does not last-
ingly increase the fat content of the blood, it must be concluded that
the body possesses the power of storing this fat very rapidly, possibly
in the liver. Even during starvation the blood-fat remains rather
constant, proving thereby that the fat is being transported from the
different depots to the starving tissues.
In the animal body the fats are usually deposited as the triglyc-
erides of the different fatty acids, those of adipose tissue consisting
of stearic, palmitic and oleic acids. Cow's milk also contains these
acids, but in addition, also the esters of butyric and caproic acids and
small amounts of caprylic, capric, lauric and myristic acids. Lard
is made up in considerable part of the glycerides of the more unsatu-
rated fatty acids, such as those of linoleic acid. It is evident, therefore,
that the composition of the fat differs even in one and the same animal,
and may in addition be varied by changing the food. This fact proves
first of all that the epithelial cells of the intestine do not merely resynthe-
tize the glycerol and fatty acids, but possess the power of forming their
^ Woodyatt, Jour. Am. Med. Assoc, Ixvi, 1916.
2 Science of Nutrition, W. B. Saunders Co., 1912.
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1045
own particular kind of chyle fat. Very similar modifications must also
be effected by the tissue cells themselves, because the fats are in all
probability rehydrolyzed here, to become at least in part important
constituents of the protoplasm. This deduction is in no way refuted
by the fact that starving animals, when fed on foreign fat, are capable
of storing this substance practically unaltered. This merely proves
that it can be utilized in this form. Thus, Munk^ has shown that an
animal fed on colza oil, deposits fat from which erucic acid may be
obtained, this acid being the basis of the glyceride contained in that
oil. In a similar way, it has been demonstrated by Lebedeff^ that the
feeding of linseed oil or mutton fat to different dogs gives rise to a
deposition of body fat which is characterized by a different melt-
ing point; that derived from mutton suet remaining solid at 50° C.
Furthermore, Liebig has pointed out that the fats of different animals
present certain peculiarities in their appearance, consistency, melting
point, and general chemical properties, and are in turn different from
the fat ordinarily ingested with the food. In fact, many animals, such
as the herbivora, do not eat fat, although they often acquire a consid-
erable amount of body fat. But this is really an old established fact,
and has been used scientifically by Larves and G. Wert in their feeding
experiments upon pigs.
These data have led in the course of time to various theories re-
garding the origin of the body fat. The modern view, which has been
placed upon a solid experimental basis by Pfluger,^ holds that it origi-
nates in part from the fat and in part from the carbohydrate of the food.
But the possibility that fat may also be derived from proteins, cannot
be excluded, because since the latter are deaminized and converted into
sugar and glycogen, these products may in turn be transformed into
fat. The proteins, however, cannot form an important source of fat
under ordinary conditions, because they constitute a relatively small
portion of the daily ingesta.
While it cannot be stated definitely which of the first two sources
is the more important, the fat of the food is no doubt the chief element
in the carnivora, and the carbohydrate in the herbivora. Man, in all
probability, makes considerable use of the carbohydrates, because they
are really more easily reduced than the fats. Beyond this mere fact,
little is known regarding the manner in which this conversion is ac-
complished. It involves, of course, a change of oxygen-rich sugar
into oxygen-poor fat. Thus, if this process may be illustrated with
stearic acid, it will be found that three molecules of glucose (C6H12O6)
give stearic acid (C18H36O2) under an evolution of 16 atoms of oxygen
The fact that such a transformation gives rise to a liberation of oxygen
is shown by animals who are depositing fat on carbohydrate food.
CO
Their respiratory quotient, ^ > is increased considerably, because
1 Virchow's Archiv, xcv, 1884, 407.
2 Centralbl. fiir die med. Wissensch., 1881.
3 pfltiger's Archiv, Ixxvii, 1899, 521.
1046 ABSORPTION
some of this oxygen will be made available for other oxidations, so that
the animal need not take in so large an amount by respiration. In
addition to this process of deoxidation, other changes are effected,
such as the reduction of glucose into two molecules of lactic acid which
in turn is converted into aldehyde and formic acid. By polymeriza-
tion, the aldehyde may then be changed into aldol which yields buty-
ric acid on oxidation or by transposition of its oxygen. ^
The Utilization of the Fats. — The final product of the metabolism
of the fats is carbon dioxid and water, and their chief function to supply
energy. This being the case, the body holds a considerable portion
of this substance in reserve as a deposit in its different storehouses.
Among the latter might be mentioned the liver, the tissues, and such
special structures as the panniculus adiposus in the deep skin, the omen-
tum, and retroperitoneal spaces. Any excess is stored in these places
to be drawn upon later on when needed. Thus, fat serves as an addi-
tional protection to the proteins, being itself safeguarded by the carbohy-
drates. It presents, however, different characteristics in accordance
with its origin and place of deposition. The ordinary depot-fat, for
example, yields 95 per cent, of its total weight as fatty acids, while the
tissue-fat yields only 60 per cent. This might imply that the former
is neutral fat, while the latter is combined into lecithin and phos-
pholipins. In the liver, the character of the fat varies with the inten-
sity of the metabolism of this organ, being more like the fat of the tissue
during its periods of relative quiescence and more like that of depot-fat
during its periods of activity. It is also apparent that the amount of
fat which may be stored in this way is almost unlimited, contrary to
glycogen which at best cannot be stored in much greater quantities
than 300 grm., i.e., 150 grm. in the liver and 150 grm. in the muscles
and other tissues.
This depot-fat is mobilized and transported to the active tissue
whenever the latter has used up its own store of energy-yielding
material, and obviously, this mobilization necessitates its conversion
into fatty acids and glycerin, which products again give rise to neutral
fat in the blood. No doubt, the chief seat of these oxidations is the
muscle-tissue itself, and principally the cardiac and skeletal muscles.
In the former, for example, enough fat is stored up to last for 6 or
7 hours. The intake then being insufficient to cover the outgo,
all the available stored fat is drawn upon. Thus, a starving animal
first exhausts its relatively small store of glycogen and then its depot-
fat to the extent of 90 per cent, of the energy required. Consequently,
a fat animal is able to survive complete abstinence from food much
longer than a lean one. Besides this important function as a source
of energy, the body-fat also serves as a factor in regulating the body-
temperature by preventing an undue heat-dissipation, and lastly, as a
factor in protecting delicate structures from mechanical injury.
The question whether the liver possesses a special influence upon
^Leathes, The Fats, Monogr. in Bioch., Longmans, Green and Co. , 1912.
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1047
the metabolism of the fats, cannot be decided at this time. It is evident
that this organ may absorb a considerable proportion of its fat directly
from the portal blood. Thus, Raper^ has shown that as much as 30
per cent, of cocoanut introduced in the intestine, may be recovered
from the liver. The same is true of unsaturated oils, such as cod-liver
oil and other fish oils. This probably accounts for their greater nutri-
tive value. In addition, it has been shown that the liver possesses
the power of desaturating fat, which may render it more easily reduci-
ble than saturated fatty acid. But, inasmuch as this organ also aids in
synthetizing fatty acid radicles into the complex molecule of lecithin,
it is entirely probable that this desaturation constitutes a preliminary
step in this process of building up lecithin. While this substance is
made up of gylcerin, fatty acids, glyceryl-phosphoric acid, and a nitrog-
enous base cholin, it also seems to contain admixtures of proteins or
carbohydrates.
Fatty Degeneration. Obesity. — Under abnormal conditions, the
cells of such organs as the liver, heart, and kidneys may undergo
degenerative changes which make them appear as if filled with ex-
tremely fine globules of fat. This is a common result of poisoning with
phosphorus, arsenic or antimony. Although formerly believed to be
due to a conversion of the proteins of the cytoplasm into a fat-like
substance, fatty degeneration is now known to be caused either by
an infiltration of the cells with fat transported from elsewhere or by a
transformation of the molecular fat of the cells into a different variety
of it. For this reason, it cannot be said that a fatty degenerated cell
contains a greater amount of fat than it did normally; in fact, in
many instances the reverse relationship holds true. Lusk, however, has
shown that these poisons also interfere with the metabolism of the
proteins in an indirect way by favoring the conversion of the carbohy-
drate-like radicle of the proteins into leucine and tyrosine, necessitat-
ing for this reason an increased consumption of protein.
Obesity signifies a disproportion between the total mass of the
body and that made up of fat. This condition is caused by an exces-
sive deposition of fat within the different depots of the body, giving
rise to changes in the contours of the latter and various interferences
with its normal activities and movements. In many instances,
however, it is difficult to say just where the abnormal begins, because
animals differ very greatly in their fat-carrying capacity. It is
evident that the great majority of animals may be made to lay on
fat by lessening their expenditure of energy or by increasing their
intake of carbohydrates and fats. Since this is a perfectly physiolog-
ical phenomenon, the only condition to explain is the excessive deposi-
tion of fat on a normal or reduced diet in the presence of a normal or
even increased expenditure of energy. It has previously been pointed
out that the metabolism of the fats may be dependent in some measure
upon the secretion of some ductless gland. In the absence of this in-
1 Jour. Biol. Chem., xiv, 1913, 117.
1048 ABSORPTION
ternal agent, the oxidation power of the tissues is interfered with,
thereby causing an excessive storage of this material. Secondly,
obesity may be due to an unusually high efficiency of those organs
which are directly concerned with fat metabolism, enabling them to
keep the body as a whole in a proper condition on an unusually low
supply of food. Obviously, this condition can only be remedied by
a lessened ingestion of food and a greater expenditure of energy.
The latter alone can do no good, because if the patient is then allowed
to control his intake in accordance with his appetite, he no doubt would
endeavor to balance the greater outgo by a greater intake. It should
be remembered, however, that a fat person actually needs a slightly
greater production of energy than a lean person, because his body sur-
face is larger, favoring heat dissipation.
THE METABOLISM OF THE PROTEINS
The Source of the Protein of the Body. — It will be remembered
that the proteins of the food are completely hydrolyzed into their
amino-acids, and are absorbed as such and passed into the portal
blood stream. Under ordinary conditions, the only slightly hydro-
lyzed products of protein digestion, such as peptone and proteose,
are not absorbed in significant amounts, because it is a well-known fact
that these substances, when injected directly into the blood stream,
produce symptoms of intoxication. This anaphylaxis, however, does
not follow if they are introduced into the intestinal canal. Whatever
proportion of them may find its way into the epithelial lining cells
must, therefore, be reduced and changed in its course through these
cells into inert proteins. This change may also be effected while they
circulate, because their concentration in the blood can never be in-
creased sufficiently to produce injurious effects. Such a result is
prevented ordinarily, because they are brought into contact with a
very large quantity of blood, and because the quantity of the still un-
reduced protein within the intestine is very small. At all events, the
evidence so far presented does not show that the intestinal lining cells
synthetize the amino-acids into the proteins of the blood, which in
turn would have to be changed into tissue proteins. Consequently,
it may be concluded that the body synthetizes its proteins from the
amino-acids directly, using in this case only those which are of^special
value to it. The others, as well as those transferred into the blood by
the cells as waste, are split into two portions, one of which represents
the ammonia and the other the remnant of the amino-acid molecule.
The urea is derived from the former, while the latter is immediately
oxidized to yield energy. For this reason, we commonly speak of the
so-called tissue-protein and circulating protein, the former being rep-
resented by that portion of it which enters the cells of the tissues to
become an intricate part of them, while the latter is broken down
immediately without having been converted into cellular protoplasm.
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1049
The proportion of each must, of course, differ with the condition of the
body. If the latter is in nitrogen-equilibrium, a more considerable
proportion of it will be oxidized directly to yield energy than when
the body is in need of this substance to make good a previous loss.
Quite similarly, the greater the amount of protein taken in under nor-
mal conditions, the greater must be that amount of it which is directly
converted into energy.
This division of the absorbed proteins into tissue and circulating
proteins shows that their catabolism is not uniform, but consists es-
sentially of two separate processes (Liebig). Obviously, the tissue
catabolism must remain rather constant under normal conditions,
while the catabolism of the circulating proteins must differ more di-
rectly with the amount of proteins ingested. Consequently, any
attempt made to determine the metabolism of the proteins requires
the reduction of the circulating proteins to a minimum. Only when
this end has been accomplished are we in a position to obtain a fair
insight into the protein metabolism of the tissues. Any analysis of
this kind, therefore, must take into account first the so-called exogenous
protein, namely, that portion of it which is derived directly from the
food, and secondly, the endogenous protein, which is the result of the
catabolism of the substance of the tissue cells. Clearly, the first has
really little to do with the life of the cells, while the latter actually
serves as a measure of the waste of the tissues.
The Utilization of the Proteins. — The amino-acids appear in the
blood in amounts scarcely sufficient for a quantitative analysis. Van-
Slyke,V however, states that their amount is fairly constant and that the
fasting animal contains from 3 to 5 mgr. in each 100 c.c. of blood.
After meals, when an active absorption of proteins is going on, their
amount may be doubled and similar increases may be obtained by the
injection of amino-acids into the intestine. Thus, 10 grm. of alanin
administered in this way yielded as much as 6.3 mgr. in each 100 c.c.
of mesenteric blood. A method by means of which such substances
may be withdrawn from the circulating blood has been described by
Abel. 2 It is known as vividiffusion. The apparatus consists of a long
tube of collodion coiled upon itself and immersed in a solution contain-
ing approximately the saitie content in salts as blood plasma. The
ends of the collodion tube are connected with the central and distal
ends of an artery. As the blood circulates through it, its diffusible
constituents dialyze into the saline solution and may be recovered
from the latter. In this way it has been possible to isolate alamine
and valine in crystalline form, and also to detect the presence in the
blood of histidine and creatine.
It is a well-known fact that a large meal of protein gives rise to a
rapid increase of the urea in the urine until about the fifth hour,
when at least 50 per cent, of the total nitrogen of the food will have
passed into the urine. If we consider that digestion is going on mean-
1 Harvey Lectures, New York, Lippincott and Co., 1916.
2 The Mellon Lecture, Science, xlii, 1915, 13§.
1050 ABSORPTION
while, we must conclude that a portion of the nitrogen of the food
passes over almost immediately. Consequently, urea may well be
employed as an index of the amount of protein absorbed. Even the
intravenous injection of solutions of the amino-acids into normal
animals does not result in their retention, as much as 90 per cent, of
the original amount disappearing from the blood in the course of 5
minutes after the injection. These facts, as well as others that might
still be mentioned, show conclusively that the amino-acids do not tarry
in the tissues, but are rapidly excreted so that their destruction prac-
tically equals their absorption. This need not surprise us, because it
has been shown previously that the tissue proteins are equilibrated in a
more exact manner than the fat and carbohydrates, and that a definite
relationship must, therefore, be retained between the amino-acids of
the blood and those of the tissues. But while the power of protein-
storage of the tissues is extremely limited, it seems that the liver is
much more elastic in this regard and is capable of assimilating 125
to 150 mgr. per 100 gr. of the original amount. Its power of absorbing
this material is also evinced by the fact that the concentration of the
amino-acids is less in the blood leaving this organ than in that enter-
ing it.^
The deduction to be made from these data is that the liver utilizes
the amino-acids in the formation of urea. But since this body may
also be produced after the removal of the liver, this organ cannot be
said to be the only place in which urea is formed, although it is safe to
conclude that it is its chief source. Moreover, since it is the endeavor
of the system to remain in nitrogen-equilibrium, it is the function of
the liver to prevent any flooding of the tissues with amino-acids.
Consequently, this organ begins its function of forming urea almost
immediately after these substances have begun to be absorbed.
Besides, the liver also takes care of the protein waste, discharged in
consequence of the catabolism of the different tissues.
The End-products of Protein Metabolism.- — Obviously, the tissue-
proteins are first split up into the amino-acids from which they were first
synthetized, and supposedly no decisive chemical difference exists
between these catabolic products and the amino-acids absorbed. We
know that the tissues possess this power of reducing their protein
material, because they are in possession of proteolytic enzymes (pro-
teases) which may be isolated from them in different ways. Thus, it
is a matter of common experience that pieces of tissues, when kept
under proper condition of temperature and moisture, undergo autolytic
changes which yield ammonia, glycine, tyrosine, tryptolane and other
basic substances. A similar process of autolysis occurs in malignant
tumors, and such a condition as cystinuria merely indicates that the
cystin is not taken care of by the body, owing to a derangement of
the metabolism of the amino-acids. It enters the urine, frequently
1 Mendel, Ergebn. der Physiol., 1911. ,
HISTORY OF DIFFERENT FOODSTUFFS IN BODY 1051
associated with leucine and tyrosine, where it may be deposited in
the form of calcuH.
Whatever intermediary stages the amino-acids may pass through,
they are finally converted -into carbon dioxid, water, and . relatively
simple substances containing nitrogen. Chief among the latter is urea
and its precursor ammonia, but there are also some which cannot be
regarded as members of the amino-acid group, such as creatine and
creatinine. These bodies are very largely the result of endogenous pro-
tein metabolism, although some of the creatine and creatinine of the
food may appear as such in the urine. Besides, some of the amino-
acids may appear in the urine as such, giving rise to the so-called amino-
nitrogen or undetermined nitrogen. But since the metabolism of the
cells also includes that of their nuclear material, and since the latter is
also ingested, for example, in the form of sweet-breads or thymus, this
list should be augmented to embrace the purin bodies. The determina-
tion of sulphur in the urine is valuable in so far as it gives a fair picture
of the metabolism of the proteins, because this foodstuff serves prac-
tically as the only vehicle for its entrance into the body.
The purine bodies arise from purine. The first product of the
oxidation of this body is hypoxanthine from which adenine i« derived.
The second product of its oxidation is xanthine and its amino deriva-
tive guanine. The trioxypurine is uric acid, which in birds and reptiles
is the chief derivative of protein metabolism. Whether this substance
is also excreted by the mammals in important amounts is still a ques-
tion. ^ It would appear, however, that the urine acquires uric acid
and also a certain amount of purine bases after a copious diet of meat
and especially after the ingestion of glandular material. For this
reason, Burian and Schur^ have recognized an endogenous and exog-
enous purine metabolism, the former having to do with the reduction
of the purine of the tissues and the latter with that of the preformed
purine constituents of the food ingested. In general, it may be said
that the exogenous purine bears a close relation to the purine of the
urine. If it accumulates in the tissues it gives rise to the condition
known as gout, and hence, purine-rich food should not be taken by
persons who suffer from this metabolic difficulty or tendency (gouty
diathesis). More recently, it has also been shown by Ascoli and Izar^
that purine may be synthetized in the mammalian body from urea and
carbon-rich residues, two molecules of the former uniting with a
carbon residue containing three carbon atoms. This purine would of
course be endogenous in its character.
1 Jones, Nucleic Acid, Monographs in Biochem., Longmans, Green and Co.,
1914.
2 Zeitschr. physiol. Chemie, xxiii, 1897, 55.
3 Ibid., xliii, 1911, 319.,
1052 ABSORPTION
CHAPTER LXXXVII
THE METABOLIC REQUIREMENTS OF THE BODY
The Effect of Starvation. — The withholding of food places the
animal upon its own resources. The tendency must then be to
conserve its most important metabolic substances, the proteins, and
to obtain its energy from the carbohydrates and fats. We observe,
therefore, that the tissues of an animal really fall into two groups,
namely, those which form the metabolic nucleus of the body and those
which serve principally as storehouses for energy-jrielding material."
A starving animal first of all draws upon its store in glycogen, then
upon its fat, and lastly, as an emergency measure, upon its proteins.
Obviously, energy must be produced even in the advanced stages
of inanition, but naturally, its amount must then be slight, because
all the activities of the body are greatly reduced during this period.
This in itself will tend to conserve the resources of the tissues. Thus,
inanition gives rise almost immediately to a feeling of fatigue and
weakness which the animal complies with by assuming an inactive
position, passing its days in sleep and semi-stupor. The rate of
respiration, the frequency of the heart, as well as the body-tempera-
ture, are those of a resting animal and remain so until a day or two
before death, when the respiratory and cardiac activities are greatly
reduced and the body-temperature falls very markedly. The quan-
tity of the urine is greatly decreased, and so is its content in urea.
Feces are formed until about the time of death, but in very small
amounts, say, 10 to 20 grm. in the course of a day. Professional
fasters, however, state that no pain is experienced at any time during
the fast and that the uncomfortable sensations of the first few days
disappear very quickly. The body-weight decreases steadily, until at
the end of 10 days this loss may amount to about 1.0 or 1.5 per cent,
of the original weight. Naturally, those tissues are reduced most
which contain the largest amount of fat, whereas the brain, spinal
cord, heart, lungs, and pancreas suffer least.
This discussion shows first of all that an animal which is in posses-
sion of a considerable amount of fat at the beginning of the period of
starvation, is in a much better position to withstand the withdrawal
of food than one not protected in this way. Thus, a well-nourished
dog may survive a period of starvation lasting 4 weeks; in fact, in
some instances death did not result until after 2 or 3 months.^
Succi, the professional faster, abstained from food for 30 days, and
Marlatti for 50 days.^ The small mammals die much sooner, and
1 Falck, Beitr. zur Physiol., Marburg, 1875, and Kumagawa, Archiv fiir
Physiol., 1898.
2 Luciani, Das Hungern,' 1890.
I
THE METABOLIC REQUIREMENTS OF THE BODY 1053
reptiles and amphibia not until after many months and possibly a
year. Secondly, it may readily be gathered that the production of
heat in starving animals must be greatly reduced. Thus, the profes-
sional faster Cetti^ required on the first day only 32.4 calories for each
kilogram of his body-weight and, on the fifth day, only 30.0 calories.
Similar values have been found by Tigerstedt.^ In accordance with
Rubner^ and Magnus-Levy,^ this loss of energy is only 7 to 15 per
cent, lower than that in a person ingesting a moderate amount of food.
The course of the elimination of nitrogen during periods of star-
vation is closely dependent upon the condition of the animal at the
time of withholding the food. If the animal has been accustomed to
ingest large amounts of protein material, its protein-catabolism will
be rather high during the first few days of the period of starvation, but
a uniformly low output of nitrogen will have been reached at the end
of about a week. Meanwhile, its store in glycogen will have become
exhausted, while its fats will have been drawn upon incessantly to
shield its proteins. As soon as all the available fat has become ex-
hausted, a more intense metabolism of the proteins sets in, in conse-
quence of which the output of nitrogen is increased. This premortal
rise in the excretion of nitrogen constitutes an unfavorable diagnostic
sign, because it indicates that the ordinary fuel of the animal has been
thoroughly depleted.
In the herbivora, conditions are somewhat different, because these
animals possess a large store of glycogen. Thus, it is commonly found
that their output of nitrogen is considerably increased during the first
days of the period of starvation, because since they have been accus-
tomed to use carbohydrates as their chief fuel, the sudden withdrawal
of this foodstuff forces them to fall back upon their store of proteins.
A very similar re'action takes place in men who have been accustomed
to eat large amounts of carbohydrates. In both instances, therefore,
starvation changes the metabolism into a type more nearly like that
of the carnivorous animals.
The ingo of oxygen and outgo of carbon dioxid soon reach a minimal
value. Urea nitrogen falls and NH3N 'rises, but the total amount of
creatinine and creatine, which form peculiar derivatives of the meta-
bolism of muscle tissue, is not changed materially. The excretion of
the purines is decreased at first and then increased, owing, in all
probabiHty, to the steady destruction of the nuclear material. As
far as the relation of the sulphur to the nitrogen is concerned, it is to
be noted that their ratio is at first as 17N: IS, and later on, as 14.5N : IS.
If anything, these values suggest that the principal source of protein
during the later stages of starvation is the protein material of muscle
tissue.
^ Virchow's Archiv, cxxxi, 1893; also: Benedict, Carnegie Inst, of Washington,
No. 126, 1910.
2 Skand. Archiv fiir Physiol., vii, 1897, 29.
3 Gesetze des Energieverbr., Leipzig, 1902.
* Pfliiger's Archiv, Iv, 1894, 96.
1054 ABSORPTION
The Effect of Sleep. — Sleep does not affect the metabolism of the
proteins to any extent, as is shown by the fact that the total nitrogen
excreted remains about the same. Instead, there appears a slight
reduction in the output of endogenous purine nitrogen, indicating a
lessened destruction of nuclear substances. Contrariwise, the ingo
of oxygen and outgo of carbon dioxid are markedly diminished, an
indication that the tonicity and activity of the muscles and glands are
considerably reduced.
The Effect of Temperature. — Within narrow limits the met?.bolism
of the warm-blooded animals is increased by a cold and decreased by
a warm outside temperature, but this result is only obtained if the
body-temperature is not greatly altered thereby. Extreme varia-
tions in the outside temperature, which in turn produce a material
change in the body-temperature, affect the metabolism in a reverse
manner. This need not surprise us, because the body constantly
attempts to retain its normal temperature of about 37.0° C. A cooling
of the air gives rise to a greater loss of heat and hence, a more intense
metabolism must immediately be instituted to counteract this effect.
Contrariwise, an increased temperature of the atmosphere lessens the
loss of heat and, consequently, less heat need be produced. But, in
case this heat-regulatory mechanism is overcome, an excessive fall
in the body-temperature invariably diminishes the oxidations and heat
production, whereas an unusual rise increases these processes. The
body having been sufficiently cooled, all chemical processes within it
come to a standstill. Evidently, in the presence of a well-balanced
heat-regulatory mechanism, any deficiency in the body-temperature
is made up at the expense of the non-nitrogenous constituents of the
tissues. This is shown by the fact that the consumption of oxygen
and elimination of carbon dioxid are increased, while the nitrogenous
excretions in the urine remain practically the same.
The Effect of Age and Sex. — The output of energy is low in the
new-born, but increases rapidly during the first year until it reaches
its maximal value at about the sixth year. Subsequent to this time,
it decreases rather rapidly until the twentieth year and then more
slowly until late in life. This steady decline is interrupted only at
the time of puberty, when the metabolism is temporarily intensified.
The output of energy by the female is about 4.3 per cent, below that
of the male.
The Effect of Muscular Exercise. — The metabolism is materially
increased even by ordinary degrees of work, although the protein
waste is no greater than during rest. After excessive exercise, on the
other hand, the latter is considerably increased, embracing urea, am-
monia, creatinine, and even uric acid and purine bases. This contra-
dicts the view of Liebig, implying that the greater energy hberated
during muscular work finds its source in a break-down of the muscular
tissue, and must, therefore, be performed at the expense of an increased
metabolism of the proteins. Such a result, however, is never obtained
)
THE METABOLIC REQUIREMENTS OF THE BODY 1055
unless the animal has been nourished exclusively on protein material
and is not in possession of normal amounts of glycogen and fat. Thus,
Voit has found that an animal which is in fat and carbohydrate equi-
librium does not exhibit a nitrogenous breakdown, and concluded, there-
fore, that the extra energy is derived wholly from the non-nitrogenous
constituents of the body.
These results soon found support in the experiments of Fick and
Wislecinus, who ascended the Faulhorn to a height of 1956 meters.
By comparing their weight with the height to which they climbed, it
was possible to compute the amount of work performed by each of
them. In the case of Fick, it amounted to 66 X 1956 = 129,096
kilogrammeters plus about 30,000 kilogrammeters of work performed
by the heart and muscles of respiration. Since only non-nitrogenous
food had been ingested by these investigators during a period of 17
hours before thie climb as well as during it, the urea eliminated by
them must have been derived entirely from their body-proteins. On
determining the heat value of this urea, it was found to be entirely
insufficient to account for the amount of work done. Very similar
results have been obtained by Parkes upon soldiers during periods of
rest and long marches, and by Atwater by means of the respiration
calorimeter.
It may be concluded, therefore, that ordinary muscular work does
not increase the metabolism of the proteins much beyond its normal
value, provided sufficient non-nitrogenous material is at hand to pro-
duce the required amount of extra energy. Accordingly, if the non-
nitrogenous substances are present in insufficient quantity, some of
this extra energy must be derived from the proteins. The elimination
of nitrogen in the urine is then increased, and naturally, this waste
must be the greater the more intense the muscular exercise.
Normal Metabolism. — The preceding discussion pertaining to
starvation is of special value, because it furnishes a means of deter-
mining the amounts of energy liberated by the body under normal
conditions, and allows us to ascertain the amount of fuel which must
be ingested in order to supply this energy. It will be found that a
marked difference exists between the various foodstuffs in this regard.
In the first place, it should be noted that an animal fed on pure fat
or carbohydrate, or a mixture of the two, does not survive thi« diet
for a much longer period than if all food were withheld. Consequently,
this diet is only little better than actual starvation. On a diet of
proteins, salts and water, on the other hand, the animal most generally
survives. In the second place, it is not correct to assume that an
animal may be kept in equilibrium for any particular foodstuff if
the intake is exactly balanced with the waste.
This is true in particular of the proteins. Thus, if a starving
animal is fed an amount of protein which exactly balances the output
of nitrogen, the excretion of the latter rises to a level practically equal
to that of starvation, plus that of the protein ingested. This implies
1056 ABSORPTION
that the waste of tissue-proteins proceeds as before. To illustrate,
if a dog of medium size excretes on the fifth day of starvation about
5 grm. of nitrogen, this loss corresponds to a combustion of 31.25 grm.
of protein. Now, if the latter amount be given to this animal as
food, it will excrete nearly 10 grm. of nitrogen-waste. In order to
cause this animal not to lose more nitrogen than it receives, or better,
in order to place it in nitrogen-equilibrium, it is necessary to give it an
amount of protein the nitrogen-content of which is at least two and
one-half times that of the starvation standard. This same conclusion
may be arrived at by a consideration of the data derived from profes-
sional fasters. Since the total output of energy, say, on the fifth day
of the period of starvation, amounts to 1979 calories and the output of
nitrogen to 11.44 grm., it requires 71.5 grm. of protein to meet this loss.
But 71.5 grm. of protein yield only 293 calories and hence, the afore-
said amount of energy cannot be derived entirely from this protein.
The balance must be supplied by the tissue-fat and glycogen. Conse-
quently, the loss in the substance of the body cannot be stopped by
balancing the output of nitrogen by an equal ingestion of proteins.
While it is quite simple to retain by this means the nitrogen-equi-
librium in the strictly carnivorous animals, it cannot be kept in this
way by the herbivora and omnivora.
Since man belongs to the latter class and requires about 3000
calories for his daily work, it will be seen that at least 3 lbs. of lean
meat must be ingested by him in order to supply this amount of heat,
1 lb. of meat yielding less than 1000 calories. But this method of
furnishing the necessary energy for the body soon overtaxes the organs
of metabolism and places the person in the condition of partial starva-
tion. These facts form the basis of Banting's cure^ for obesity which,
by the ingestion of lean meat, attempts to give the feeling of satisfac-
tion connected with a *' square" meal, and at the same time causes
the body to burn up its reserve materials, retaining as far as possible
its proteins.
If the starving animal is fed a mixed diet instead of pure protein,
it is able to retain its nitrogen-equilibrium with much less difficulty,
because the ingestion of the proteins can then be made to approximate
the waste. The carbohydrates and fats are protein sparers. This is
true especially of the carbohydrates, because it has been shown that the
combustion of proteins during starvation may be greatly reduced by the
ingestion of this foodstuff. Thus, the administration of a large meal of
carbohydrates to a starving animal may raise its respiratory exchange
20 to 30 per cent. Furthermore, it is possible by this means to reduce
the daily output of nitrogen in men who partake of an average diet
of from 15 grm. to 6 grm. and less, without causing them to lose their
nitrogen-equilibrium. The amount of carbohydrate ingested must, of
course, balance the normal daily expenditure of energy. This subject
may also be approached the other way, i.e., by determining the amount
1 Advocated by Wm. Banting, an undertaker of London, 1797-1878.
THE METABOLIC REQUIREMENTS OF THE BODY 1057
of protein which must be ingested in order to bring a person into nitro-
gen-equihbrium. To attain this end we need 30 grm. of the proteins
of meat, 31 grm. of the proteins of milk, 54 grm. of the proteins of beans,
76 grm. of the proteins of bread, and 102 grm. of the proteins of corn.
This outHne shows very clearly that the proteins of the vegetables
are not so easily assimilated as those of meat.
Excessive Metabolism. — The body safeguards itself against possi-
ble disorders in its metabolism first by the quality and secondly, by the
quantity of the food. It constantly endeavors to retain a normal
balance sheet. Under ordinary conditions, however, more material
is ingested than is actually required to preserve its metabolic equi-
librium. This fact has led some physiologists to believe that a certain
luxus consumption is a necessity in order to allow for a definite waste.
Any excessive ingestion, on the other hand, leads as a rule to a certain
deposition of the superfluous material in the tissues. Thus, if a
normal animal is given excessive amounts of fats and carbohydrates,
a large portion of these, foodstuffs is converted into glycogen and
tissue-fat without materially increasing the general metabolism. In
the case of hyper amounts of proteins, however, no significant storage
takes place, and by far the largest part of this substance is excreted
directly. Consequently, the output of nitrogen may be employed
as an index of the amount of proteins ingested.
This fact shows very clearly that a luxus consumption in the case of
proteins cannot serve an important purpose, and is very expensive be-
sides. Chittenden has proved that a normal nutritive condition may be
attained on a mixed diet containing only 7 grm. of nitrogen daily. Men
partaking of this diet followed their ordinary vocations without diflS-
culty, and yielded from 32 to 35 calories per kilo of their body-weight.
In fact, when somewhat larger quantities of carbohydrates and fats
were given, the nitrogen ingo could be reduced to 5 grm. daily (33
grm. of protein). While these experiments indicate that a normal
person can get along with less protein than he usually takes, the ques-
tion as yet to be decided is: should he actually so deprive himself
for his own benefit ? Quite aside from an actual luxus consumption,
the answer might be that a material reduction in the ingo of pro-
tein material would undoubtedly lower the resistance of these persons,
at least in the course of time. Much also depends upon the quality
of the protein. The accepted view, however, is that a reduction in
the intake of proteins of one-third to one-half might be effected without
injury and, naturally, this necessary minimum of about 50 to 60
grm. of proteins, instead of the usual 100 to 150 grm., must be sup-
plied in the form of meat and vegetables to the exclusion of neither.
As has been stated above, much larger amounts of the latter must be
ingested in order to furnish the same amount of energy.
The foregoing discussion must have shown that an animal may be
in nitrogen-equilibrium and not in carbon-equilibrium. The latter,
however, is not so important, because the quantity of fat may vary
67
1058
ABSORPTION
considerably, while the nitrogen content remains practically the same.
Obviously, a gain in carbon means a gain in fat, and vice versa. In
the carnivorous animals, the carbon-equilibrium is retained on an
abundant protein diet, but this foodstuff must be supplied in excessive
amounts. Thus, Voit has shown that the larger carnivora need at
least 1500 grm. of meat daily to prevent a loss of carbon. For a
man weighing 70 kilos, this would mean an ingestion of 2000 grm.
of lean meat, and a combustion and elimination of nitrogen about three
times greater than normal. Obviously, a metabolism of this kind
could not be continued for any length of time. This again shows the
necessity of a mixed diet, as being more beneficial and economical.
CHAPTER LXXXVIII
THE NUTRITIVE VALUE OF FOOD
The Normal Diet of Man. — The quantity of food which is required
to keep a person in a condition of health is determined by its power
of sustaining the energy which he is called upon to liberate. While
the latter must vary considerably with the activities of the body,
we may adhere rather closely to the data of Rubner which show the
following energy requirements:
Weight, kilos
Area, sq. m.
Calories
Calories per kg.
80
2283
2864
35.8
70
2088
2631
37.7
60
1885
2368
39.5
50
1670
2102
42.0
40
1438
1810
45.2
Thus, it will be seen that a vigorous man weighing 70 kilos necessi-
tates close to 37 calories for each kilogram of weight, or about 2600
calories in all. During starvation this same person needs 32 calories
per kilogram, or 2200 calories in all. Consequently, the ordinary re-
quirement is about 14 per cent, above that of starvation. In order to
supply this energy, Voit gives the following ration for the use of work-
men performing 8 to 9 hours of work: proteins 118 grm., fat 50 grm.,
and carbohydrate 500 grm. This would yield 3055 calories which,
owing to a certain non-utilization, may be reduced to about 2700
calories. Rubner allows 127 grm. of protein and Atwater^ 125 grm.
for this class of workmen. Furthermore, in the case of severe work
1 Physiologie des Stoffwechsels, 1881.
2 Mem. of the Nat. Acad, of Sciences, Washington, 1902.
THE NUTRITIVE VALUE OF FOOD 1059
this supply must be increased considerably, thus: proteins 135 grm.,
fat 80 grm., and carbohydrate 500 grm. This represents a total value
of 3348 calories.
It will be observed that -the amount of protein remains fairly con-
stant, while the proportion of carbohydrate and fat varies considerably.
Moreover, these nutritive substances may be substituted for one an-
other within narrow limits, but none of them should be eliminated
from the diet altogether, because the retention of perfect health re-
quires the ingestion of a certain minimum amount of each. Various
other factors must also be considered. For example, if there has
been a loss of protein material from one cause or another, it is impera-
tive to ingest an extra amount of protein to allow for its storage in
the form of tissue proteins. Quite similarly, it is desirable to increase
the protein metabolism during periods of training, when a perfect
stability of the musculature is to be attained. A limited reduction
in the amount of the protein is justifiable only in vigorous persons.
Whether the prerequisite amount of protein is derived from animal
food or from vegetables is rather immaterial, although much quicker
results are obtained with the former. Both have their advantages
and disadvantages. While vegetables are efficient protein producers,
much larger quantities of them must be ingested in order to yield the
same degree of energy. In the end, this may not prove to be an eco-
nomical advantage, at least not at the present time. They possess,
however, certain stimulating qualities upon peristalsis and bring into
the body a greater variety of proteins than could possibly be introduced
by meat alone. It appears, therefore, that the ordinary person should
partake of a mixed diet rather than of one strictly vegetarian in its
character.
It has been observed by Rubner that a starving animal, when fed
with carbohydrate, shows an increase in its heat production of from
30 to 40 per cent. The feeding of meat also gives rise to an increase
under this condition, but the increase is then almost three times
greater. It will be seen, therefore, that the proteins are actual stimu-
lants of metabolism and possess for this reason a specific dynamic
action upon the organs of metabolism.
The Factor cf Growth. — In accordance with the well-established
fact that the intensity of the metabolism increases inversely with the
size of the animal, it cannot surprise us to find that children must com-
pensate for a much greater expenditure of energy than adults. Small
animals invariably lose more heat in proportion to the mass of their
body than large ones, although area for area of their body-surface
their dissipation of heat is practically the same. In order to make up
for this greater loss of heat, children must be more active. This is
true especially of boys before the .age of puberty. In addition, it is
not at all improbable that a second factor is at work at this time in the
form of some stimulus derived from energized and growing protoplasm.
Thus, a body between the ages of nine and fourteen requires as much
1060 ABSORPTION
food as an adult, and between the ages of fourteen to nineteen even
more than that. In the females there is a similar absolute increase
to about the eleventh year, when it becomes more constant and equals
about that of a woman of thirty. These brief data show very clearly
that the total energy and food requirements of the young animal are
higher than those of the adult. In the second place, it has been made
evident by the work of Mendel^ and others that growing tissues de-
mand not only an abundance of protein, but proteins of the proper
kind.
This statement leads us to infer that a diet may be well balanced,
as far as the ingo and outgo of the proteins are concerned, and yet fail
absolutely in supplying those substances which are absolutely essential
to growth. Thus, it has been shown by Osborne, McCoUum and
others that such proteins as legume.lin (soy bean), gliadin (wheat and
rye), legumin (pea), hordein (barley), zein (maize), and phaseolin
(kidney bean) may maintain life, but prove quite insufficient for
growth. Other proteins which are capable of sustaining growth are
glycinin (soy bean), glutein (wheat), glutelin (maize), globulin (squash
seed), edestin (hemp seed), and casein. In the case of casein it is of
interest to note that it does not contain glycocoll, one of the simplest
of the amino-acids, but this deficiency does not prove disturbing,
because the body is in a position to synthetize this substance from
other sources. Just the opposite result follows the withdrawal of
cystine, which the body cannot build up and must, therefore, obtain in
an available form. Quite similarly, the tissues may be maintained
in their present condition without lysine, although they cannot grow
in its absence. This substance seems to be a requirement of all
growing tissues, because it is present in large amounts in casein,
lactalbumin and egg vitellin. It will be seen, therefore, that the body
demands a mixture of protein foodstuffs from which it may then select
those amino-acids which are most essential for its growth. An ex-
clusive vegetable diet might easily prove insufficient, because it lacks
the aromatic amino-acids, tyrosine and tryptophane, the diamino-
acid, lysine, and the sulphur amino-acid, cystine. But this is also
true of certain proteins of animal origin; for example, gelatin, which
for this reason cannot be regarded as an adequate food.
Since milk is practically the sole food of the growing mammal, we
should expect to find its content in proteins to correspond closely to
the above principles. In support of this contention it might be men-
tioned that the analyses of milk from different animals have shown
that the protein content of this secretion varies with the speed with
which their young grow. For example, since the infant doubles its
weight in about 180 days and the kitten in 7 days, human milk
contains only 1.6 per cent, of protein and that of the cat 9.5 per cent.
Furthermore, the infant receives a relatively much greater proportion
of protein than the adult and, besides, an excess of fat in order to be
1 Harvey Lectures, Lippincott and Co., New York, 1915.
* THE NUTRITIVE VALUE OF FOOD 1061
able to utilize the former as tissue-protein and to burn the latter to
produce heat. In view of the larger body-surface of the infant and
its more intense metabolism, such a relationship is rather to be ex-
pected. Milk is also rich 'in calcium and phosphorus, a peculiarity
which greatly favors the growth of the skeleton.
The Inorganic Salts. — So far special attention has been paid to
the carbohydrates, fats and proteins. It is to be noted, however,
that an animal which receives these foodstuffs without the salts,
succumbs even more rapidly than one fed with an absolutely inade-
quate diet. Evidently, the inorganic constituents are as important
for the maintenance of life as the organic constituents, and this in
spite of the fact that they do not yield energy. They are absolutely
essential to the body for the reason that they help in maintaining the
composition and osmotic pressure of the body-fluids and determine,
therefore, the interchanges of its metabolites. Secondly, they form
essential constituents of the frame-work of the body and even enter
into the composition of its soft parts. Thus, it will be found that
the incineration of the body yields about 4.3 to 4.4 per cent, of its
weight in ash. Of this amount, five-sixths must be apportioned to
the bones and one-sixth to the soft parts. The ash consists of the
chlorids, phosphates, sulphates, carbonates, fluorides and silicates of
potassium, sodium, calcium, magnesium and iron. Besides, iodin occurs
in the tissue of the thyroid gland. It is also evident that the potassium
salts belong more particularly to the organized elements of the tissues,
whereas the sodiu'm salts are more directly concerned with the com-
position of the body-fluids, and the calcium salts with that of the bones.
In the latter case, it has been demonstrated beyond doubt that a
diet poor in calcium gives rise to rickets, a condition characterized by
a deficient and imperfect growth of the bones. In adult life, most of
the calcium ingested is again excreted in the feces and urine, although
an excessive storage may result later on which leads to a brittle condi-
tion of the bones and calcareous infiltrations of different tissues, such
as the walls of the blood-vessels. Iron enters the body in organic
combination, and it is still a much debated question whether inorganic
iron can actually be taken up and converted into so complex a sub-
stance as hemoglobin.
Bunge^ has called attention to the fact that man and the carnivor-
ous animals have no especial longing for salts, whereas the herbivora
and vegetarians seek it eagerly. With the exception of sodium chlo-
rid, however, these salts are taken into our system unconsciously
in combination with the different foodstuffs, but the addition of con-
siderable amounts of the former to our food does not seem to be a
necessity, inasmuch as 1 to 2 grm. of it suffice for ordinary purposes.
Consequently, the daily ingestion by the average man of 10 grm. of
this salt may rightly be considered to be far in excess of his actual
needs. Bunge explains this large intake of sodium chlorid by saying
1 Physiol, des Menschen, 1901.
1062 ABSORPTION
that the potassium sulphate, which is so abundant in vegetables in-
teracts with the sodium chlorid of the blood, forming potassium chlo-
rid and sodium sulphate. Both salts are then removed in the urine
and hence, it becomes imperative to renew the sodium chlorid content
of the blood repeatedly in order to keep it fairly constant.
Accessory Factors. — Besides the digestibihty and nutritive value
of the diet, practical dietetics must also pay attention to its palata-
bility. This involves cooking and the addition to the food of flavors,
condiments and stimulants. The first factor is important first of all
from an economic standpoint, because it tends to render the cheaper
foods more available and to decrease the perfectly appalling waste of
all food. Secondly, it makes the food more appetizing and destroys
its indigestible envelopes so that the digestive juices are able to attack
the nutritive material directly. Thirdly, it destroys parasites and
microorganisms and those antibodies which might inhibit the action
of the digestive juices. Thus, it is a well-known fact that raw white
of egg is not digested in the stomach, because it contains an antibody
which hinders the action of the pepsin, while a finely divided boiled
egg is more rapidly acted upon by this enzyme. Lastly, cooking is
of importance because it renders the food more bulky and macerates
the cellulose material of green food so that it can be more advanta-
geously utilized as ballast for the feces. This in itself stimulates peri-
stalsis and liberates certain substances possessing a laxative action.
The flavors and condiments have no especial food-value, but are
of importance because they make the food more 'appetizing. They
are divided into (a) aromatics, inclusive of such substances as cinna-
mon, vanilla and nutmeg, (6) pepper, (c) alliaceous substances, such
as garlic and mustard, {d) acid condiments, such as pickles, vinegar
and citron, (e) salty substances, such as the ordinary table salt, and
(/) sugar.
The stimulants consist of wine, beer, tea, coffee, chocolate and
cocoa. While some of these contain considerable amounts of nutritive
material, their principal action is very similar to that of the condiments,
i.e., they render the food appetizing and stimulate the secretions.
However nourishing a food may be, it eventually produces an antago-
nistic effect unless mixed with these stimulants. Thus, the rind of the
bread, the skin of fruits, and extracts of meat are almost as important
as the foodstuffs contained in these articles of diet. Besides, such
articles as beer and cocoa possess a distinct nutritive value, although
they do not form an adequate food when ingested alone. Thus, 14
liters of beer would be required to yield 15 grm. of nitrogen, and 10
liters of it to furnish 250 grm. of carbon. In the case of cocoa, we obtain
as much as 50 per cent, of fat, 4 per cent, of starch and 13 per cent, of
proteins, but excessive quantities would have to be consumed in order
to satisfy our caloric needs. Its stimulating alkaloid is theobromine
or dimethyl xanthin (C7H8N4O2), which exerts a tonic action upon the
nervous and vascular system similar to that of caffeine.
THE NUTRITIVE VALUE OF FOOD 1063
The usual stimulant taken by healthy persons is coffee or tea. In
addition to ethereal oil, tannic acid and other substances, these articles
contain the alkaloid caffeine {Runge, 1820) or theine. Coffee differs
from tea in being rich in aromatic material (caffeal). Tea contains
a bitter substance, tannin, and hence, it should not be allowed to draw
for longer than a few minutes, otherwise too much tannin will enter
the solution and produce injurious effects. Similar stimulating drinks
are the mate of Paraguay, the guarana of Brazil, the bush-tea of
South Africa, and the cola of Central Africa. Not being in possession
of caffeine plants, the inhabitants of Mexico derive their stimulating
beverage from the fermented seeds of the chocolate plant which contain
theobromine.
Among the alcoholic stimulants might be mentioned the malt
liquors, red and white wines, fortified wines, distilled liquors, or spirits,
and elixirs. Having a great affinity for water and being a coagulant
of protein, alcohol tends to destroy the cells. It should, therefore, be
regarded essentially as a protoplasmic poison. Regarding its action
as a stimulant and its value as a food, the reader must be referred to
the more specialized literature upon this subject, because it is alto-
gether too contradictory and extensive to be included in a book of
this kind.^ In general, however, it may be said that alcohol does not
build up the tissues, although it may serve to spare and to replace fats
and carbohydrates for a time and also to protect the proteins. For
this reason, it may be considered as an adjunct article of diet but not
as a true food. Obviously, its properties of yielding energy are com-
pletely overshadowed by its pharmacologic actions as a depressant and
irritant.
1 Welch, "The Pathological Effects of Alcohol;" Abel, "The Pharmac. Action
of Alcohol," and Atwater, "The Nutritive Value of Alcohol," in Physiol. Aspects
of the Liquor Problem, 1903.
SECTION XXVIII
EXCRETION
CHAPTER LXXXIX
THE SECRETION OF URINE
General Discussion. — The term excretion is commonly applied to
that process which purposes to remove the waste products from the
body. Living matter undergoes constant metabolic changes, and it is
• essential that the substances formed in the course of these processes
be removed as quickly and thoroughly as possible. But this state-
ment does not imply that the substances previously taken into the
body, are simply split into their components and excreted, because in
several instances the end-products are first converted into by-products
by synthesis. In other words, excretion should not be thought of as
a passive elimination of* the simple constituents of the food, but rather
as an active cellular synthesis. It is also evident that this process
must concern itself with the elimination not only of fluids, but also of
semi-solid material as well as of gases, and this is true of each in-
dividual cell as well as of the body as a whole. Thus, cellular dis-
similation counterbalances cellular assimilation, whereas excretion
counterbalances the nutritive material ingested.
On the excretory side of metabolism matters are relatively simple,
because, while gases and liquids of varying composition are in-
volved, the number of the excretory channels may really be reduced
to four, namely, the skin, lungs, alimentary canal and kidneys. The
chief gaseous excretion is furnished by the lungs in the form of carbon
dioxid. It constitutes the final stage in the elimination of the carbon
of the absorbed food. The principal fluid excretion is furnished by the
kidneys in the form of the urine, which contains the hydrogen and
unchanged water of the food as well as the various end-products of
protein metabolism. But the hydrogen and unchanged water of the
food are also eliminated by the skin, .lungs, intestinal canal and, in a
small measure, also by the nasal mucosa, lacrimal glands and mucous
glands. The undigested and unabsorbed portions of the food, as well
as certain true excretory materials, are eliminated in the feces.
The Structure of the Kidney. — The urinary organs embrace the
two kidneys, the two ureters, and the urinary bladder with the urethra.
In man each kidney is invested by a fibrous capsule and is deeply
imbedded in the fatty tissue of the lumbar region. Its capsule is only
1064
THE SECRETION OF URINE
1065
slightly adherent to its substance and is continued onward as the
external coat of the upper and dilated segment of the ureter. In
transverse section each kidney presents two rather sharply differen-
tiated portions, namely, an outer or cortical and an inner or. medullary.
This difference in the appearance of its cut surface is due to the peculiar
distribution of the urinary tubules, of which practically its entire
substance is composed. Consequently, it may be said that the
kidney is a compound tubular gland, the individual secretory units
of which are directed radially outward from a common central reser-
voir, known as the pelvis. For this reason, the beginning portion, or
glomerulus, of each urinary tubule must come to lie much closer to
Fig. 522. Fig. 523.
Fig. 522. — Diagraaimatic View op the Kidney in Longitudinal Section, Showing
THE ArBANGEMENT OF THE UriNIFEROUS TuBULES.
G, Glomerulus; P, pelvis; V, ureter; C, cortical substance; M, medullary substance.
Fig. 523. — Glomerulus with the Beginning Segment of the Uriniferous Tubule.
G, Glomerulus; A and E, afferent and efferent blood-vessels; C, capsule of Bowman;
N, neck of uriniferous tubule; CT, distal convoluted tubule.
the surface of the organ than its collecting segment. The renal cortex,
therefore, is made up principally of the glomeruU and distalmost por-
tions of the uriniferous tubules, while the medulla contains chiefly
the smaller and larger collecting channels as they strive to attain the
cavity of the pelvis.
Each tubule begins as a dilatation in which is suspended a coil of capillaries.
The former constitutes the capsule of Bowman and the latter the corpuscle of Mal-
pighi. At its point of exit from this enlargement the tubule is highly constricted,
forming here the so-called neck of the tubule. It then pursues a serpentine course,
this entire segment of it being known as the first or distal convoluted tubule. Then
follows a narrow, straight portion which actually enters the medulla but soon recurs
as a straight segment parallel to the former. These constitute the descending and
ascending limbs of the U-shaped loop of Henle. Having reentered the cortex, the
tubule again pursues a wavy course and forms the second or proximal convoluted
tubule. It now unites with others of the same kind into smaller collecting channels
1066
EXCRETION
and these in turn into larger ones until about a dozen conical bundles have been
formed, each of which constitutes what is known as a pyramid. The pointed ex-
tremity or apex of each pyramid projects well into the pelvic cavity, subdividing
the latter into a number of recesses. The pelvis is in free communication with the
ureter of which it really forms its funnel-shaped upper expanse.
The flattened epithelium of Bowman's
capsule is reflected over the tuft of capil-
laries. In the distal convoluted tube,
however, the lining consists of high and
markedly granular cells which exhibit a
peculiar brush-like outer margin and vesic-
ular formations. In the descending limb
of the loop of Henle, the cells are flat and
clear, while those of the ascending limb
are again higher and striated. These
changes in the character of this epithe-
lium are responsible for the relative nar-
rowness of the lumen of the ascending
limb. The cells of the proximal con-
voluted tubule again present a decided
fibrillated appearance. Those of the
collecting channels are cuboidal or colum-
nar in shape and quite clear.
The arterial supply of the kidney is
derived from the renal artery. Its two
terminal branches break up into smaller
ones which pass at first directly outward
but bend at almost right angles as soon as
they have reached the junction between
the medulla and cortex. From these
arched transverse vessels arise the inter-
lobular arteries which are directed straight
toward the surface of the organ and give
off here and there transverse branches
which finally form the tufts of capillaries,
previously described as the Malpighian
corpuscles. Each glomerulus, therefore,
consists of an afferent vessel representing
one of these branches, and a much nar-
rower efferent vessel which, after leav-
ing this structure, ramifies extensively
between the different convoluted tubules.
This capillary network then gives rise to
the interlobular veins and these in turn to
the renal vein. The medulla derives its
blood-supply -from straight arterioles
which arise from the transverse arterial
arches. These constitute the arterial
rectse.
The nerves innervating the kidney are
derived from the suprarenal plexus and
follow the highway of the artery around
which they form a rather close network. This plexus is known as the renal
plexus. It contains afferent and efferent fibers which are chiefly concerned with
the activity of the blood-vessels, although it has been claimed that they are also
secretomotor in their function. Preganglionically these fibers are contained in
the greater and lesser splanchnic nerves.
Fig. 524. — Diagrammatic Represen-
tation OF THE Blood-supply and Course
OF THE UrINIFEROUS TuBULE.
J, Interlobular blood-vessels derived
from arches between cortex and medulla ;
G, glomeruli; C, distal convoluted tubule;
D and A, descending and ascending
limbs of the loop of Henle; CT, collect-
ing tubule; P, papilla and pelvis of the
kidney.
THE SECRETION OF URINE 1067
Theories of Urinary Secretion. — The kidney is the most important
excretory organ of the body. Its function is to separate the constitu-
ents of the urine from the blood— its watery part as well as its solids.
Upon it, in particular, rests the maintenance of the composition of the
body-fluids; and hence, it must keep up an almost continuous activity
which cannot be compensated for by any other organ. Thus, it is a
well-known fact that the removal of both kidneys is fatal, owing to
the accumulation in the blood of the end-products of protein metabo-
lism. The same result follows the ligation of botli renal arteries,
but the extirpation of only one organ usually produces no untoward
effects, because the opposite organ then enlarges and accomplishes
the work previously performed by the two organs together.
The modern views regarding the manner in which the renal tubules
perform their work, is based upon the older theories of Ludwig^ and
Heidenhain.2 The former embodies the simple physical principles of
filtration and diffusion and the latter, these principles in conjunction
with a secretory activity on the part of the lining cells of the tubules.
The filtration theory of Ludwig holds that the glomerulus plays the
part of a filter, giving rise to a quantitatively and qualitatively com-
plete urine under the pressure of the blood. This structure, therefore,
constitutes the most important segment of the urinary tubule, while
the others fulfill merely the function of a conducting channel. In
substantiating this view, Ludwig laid particular stress upon the struc-
tural peculiarities of the glomerulus, emphasizing the fact that it
consists of a coil of capillaries which are suspended in a double-walled
capsule. Moreover, the narrowness of the efferent vessel tends to
augment the lateral pressure and to diminish the velocity of the blood-
flow. As far as the pressures are concerned, it will be noted that a
capillary blood pressure of 40 to 60 mm. Hg. is in this instance con-
trasted against a pressure of about zero, thus affording most favorable
conditions for a passive transfer of the constituents of the blood into
the capsule of Bowman. In the tubule this process is then augmented
by an endosmosis between the concentrated blood and the watery
urine which leads to a passage of the molecules of water from the urine
into the blood until the former has acquired its normal consistency.
This process of reabsorption of water from the urine Ludwig conceived
as purely physical diffusion, although he clearly recognized the fact
that this process may undergo decided changes in consequence of the
administration of diuretics, such as urea and sodium chlorid.
In 1842 Bowman^ expressed the idea that the glomerulus serves
merely as the seat of the secretion of the watery part of the urine,
whereas its solid constituents are formed in the tubule itself. In
analogy with his work upon other glands, Heidenhain then promulgated
the theory that the urine is not produced solely by filtration and
1 Wagner's Handworterb. der Physiol., ii, 1844, 628.
2 Hermann's Handb. der Physiol., v, 1883, 279.
3 Phil, transact., London, i, 1842, 57.
1068 EXCRETION
osmosis, but is materially modified by the activity of the cells lining
the convoluted tubule. It is assumed that the glomerulus furnishes
the water and inorganic salts, while the distal convoluted tubule
produces the specific organic constituents, together with an inconsider-
able quantity of water. Thus, the character of this secretion depends
in reality upon the activity of both groups of cells and varies with the
differences in the composition of the blood, the blood pressure, and the
velocity of the capillary blood-stream. Th vS rather schematic presenta-
tion of these two theories, however, should not convey the idea that
they are directly opposed to one another. They are not, because
Heidenhain does not deny the occurrence of filtration, but merely
amplifies this process by the secretory activity of the cells.
Facts Contradicting the Pure Mechanical Theory. — The kidney
is one of the most vascular organs in our body, receiving about 150
c.c. of blood per minute for each 100 grm. of substance; moreover,
its blood-supply is accurately controlled by a vasomotor mechanism
contained in the renal and suprarenal plexuses.^ The division of these
fibers gives rise to a relaxation and injection of the blood-vessels of
this organ, this change being associated as a rule with a copious flow
of urine and a slight albuminuria. - It is also a well-established fact that
urinary secretion is closely dependent upon the blood pressure, because
a fall in the latter is usually followed by a diminution in the quantity
of the urine, and vice versa. While this relationship is entirely in
accord with filtration, it can easily be shown that pressure is not the
only factor here at work, because if the renal vein is temporarily ob-
structed, a procedure which must necessarily raise the intraglomerular
pressure, the flow of urine stops altogether. In a similar way it has been
shown that a partial obstruction of the venous return produces only a
slight diminution in the rate of flow, which may immediately be in-
creased by the administration of a diuretic. This latter fact is of
importance, because SoUmann's experiments upon perfused excised
kidneys have shown that the stoppage of the flow of urine following
the ligation of the renal vein, may be caused by a mechanical obstruc-
tion of the uriniferous tubules caused by the distention of the entire
organ. A dissociation between the renal blood-supply and the flow of
urine may also be effected by the temporary ligation of the renal
artery, or by the stimulation of the vagus nerve. ^ Almost directly
thereafter the flow of urine ceases, as might be expected, but the flow
does not regain its former value immediately upon the reestablishment
of normal circulatory conditions, but in many instances only after an
interval of from 30 to 60 minutes. Consequently, while it may be
granted that the function of the kidney, like that of other organs,
is closely dependent upon the blood-supply, it is easily apparent
that some outside factor is here at work. In this connection, brief
1 Bradford, Jour, of Physiol., x, 1889, 358, Asher and Pearce, Zeitschr. fur
Biol., Ixiii, 1913, 83, and Burton-Opitz, Jour. Exp. Med., xl, 1916, 437.
2 Richards and Plant, Am. Jour, of Physiol., xlii, 1917, 592.
THE SECRETION OF URINE 1069
reference should also be made to the action of adrenalin which
stops the secretion of urine in spite of the fact that it heightens the
blood pressure. This discrepancy, however, is only an apparent one,
because upon its entrance into the kidneys, this agent constricts the
local blood-vessels and gives rise to an anemia which effectively blocks
the activity of these cells.
Secondly, it might be mentioned that a certain secretory resistance
does not retard the function of the renal cells but actually stimulates it.
While it is true that urine is formed under a glomerular pressure of
from 40 to 60 mm. Hg and a ureter pressure of about zero, the latter
may be heightened considerably before the cells actually cease their
function. The upper limit is reached at about 60 to 80 mm. Hg, i.e.,
at a pressure less than half of that necessary to stop the secretion of
saliva. The reason for their inability to raise the urinary pressure
more decidedly above that prevailing in the capillaries, is due in
largest part to the early occurrence of hydremia which indicates that
the watery constituents of the urine escape into the interstitial spaces
and are reabsorbed. Slight increases of the urinary pressure, on the
other hand, invariably augment the activity of these cells.
Thirdly, mention should be made of those experiments which
jointly establish the fact that the epithelial lining of the urinary tubules
possesses true secretory properties. Heidenhain first attempted to
prove this positively by injecting coloring material into the blood-stream
of rabbits and demonstrating its presence in the cells of the urinary
tubule by histological means. In order to eliminate the factor of
pressure as much as possible, the spinal cord was cut previous to the
injection. The vascular relaxation then ensuing gave rise to so low
a blood presssure that practically no fluid came down the tubules.
In all these cases, the indigo-carmine appeared in the form of blue
granules within the cytoplasm of the rodded epithelium, lining the con-
voluted tubules and ascending limb of the loop of Henle, but not in
the cells of the glomeruli. In fact, some of these granules could also
be detected in the lumen of the urinary tubule This was invariably
the case in all those animals whose spinal cord had not been divided
before the injection. Evidently, the retention of the vascular tonus
of the kidney tends to wash these granules rapidly out of the cells
into the secretory duct.
More recently Schaffer^ has confirmed these results by means of
leuco-indigo-carmine, a colorless reduction derivative of indigo-car-
mine. This pigment remained colorless in the cells themselves, but
appeared in its oxidized (blue) form in the lumen of the tubule. It
could not be detected in the capsule of Bowman. Heidenhain has also
shown that urate of soda is excreted by the lining cells of the tubules.
In attempting to prove that the glomerulus acts independently of the
convoluted tubule, Lindemann^ sought to isolate this structure by
1 Am. Jour, of Physiol., xxii, 1908, 323.
2 Zeitschr. fiir Biol., xlii, 1902, 161.
1070
EXCRETION
injecting oil into the circulation, but since oil embolisms were then also
found in the blood-vessels of the tubules, this method yielded no positive
results, although it was evident that the tubular vessels ridded them-
selves of these embolisms much sooner than the glomerular vessels.
Indigo-carmine injected at this time found its way in increasingly small
quantities into the urine, indicating thereby a gradual opening up of
the cells lining the convoluted tubules. The opposite condition may
be produced in rabbits by means of sodium tartrate which substance
gives rise to an inflammation or nephritis of the tubule.^ If a solution
of sodium chlorid and urea is then injected
into the circulation, the chlorin enters the
urine but not the urea. Obviously, the urea
is ordinarily secreted by the lining cells of the
tubule and not by those of the glomerulus.
Fourthly, the secretory character of the
tubular epithelium may be established as
follows: In the frog it is possible to render
either the glomerular or the tubular segment
of the urinary tubule bloodless, because the
kidney of this animal receives a double blood-
supply. The one from the renal artery nour-
ishes the glomerulus and the one from the
renal portal vein, the tubule. Nussbaum^
has shown that the ligation of the renal
artery greatly diminishes the flow of urine.
If urea is now injected into the dorsal lymph
sac of this animal, a very considerable amount
of this substance may be removed from the
urine. Obviously, therefore, the urea must
have found its way through the cells of the
tubules. The successful outcome of this ex-
periment requires a constant supply of oxygen
in order to retain these cells in a proper con-
dition of activity. This end can be accom-
plished by placing the frog in an atmosphere of oxygen. Contrariwise,
sugar, peptone and egg-albumin, when injected into the blood-stream, do
not enter the urine under these circumstances. These results have in
the main been confirmed by Beddard.^ In addition, it has been shown
that the cells of the convoluted tubule eventually degenerate when
supplied only with renal-portal blood, because this blood is deficient
in oxygen. The stimulating action of this gas upon the secretory
power of the renal cells is also indicated by the experiments of Collis,'*
which show that the perfusion of the frog's kidney with non-
lUnderhill, Wells and Goldschmidt, Jour, of Exp. Med., xviii, 1913, 347.
2 Von Fiirth, Ergebn. der Physiol., 1902, 395.
3 Jour, of Physiol., xxviii, 1902, 20.
* Ibid., xxxvii, 1908, &
Fig. 525. — Section
through the convoluted
Tubule (Frog) after In-
jection OF TOLUIDIN.
L, Lumen of tubule; C,
blood capillary. The lining
cells show blue pigment and
vesicles.
THE SECRETION OF URINE 1071
oxygenated saline solution greatly diminishes the flow of urine.
Contrariwise, the perfusion of this organ with oxygenated salt solution
increases its quantity.
Fifthly, attention should be called to the fact that the cells lining
the distal urinary tubule, possess all the essentials of secretory cells.
Thus, vesicles may be seen to form within their cytoplasm, the con-
tents of which are later on discharged into the lumen of the tubule.*
Besides, Bowman has observed crystals of uric acid within the cells
of the convoluted tubules of birds. Lastly, it is a well-known fact
that the secretion of urine may be stimulated by means of various
agents to which the name of diuretics has been given, and which in
accordance with their stimulating action upon the cells themselves,
may be placed in the same class with the lymphagogues, cholagogues
and lactagogues. Their action may be tested most advantageously by
perfusing the renal portal system of the frog with oxygenated salt
solution to which either caffeine, urea, phloridzin, or sodium sulphate
has been added. All these agents incite a copious secretion of urine
as well as a very striking increase in the oxygen consumption of this
organ. Very similar results may be obtained in mammals, but it is
to be noted that the urine secreted under the influence of these secreto-
gogues, is not at all like the blood plasma in its composition and also
varies with the character of the diuretic employed. The vital activity
of the renal cells is elucidated further by the fact that the sugar
and proteins of the blood are normally retained in the body, whereas
peptone and egg albumin, when injected into the circulation, are
eliminated almost immediately. Moreover, the kidney possesses
the power of abstracting urea from the blood, but does not excrete
significant amounts of sugar, and this in spite of the fact that the latter
substance is present in much larger quantities than the former.
Absorption from the Tubules. — While the preceding experiments
fully disprove the pure filtration theory of urinary secretion, there is
still another point embodied in Lud wig's theory which has given rise
to much discussion. Reference is now had to the absorption of water
from the urinary tubule to render the urine more concentrated than
when first secreted. This reabsorption, it is claimed by Ludwig, is
effected through the blood as well as through the lymph. In the first
place, it must be admitted that the constituents of the urine may be
made to pass in the reverse direction, as can be done by blocking the
ureter and allowing the pressure in the tubules to rise well above that
prevailing in the renal capillaries. Moreover, when substances,
such as potassium iodid, are at this time injected into the pelvis of
the kidney, they soon find their way into the blood where they may
be recognized chemically. The only question to be decided is whether
1 Gurwitch, Pfliiger's Archiv, xci, 1902, 71; Courmont and Andre, Jour, de
Physiol, et path, gen., vii, 1905, 255; and Hiiber and Konigsberg, Pfliiger's Archiv,
cviii, 1905, 323.
1072 EXCRETION
this process as outlined by Ludwig and more recently by Cushny,i
also takes place under normal conditions. In general, it may be said
that this point has not been satisfactorily proven; at least, the evi-
dence so far presented does not point toward a reabsorption of suffi-
cient magnitude to account for the complete concentration of the
freshly formed watery urine.
The factor of reabsorption has been emphasized in more recent
years by Brodie and Callis,^ and especially by Cushny. Possibly the
strongest point against this contention is that the amount of water
which would have to be reabsorbed from the uriniferous tubules, ap-
proximates the enormous value of 70 liters per day, but Cushny believes
that this is not a convincing criticism, inasmuch as the secretion
for each tubule would even then be only about 0.014 c.c. in the course
of one hour. Ribbert^ has approached this problem by removing
as extensive a portion of the tubules as possible, the contention being
that if reabsorption actually takes place, a much more fluid urine should
then be obtained. While this was actually the case, these results and
their interpretation in favor of the absorption theory have been ad-
versely criticized by Boyd^ and H. Meyer. ^ The latter in particular
lays stress upon the fact that the character of the urine after partial
removal of the medullary substance more closely approaches that of
an albumin-free filtrate. Furthermore, Gurwitsch^ has pointed out
that the ligation of the renal portal system in frogs diminishes the
quantity of the urine, as compared with that secreted by the normal
organ on the opposite side. Consequently, if the tubules actually did
absorb a large portion of the water of the newly formed urine, the
abolition of their function should really give rise to a more copious
and watery urine. As has just been stated, this is not the case. In
addition, it must, of course, be evident that a process of secretion
invariably necessitates two solutions, namely, the blood and the secre-
tory product separated by an animal membrane, and Magnus, Soll-
mann and others have shown repeatedly that any interchange between
these cannot be effected without the participation of the dissolved
substances. For this reason, a slight reabsorption may be essential
at times to equalize osmotic conditions, but not at all for the singular
purpose of removing only the water.
"Modem" Theory of the Secretion of Urine. — The so-called
"modern" theory of Cushny embodies the principles of urinary secre-
tion as outlined by Ludwig, and in addition, a reabsorption of the water
and inorganic constituents of the newly formed urine. The latter
is effected by a vital activity on the part of the epithelium of the tub-
1 The Secretion of Urine, London, 1917; also: Addis and Sheoky, Am. Jour, of
Physiol., xliii, 1917, 363.
2 Jour, of Physiol., xxxiv, 1906, 224.
5 Virchow's Archiv, xciii, 1883, 169.
* Jour, of Physiol., xxviii, 1902, 76.
^ Marb. Sitzungsber., 1902.
« Pfliiger's Archiv, xci, 1902, 71.
THE SECRETION OF URINE 1073
ules. It is held that a large quantity of plasma is filtered through the
glomerular vessels under the pressure of the blood and under exclusion
of the colloidal proteins. The non-colloidal material being allowed to
pass, owing to the permeajbility of the vessel-wall, imparts to the urine
a concentration approximately equal to that of the blood. Conse-
quently, the blood leaving the glomeruli, may be compared to a con-
centrated colloid solution which requires salts and water to reconvert
it into its original form. This end the blood attains as it traverses
the tubule by absorbing the constituents required by it from the
glomerular filtrate. Those substances which the plasma must again
obtain, are called threshold substances, while those which it does not
need again, are designated as non-threshold substances. The latter
remain in the urine to be excreted. Thus, urea must leave the body
as long as any of it is present in the blood, whereas the urinary sugar
must again pass into the blood, provided its concentration remains
below the physiological limit.
This theory may well be employed to explain several perplexing
points regarding the pathology of the kidney, particularly such as
concern diuresis, albuminuria and the phenomena associated with the
stagnation of the urine in consequence of urethral obstructions. In
spite of this fact, however, it cannot be said that it rises above the
dignity of a mere working hypothesis, because in view of the uncertain
and contradictory character of the evidence presented in its favor,
it seems risky to accept it as a truity. None seems sufficiently definite
to allow of no other and, possibly, more correct interpretation. It
appears, therefore, that the student who accepts Heidenhain's theory
which does not wholly exclude the factor of glomerular filtration, can-
not be considered as less "modern" than the one who adheres to the
absorption-hypothesis. Thus, it may be said that water and salts,
and even such substances as sugar, egg-albumin, peptone and hemo-
globin when injected into the blood-stream, are mainly excreted by
the glomeruli, whereas urea, uric acid, and the other organic constitu-
ents, together with small ' amounts of water and salts, are excreted
by the epithelium of the uriniferous tubule. Neither process is accom-
plished by filtration alone, but embraces a definite vital element
consisting of unknown physicochemical factors resident in the renal
cells. Both processes are closely dependent upon the pressure and
velocity of the renal blood flow. In this connection, it should also
be mentioned that the existence of separate secretory nerves to the
kidney has not been proved,^ although it must be granted that the
stimulation of the fibers constituting the renal plexus, profoundly
affects the quantity and quality of the urine. These results, however,
may be due wholly to vasomotor influences.
Dimresis. — ^The diuretics produce their characteristic effect in two
ways, namely, by augmenting the secretory pressure and concentra-
1 Asher and Pearce, Zeitschr. fiir Biol., Ixiii, 1913, 83; and Pearce and Carter,
Am. Jour, of Physiol., xxxviii, 1915, 350.
68
1074 EXCRETION
tion of the blood, or by furthering the activity of the renal cells. Con-
sequently, either the glomerulus or the tubule may be involved in this
process. Thus, we might say that digitalis enhances the circulatory
conditions, because it stimulates the cardiac musculature and raises
the tonicity of the vascular channels. Caffeine possesses a similar
action.^ It is evident, however, that a mere increase in the vascularity
or a passive injection of the renal capillaries does not give rise to a flow
of urine. Another way in which the secretory conditions might be
altered, is to change the osmotic pressure of the blood. For example,
if a hypertonic solution of sodium chlorid is injected into the circula-
tory system, the osmotic pressure of the blood is increased, and fluid
is drawn into the vascular channels from the lymphatics until
it acquires a lower osmotic pressure. ^ This condition is called
hydremic plethora. It follows then that the renal blood flow is more
rapid and forceful, a change which greatly favors the transudation
of the excess of fluid through the renal capillaries. The same effect
may be produced intentionally by the ingestion of large quantities
of water or by means of dialyzable substances, such as sodium sul-
phate, sodium or potassium bicarbonate, the acetate, citrate or bitar-
trate of potassium, liquor ammonii acetatis, liquor ferri et ammonii
acetatis, urea, and dextrose. The most efficient of these are the
bicarbonates and potassium acetate. Urea and dextrose may act
chiefly as direct stimulants to the renal cells, but also, in a measure,
by changing the osmotic conditions. Pituitary extract seems to
possess a direct action upon the cells although its action upon the
circulatory system cannot be excluded.
A more detailed explanation of diuresis cannot be given unless re-
sort is taken to the well-conceived but still hypothetical absorption
''theory. '^ If the polyuria of diabetes mellitus is taken as an example,
it might be said that the kidney is quite unable to concentrate the
urine against the concentrated sugar-urine in the tubules. In accord-
ance with the preceding discussion, this would imply that sugar be-
comes a ''non-threshold" substance, owing to the presence of sugar
in the blood in amounts greater than the optimum.
Albuminuria. — While the proteins of the blood do not enter the
blood under normal conditions, their escape cannot be prevented if
the permeability of the glomerulus is increased. A condition of this
kind develops in acute nephritis and cardiac failure. The quantity
of the urine is then usually diminished, but the question of whether
this disease remains confined to the glomeruU or also involves the
tubules, cannot be decided with certainty. Theoretically, however,
we might expect to obtain a glomerular as well as a tubular nephritis.
In the chronic type of this disease the urine retains a low specific
gravity and viscosity^ and, using the absorption hypothesis as a basis,
1 Lowi, Arch, fiir exp. Path, und Pharm., liii, 1905, i.
2 Gottlieb and Magnus, ibid., xlv, 1901, 223.
3 Burton-Opitz and Dinegar, Am. Jour, of Physiol., xlvii, 1918, 220.
THE EXPULSION OF THE UKINE. MICTURITION 1075
it might be said that this condition is dependent upon an impairment
of the resorbing mechanism.
Let us also remember that the removal of one kidney is not followed
by any untoward results, because the opposite organ then enlarges
and continues to do the work previously accomplished by the two.
The extirpation of both kidneys, however, proves fatal invariably, the
animal dying a few days later of uremic poisoning. The same re-
sults follow the ligature of both renal arteries. ^ While the conditions
of anasarca, ascitis, and others, would furnish many points of physi-
ological interest, they more properly belong into the field of general
pathology.
CHAPTER XC
THE EXPULSION OF THE URINE. MICTURITION
The Function of the Ureter. — The duct of each kidney, or ureter,
is a muscular tube measuring about 30 to 45 cm. in length. It begins
above at the pelvis and terminates below in the wall of the bladder.
It is lined by mucous membrane and consists of an inner circular coat
of smooth muscle tissue and an outer coat of fibrous tissue. As the
small globules of urine escape from the different collecting tubules,
they are retained at first in the pelvic cavity until this reservoir has
become sufficiently distended. A reflex is then set up which gives
rise to peristaltic waves which travel slowly in the direction of the
bladder, each contraction forcing a small amount of urine ahead of it.
These waves recur at rather regular intervals and increase in frequency
as larger amounts of urine are secreted. Their number is usually 3
to 6 in a minute and their rate of progression 2 to 3 cm. in a second. ^
The activity of the ureter is controlled by nerve fibers derived from
the renal plexus as well as from the hypogastric nerves. Their central
segments, however, are said to be free from them, although ganghon
cells have been detected throughout their entire length. In accordance
with this rather deficient nerve-supply, Engelmann^ has formulated
the theory that these rhythmic contractions are of myogenic origin.
This view finds additional support in the fact that even excised portions
of the ureter show a peristaltic activity which may be greatly increased
by immersing them in warmed saline solution. Equally convincing
data, however, might be submitted in favor of the neurogenic theory,
and hence, no definite statements can be made at this time regarding
1 Pilcher, Jour. Biol. Chem., xiv, 1913, 387.
2 Heidenhain, Archiv fiir mikr. Anat., 1874; and Protopow, Pfliiger's Archiv,
Ixvi, 1897.
3 Pfliiger's Archiv, ii, 1869.
1076 EXCRETION
this matter. The pelvic segment of the ureter is undoubtedly well
equipped with nerve fibers and it appears that this portion acts as the
pace-maker for the lower segments. Experimentally, however, it is
possible to evoke peristalsis in any part of this organ. Since smooth
muscle tissue is seldom richly supplied with nerve tissue, the relatively
''nerve-free" central portion might normally be dependent upon in-
fluences conveyed to it from the pace-maker through the agency of
the aforesaid ganglion cells. ^
The Urinary Bladder. — ^The bladder is composed of a mucous,
submucous, muscular and serous layer. Its muscular coat contains
an outer longitudinal, a middle circular, and an inner anastomosing
or oblique layer of fibers. The fibers of the first pass in an almost
direct line from the fundus to the urethra, where some of them become
attached to the pelvis as the pubovesical muscle. Posteriorly, the
strands end, in the male, in the prostate and, in the female, in the
urethral-vaginal septum. The median coat is much thicker and con-
sists of fibers arranged transversely to the long axis of the organ. At
the cervix, this layer is materially strengthened, forming here the inter-
nal sphincter vesicae. Farther outward and enveloping the root of
the urethra, is a second sphincter which is composed of striated muscle
tissue, and is usually designated as the external sphincter or sphincter
urethrse. The inner coat of muscle tissue consists of obliquely ar-
ranged fibers which are distributed in an irregular manner and per-
meate the different layers.
As each ureter continues to empty small quantities of urine into
the fundus of the bladder, its walls are forced outward more and more
until they have attained a physiological degree of distention. A
pontraction of the musculature then ensues which drives the urine
through the relaxed sphincters to the outside. Under ordinary con-
ditions, therefore, the peristaltic waves of the ureters need not over-
come a considerable resistance and their power is more than ample to
force the urine into the fundus. But a regurgitation of the urine into
the ureters is quite impossible even during the interims, because the
orifices of the ureters are firmly closed. This end is not accomplished
by special sphincters, but in an indirect way by the distention of the
walls of the bladder. Inasmuch as the ureters perforate the latter in
an oblique direction and open by means of slit-like orifices, the gradual
filling of the bladder must cause the lip-like margins of these openings
and neighboring segments of the ureters to become firmly approxi-
mated. Consequently, the greater the internal pressure, the more
firmly will these orifices be closed. In general, therefore, it may be
said that three factors are at work to prevent the regurgitation of
the urine, namely, gravity, the peristaltic action of the ureters, and the
mechanical closure of their orifices by the distention of the walls of
the bladder.
The foregoing discussion also shows that the high pressures which
^ Lucas, Am. Jour, of Physiol., xvii, 1906, 392.
k
THE EXPULSION OF THE URINE. MICTURITION 1077
are developed at times within the bladder during its periods of con-
traction, cannot possibly interfere with the vascular supply nor
the secretory function of the kidneys. ^ Very different conditions,
however, arise if the pressure in the ureter itself is raised excessively,
a condition commonly associated with the stagnation of the urine in
consequence of renal calculi. A very decided reduction in the blood
flow through the corresponding kidney then results which cannot
remain without effect upon its secretion.
Physiologically, the bladder must be considered as a hollow muscu-
lar organ, the contraction of which places its contents under a consider-
able pressure. 2 Since the orifices of the ureters are closed, the pressure
so developed must be directed toward the internal and external sphinc-
ters. The resistance of the latter, however, cannot be overcome by
pressure alone, and hence, the voiding of urine or act of micturition
must also necessitate the relaxation of these bands of muscle tissue,
the inner one by reflex action and the outer one volitionally. A third
factor at work during this process is the abdominal press. It will be
remembered that the latter consists in an inspiratory action which
is immediately followed by a closure of the laryngeal orifice and a con-
traction of the abdominal muscles and diaphragm. The increase in
the abdominal pressure produced thereby is propagated unto the pelvic
organs and favors micturition as well as defecation. In most in-
stances, however, it is not brought into play until the final stages of
these acts.
Under ordinary conditions, micturition does not result until the
pressure in the bladder has risen to about 150 mm. II2O, i.e., at a time
when this organ has been distended sufficiently to contain between
230 and 250 c.c. of urine. To begin with, of course, the pressure
increases very slowly, owing to the constant relaxation of the walls of
the bladder. Eventually, however, as the tissues have about attained
their maximal degree of stretching, the pressure rises more rapidly
and finally evokes a series of slight rhythmic oscillations which are
soon succeeded by more forcible contractions. But, much depends
upon the rapidity with which the bladder is being filled, because a slow
influx of urine enables the different muscle fibers to lengthen more
gradually, while a more rapid influx causes them to react antagonisti-
cally by tonic or rhythmic contractions, thereby evoking micturition
much sooner. Furthermore, since the external sphincter is under the
control of the will, the forceful contraction of this ring of muscle tissue
may overcome these reflexes, at least for a short time. When aided
by the abdominal press, a pressure of 2 m. H2O may be produced.
The Nervous Control of the Bladder. — The reflex center for mictu-
rition is situated in the lumbosacral segment of the spinal cord, whence
connections are formed with the higher centers. In this way, volition
1 Burton-Opitz, Pfliiger's Archiv, cxxiii, 19.
2 Rehfisch, Virchow's Archiv, xl, 1897, iii; also: Mosso and Pellacani, Arch,
ital. de biol., i, 1882, 291.
1078
EXCKETION
and various afferent impulses may be brought to bear upon this reflex
mechanism. Thus, we have previously found that micturition may
also be evoked by associations resulting in consequence of visual and
auditory impressions, such as the sight or sound of running water.
Secondly, the action of the simple center may be inhibited or accelerated
by volition. In the latter case, however, the impulses seem to be con-
centrated upon the sphincter mechanism and upon those perineal mus-
cles which normally aid in the closure of the urethra. Contrariwise,
Bud. mes. ganglion.
StA Iamb. Te'rt
••flypogasfrlc
plexus
..Sciatic n.
.Sacral nervea
Fig. 526. — Nebvb Supply to Bladder of Cat. (Nawrocki and Skabitschewsky.)
the relaxation of these sphincters may be hastened by the con-
traction of the abdominal muscles; in fact, it is held by some investi-
gators that even the involuntary muscle tissue of the bladder is partially
under the control of the cortex of the cerebrum. This view is based
upon the fact that the destruction of the crus cerebri in animals whose
abdomen had been opened, gives rise to a contraction of the bladder.
Since the local mechanism of micturition requires efferent impulses
which, on the one hand, lead to a contraction of the musculature of
THE EXPULSION OF THE URINE. MICTURITION 1079
the bladder, and, on the other, to a relaxation of the sphincter, two
separate nerve paths must be provided for. According to Langley
and Anderson, 1 one of these arises in the four upper lumbar nerves and
the other, in the second and third sacral nerves by way of the visceral
nerves of the pelvis, the nervi erigentes. The former eventually termi-
nate in the bilateral inferior mesenteric ganglion, whence a new relay
of fibers is formed which extends in the form of two nerves, the hypo-
gastric nerves, into the pelvis on each side of the rectum. They termi-
nate finally at the base of the bladder in an extensive ramification
which is known as the hypogastric plexus. From here these fibers
ascend to the fundus of the bladder. The second set of fibers passes
from the second and third sacral nerves directly to the hypogastric
plexus, and hence, they do not first enter the sympathetic system.
Their relay stations lie in the aforesaid plexus and in the walls of the
bladder itself. The afferent impulses from this organ select chiefly
these visceral fibers of the pelvis in reaching central parts. ^
This brief enumeration shows that the hypogastric plexus is sup-
plied with sympathetic fibers from the lumbar cord and with para-
sympathetic fibers from the sacral cord. As far as the individual
action of these fibers is concerned, further investigations are needed to
be able to cite definite results. All physiologists, however, are agreed
that the excitation of the sacral fibers on either side produces a strong
contraction of the bladder, leading to the relaxation of the sphincters
and the discharge of the urine. But, the question whether these
nerves actually contain inhibitory fibers for the sphincters, has not been
definitely settled. Fagge,^ for example, claims that they do not and
that the relaxation of the sphincters takes place indirectly in conse-
quence of the high intrave^cal pressure. The function of the hypo-
gastric nerves has not been clearly established, because it is not the
same in all animals. In the dog, their stimulation leads to a strong
contraction of the musculature around the base of the bladder, whereas
in the cat and rabbit this procedure gives rise to an inhibition. It
appears, however, that they are never without motor fibers for the
sphincter vesicae and the constrictor tissue of the urethra.
1 Jour, of Physiol., xix, 1895, 71; also Stewdrt, Am. Jiour. of Physiol., xxx,
i.
2 Nawrocki and Skabitschewsky, Pfliiger's Archiv, xlix, 1891, 141.
3 Jour, of Physiol., xxviii, 1902, 305.
1080 EXCRETION
CHAPTER XCI
THE COMPOSITION OF THE URINE
General Characteristics of Urine. ^ — The urine of man is a clear,
fluorescent fluid, the color of which varies from light yellow to dark
yellow in accordance with its content in pigmentous material. The
latter consists chiefly of urochrome, which is composed of 11.1 per cent,
of nitrogen and 5 per cent, of sulphur, and is in all probability derived
from protein. Urobilin, another pigment, is present in normal urine
in only very small quantities. It is derived from the coloring mate-
rial of the bile which is converted in the intestines into stercobilin.
While the latter leaves the body principally in the feces, some of it
is reabsorbed to be finally excreted in the urine. Its mother-sub-
stance, known as urobilinogen, is present in somewhat greater quanti-
ties and is easily oxidized into urobilin proper. The pink coloring
material of the urates is uroerythrin. A trace of hematoporphyrin
is also present normally.
The odor of urine depends upon the quality of the food ingested.
When meat, bread and butter are taken, it is not at all unpleasant.
A most peculiar odor is imparted to it by asparagus. To the taste urine
is bitter and salty. The quantity of urine varies considerably, and de-
pends upon the intake of water and the proportion of it which is ex-
creted through other channels, such as the intestines, sweat glands and
respiratory passage. Under ordinary conditions, from 1400 to 1800
c.c. are voided in the course of twenty-four hours, the smallest portion
of this amount being excreted during the night. If a reverse relation-
ship exists so that the person must micturate during the night, sus-
picions of renal disease should be aroused, but naturally, only if moder-
ate amounts of water and other fluids have been taken on the
evening preceding. .
The specific gravity of the urine varies greatly in different persons as
well as in the same person at different times of the day. The chief
factor tending to vary its value is the proportion of water to the amount
of solids ingested, and the relationship between the activity of the
kidneys and that of the other excretory channels. Under ordinary
conditions, values between 1.015 and 1.025 are encountered, while
a constant value of 1.010 and less would point toward the presence
of hydruria, and one of 1.030 and over, toward diabetes. Temporary
variations of this kind, however, are common and may easily be pro-
duced by an intake of large quantities of water or by profuse sweating.
1 For a more detailed discussion the reader is referred to Mathew's Biological
Chemistry, Hamburger's Osm. Druck and Jonenlehre, and Oppenheimer's Handb.
der Biolog. Chemie.
THE COMPOSITION OF THE URINE 1081
The viscosity of urine is normally 1.2 as great as that of distilled water
at 37° C-. While blood freezes at -0.56° C, urine freezes at -°1.0 to
— 2.5° C. If very dilute, the freezing point may lie at 0.075° C, and if
very concentrated at — 5^ C.
The reaction of the urine of man and the carnivora is acid to litmus
and phenolphthalein. This is due to the fact that neutral constitu-
ents of the food are eventually transformed into acid end-products, the
sulphur of the proteins giving rise to sulphuric acid, and the phosphorus
of lecithin to phosphoric acid. An ingestion of large quantities of
vegetables and fruits, however, will make it alkaline and ttirbid, owing
to the precipitation of earthy phosphates. In the herbivora, the urine
is alkaline, because their food embraces fruits and vegetables which
contain salts of dibasic or polybasic acids, such as acid potassium
malate, citrate, acetate and tartrate. The oxidation of these bodies
during metabolism gives rise to carbonates. Some of the carbonic
acid leaves the body through the lungs, whereas their bases are excreted
in the urine as alkaline carbonates. For this reason, the urine of these
animals frothes on addition of an acid. Furthermore, if these animals
are starved, their urine becomes acid, because they then live upon their
tissues and are converted, so to speak, into carnivorous animals. This
is also true of man, because the withholding of fruits and vegetables
removes all possibility of the urine becoming alkaline. In disease,
it is more generally acid, this change being due in most instances to the
restriction of the diet. With the increase in acidity, the excretion of
ammonia is usually augmented.
The composition of the urine differs somewhat with the type of
food ingested and the quantity of water eliminated through this channel.
In general, however, it may be said to contain 60 grm. of solids, of
which 25 grm. are in the form of inorganic and 35 grm. in the form
of organic substances. Thus, an adult man on a mixed diet yields
about 1500 c.c. of urine in a day which shows the following compo-
sition:^
Inorganic substances Organic substances
Sodium chlorid 15.0 grams Urea 30 . 0 grams
Sulphuric acid 2.5 grams Uric acid 0.7 grams
Phosphoric acid 2.5 grams Creatinine 1.0 grams
Potassium 3.3 grams Hippuric acid 0.7 grams
Ammonia 0.7 gram Other constituents 2.6 grams
Magnesia 0.5 gram
Lime 0.3 gram
Other constituents 0.2 gram
THE INORGANIC CONSTITUENTS OF URINE
Chlorid s. — The inorganic or mineral constituents of urine consist
principally of chlorids, phosphates, sulphates and carbonates of sodium,
potassium, ammonium, calcium, and magnesium. The total amount
1 Mosenthal, Arch. Int. Med., xvi, 1915, 733.
1082 EXCRETION
of these salts varies between 19 and 25 grm. per day, of which sodium
chlorid is the most abundant, because it is excreted in amotmts of 10
to 16 grm. in a day. Evidently, the chlorids of the urine are derived
almost wholly from the chlorids of the food and hence, their amount
must vary very closely with the character of the material ingested. If
the latter is rendered relatively chlorin free, the chlorids may dis-
appear almost completely from the urine, although the blood retains
its normal composition in this regard. Quite similarly, the intake of
large quantities of table salt raises the chlorin content of the urine.
It is diminished in certain diseases, such as acute pneumonia.
Sulphates. — The sulphates of urine are principally those of potas-
sium and sodium, but since the salts of sulphuric acid, owing to their
bitter taste, etc., do not form an important constituent of our food,
the sulphates in the urine are derived almost exclusively from the
oxidation of the sulphur of the proteins. The nitrogen of these sub-
stances leave the body chiefly as urea, while their sulphur constituents
are converted into sulphuric acid which is passed into the urine in the
form of sulphates. Consequently, the output of sulphates may be
employed as an index of protein metabolism, in the same way as urea.
The average daily output of sulphates varies between 1.5 and 3.0 grm.
In addition to the sulphates of the alkaline metals, urine also con-
tains a small proportion of them in the form of conjugated or ethereal
sulphates (10 per cent.), principally as phenyl sulphate and indoxyl
sulphate of potassium. The latter originates in largest part in the
putrefactive processes within the intestine, chiefly from indole, and as
it yields indigo when treated with certain reagents, it is usually called
indican. The presence of this substance is of some importance, be-
cause it allows us to estimate the intensity of intestinal putrefaction
and the power of our body to convert these poisonous derivatives into
the innocuous ethereal sulphates. A small proportion of the sulphur
contained in urine, is present as neutral sulphur representing its un-
oxidized form.
Carbonates. — These salts are present only in alkaline urine, and
are represented by the carbonates and bicarbonates of sodium, calcium,
magnesium, and ammonium. They arise from the carbonates of the
food, and must, therefore, be most evident in herbivora and vege-
tarians. A urine of this kind becomes cloudy on standing, owing to
the precipitation of its carbonates, chiefly calcium carbonate, and also
phosphates.
Phosphates. — These salts are derived partly from the phosphates
of the food and partly from the oxidation of the organic phosphorus-
containing bodies of the tissues, such as nuclein, lecithin, etc. Their
daily excretion varies between 1.0 and 5.0 grm., calculated as P2O5,
and is almost wholly dependent upon the phosphate content of the
food. Thus, if much calcium or magnesium is present in the latter,
they are excreted in the feces as calcium and magnesium phosphate,
sometimes as much as 30 per cent, of the total choosing this medium
THE COMPOSITION OF THE URINE 1083
for leaving the body. The remainder exists in the urine as mono-
and disodium hydrogen phosphate, the amount of each varying with
the reaction of this medium. If neutral or alkaline, a deposit of
earthy phosphates results- which may immediately be cleared up by the
addition of acid. This condition generally arises after a copious vege-
table diet, when a large amount of disodium hydrogen phosphate is
produced. Quite similarly, an abundant ingestion of protein sub-
stances, gives rise to an acid urine, owing to the formation of sulphuric
and other acids. In the latter case, there is a greater formation of phos-
phoric acid and production of monosodium hydrogen phosphate.
On standing, the urine assumes an alkaline reaction, owing to the
conversion of the urea by the micro-organisms into ammonium car-
bonate. Under these circumstances, a creamy white precipitate is
formed which consists of triple phosphate or ammonium-magnesium
phosphate, and stellar phosphate or calcium phosphate. It should be
remembered, however, that even normal human urine contains a
small quantity of ammonia, i.e., from 0.6 to 0.8 grm. in a day.
This amount may serve as an index of the excess of acids over bases
which are to be excreted. While it is possible to vary this amount arti-
ficially, for example, by the administration of mineral acids, any
increase during the normal ingestion of food invariably signifies that
abnormal acid substances are formed in the body. This is the case in
diabetes mellitus, a disease in the course of which the fatty acids
accumulate in consequence of their diminished oxidation. This accu-
mulation must necessarily lead to a rise in the ammonia content of the
urine.
THE ORGANIC CONSTITUENTS OF URINE
Urea or Carbamide. — ^The greatest amount of the organic material
in urine is made up of nitrogenous bodies which are derived from the
proteins of the food. We have seen that the substances are broken
up in the intestinal canal into their amino-acids which after their
absorption are either converted into the proteins of the tissues or are
diamidized. In the latter case, the principal portion of the carbon,
oxygen, and hydrogen is oxidized to form CO2 and water, whereas the
smaller portion is combined with nitrogen to form urea, ammonia,
uric acid, and other bodies. This same fate awaits the tissue-proteins
which are constantly broken down 'and replaced by new material. It
has also been pointed out above that by far the largest amount of the
nitrogen of the food is excreted in the urine, and that only a small
portion of it enters the feces or is lost in the sweat. Consequently,
the total nitrogen content of the urine gives in a fair way the total
amount of nitrogen ingested, because under ordinary conditions, the
body is in nitrogen-equilibrium and its N-ingo equals its N-outgo.
This relationship, however, does not hold true when the body is grow-
ing and needs nitrogenous material for the construction of its cells. It
may also be disturbed for a time for other reasons. Thus, a reduc-
1084 EXCRETION
tion in the amount of the proteins ingested finally causes a diminution
of the body-proteins, which in turn are drawn upon later on to make
good the loss in the intake. Quite similarly, any increase in the protein
content of the food gives rise to an increase in the nitrogen of the urine.
The nitrogen metabolism of the body, however, cannot be estimated
precisely unless a comparison is made between the total nitrogen of
the urine and the amount of nitrogen ingested, because only when
both factors are known is it possible to determine the character of
the intermediary processes.
The most important nitrogenous constituent of urine is urea.
Formerly thought to be produced in the kidneys, it is now a well
established fact that it arises elsewhere in the body and is brought to
these organs in the form of a rather complete precursor. The renal
cells, therefore, merely remove this product from the blood by virtue
of a peculiar selective power. We know this to be true, because the
formation of urea and other waste products of this type continues
even after the kidneys have been extirpated or have been rendered
functionally useless by disease. This substance then accumulates in
the blood and gives rise to the condition of uremia. It should be
noted, however, that the poison acting at this time, is not the urea nor
any other normal constituent of urine, but some intermediary product
of protein catabolism. The question pertaining to the place of origin
of this substance seems to have been decided in favor of the liver,
because :
(a) The removal of this organ in mammals proves fatal owing to the accumula-
tion of certain catabolic substances. This is indicated by the gradual diminution
of the urea content of the urine. A similar effect may be produced by the establish-
ment of an Eck fistula, the urea of the urine then being lessened and the ammonia
increased.
(b) The extirpation of the liver in the frog and allied animals brings about a
substitution of the urea by ammonia.
(c) Such diseases as cirrhosis and yellow atrophy of the liver are characterized
by a similar change. In the latter case, the amino-acids, such as leucine and
tyrosine, appear in the urine, because they escape further reduction in the liver
and pass directly into the urine.
(d) If amino-acids, such as glycine, leucine, arginine, and others are adminis-
tered by the mouth or are injected into the blood-stream, the urea excretion is
increased.
This view, that urea is the result of a conversion of the amino-acids
by the cells of the liver, is also strengthened by the fact that some of
these bodies may be made to undergo this change in the test tube.
In the case of arginine, Kossel and Dakin^ have found that it consists
of a urea radicle and a substance known as ornithine. On hydrolysis
it splits into urea and ornithine. This same reaction is supposed to
occur in the liver under the influence of arginase, the arginine then
being split up into simpler compounds which are again combined
. 1 Zeitschr. fur Physiol. Chemie, xlii, 1904, 181.
THE COMPOSITION OF THE URINE 1085
differently into urea. Schroder^ has shown that one of these simple
compounds, although not the principal one, is ammonium carbonate.
Thus, it may be concluded that urea is a synthetic product of the liver
cells.
In accordance with our previous discussion, urea may be regarded
as partly exogenous, and partly endogenous, because it is derived, on the
one hand, from nitrogenous bodies which have been absorbed but have
not become intimate constituents of the tissue cells, and, on the other,
from bodies which have been discharged by the cells after they have
previously formed a part of them. In other words, urea finds its
origin in the circulating proteins, as well as in the tissue proteins. It
may then be reasoned that a person in nitrogen-equilibrium discharges
only a small and rather constant amount of tissue proteins and that,
therefore, the endogenous urea must possess a small and constant value.
Contrariwise, it may be assumed that the amount of the exogenous
urea is much larger and variable, because it is taken from the variable
and excess quantities of proteins ingested. It is true, however, that
the endogenous variety may also undergo marked alterations, for
example, in fevers and other pathological conditions causing a rapid
destruction of the tissue proteins.
Although subject to variations for reasons just stated, the amount
of urea excreted in the course of a day is usually given as 33 to 35
grm., provided about 100 to 120 grm. of protein are ingested. ^
Its amount becomes greatest three hours after a mixed meal and may
constitute as much as 90 per cent, of the total nitrogen if large quanti-
ties of protein are ingested. Upon a low protein diet, such as has been
advocated by Chittenden, the urine shows a nitrogen-content consid-
erably below that ordinarily regarded as normal. The proportion
of urea may then be diminished to 60 per cent., because its chief source,
the exogenous nitrogen, has been eliminated in part. Muscular exer-
cise does not affect the urea output, showing that the energy is derived
in this case from the combustion of non-nitrogenous substances,
chiefly the carbohydrates. Some authors also state that a direct
relationship exists between the rate of urine secretion and the amount
of urea in the blood and urine, and claim to be able to evaluate the
functional power of the kidney by a comparison of these factors.^
Urea possesses the formula CO(NIl2)2 and is isomeric with ammo-
nium cyanate (NH4CNO) . This implies that it has the same empirical
but not the same structural formula. This substance was employed
by Wohler in 1828 in the synthetic preparation of urea. Crystals of
this substance may be obtained by warming potassium cyanate to-
gether with ammonium chlorid. In this form, urea is readily soluble
in water and alcohol and possesses a salty taste and a neutral reaction
to litmus On treatment with nitric acid, the nitrate of urea is formed
1 Archiv fur exp. Path, und Pharm., xv, 1882, 364.
2 Addison and Watanabe, Jour. Biol. Chem., xxvii, 1917, 381.
3 Ambard and Weil, Physiol, norm, et path, des reins, Paris, 1914.
1086 EXCRETION
(CON2H4.HNO3), and on treatment with oxalic acid its oxalate (CON2
H4.H2C2O4+H2O). Urea melts at 130° C, undergoing finally a decom-
position which yields ammonia, biuret and cyanic acid, the latter
being polymerized to cyanuric acid. On hydrolysis by means of
heating with strong acids or alkalies, it yields carbon dioxid and
ammonia.
Ammonia. — The urine of man and the carnivora contains a small
quantity of ammonium salts which serve as a means of transfer for
the acid radicles which have been ingested or have been formed in
the body. The chief source of these salts is the ammonia of the blood,
derived from the nitrogenous portion of the diamidized amino-acids.
This ammonia is carried to the liver where urea is synthetized, but
some of it escapes and reaches the kidneys where it slips through into
the urine. Some of it is also derived from the ammonium salts in-
gested from the ammonia produced in the course of the intestinal
putrefaction of the proteins. In the body, it exists as ammonium
carbonate which is the precursor of urea. It is for this reason that so
little of it circulates, but when mineral acids are administered, or when
excessive quantities of acids are produced, as in diabetes mellitus, the
body makes use of the ammonia as a base and an extra amount of it
appears in the urine. An excess of alkali, on the other hand, causes
it to be transferred into urea and to disappear as such from the urine.
This accounts for the fact that it is not present in the urine of vege-
tarians nor in that of the herbivora. Ordinarily, the daily output of
ammonia-nitrogen varies between 0.3 and 1.2 grm., the average being
0.7 grm., or 3.5 per cent, of the total amount of nitrogen.
Acidosis. — It has been known for some years that the urine of
diabetics is loaded with acetone, diacetic acid and /3-oxy butyric acid.
It was supposed at first that these bodies are derived from glucose,
because they are present in glycosuria, but it is now known that they
are the result of a disordered process of breaking down the fats.
Ordinarily, this foodstuff is converted into carbon dioxid and water,
but in certain abnormal conditions there is produced /3-oxybutyric
acid, then diacetic acid and lastly, acetone. Since a small amount of
acetone is normally present in urine and especially after the ingestion
of butter consisting of the lower fatty acids, and since none of these
substances is poisonous, except in enormous doses, it may be asked
why they cause such serious disturbances when formed in the course of
metabolism. Briefly, the answer is this: Fats are converted into these
abnormal acids instead of into carbon dioxid and water whenever
the tissues are unable to obtain sugar from the blood. The blood is
normally alkaline and the functions of the tissues are adapted to this
particualr reaction. In consequence of the production of diacetic and
especially of jS-oxybutyric acid, its alkalinity is greatly reduced. The
functional disturbances then ensuing constitute the condition of
acidosis. It would seem, therefore, that an artificial supply of alkalies
should place the body in a position to withstand the presence of these
I
. THE COMPOSITION OF THE URINE 1087
acids. ^ This is true to a large extent, because even the body attempts
to remedy this defect by caUing to its defense first its reserves of
sodium and potassium and lastly, and most effectively, large quantities
of ammonia. We have seen that the proteins turn their effete nitrogen
into ammonium carbonate and carbamate which are then converted
into urea in the liver. When the body employs this ammonia as a
defense, it combines it with the diacetic and jS-oxybutyric acids and
does not convert it into urea. Consequently, the ammonia escapes in
this case into the urine as ammonium diacetate and ammonium
/3-oxybutyrate. Finally, when the body has reached its limit in this
regard, the normal alkalinity of the blood can no longer be maintained
and dyspnea, collapse and coma result.
Creatin and Creatinin (C4H7N3O). — On a diet free from meat,
creatin is excreted in amounts varying between 7 and 11 mgr. per
kilogram of body weight. Folin^ regards it as a criterion of the inten-
sity of the endogenous nitrogenous metabolism and believes that" it is
formed in the liver and not in the muscles which usually contain it
in abundant amounts. Any gross variation from the amount just
given signifies an accumulation of this substance in the blood. Mel-
lanby claims that creatinin is derived from certain . derivatives of
protein catabolism in the liver and is then conveyed from this organ
to the muscles, where it is converted into its anhydride, creatin. As
soon as this tissue becomes saturated with this substance, creatinin
is excreted in the urine, and hence, a renal deficiency would invariably
be followed by an accumulation of the latter in the blood.
Uric Acid (C5H4N4O3). — The quantity of uric acid normally present
in the urine of man is small. It varies between 0.3 and 1.2 grm. per
day or between 0.02 to 0.10 per cent. This amount may be derived
from the ordinary purin metabolism of the body (endogenous) or from
the food ingested (exogenous). For this reason, it may readily be
increased by the ingestion of food rich in nucleins, or substances
containing the purin bases in a free state. Since the human body
does not possess the power of destroying any of the uric acid, it must
be excreted as such in the urine. This being the case, one of the
earliest symptoms of renal insufficiency is the increase of uric acid in
the blood. The reason for this is not quite clear, unless it is taken
into account that its salts are the least soluble of any excreted in the
urine. This also explains the fact that urine when cooled, yields a
pink deposit of urates. Uric acid is present in large amounts in the
urine of birds and snakes, forming here acid ammonium urate.
The purin bases are largely transformed into uric acid and only
their residue appears in the urine. Only traces of hippuric acid are
present under normal conditions (0.7 grm. per day), but the ingestion
of fruits and vegetables may raise it to 2 grm. per day. Amino-acids
1 Von Noorden, "Diabetes Mellitus," Wright and Sons, Bristol, 1906.
2 Am. Jour, of Physiol., xiii, 1905, 66 and Jaffe, Zeitschr. fur physiol. Chemie.,
xlviii, 1906, 430.
1088 EXCRETION
may also be present in amounts equalling 1.5 per cent, of the total
nitrogen.^ Aromatic oxyacids, such as phenol, indoxyl and skatoxyl,
are normally present in varying amounts, and serve as an indication
of the putrefactive decomposition of the proteins in the large intestine.
Ordinarily, the body protects itself by oxidizing them and combining
them to sulphuric acid to form the ethereal sulphates.
1 Van Slyke and G. M. Meyer, Jour. Biol. Chem., xvi, 1913, 197.
SECTION XXIX
ANIMAL HEAT
CHAPTER XCII
THE PRODUCTION AND DISSIPATION OF HEAT
Thermometry and Calorimetry.— Inasmuch as all chemical proc-
esses require an optimum degree of temperature for their completion,
it raay be concluded that the assimilation and dissimilation of the
different foodstuffs cannot be effected in the absence of a definite
measure of heat. This heat may be derived from two sources, namely,
as radiating or bound energy from without, or as energy liberated in the
course of the different chemical changes to which the tissues and organs
of the body are subject. Under ordinary circumstances, the latter
form of heat is of by far the greatest functional importance to us, but
its detection and actual measurement presents many rather unexpected
difficulties, so that very sensitive instruments must be employed in
order to prove its liberation. In the case of such structures as the
muscles and glands, we make use of the so-called thermo-electric ele-
ments which consist of two dissimilar metals, such as German silver
and iron, soldered together. One of these is placed in some indifferent;
tissue or in the blood-stream, while the other is inserted in the organ,
the temperature of which is to be determined. If the binding posts
of these two pairs of elements are then connected with a galvanometer,
it will be found that the least production of heat at the point of solder-
ing gives rise to a difference in potential which will be accurately in-
dicated by the deflection of the galvanometric needle.
It is evident, however, that this method cannot be employed to
determine the total heat-production of an animal nor its body-tempera-
ture, because this method must necessarily remain restricted to single
and separate organs. Should we desire to determine the temperature
prevailing within the body of an animal we must, of course, make use of
a thermometer which is inserted in any one of its cavities or recesses
and is allowed to remain there until the mercurial indicator has as-
sumed a stationary position.^ It must be evident, however, that
thermometry merely serves as a means of determining the tempera-
ture existing at any particular moment and cannot yield data regarding
the total amount of heat produced by the animal. Should we wish to
* The thermometer was devised by Galilei in 1603. The first thermometric
determinations upon man were made by Sanctorius in 1626.
fifl • 1089
1090
ANIMAL HEAT
ascertain the latter factor, it becomes necessary to employ an instru-
ment which is known as the calorimeter,^ and presents itself in the form
of two modifications, designated as the water-calorimeter and air-
calorimeter. In either case, this apparatus consists of a central
compartment in which the animal is kept, and a narrow outer com-
partment which is filled either with water or with air. Externally its
walls are covered with a heavy layer of some non-conductile material
to prevent all losses of heat. The heat liberated by the animal is then
Fig. 627. — Water Calorimeter. (Reichert.)
A, Inner compartment for animal; SH, space filled with non-conductile material;
ENT and EXT, tubes for the respiratory air; CT, thermometer in jacket filled with
water; S, stirrer to equalize the temperature of the water.
transmitted to the water, the temperature of which is read off by
means of a stationary thermometer. 2 In the case of the air calorime-
ter, the heat evolved by the animal gives rise to an expansion of the
air contained in the outer compartment, which is then transferred by
calculation into degrees of heat. Consequently, since the total amount
of the animal's heat is derived under this condition from the chemical
energy of its food, the former must constitute a direct index of the
oxidative processes.
The unit generally employed in measuring the amount of heat
1 The first calorimeter experiments upon animals were made by Lavisier and
Laplace in 1780 (Mem; de I'Acad. d. Sciences).
2 Equally large masses of different bodies require different amounts of heat,
that of water being nine times greater than that of iron.
THE PRODUCTION AND DISSIPATION OF HEAT
1091
evolved is the calorie, i.e., the quantity of heat which is necessary to
raise 1 kilogram of water 1° C. (from 15° to 16° C.)- We also speak at
times of the small calorie which refers to the amount of heat which is
required to raise 1 gram of water 1° C. Supposing, therefore, that the
quantity of water in the calorimeter weighs 10 kilos and that the
temperature rises 1° C. every half -hour, then the amount of heat liber-
ated by the animal during this time amounts to 10 calories or to 480
calories in the course of a day. This calculation, however, can be
correct only if the body-temperature of the animal has remained the
same during this period, and if the metal of the calorimeter has not
absorbed an undue amount of this heat. The latter factor cannot
possibly interfere with this determination if the instrument is well
Fig. 628. — Schematic Outline of the Respiration Calorimeter.
A, Dead air space between copper and zinc walls; B, dead air space between zinc
wall and wooden wall; C, dead air space between inner and outer wooden walls. E,
tube for food; S and H, inlet and outlet for water; V, air circulation. (Atwater and
Benedict.)
protected against heat-loss, and if the experiment is continued for a
relatively long period of time.
More recently, Atwater has made use of calorimeters large enough
to accommodate human beings, so that the heat produced by them may
be brought into relation with their respiratory interchange. The
air within this chamber is kept at a constant temperature by a stream
of water passed through it in a series of tubes. If the temperature
of this water, as well as the volume of the through flow which is required
to accomplish this end, is then ascertained, it is possible to obtain
from these values the amount of heat liberated by the person. Besides,
air is drawn out of this chamber by an engine, its volume being reg-
istered by a gas-meter. From time to time samples of this air are
withdrawn for analysis which includes the determination of its carbon
1092
ANIMAL HEAT
dioxid content by means of baryta water and of its aqueous vapor by
means of drying-tubes containing sulphuric acid. These values are
then compared with the data derived from analyses of the air entering
the calorimeter. These principles which have first been made use
of by Pettenkofer, are also embodied in the micro-calorimeter of Hill.^
This apparatus which is especially adapted for the detection of very
small amounts of heat, consists of two thermos bottles in which the
loss of heat is prevented by exhausting the air from the space between
their outer walls. Each bottle is equipped with thermo-electric
elements which are connected in turn with a galvanometer. Both
are packed in sawdust. The organ to be experimented upon is then
placed in one of these bottles, while the other is filled with water as a
/^^-^
^-« 3.949
Levulose 3.755 Starch 4. 182
Galactose 3.721 Dextrin 4. 112
Cane sugar 3.955 Cellulose. 4.185
Milk sugar 3.951
From these figures Rubner^ has deduced the following "standard" values:
1 gram of protein 4.1 calories
1 gram of carbohydrate 4.1 calories
1 gram of fat 9.3 calories
These values, however, are physical values and represent the heat
evolved by them when completely oxidized to carbon dioxid and
water. In the animal body these substances are not always thoroughly
utilized and hence, their nutritive value may not correspond precisely
with these figures. This is true in particular of the proteins, because
in the bomb-calorimeter the nitrogen of these substances is converted
into nitric acid, while in the body they are oxidized to urea. Conse-
^ Schlossmann, Zeitschr. fiir phys. Chemie, xxxvii, 1903, 324.
2 Zeitschr. fiir Biol., xlii, 1901, 261; also: Atwater, Am. Jour, of Physiol., x,
1904, 30.
1104 ANIMAL HEAT
quently, the heat Uberated by the proteins in the body is less than that
obtained when they are burned in the bomb-calorimeter. The
carbohydrates and fats, on the other hand, are reduced to carbon
dioxid and water and produce, therefore, practically as much heat
in the body as when oxidized in the bomb. In the latter case, the
discrepancy amounts to only 3 per cent, and is dependent upon the
fact that some portions of these substances escape unutilized into the
feces. In the case of the proteins, on the other hand, this loss
amounts to 20 or 25 per cent, which is caused in part by their entrance
into the feces (1.0 to 1.3 per cent.) and in part by their incomplete
reduction into urea. But as this compound may be further split
up in the bomb to carbon dioxid and water under liberation of heat,
it becomes necessary to deduct this amount of heat from that obtained
during their physical combustion. According to Rubner, 1 grm. of
urea yields 2.523 calories; moreover, since this amount of urea re-
quires the oxidation of 3 grm. of protein, the amount of heat to be
deducted from the heat-value of protein substance is 0.841 calorie.
This loss, together with that incurred by the escape of protein into the
feces, reduces the physiologic heat-value of this foodstuff to about
4.124 calories.^
The experiments of Voit and Rubner upon dogs have shown a very
close correspondence between the heat values of the different foodstuffs
calculated in the above manner and those obtained in the calorimeter.
These results are fully upheld by the determinations of the heat-pro-
duction in normal men under different conditions of life. Thus, it
has been found that the basal value in an adult weighing 70 kilos (156
pounds), is 70 calories in 1 hour or 1 .680 calories in 24 hours. This term
of basal heat-production, however, signifies that the person has received
no nounshment during the preceding 15 hours and lias continued to
rest m beTafter a night of sleep. If any food has been taken during
this period, about 168 calories should be added to this total, which
makes 1.848 calories in all. Exercise increases this value very materi-
ally, and naturally, this increase must be compensated for by a larger
intake of food. According to the experiments of Atwater and Bene-
dict, ^ the efforts connected with arising and sitting in a chair increases
the basal heat-production by 8 per cent, and the ordinary movements
performed by us in the course of a day, by 20 per cent., thus:
Night 616 calories
Day 1 .552 calories
Total 2.168 calories
A man of medium weight, leading a sedentary life, requires 320 calories
in addition to these 2.168, or 2.500 calories in all, in order to supply him
^ Rubner, Die Gesetzedes Energieverbrauchs., 1902, also: Calorim. Methodik,
Marburg, 1891.
2 Ergebn. der Physiol., iii, 1904.
THE PRODUCTION AND DISSIPATION OF HEAT 1105
with sufficient fuel to carry on even the most moderate muscular
activity.^ Beyond this ordinary, heat-production, the amount of fuel
needed by a person is in agreement with the character of the exercise. ^
Farmers require on an average 3500 calories and six-day bicycle riders
10,000 calories per day. Boys, on the other hand, need only about
1500 calories, and babies 100 calories for each kilogram of body weight.
The Effect of Varnishing the Skin and Other Procedures. — The
larger the surface of the body exposed to the cooler medium, the greater
must be the loss of heat. Consequently, since a small animal presents
a proportionately larger surface to the surroundings in relation to its
mass than a large animal, its loss of heat must exceed that of the latter.
Obviously, this more considerable thermolysis must be accurately
balanced by a greater thermogenesis, and hence, the smaller animal
must possess a more intense metabolism. This is evinced by its more
rapid respiratory and cardiac rates.
While warm-blooded animals may survive a brief exposure to an outside
temperature of from 100° to 132° C, owing to the profuse loss of latent heat then
ensuing, cold-blooded animals are usually killed at about 40° C, because their
musculature enters at this temperature the state of rigor caloris. Insects commonly
withstand a temperature of 64° C. Even the ordinary temperature of a beehive
varies between 30° and 40° C. which represents stagnated heat produced by the
bees themselves. Plants wither at a temperature of 52° C. If left to themselves,
warm-blooded animals usually do not survive when their body-temperature has
been reduced to 20° C, but if artificial respiration and warmth are applied to them,
they may recover from a temperature even lower than the one just given.
Cold-blooded animals are able to withstand 1° C. and may even be partially frozen. ^
The hibernating animals show signs of depression when their temperature falls
below 28° C. At 18° C. they exhibit a decided drowsiness, at 6° C. semi-sleep and
at 1.6° C. deepsleep.^ At this time, the heart beats only 8 to 10 times in a minute,
while the respiratory movements cease altogether. The very small amount of
oxygen which they now require is obtained by means of the volumetric changes
which the heart undergoes during its cycle. On systole this organ becomes smaller,
causing a slight amount of air to flow into the lungs, while on diastole, it becomes
larger and forces an equal amount of air outward. This constitutes the so-called
cardio-pneumatic phenomenon. When the hibernating animal awakes, its body-
temperature may rise as much as 20° C. in the course of two hours. ^
A rise in temperature may also result directly after death. Obviously, this
effect must be produced by a continued heat-production and a diminished heat-
dissipation, establishing a balance in favor of the former process. Thus, it may
happen that the sudden cessation of the circulation prevents the escape of heat
from the still active tissues. A most favorable condition of this kind is created
when the body-temperature has been high beforehand, so that the interruption of
heat-dissipation may allow an excessive stagnation of heat in the highly active
tissues. Muscular spasms at the time of death augment this effect. Heat is also
produced during the fixation of the muscles coincident with the onset of rigor mortis.
Covering the skin with a layer of varnish or paraffin has the same effect as cooling,
because an animal so treated loses heat very rapidly, owing to the dilated condition
^Lusk, Science of Nutrition, W. B. Saunders and Co., 1909.
2 Rumf, Pfluger's Archiv, xxxiii, 1884, 538, and Knoll, Archiv fiir Exp. Path,
und Pharm, xxxvi, 1895, 305.
^Muller-Erzbach., Zoolog. Anz., 1891.
^ Merzbacher, Ergebn. der Physiol., iii, 1904, 14.
5 Pembrey, Jour, of Physiol., xxix, 1903, 195.
70
1106 ANIMAL HEAT
of its cutaneous blood-vessels. ^ If placed in a warm chamber or covered with
straw or blankets, it invariably survives the critical period directly after the appli-
cation of the varnish, because later on the hairs grow out sufficiently to disengage
the varnish from the skin, allowing the latter at least partially to protect itself
against this enforced loss of heat. The view that this procedure prevents the
elimination of toxic substances through the skin, has not found experimental
substantiation. The administration of nervous depressants most generally evokes
a loss of heat against which the patient must be carefully guarded. Thus, extra
blankets are to be placed upon a person who has been given chloral.
Hjrperthermy and Hjrpothermy. — In addition to the variations in
the body-temperature noted in the course of the previous discussion,
brief reference should also be made at this time to the hyperthermy
commonly following the entrance into the body of pathogenic bacteria
and toxic substances, such as the derivatives of fermentative processes.
This condition which is usually designated as fever, is represented by
a complex of symptoms of which a decided and rather lasting elevation
of the body-temperature is the most characteristic. Rises to 38° or
39° C. are usually spoken of as ''low fever " or pyrexia, and rises to 41° C.
as ''high fever" or hyperpyrexia. Among the other readily recog-
nizable signs are thirst, painful sensations, weakness, apathy, nausea,
vomiting, alterations in the quantity and quality of the various secre-
tions and excretions of the body, and such other changes as may be more
specifically related to the infection. Fever may begin gradually, and
more abruptly with a chill; it may be constant, remittent and intermit-
tent; it may last a variable period of time and disappear either gradu-
ally or rather suddenly. In every case, however, it represents a physi-
ological attempt on the part of the body to correct a disturbance of
function, and hence, it is quite proper to refer to it as a reaction.
Fever or pyrexia may be due either to an increased production or
to a diminished dissipation of heat, or both. Evidently, any dispropor-
tionality between these two factors which leaves a positive balance for
heat, must bring about an elevation of the body-temperature. Con-
cerning the first factor, we have the positive statements of Krauss,-
Nebelthau,^ May,^ Staehelm,^ and others that thermogenesis is in-
creased during fever, the difference amounting to as much as 25 to 50
per cent. Direct calorimetric determinations have also proved that
the loss of heat is increased during fever, but in comparison with the
the enormous production of heat, the dissipation is undoubtedly dimin-
ished. In other words, the heat is stagnated, as is evinced by the
livid, blue and cold character of the skin following the contraction of
the cutaneous blood-vessels and the cessation of evaporation from the
skin. When these changes first occur, a sensation of cold is experi-
enced which causes the patient to draw his body into as small a mass as
possible and to cover himself thickly with blankets. The quivering
1 Krieger, Zeitschr. fur Biol., 1869; also Babak, Pfluger's Archiv, cviii, 1905, 389.
2 Zeitschr. ftir khn. Med., xviii, 1890, 91.
3 Zeitschr. fiir Biol., xxxi, 1894, 293.
^ Ibid., XXX, 1893.
5 Zeitschr. fiir klin. Med., Ixvi, 1904, 77.
THE PRODUCTION AND DISSIPATION OF HEAT 1107
of the muscles and goose-flesh appearing at this time greatly aid in
sending the body-temperature upward. The height of the fever
having been attained, heat-dissipation more nearly balances heat-
production/ but is still inadequate to allow the abnormally large
amounts of heat to escape. During the last stages of fever, the pro-
duction of heat is diminished, while the dissipation of heat gradually
increases, owing to the reestablishment of a proper control over the
capillaries of the skin and the reappearance of the sweat.
The underlying causes of fever having been established, the ques-
tion may now be asked how these changes are brought about. The
two most acceptable explanations are contained in the so-called neuro-
genic and toxogenic theories of fever. The former has been put forth
by Liebermeister^ and holds that the heat centers regulating the body-
temperature are raised to a higher pitch during fever, simulating our
means of adjusting the regulator of a thermostat in such a way that
the latter may yield a temperature of 40° C. instead of 35° C. In
accomplishing this end, the heat centers make use chiefly of the vaso-
motor and secretomotor mechanisms. In this restricted form this
theory seems to have little in its favor, but naturally, this statement
does not imply that the ordinary reflexes are excluded as adjunct
causative factors in the production of this form of hyperthermy. In
fact, the evidence is against such a view, because the brief febrile
reactions following the passage of biliary or renal calculi, catheriza-
tion, and various operative procedures, are undoubtedly produced by
a diminished loss of heat incited by the reflex constriction of the cuta-
neous blood-vessels. Hirsch, Miiller and Rolly^ have put forward the
view that fever results in consequence of a derangement of the meta-
bolic condition of the tissue cells by poisonous substances. This
explanation has much in its favor, and is well adapted to those febrile
reactions which follow upon the entrance of pathogenic bacteria into
the system. The implication is that the cells respond to these sub-
stances with an increased activity,^ thereby endeavoring to accomplish
some beneficial effect. Since the intake of food is much diminished
at this time, this metabolic augmentation is had mainly at the expense
of the organized constituents of the body.
The preceding conclusion is upheld by the fact that fever greatly
affects the metabolism, but probably not so much its intensity as the
manner in which it involves the different foodstuffs. The deduction
that it is not merely a matter of intensity of oxidation, is upheld by the
fact that the amount of the oxidation products derived from febrile com-
bustions is very small, as well as by the fact that the respiratory quotient
remains practically unchanged.^ It appears, therefore, that these
1 Krehl, Zeitschr. fiir allg. Physiol., i, 1902, 29.
8 Pathologie des Fiebers, 1875.
3 Deutsch. Archiv fiir klin. Med., Ixxv, 1903, 265.
4 Roily and Meltzer, ibid., xciv, 1908, 335.
5 Senator and Richter, Zeitschr. fiir klin. Med., lix, 1904, 16.
1108 ANIMAL HEAT
disturbances do not lie in the oxidation of the non-nitrogenous sub-
stances, but rather in that of the proteins. Furthermore, since the
intake of food is greatly diminished in fever, the oxidations must go
on chiefly at the expense of the protein of the tissues. This is proved
by the fact that the total excretion of nitrogen is increased, at least,
in proportion to the amount of protein ingested, and reaches its highest
value directly after the crisis and during the period of defervescence.
It appears, therefore, that the products of the bacteria give rise to
some derangement of the protoplasm of the cells, in consequence of
which they are rendered especially vulnerable to the hydrolyzing and
oxidizing agents which are always present in the tissues. The constant
drain upon the store of the tissue-proteins then ensuing, cannot be
made good by a corresponding intake nor are the cells able to protect
their proteins suflftciently by means of carbohydrates and fats. Conse-
quently, this tearing down process must continue and give rise eventu-
ally to an excessive production of heat which is not compensated for
by an equally intense dissipation. In other words, fever is the result
and not the cause of this disorder in the metabolism of the tissues.
The common view is that fever is a pathological process and must
be combated, because the body cannot long withstand a temperature
of from 44° to 45° C. But since fever is merely one of the expressions
of a cellular reaction instituted in consequence of pathogenic influences,
its removal by cold baths and drugs cannot give permanent nor bene-
ficial results. Whether fever as such possesses a favorable influence
upon the body and actually helps in combating the pathogenic proc-
ess is a much debated question. Bacteriologists, however, claim that
it serves as a protective mechanism, because many bacteria are killed
at a temperature slightly above that of the body. This is true of the
streptococcus of erysipelas which does not develop at 39° to 40° O.,
as well as of the bacillus of anthrax which, when kept at 42° C, is
greatly attenuated. Even the temperature range of the bacillus of
diphtheria and of the pneumococcus is limited. It has also been sug-
gested that a high body-temperature may be required for a copious
formation of immune bodies which would then remove the cause of
the abnormal protein-metabolism by antagonizing the agent of the
infection.
PART IX
REPRODUCTION
SECTION XXX
THE REPRODUCTIVE ORGANS
CHAPTER XCIII
GROWTH, REGENERATION AND REPRODUCTION
Direct Cell-division or Amitosis. — The preceding pages have been
devoted very largely to a discussion of the processes of life as we find
them in the adult animal. Looked at in a very general way, these
processes present themselves as phenomena of activity and growth.
Both of these take place at the expense of the inorganic and organic
material of the surrounding medium, and are the direct outcome of
stimulations. Consequently, life is not . spontaneous, but consists
merely of responses to external and internal impressions. Sooner or
later, however, these reactions cease and retrogression gains the upper
hand. Henceforth dissimilation continues uninterruptedly until the
complex animal machine has ceased to exist as a living entity. Thus,
death is merely a phenomenon of nature, brought about by a serious
derangement of the processes upon which life is based. It is the
climax of all physiological activities.
Since the chief consequence of death is the extinction of the indi-
vidual, not only the existence of a certain species but also that of all
animal Ufe would be endangered. In order to prevent such an out-
come, nature has provided a process of rejuvenation by means of which
new living entities may be brought into existence to take the places of
those used up. This constitutes the process of reproduction. Funda-
mentally considered, the aspect of reproduction is the same as that of
growth, because it strives to accomplish a multiplication of the living
substance at the expense of the surrounding material. In the case of
growth, however, the new substance is affixed to the same entity, while
in the case of reproduction, it is moulded into an entity sparate from
the original.
Attention has previously been called to the fact that the size of
any given unit of Hving matter is limited, because it is held together
1109
M! ;''! ( ) H ;
1110 THE REPRODUCTIVE ORGANS
by nt)thing more than the ordinary force of cohesion. Hence, if its
mass becomes too large, this force, ampHfied by adhesion, is no longer
sufficient to act throughout its substance, in spite of the fact that the
proportion of its surface to its mass becomes less as its size increases.
Moreover, since the processes of life are controlled by the nuclear
material and not by the cytoplasm, the mass of the latter must be
restricted, otherwise the nucleus cannot make its influence felt through-
out the cell. It is for this reason that those cells which must of
necessity attain a large size, such as the leukocytes and giant cells,
invariably embrace several isolated nuclei. To begin with, of course,
the growth of these simple protoplasmic units depends upon the fact
that their acquisition of new material exceeds the destruction. Even-
tually, however, when a limit in their size has been reached, their assimi-
lative power is gradually diminished. Even a division of their mass
may then result, but only if it is also in possession of a sufficient
amount of nuclear substance. When the latter is removed completely,
the cytoplasm cannot continue to exist for any length of time, because
it then lacks its 'Hrophic^^ factor.
Contrary to growth, therefore, the process of reproduction
depends upon the formation of daughter-cells by the division of the
mother-cell; but it will be seen that these occurrences are not inde-
pendent of one another, because without activity and growth there can
be no reproduction. The manner in which this rejuvenation of living
matter is accomplished differs greatly in different animals. The
simplest procedure prevails in the unicellular organisms, because
these entities multiply by the asexual process of simple division or
amitosis. The mother-cell splits into two parts, each of which is
equipped with a certain amount of nuclear substance. In accordance
with Remak (1858), cell-division begins with a splitting of the nucleolus
which is then followed by a constriction and division of the nucleus,
cell-body and enveloping membrane. The daughter-cell so formed
grows and gradually acquires the characteristics of the mother-cell, but
only if it is subjected, to identical conditions. If not, its molecular and
general morphological character may be altered in such a manner that
it may give rise to an entirely new species.
This amitotic manner of reproduction frequently gives rise to a
perfectly amazing multiplication. Thus, it has been stated that a
Paramecium, if it were plentifully supplied with food and protected
against injurious influences, would be able to form in the course of a year
a mass of living matter as large as the earth. If nothing more, this
computation gives us an idea regarding the perfectly phenomenal pos-
sibilities of this process. But, it is also true that amitosis cannot con-
tinue for an indefinite period of time and certainly not if the organisms
are forced to exist under unfavorable circumstances. It seems that
they then lose their vigor and become non-resistant so that they are
more easily affected by outside influences. Under these conditions, a
type of reproduction is frequently brought into play which is called
GROWTH, REGENERATION AND REPRODUCTION 1111
conjugation and which undoubtedly is a prototype of the interaction
of the germ-cells of the multicellular forms. Conjugation is essen-
tially a union of the nuclei of the conjugating cells, although in unicellu-
lar plants the cell-bodies -are fused as well, while in the infusoria this
union is only temporary. Maupas^ believes that this process invari-
ably follows a long period of multiplication by cell-division and may
be compared to the attainment of sexual maturity of the higher
animals. According to Biitschli, its purpose is to prevent senile
retrogressive changes and to instil new vigor into the descendents.
In the infusoria, Wilson^ recognizes the following changes: To
begin with, each cell possesses two kinds of nuclei, namely, a large
macronucleus and one or several micronuclei. As soon as the cells
have become applied, the former degenerates and disappears. In
consummating this process, the micronucleus divides twice to form four
spindle-shaped bodies. While three of these degenerate, the fourth
splits into smaller masses. These micronuclei are then exchanged,
one from A passing into B and one from B into A . Very soon after
these cells have again separated each pair of nuclear masses unite into
one. This single micronucleus then divides three times to form eight;
while the cell meanwhile splits into four parts, two nuclei being
apportioned to each daughter-cell. One of the latter enlarges to form
the macronucleus, while the other continues as the micronucleus.
Indirect Cell-division or Mitosis. — By far the greatest number of
animal and vegetable cells multiply by the process of mitosis or
karyokinesis, which differs from amitosis chiefly in the fact that the
nucleus undergoes a number of very characteristic changes. In order
to be able to follow these more conveniently, they may be divided into
the following phases:
(a) Prophases, during which the division is initiated.
(6) Metaphase, during which the nucleus undergoes its most important change.
(c) Anaphases, during which the nuclear material is arranged in a peculiar
manner, preparatory to the
(d) Telophases, during which the active cell divides, giving rise to the daughter-
cells.
During the prophase the chroniatine substance of the nucleus acquires a greater
power of staining, loses its net-like character and is eventually resolved into a
definite number of separate bodies possessing intense staining qualities. These
so-called chromosomes are generally rod-shaped, straight or curved, but may also
be spherical, ovoidal or ring-like. They arise in consequence of the transverse
division of the spireme-thread into which the nuclear substance first resolves it-
self. In the place previously occupied by the nucleus, the cytoplasm assumes a
radiate appearance, giving rise to a star or aster. In the center of each aster lies
a centrosome, while in between them is a spindle of fine fibers, known as the
achromatic spindle. The otiromosomes arrange themselves in a plane at the
equator of the spindle.
The metaphase is characterized by a lengthwise splitting of the chromosomes
into equal halves, thus initiating the actual division of the cell. During the ana-
phase these daughter-chromosomes move toward the opposite poles of the spindle
1 Arch, de Zoologie, Sec. II, vii, 1889.
2 The Cell in Development and Inheritance, Macmillan, 1919.
1112
THE REPRODUCTIVE ORGANS
and collect liere in groups, finally evoking the formation of a daughter-nucleus.
As they diverge, the zone between them shows a bundle of achromatic connecting
fibers which are not identical with the fibers of the original spindle. Later on in
A
B
C JD
Fig. 530. — The Prophases of Mitosis (Heterotypical Form) in Primary Spermato-
cytes OF Salamandra.
A, Early segmented spireme; two centrosomes outside the nucleus in the remains of
the attraction-sphere. B, longitudinal splitting of the spireme, appearance of the
astral rays, disintegration of the sphere. C, early amphiaster and central spindle.
Z), chromosomes in the form of rings, nuclear membrane disappeared, amphiaster en-
larging, mantle-fibers developing. {Meves.)
the course of the anaphase and during the telophase, the entire cell splits into two
portions, each of the daughter-cells receiving a group of chromosomes, half of the
spindle and connecting fibers and an aster with its centrosome. Meanwhile, the
nucleus of the daughter-cell has been reconstructed. .
GROWTH, REGENERATION AND REPRODUCTION
1113
It has been shown that the number of chromatic loops differs
greatly in different animals but is constant in the same species. Man
has sixteen chromosomes in the nucleus of his somatic cells, while the
mouse and salamander have twenty-four, those of Ascaris two or
four, and those of the crustacean Artemia one hundred and sixty-
eight. It appears, therefore, that mitosis effects a meristic division of
Fig. 531. — Metaphase and Anaphases of Mitosis in Cells (Spermatocytes) of the
Salamander.
E, Metaphase. The continuous central spindle-fibers pass from pole to pole of the
spindle. Outside them the thin layer of contractile mantle-fibers attached to the di-
vided chromosomes of which only two are shown. Centrosomes and asters. F, Trans-
verse section through the mitotic figure showing the ring of chromosomes surrounding
the central spindle, the cut fibers of the latter appearing as dots. G, Anaphase; diver-
gence of the daughter-chromosomes, exposing the central spindle as the interzonal
fibers; contractile fibers (principal cones of Van Beneden) clearly shown. H, Later
anaphase (dyaster of Flemming) ; the central spindle fully exposed to view; mantle-fibers
attached to the chromosomes. Immediately afterward the cell divides. {Drilner.)
the chromatin of the mother-cell, so that the daughter-cells may be
equally provided with this material. Amitosis, on the other hand,
presents itself rather as a division of mass.
Regeneration. — Besides growth, an organism has two duties to
perform, namely, to reproduce the cells which have been used up in
its processes of life, and secondly, to reproduce its like in the form of
1114 THE REPRODUCTIVE ORGANS
a new living entity. The former process or regeneration may be
participated in by practically any one of the constituents of its several
tissues, while the latter or reproduction, is effected by a special group
of cells. In fact, the propagation of the species is so important a
function that it is generally mediated by a set of specialized cells con-
stituting the organs of reproduction. Thus, the cells of a multicellular
organism really arrange themselves into two groups, namely, into those
mediating its ordinary processes of life and those concerned with the
generation of a new organism. Weissman applies to the former the
term of somatic cells, and to the latter, the term of germ-cells. As far
as the actual life of the animal is concerned, these reproductive
units are of relatively slight importance and are brought into play
only when new entities are to be formed. But since even somatic
cells are able to reproduce their like, this distinction is not absolute,
but merely serves to indicate a physiological division of labor of the
cells of the metazoan.
The life of the organism as a whole is limited and so is that of the
numberless constituents of its different tissues. Cells are constantly
being destroyed, more so in some tissues than in others, and their places
are taken by new units. This implies that even the ordinary tissue-
cells must possess the power of reproducing their like. Thus, we have
previously noted that the red blood corpuscles disintegrate while they
traverse the circulatory system, and are constantly being replaced by
new cells derived from the red marrow of the bones. A similar regener-
ation takes place in the outermost layer of the skin where the squa-
mous epithelium is worn away and is restored by newly formed cells
of the deeper Malpighian layer. When exercised, the skeletal muscle
acquires new cells, and so does the uterus after its reception of the
impregnated ovum. The periosteal cells proliferate when the adjoin-
ing bone is broken (callus), giving rise to numberless bone-corpuscles,
many of which are again absorbed later on. Under ordinary circum-
stances, however, some of the adult tissue-cells are quite unable to
reproduce their like, which implies that other cells must step in to
consummate this process. Thus, a wound in a muscle is usually closed
by a proliferation of its connective tissue elements and not by a mul-
tiplication of its muscle cells. This gives rise to the formation of
scar-tissue. Furthermore, these processes of regeneration are in-
variably retarded after middle life and may in fact be abolished
altogether. As an instance of this abolition might be mentioned the
abortive proliferation of the cells of the periosteum, causing a per-
manent separation of the ends of the fractured bone.
In general, it may be said that the more highly organized tissues
are regenerated with greater difficulty than those of a more elementary
kind. This is especially true of the master tissue of our body, at
least insofar as the cell-bodies of the different neurons are concerned,
because defects of the central gray matter are always repaired with
GROWTH, REGENERATION AND REPRODUCTION 1115
extreme tardiness. Harrison,^ however, has proved that nerve cells
may also be grown outside the body in suitable culture media. When
clotted lymph is used, the cell-body grows and sends out its oxone and
dendrites which may be traced far into the surrounding medium.
This observation also proves that nerve fibers are the outgrowths of
the hyaline protoplasm of the nerve cells which at this stage of develop-
ment is actively ameboid. These long drawn out pseudopodia
eventually become the organized • fiber processes. Consequently,
the central complexes of ganglion cells must exert a commanding
influence upon the development of the fiber paths. This view finds
substantiation in the fact that the transplanted limbs of the embryos
of the toad and frog eventually acquire a normally arranged system of
nerves. 2 No matter where the new limb is united with the body,
these nerves show a perfectly normal distribution in relation to those
of the host. Thus, a limb ii^planted in the region of the head, in-
variably acquires nervous outgrowths which are derived in regular
order from the facial nerve or some other nerve, if closer to the graft.
In this category also belong the morphological and embryological
experiments of Pflliger, Roux, Born, and others, purposing to test the
regenerative powers of animals when injured during their period of
development or when the organic constituents of the egg itself are
either removed or transplanted from one animal to another. One
of the most interesting discoveries was made by Born^ in 1894. While
performing certain experiments pertaining to the reformation of lost
parts of the embryo of the frog, he found that pieces which had first
been absolutely separated from the main mass, might again be made to
unite with it by simply holding them against it for a few hours. This
preliminary fact having been established, he then succeeded in uniting
these pieces in all possible ways, producing even monsters with two
tails or two heads or a head in the place where the tail ought to be.
Even pieces from different animals could be used in the production
of these odd forms. With the help of the Zeiss binocular dissecting
microscope and delicate instruments, Spemann^ was able to perform
transplantations of much greater delicacy than those just related.
These included the removal of certain areas of the epidermis or of the
Gasserian ganglion and their implantation in some other part of the
body; the removal and reversal of the auditory vesicle, as well as the
interchange of the right and left ears. By the same means Lewis^
proved later on that the epidermis of any part of the body may be
brought into contact with the optic vesicle at the proper stage of
• development and give rise to a crystalline lens.
1 Proc. Soc. for Esp. Biolog. and Med., 1907.
2 Held, Verhandl. der anat. Gesellsch., Rostock, 1906, and Harrison, Jour,
of Exp. Zoology, iv, 1907.
3Archiv fiir Entwickelungsmechanik, iv, 1896-1897; also Brans, Propfungbei
Tieren, Verhandl. des naturhist. med. Vereins, Heidelberg, iii.
* Verhandl. der deutsch. zoolog. Gesellsch., 1906.
6 Am. Jour, of Anat., iii, 1904, and Jour, of Exp. Zoolog., ii, 1905.
1116 THE REPRODUCTIVE ORGANS
This list of regenerative possibilities, however, ^ need not remain
confined to the developing animal, but may also be extended to adult
forms, because while the growth of the latter is greatly diminished,
their power of reforming injured tissues is by no means lost. It is
true, however, that their property of regeneration is rather dormant
at this time, in consequence of certain inhibitory influences, but may
be awakened temporarily by stimulation. Thus, it is a well-known
fact that the adult starfish is capable of reforming a lost arm, and that
a worm cut into is able to develop from the posterior extremity of its
anterior segment a new tail, and from the anterior end of its posterior
segment a new head.^ In fact, even the severed arm of the starfish
may eventually give rise to a complete animal, while artificial mouths
surrounded by tentacles may be produced in sea-anemones by simply
incising their body- wall and keeping the wound open. Of even greater
interest are those experiments which show that parts of different
animals may be united to form a single new one.^ In this way, com-
pound worms have been formed which lived for many months, and
Harrison has even succeeded in uniting the anterior half of Rana
virescens with the posterior haK of Rana palustris (parabiosis).
Although both parts retained their special characteristics, this com-
pound frog gave rise to young. Most remarkable changes may also be
effected in plants. Thus, it is a well-known fact that a whole plant
may be produced from the cuttings of its branches and roots, and even
from its leaves. In this category also belong the transplantations
practised to enrich the flower and fruit bearing qualities of certain
plants and trees. With regard to the growth of malignant tumors,
it might be mentioned that connective tissues may readily be grown
outside the body and that this growth may be greatly accelerated by
extracts of tissues, particularly of embryos, spleen and malignant
tumors.* Tissues may also be kept at a low temperature without ap-
parently losing their power of regeneration. Thus, skin niay be kept
for 2 to 6 "weeks in cold storage and be grafted successfully at the end
of this period.
Reproduction. — These examples, no doubt, suffice to show that
regeneration is really a form of reproduction; but a reproduction of a
local or restricted kind which does not pass beyond the reformation
of the individual tissues. Thus, while a newt may reproduce an
amputated toe, the newt itself is left in. its original condition. Its
cells are gradually used up until its existence as a living entity ceases
altogether. But this natural limitation of life is prevented from
1 Joest, Transplantationsvers. an Regenwurmern, Ber. Gesellsch. der Naturw.,
Marburg, 1895; also Morgan, the Physiology of Regeneration, Jour. Exp. Zoology,
iii, 1906, or ''Experimental Zoology," New York, 1907.
2 The earliest experiments in grafting were performed upon hydra by Trembley
(M6m. pour servir a I'histoire d'un genre de polypes d'eau douce, Leide, 1774).
Later on Hunter and Durhamel grafted the spur of a cock to the comb where it
continued to grow.
3 Carrel, Jour. Exp. Med., xiv, 1911, 571, and xvi, 1912, 165.
1117
terminating the existence of the species by a process of regeneration
or reproduction in mass. A special group of organs is set aside for
the formation of what might be termed in brief the germ-plasm, a
specialized substance which is capable not only of reforming a par-
ticular type of cell but also of reproducing the counterparts of all
cells within a single entity which then takes the place of the one gone
out of existence. The organs to which this function is assigned are the
reproductive organs. Their chief product is the ovum, a cellular
unit containing the germ-plasm. In this germinal cell begins the
development of every new living entity.
In the majority of living forms, however, the ovum is not capable
of undergoing division unless it is energized by another cell which is
known as the sperm-cell or spermatozoon. Thus, reproduction may
be either asexual or sexual. The former process or parthenogenesis
is confined to some of the lower and simpler types of life, while the
latter is peculiar of all higher forms. In sexual reproduction the ovum
represents the female element, and the spermatozoon the male element.
The former consists essentially of cytoplasm which contains a consider-
able quantity of nutritive material, while the latter is principally
composed of nuclear substance. The essence of this mechanism is
the meeting and fusion of these two elements into a single one from
which a new individual is then developed. This fusion by means
of which two independent units are blended into one, constitutes
the process of fertilization oi fecundation.
In explanation of this interaction two theories have been promulgated, namely,
one emphasizing the importance of the spermatozoon and one emphasizing that
of the ovum. The advocates of the former are known as animalcvlists and hold
that the spermatozoon is a complete animal en minuture, possessing all the char-
acteristics of the parent but lacking a fertile medium in which to grow. This
medium it seeks and finally attains by virtue of its inherent powier of movement.
The advocates of the second view, who are known as ovists, believe that the ovum
contains all the essentials of the full grown organism, but needs a stimulus to make
it develop. This impetus is given to it by the spermatozoon. In accordance with
this view the ovum may be likened to the bud of a plant which unfolds its leaflets and
begins to grow as soon as the proper stimuli have been received by it. Both these
conceptions are based upon the idea that either the spermatozoon or the ovum are
preformed and hence, they may be collectively referred to as the theory of preforma-
tion. Subsequent investigation, however, has shown that the spermatozoon as
well as the ovum are but single cells and have a perfectly definite life history.
Both originate in the germinal cells of two separate individuals, and both pass
through definite preliminary changes before they actually attain their maturity.
Furthermore, while the part played by them in fertilization is not exactly the same,
their purpose is identical, i.e., both strive to produce a new individuaL Conse-
quently, neither can be said to be more important than the other.
It must be admitted, however, that we are still in ignorance regarding the physi-
ological principle underlying this fusion of the germinal elements. Harvey and
others have advocated the view that the ovum is animated by the spermatozoon
and is thereby made to develop. This idea is embodied in the so-called dynamic
theories of Spencer, Biitschli, and Hertwig, which assume that protoplasm
becomes increasingly inactive and finally requires fertilization to imbibe it with
a new force developed under different conditions. This process, therefore, could
1118 THE REPRODUCTIVE ORGANS
be compared with the rejuvenation effected in "senile" pro.tozoon by the method
of conjugation. A somewhat different explanation is made possible by the sugges-
tions of Trivianus, Brooks, and Weismann, that fertilization is essentially a process
by means of which variations are produced in consequence of the acquisition of second-
ary elements, insuring a constant mingling and repeated renewal.
The Fertilization of the Ovum. — The physiological prineiple
underlying sexual reproduction, is the process of fertilization effected
by the fusion of the two germ-cells, one of which is of maternal and
the other of paternal origin. In most cases, this union takes place
within the body of the mother, but may also be accomplished in an
outside medium which is accessible to both the female and male germ-
cells. The manner in which these elements are brought together
differs greatly in different animals, and hence, the subsequent discus-
sion pertaining to the mechanics of sexual reproduction, must nec-
essarily be restricted to an enumeration of the functions of the
different sexual organs of the mammals. The minute changes, how-
ever, are usually studied in the eggs of the lower forms, for example,
in those of the sea-urchin and the thread-worm.
Subsequent to the discovery of the spermatozoon by Hamm
(1677), Leeuwenhoek expressed the idea that this element must pene-
trate the egg, an assumption which was later on confirmed by Spal-
lanzani (1786), Newport (1854), and Pringsheim (1855). It seems,
however, that only the head of the spermatozoon actually takes part
in the fertilization, because in some animals, such as the echinoderms,
the tail remains entirely outside the egg. But it is also true that
the eggs of the molluscs, insects, nematodes and some annelids fre-
quently display the tail of the spermatozoon within their cytoplasm,
forming here a delicate coiled up structure. At the time of contact
between the male and female elements, the ovum produces two minute
globular masses at its upper extremity which are known as the polar
bodies. Since these projections take no part in the subsequent changes
but degenerate and may make their appearance even before the en-
trance of the spermatozoon, it seems that they merely indicate that
the egg has reached its mature state and is ready to receive the male
sperm-cell. In all probability, a place of least resistance is formed by
this means, through which the spermatozoon first arriving in this
vicinity, is enabled to enter. Immediately upon conception, a tough
envelope, the vitalline membrane, is developed around the ovum,
thereby preventing the entrance of those spermatozoa which may have
reached their destination during the interim. As soon as the head of
the successful spermatozoon has been lodged in the cytoplasm, the
tail atrophies and disappears. Now follows a gradual enlargement of
the former and the breaking up of its chromatin material into a thread-
Uke formation and its characteristic number of chromosomes. The
egg then embraces two nuclei (Hertwig, 1875), one of which is of pater-
nal and the other of maternal origin. This is the crucial point of
fertilization, because these male and female pronuclei, containing
Outer cell. Outer cells
Polar bodies
Inner cells
Inner cells.
Outer cells.
Inner cells
Inner cells.
Outer cells.
Oute
cells
Fig. 532. — 1, 2, 3. Diagrams Illustrating the Segmentation of the Mammalian
Ovum (Allen Thomson, after van Beneden). 4. Diagram Illustrating the Rela-
tion OF THE Primary Layers of the Bi^astoderm, the Segmentation-cavity of this
Sta(}e Corresponding with the Archenteron of Amphioxus (Bonnet).
GROWTH, REGENERATION AND REPRODUCTION 1119
equal amounts of chromatin of dual origin, now approach one another
and are joined or even fuse into one which is known as the cleavage
or segmentation-nucleus. Shortly afterward the nuclear membrane
disappears, a spindle is developed and a number of chromosomes
arise from the cleavage-nucleus which in all probability have been
derived in equal proportions from the two germ-nuclei. Fertilization
is then rapidly followed by the division of the cell, the stimulus for
it having been given by the centrosome which thus becomes the
controlhng agent in the further development of the embryo.
The successive divisions now following eventually give rise to numerous cells
which arrange themselves in the form of either a spherical mass (morula) or a
circular disc. In the former case, the center finally becomes hollow, forming the
blastula. These cells then arrange themselves as a uniform layer which is known
as the blastoderm. Somewhat later the blastula is invaginated (gastrula), thereby
giving rise to two layers of cells, namely, an outer or ectoderm, and an inner or
entoderm. The next step in this development is the formation of a third or
median layer which is known as the mesoderm. In this way, the foundation is
laid for a physiological division of labor, because from these three layers are de-
rived the various organs of the adult individual. But the question of whether
this mesoderm arises from the entoderm or from the ectoderm, has not been defi-
nitely settled as yet; in fact, it seems that it may originate from either. This
differentiation of the germinal layers having been completed, genesis begins. The
ectoderm or epiblast eventually gives rise to the central nervous system and the
epidermal tissues, while the mesoderm or mesoblast originates the vascular, mus-
cular and bony tissues as well as the generative and excretory organs, •exclusive
of the bladder, the first part of the male urethra and the female urethra. The
entoderm or hypoblast forms the epithelium of the intestines as well as that of the
intestinal glands and respiratory passage, the prostatic portion of the male urethra
and the entire female urethra. ^
Parthenogenesis and Artificial Parthenogenesis. — Sexual repro-
duction necessitates the conjugation of two cells and the fusion of
their nuclei. During this process the number of the chromosomes in
the germ-cells is reduced to one-half the number characteristic of the
somatic cells. ^ In a few instances, however, the ovum alone is capable
of producing a new individual; but this mode of reproduction, which is
known as parthenogenesis, remains confined to the simplest forms,
such as the insects and the lower crustaceans and rotifers. It should
also be noted that in some species parthenogenesis alternates with
sexual generation, but the variability of the non-sexual offsprings is as
great as that of the sexual ones. This fact speaks against the concep-
tion of Weissman, according to which the purpose of sexual reproduc-
tion is to induce variations.
In parthenogenesis the stimulus is given by the second polar body
which thus takes the place of the spermatozoon. The ovum develops
1 For a more detailed discussion of the process of fertilization the reader is
referred to textbooks on Embryology, and especially to such books as Wilson's
**The Cell in Development and Inheritance." This brief account has been
inserted here merely to serve as a connecting link between the substance of this
chapter and that of the succeeding.
2 Van Beneden, Arch, de Biologic, iv, 1883.
1120 THE REPRODUCTIVE ORGANS
with the chromosomes of the female pronucleus, i.e., with one-half the
number allotted to it in sexual reproduction. A similar result is ob-
tained during the development of denucleated portions of mature ova
when fertilized by spermatozoa. Since the nucleus is the essential
factor, the development occurs in the former case without admixture
with the male element and, in the latter, without the properties of the
female.
Parthenogenesis may also be incited artificially. Shortly after
Bataillon succeeded by means of mechanical impacts in causing unfer-
tilized eggs to develop, J. Loeb^ showed that the fertilized egg of the
sea-urchin may be prevented from developing by abstracting the oxy-
gen from the sea-water by means of KCN or NaCN. In 1899,. this
author found that the unfertilized eggs of the same species may be
made to develop into larvse by exposing them during a period of two
hours to hypertonic salt solutions. ^ By altering the medium by the
addition of formic or lactic acid he finally succeeded in causing the
unfertilized ova of this and other species to develop their membrane
as well as those initial changes which normally require the entrance of the
spermatozoon. After their exposure to the aforesaid acids, the eggs were
transferred into concentrated sea-water and subsequently into ordinary
sea-water. Loeb suggests that the action of the spermatozoon is
chemical in its nature, because it brings a certain substance into the
ovum which is capable of inciting therein a definite chemico-physical
reaction. The nature of this substance is still unknown, although
repeated attempts have been made to isolate it. The eggs of the sea-
urchin, however, have yielded upon extraction with a hypotonic salt
solution and ether a substance which possesses strong fertilizing,
agglutinating and cytolytic properties. Furthermore, a chemical
substance has been isolated from the head of the Rhine salmon which
consists of nucleic acid and a protamin. It is known as salmin.
Similar substances are the clupein of the spermatozoa of the herring,
and sturin from those of the sturgeon.^
The Law of Mendel. — The general conception is that the perplex-
ing multiformity among animals and plants is due to the propagation
of established forms by heredity, and that new types find their origin
in variation. Darwin's ''Origin of the Species" is the first attempt to
analyze these phenomena in a rational way and to refer them to natural
selection, in accordance with the practice of breeders and experimental
botanists to fix characteristics and to produce new ones by interbreed-
ing and grafting. In this case, heredity may be amplified by the adap-
tation of the individual to dominating conditions, as is clearly depicted
by the struggle for existence "and the consequent survival of the
fittest. '^ Herbert Spencer, in particular, has made use of this hypoth-
esis in explaining many structural and functional characteristics of
1 Pfliiger's Archiv, Ixii, 895, 249.
2 Untersuchungen iiber kiinstl. Parthenogenese, Leipzig, 1906.
3 Burian, Ergebn. der Physiol., i, 1904.
GROWTH, REGENERATION AND REPRODUCTION 1121
animals and plants. Moreover, stimulated by the close similarity
between the changes presented by the developing ova of widely differ-
ent species, Hackel formulated his Gastraea-theory which states that
all forms of blastoderms, consisting of two germinal layers, may be
regarded as a modified simple gastrula. In the same way as the gas-
trula is the beginning of the formation of a single individual, so may
an animal of similar simple construction be considered as the ancestor
of all multicellular forms. While this view has been widely dissemi-
nated, it lacks confirmation, because it has not been proved that a
gastrula gives rise to any other entity than that from which it has
arisen. Furthermore, the preceding discussion pertaining to the ferti-
lization of the ovum must have shown that the differentiation really
takes place much sooner, i.e., at the time of fusion of the pronuclei.
The Darwinian theory of evolution is based upon slowly developing
anatomical peculiarities to which have been added certain data
derived from artificial selection. Thus, an experimental element was
introduced for the first time which, however, was again lost sight of
later on. Opposed to this contention is the theory of mutation which
is founded upon phenomena of cell-life.^ Since racial characteristics
are no doubt mapped out in the segmenting ovum, all homologies or
similarities appearing later on, must find their origin in the material
substance of the fertilized egg. Quite similarly, any modification in
the germinal arrangement must give rise to mutations which charac-
terize evolution.
In sexual reproduction it may be surmised that the carriers of the
characteristics are the chromosomes, which thus impart to the new
individual the peculiarities of its parents. This transfer, however,
is not always effected in a proportional measure, but often favors
more particularly the male or female parent. We have seen that the
mitosis then occurring, is associated with a reduction of the number of
chromosomes, and hence, any variation shown by the offsprings may
be referred to the qualitative differences in the chromosomes which
have been formed during the development of the ovum. The manner
in which gross as well as minor characteristics may be transmitted has
been more fully illustrated by the results of an elaborate series of
experiments performed by MendeP upon different varieties of peas.
The bearing of these experiments, however, has not been fully appre-
ciated until about the year 1900. At this time DeVries found that
the seeds of Lamark's primrose, sown in his experimental garden, gave
rise not only to a small percentage of the same type but also to new
types of which he recognized seven. When self-fertilized, these muta-
tions not always bred true to their type, but produced at times new
varieties. MendeFs first experiments were carried out upon peas.
1 Buffon, Historie naturalle, 1755; Lamarck, Rech. sur Torigination des corps
vivants, 1802; St. Hilaire, Princ. de philosophic zoologique, 1830; Weissman,
On germinal selection as a source of definite variation, 1896, and DeVries, Ernahr-
ung und Zuchtwahl, Biol. Zentralbl., xx, 1900.
2 Versuche iiber Pflanzenhybriden, Brtinn, 1866.
71
1122 THE REPRODUCTIVE ORGANS
On crossing a plant of a tall variety with one of a dwarf type, he
noted that the seeds obtained from them gave rise exclusively to tall
plants. When the latter were then recrossed among themselves, the
result was 75 per cent, of tall and 25 per cent, of dwarf plants. The
subsequent crossing of the latter with one another yielded only dwarf
plants through successive generations. The former, on the other hand,
fell into two groups, because while 25 per cent, of them continued to
yield tall types, the other 50 per cent, gave rise to 75 per cent, of tall and
25 per cent, of dwarf plants. Mendel explained these results by stating
that characters are either dominant or recessive. In the preceding ex-
ample, the tallness is dominant and the dwarf condition recessant.
This principle may be made clearer at the hand of the following example: If
a gray (A) and white {B) mouse are crossed, the offspring (Ci) will be all gray.
If the gray mice are now bred to each other, the young (C2) will be either gray or
white in the proportion of 3:1. On crossing the white of this generation, only
white offspring will be obtained throughout. The gray individuals, on the other
hand, will give rise to one-third of gray and two-thirds of white offsprings. On
recrossing the former only gray young are gotten, while the latter yield both white
and gray. From the white of this last generation only pure white are obtained,
while the gray may be either pure gray or gray-dominant-white recessives A (B).
In applying Mendel's Law to animals, it may be assumed that the
two kinds of germ-cells are individualized as dominants and recessants
or that the germ-cells of the hybrid are alike, i.e., that they contain
both dominant and recessive characters which are then either brought
forth or suppressed during fertilization in consequence of certain
external and internal factors. While the former explanation is the
more simple, it nevertheless fails to account for certain phenomena,
as does, in fact, Mendel's Law itself: Thus, the crossing between
members of the white and black races of man does not give rise to
either type, but to an intermediate progeny, showing various degrees
of admixture.
CHAPTER XCIV
THE MALE AND FEMALE REPRODUCTIVE ORGANS
The Testicles. — The reproductive organs of the higher animals
may be divided into two classes, namely, those actually producing the
generative elements, and those serving as a means of bringing these two
elements together. The former embrace the testes and ovaries, and the
latter, the penis, seminal ducts, vagina, uterus and Fallopian tubes.
The essential sexual organ of the male comprises the testes, two oblong
glands, each of which measures about 4 cm. in length, 3 cm. in breadth
and 2 cm. in thickness it weighs 15 to 25 grams. These organs are
contained in a sac-like appendage, the scrotum, which is divided into two
THE MALE AND FEMALE REPRODUCTIVE ORGANS
1123
halves by a median raph^ and incomplete septum. The skin, with the
underlying dartos, assumes a corrugated appearance under the influence
of cold, this effect being due to the contraction of the smooth muscle
cells which are scattered throughout this tissue. The activity of these
muscle fibers is greatly influenced by the general condition of the
body, their tonicity and contractility being much diminished during
states of depression and in old age. The areolar envelope of the tes-
ticle embraces scattered bundles of striated muscle which constitute
the so-called cremaster muscle. They are continuous with the lower
fibers of the internal oblique muscle, and their contraction shortens
the funiculus and raises the testicle. Their action is controlled by
the genital branch of the genito-femoral nerve.
In cross-section each testis is seen to be enveloped by a dense fibrous mem-
brane, or tunica albuginea, which enters its interior as radial septa and divides
it into numerous compartments. These spaces are occupied by the secreting
Fig. 533. — Diagrammatic View of the Seminiferous Tubules.
A, Tunica albuginea; S, septula; M, mediastinum, and vasa recta; R, rete testis;
E, vasa efferentia; Ep, epididymis; G, globus major; GM, globus minor; D, vas
deferens.
elements, the seminiferous tubules, all of which are arranged divergently from a com-
mon center, formed by the vasa recta. Each tubule pursues at first a very circui-
tous course, but straightens out as soon as it approaches the mediastinal septum,
where it unites with others into from 20 to 30 straight tubes or vasa recta. The
latter traverse the mediastinum to form the rete testis. The total number of seminif-
erous tubules has been estimated at from 800 to 1000. When completely unfolded,
each measures from 30 to 50 cm. in length, and possesses a diameter of 0.3 mm.
Centrally to the rete, the small ducts again become convoluted, and unite to form
the vasa efferentia. In this way is formed the epididymis, a convoluted single duct
measuring about 7 m. in length and 0.4mm. in diameter. This collecting channel
descends behind the testicle to its lower border, where it passes over into the
z;as deferens, an ascending, rather straight tube which traverses the abdominal ring
and, by following the under surface of the base of the bladder, eventually termi-
nates in the prostatic division of the urethra. The vas deferens is about 60 cm. in
length and possesses a diameter of from 2 to 3 mm.
This recurrent course of the seminal collecting tube finds its origin in the fact
that the testes are developed in the peritoneal cavity from the germinal epith©-
1124
THE REPRODUCTIVE ORGANS
Nucleus..
End-knob.
Middle-piece.
Envelope of the tail.
■ Axial filament.
lium, and descend later on through the abdominal ring into the gradually enlarg-
ing scrotum. Their descent through the ring takes place shortly before birth.
This fact also accounts for the peculiar blood supply of these organs which is de-
rived from the abdominal aorta by the slender and unusually long spermatic
arteries. The venous return is effected by the spermatic veins, the right one
entering the inferior cava directly, and the left one, the left renal vein. Inasmuch
as the latter joins the renal almost at right angles, it cannot discharge its blood
with absolute freedom, a condition which in later
years often gives rise to a venous engorgement
Apical body or acrosome. and a lower position of the corresponding organ.
The Development and Character of the
Spermatozoa. — Up to the time of puberty,
the seminal tubules are filled with cells
containing unusually large nuclei. Among
these are found the spermatogonia which
then discontinue their divisions and rapidly
develop into the so-called spermatocytes.
From these arise by hetero-mitosis the sper-
matids or sperm-cells, and from these in turn
the adult spermatozoa. Each spermatocyte,
however, divides into two daughter-cells
and the latter in turn into two, so that
really four spermatids and spermatozoa are
developed from each primary spermatocyte.
The nuclear material of the spermatid is
transformed directly into that of the sper-
matozoon, while its cytoplasm is appor-
tioned to the tail. In some cases, however,
the centrosome of the spermatid is con-
verted into the middle piece and the axial
filament of the tail. This process, there-
fore, is not a mere division of the cell, but
a reduction-mitosis, the chromosomes being
reduced by one-half. In this regard, the
formation of the spermatozoon is analogous
to the maturation of the ovum during the
projection of the polar bodies, but since
the union of these two elements eventually
restores the original number of chromo-
somes, the spermatozoon and ovum really
supplement one another.
When fully formed, the spermatozoa are forced into the epididymis
and vas deferens, but since they do not become motile until they have
reached the former, their progress through the more distal channel
must be effected by the lining cells of the seminiferous tubules and
differences in pressure. In the vas deferens, they are then able to
unfold their power of movement more fully and, besides, this tube
greatly facilitates their progress by its peristaltic contractions as
End-piece.
Fig. 534.— Diagram of the
Flagellate Spermatozoon.
(From Wilson, "The Cell in De-
velopment and Inheritance.**)
THE MALE AND FEMALE REPRODUCTIVE ORGANS
1125
well as by the action of the cilia-like appendages of some of its lining
cells.
The spermatozoon is a complete cell, consistingi of a nucleus and cytoplasm.
In many cases, however, it is i r^r^ r^r^r. times smaller' than the germinal cell of the
opposite sex, the ovum. It has the appearance of a minute tadpole and presents a
nucleus which forms the principal portion of its conoid and slightly flattened head,
an apical piece or acrosome at the front of the head, a middle piece directly behind
the head, and a long slender tail or flagellum. Its total length measures from
50 to 80 )U.i Physiologically considered, its nucleus derives its importance from the
fact that it contains the chromatin, while its
middle piece represents the centrosome
element which serves as the stimulus to
division. Its apical piece is of importance
because it enables the spermatozoon to bore
its way into the ovum, and its tail because
its contractile substance furnishes the motile
power by means of which this chemical
complex is enabled to reach the passive
ovum.
The formation of spermatozoa be-
gins at the time of puberty or sexual
maturity, i.e., in temperate climates at
about the fifteenth year. Some of
Fig. 535. Fig. 536.
Fig. 535. — Diagram to Represent the Progressive Serpentine Movements op
THE Tail of the Spermatozoon.
Fig. 536. — Diagram or the Bladder, Prostate Gland, Root of Penis, etc.
CI, Part of base of bladder covered by peritoneum, separated by a dotted line from a
triangular space • left uncovered by that membrane; V, ureter; S.V, seminal vesicle;
ED, ejaculatory duct; P, prostate; M, membranous part of the urethra; B, bulb; C.S,
corpus cavernosum urethrse; C, crus penis; C.G, Cowper's gland. (J. Symington.)
the adjunct powers of the sexual mechanism, however, may have
been active for some years before this time; for example, the erec-
tion of the penis and sexual desire. Thus, the only definite sign of
maturity is the presence of fully developed spermatozoa in the semen.
This change is associated as a rule with a greater stability of the body
as a whole. The voice becomes deeper, owing to a more rapid growth
1 Eberth, in Bardeleben's Handb. der Anatomic des Menschen, Jena, 1904.
1126 THE REPRODUCTIVE ORGANS
of the larynx, while the legs, arms and other parts cease their often
very prolific growth and increase in compactness rather than in length.
The Seminal Vesicles. The Semen. — Shortly before its entrance
into the prostatic urethra, the vas deferens receives a duct from the
vesicula seminalis, and is now known as the ejaculatory duct. Each
seminal vesicle is about 4 cm. in length, pyriform in shape, and oc-
cupies with its fellow-organ the under surface of the bladder, directly
behind the prostate gland. Its wall consists of an external fibrous
coat, a middle muscular coat and an internal mucous coat. The
mucosa is beset with numerous tubular albuminous glands which add
a stringy constituent to the semen, consisting chiefly of globulins.
Since the semen becomes more fluid upon standing, it seems that these
globular masses, which have been added to it by the seminal vesicles,
merely serve the purpose of giving a greater volume to it. In fact, in
some animals this material is made to clot through the agency of a
ferment derived from the prostate gland. Obviously, this would
tend to obstruct the orifice of the vagina and thus prevent the loss of
spermatozoa. But it cannot be said that the seminal fluid, plus the
spermatozoa and testicular secretion, constitutes the entire semen, be-
cause this medium receives in addition the products of the prostatic
and urethral glands.
The prostate gland attains the size of a chestnut and consists of 30
to 50 lobules with 15 to 30 ducts which open near the orifice of the
ejaculatory duct. The prostatic secretion is thin, cloudy, slightly
alkaline, and contains albumin but no mucin. The urethral or Cow-
per's glands are represented by two small globular masses, one on each
side of the prostate, which empty their product into the cavernous
portion of the urethra. Their ducts measure 3 to 4 cm. in length.
Their secretion is alkaline and rich in mucin. Droplets of it appear
sometimes in the meatus urethrse after micturition or after sexual
excitement which has not actually led to an emission of semen.
The semen is grayish-white in color, and possesses a mucilaginous
consistency. Its specific gravity varies between 1.027 to 1.040. Its
very characteristic odor is derived from the spermin of the prostatic
secretion. The amount discharged during one ejaculation varies
between 1 and 6 c.c. in accordance with the sexual activity of the indi-
vidual, and each emission may furnish as many as 223,000,000 of sper-
matozoa.^ These elements are formed constantly and are then stored
in the seminal vesicles and adjoining tortuous portion of the vas
deferens. The fact that the liquid here collected contains about 70,-
000,000 of spermatozoa per cubic centimeter, although only one of
them is sufficient to fertilize the ovum, shows how liberal and fixed
in its purpose nature actually is when the propagation of the species
is at stake.
The Erectile Tissues of the Male. — The transfer of the semen into
the seminal receptacle of the female is made possible by the act of
1 Lode, Pfluger's Archiv, 1, 1891, 278.
THE MALE AND FEMALE REPRODUCTIVE ORGANS 1127
erection of the penis, the male organ of copulation. It is composed
chiefly of cavernous tissue which is arranged in three long and some-
what cylindrical masses, forming the corpus spongiosum below and
the two corpora cavernosa, one on each side, above. The former is
traversed by the urethra and terminates anteriorly in a conical struc-
ture, the glans penis. Externally, these bodies are enveloped by
fibrous sheaths and a thin layer of very movable and distensible skin,
which is then reflected upon the glans penis to form the prepuce.
The erectile tissue of which these bodies are composed, is made up of
cavernous spaces which are really venous sinuses lined with a layer
of flattened epithelium. Their walls consist of membranous parti-
tions which are derived from the external fibrous investment, the tunica
albuginea, as well as from the median septum of the penis. In this
way ^ a spongy network of connective tissue is formed which is much
denser near the circumference than near the center. The central
spaces, therefore, are larger than the outer ones, but all of them are
supplied with blood from branches of the internal pudendal artery
through capillaries which are rather more widely open than those of
other tissues.
The erection of this tissue is dependent upon a dilatation of these
afferent channels through which the blood is then poured freely into
the lacunae, but since the venous collecting tubules begin with a nar-
row orifice which is strengthened by rings of smooth muscle tissue,
th3 oflflow is somewhat hindered both in a mechanical way as well as by
an active constriction of these sphincters. Consequently, the erection
of the penis cannot be regarded as a pure vaso-dilator phenomenon,
but as an active venous retardation which is brought about chiefly by
the contraction of those muscle cells with which the outlets of the
several blood-spaces are beset. In addition, it is entirely probable that
the action of this intrinsic muscle tissue is materially strengthened by
the contraction of certain extrinsic muscles, such as the ischio and
bulbo-cavernosi. By compressing the larger collecting channels,
these muscles tend to raise the venous pressure without actually
blocking the return of the blood. Meanwhile, the inner walls ofthe
cavernous spaces are fully exposed to the arterial blood-pressure,^ which
causes them to move outward as far as their tough fibrous constituents
as well as the fibrous investment of the entire organ will allow.
The length of time during which copulation must be continued in
order to give rise to an ejaculation of the semen differs greatly with
the condition and type of the animal. It is safe to assume, however,
that the erection of the penis cannot be attained by vaso-dilatation
alone, because a reaction of this kind is neither sufficiently intense nor
lasting. Nor can it be due to venous stagnation alone, because the
erected organ does not become cyanosed and retains a higher tempera-
ture throughout this act. These facts unmistakably point toward a
more copious blood supply and greater through-flow and not merely
1 Frangois-Frank, Arch, de Physiol., 1895, 122.
1128 THE REPRODUCTIVE ORGANS
toward a more abundant content in blood at any one time. This con-
clusion is strengthened by the fact that in priapismus this organ may
retain its erected condition for hours and even for days without show-
ing an actual impairment of its tissues or gangrene. Naturally, the
size and shape of the erected organ are determined not only by the dis-
tention of the cavernous spaces, but also by the arrangement of its gross
anatomical structures, such as its dorsal fascia and the fascia situated
in the vicinity of its base. The former acts in the manner of a ligament.
Since it is shorter than the one investing the under surface of this
organ, the dorsal aspect of the erected penis must exhibit a decided
concavity. This change in its shape imparts to it a greater penetrating
power and increases its receptive power to stimuli, because it tends to
retract the prepuce and to uncover the tactile receptors of the glans
penis. During this period it is quite impossible to void urine, because
the sphincter vesicae remains firmly closed. Not until the erection
has ceased does this sphincter regain its power of relaxation.^
The reflex center controlling this act is situated in the lumbar
segment of the spinal cord. The corresponding autonomic fibers
leave this structure in the first to third sacral nerves to form the pelvic
plexus and nervi erigentes and cavernosi. The fact that the latter
contain vaso-dilator fibers to- the penis has been proved by Eckhard,
Loven and others by stimulating them electrically. Afferently, this
reflex center may be activated by stimuli applied to the genitals
directly, as well as by stimuli received from other sense-organs and the
cortical association centers.
The Act of Ejaculation. — The discharge of the semen is initiated
by a powerful peristalsis of the vas deferens, seminal vesicles and
ejaculatory duct which forces the secretion into the urethra. Here it
is prevented from entering the deeper urethra by the sphincter vesicae^
and is mixed with the secretions of the prostate and Cowper's glands.
The latter are poured into the urethra in the hollow at each side of
the colliculus seminalis. Then begin the rhythmic contractions of
certain striated muscles which, however, are not under the control
of the will. Chiefly involved in this process are the ischio-cavernosus,
the bulbo-cavernosus and the sphincter urethrse membranacese or
sphincter of Henle.
The act of ejaculation is controlled by a reflex center which is
situated in the lumbar segment of the spinal cord. The latter may be
activated by afferent stimuli arising in the genital organs and evoked
chiefly in Krause's corpuscles with which the glans penis is abundantly
supplied. Other sense-organs, such as the general cutaneous receptors,
the retina, and organ of Corti may also be involved, but only in so far
as their impressions give rise to erotic associations. In the absence
of peripheral stimuU, the activation of the psychic centers may lead to
^'spontaneous" emissions, those occurring in consequence of dreams
1 Zeiss! 8,nd Holzknecht, Wiener med. Blatter, 1902.
2 Walker, Archiv fur Anatomie, 1899.
THE MALE AND FEMALE REPRODUCTIVE ORGANS 1129
being called pollutions. Among the nerves concerned in the acts of
erection and ejaculation may be mentioned the nervus pudendus,
nervus erigens, and nervus ileo-inguinalis. The first sends one of
its branches, the nervus perinei, to the ischio and bulbo-cavernosi,
the bulbus urethrse and the mucous membrane of the upper urethra.
This nerve, therefore, is the one controlling ejaculation. Another of
its branches, the nervus dorsalis penis, innervates the skin, prepuce,
corpora cavernosa, and outer portion of the urethra. This nerve,
therefore, conveys sensory impulses from the largest part of the penis.
The nervus erigens, as has been stated above, is chiefly vasomotor in
its function, while the ileo-inguinalis innervates the base of the penis.
The Ovaries. — The essential reproductive organ of the female is
represented by the ovaries, two flattened, more or less almond-shaped
bodies which are situated in the upper part of the pelvic cavity in a
slight depression in the obturator muscle. Although subject to con-
siderable fluctuations, the adult ovary measures 2.5 to 5 cm. in length,
1.5 to 3 cm. in breadth, and 0.6 to 1.5 cm. in thickness. In cross-
section each organ is seen tabe made up of two portions, a cortex and
a medulla. The former varies in thickness, becoming thinner with
advancing years, and consists of connective tissue containing isolated
primordial and Graafian folHcles. The- central medullary portion is
made up of loose connective tissue containing large numbers of blood-
vessels and smooth muscle cells. ^
In the child, the greater portion of the ovary is composed of cortical
substance which is closely packed with primordial follicles in different
stages of development. This is also true of the ovary of young
women, but the follicles are then more widely separated from one an-
other by layers of connective tissue of varying thickness. Each
follicle consists of an oocyte surrounded by a single layer of epithelium
and measuring from 48 to 69 ju in diameter. At birth each ovary
contains at least 100,000 oocytes, while at puberty it embraces only
from 30,000 to 40,000; but even this number is more than sufficient to
supply the necessary ova for fertilization, because only one of them is
discharged 'during each menstrual period. It may also happen that
one of these follicles contains two and more distinct ova, a fact which
has been made use of in explaining multiple pregnancies.
These primordial follicles eventually develop into the mature Graafian follicle,
a process which begins at birth and does not cease until the menopause has termi-
nated the sexual life. To begin with, the spindle-shaped epithelial investment is
changed into a single layer of cuboidal cells which then proliferate rapidly until
the central ovum has become enveloped by several layers of epithelial cells. By the
degeneration of certain ones of these cells a space is eventually formed around the
ovum which becomes filled with fluid, the liquor folliculi. The ovum itself grows
larger constantly and is gradually pushed to one side, where it becomes surrounded
by a layer of cells, forming the discus proligerus. Its nucleus undergoes important
changes which finally terminate in the formation of the first polar body, a deposi-
tion of yolk granules in the cytoplasm, and the formation of a thin investment, the
^ Clark, Contrib. to the Science of Med., Johns Hopkins Univ., 1900.
1130
THE REPRODUCTIVE ORGANS
zona pellucida. The entire follicle is marked off against the now very vascular
connective tissue stroma by the membrana granulosa.
The Mature Graafian Follicle. — Beginning shortly after birth,
the developing prim or diaL follicles pass from the inner realm of the
cortex toward its periphery, but do not actually reach the surface.
Later on, however, the more superficial ones pursue the same course
and actually appear externally in the form of projecting vesicular
bodies, the diameter of which varies between 2 and 15 mm. The outer
wall of these vesicles is thin and nearly bloodless (stigma), while their
remaining investment is really more vascular than previously. At
this time, therefore, the projecting Graafian follicle consists of a
i Ji.
>
Fig. 537. — Graafian Follicle of Mammalian Ovary.'
ov, Ovum; dp, discus proligerus; Iq.f, liquor folliculi; ch, theca; gr. membrana granu-
losa. (Prenant and Bouin.)
connective tissue investment, or theca follicula, an epithelial covering,
or membrana granulosa, the ovum, and the liquor folliculi. The ovum
itself now measures 0.2 mm. in diameter, as against 48 to 69 yu when
first formed, and contains large numbers of irregularly shaped and
highly refractive granules, the so-called deuteroplasm. Its nucleus
or germinal vesicle presents a well differentiated nucleolus, or germinal
spot. It is also of interest to note that the connective tissue stroma
gives rise at this time to a peculiar type of cells which contain a yel-
lowish pigment and are destined to play an important r61e later on
in the formation of the corpus luteum.
THE M^LE AND FEMALE REPRODUCTIVE ORGANS 1131
The Corpus Luteum. — According to Clark, ^ the rupture of the
Graafian follicle is brought about by complex changes in the vascu-
larity of the ovary, leading to a congestion of the entire organ. In
consequence of this increased tension, the follicle is pushed far out-
ward. The stigma of its outer wall becomes necrotic and bursts,
allowing the liquor as well as the ovum and a part of the torn mem-
brana granulosa to escape into the tube. The walls of the empty
follicle then collapse, but are distended again by blood derived from
the vessels of the theca. To begin with, therefore, the corpus luteum
is represented by a ruptured Graafian follicle, filled with blood and
invested by a layer of yellow lutein cells of the theca. The latter
multiply rapidly and presently enter the hemorrhagic extravasate
which they occupy completely with the exception of a small central
area. Connective tissue strands and blood-vessels follow them in
increasing numbers so that the corpus finally assumes the appear-
ance of an organized and growing structure. Very soon, however,
retrogressive changes set in which terminate in a hyaline degeneration
of the lutein cells and their final absorption. This obliteration of the
corpus luteum takes place more rapidly in young persons, because the
circulation of the adult ovary has lost much of its original vigor.
Eventually, the corpora appear merely as small whitish granules
resembling scar tissue. They are then known as the corpora fibrosa or
albican tia. 2
It is to be emphasized, however, that it is not real scar tissue; in
fact, the reason for the formation of the corpora lutea is to prevent
the conversion of the ovarian parenchyma into a tissue of this type
which would effectively prevent the formation and discharge of other
ova.^ Besides, the corpus luteum seems to furnish an internal secre-
tion which is intimately concerned with the future development of the
ovum.^ Thus, it has been noted by Frankel that the next succeeding
menstruation invariably fails to take place if the corpus luteum has pre-
viously been destroyed by means of a cautery. Further evidence to
show that it is a temporary gland, is presented by the fact that its
atrophy and degeneration are closely connected with the fertilization
of the ovum. If the latter is not fertilized, this retrogression will be
completed in the course of 2 or 3 weeks, while if it is fertilized, the
consummation of this process may require 6 months and longer. For
this reason, it is customary to speak of true and false corpora lutea.
The former is larger and persists until the development of the ovum is
well advanced, whereas the latter is fully reduced within a short time
after the menstrual period. According to Miller, it is possible to dis-
tinguish between these corpora by histological and micro-chemical
^ Johns Hopkins Hosp. Rep., 1898.
2 Frankel, Archiv fur Gynec, Ixviii, 1903, 438, and xci, 1910, 705; also: Meyer,
ibid., c, 1913, 1, and Ruge, ibid., c, 1913, 20.
3 Marshall, Physiol, of Reproduction, London, 1910.
* L. Loeb, Jour. Am. Med. Assoc, xlvi, 1906, 416.
1132 THE REPRODUCTIVE ORGANS
means, because neutral fat is readily demonstrable in the corpus luteum
of menstruation.
Menstruation. — The process of menstruation is a periodic change
in the life cycle of the female which is most plastically betrayed by a
discharge of blood from the genitals, derived chiefly from the mucous
membrane of the uterus. In general, it may be said that this phenome-
non appears for the first time at puberty and is continued thereafter
at intervals of 28 days until about the forty-fifth year. This statement
would imply that it begins in temperate climates at about the twelfth
year and in cold climates at about the fifteenth year, but much depends
upon the physical condition of the individual as well as upon her sexual
development and mode of life. Thus, we are reminded at this time
of the child-woman of certain sections of India, where menstrua-
tion is regarded as a disgrace and where corresponding measures are
taken to prevent it with not especially flattering results to the off-
spring nor to the mother. In fact, Haller mentions a case of a child-
mother who menstruated regularly from her second year and gave birth
to a child at the age of nine.
Before the first menstrual period, the approaching sexual maturity
betrays itself by a more rapid growth. The pelvis assumes a typically
feminine shape, the mammae become enlarged and hair begins to grow
upon the genitals as well as in the axillae. Although prone to be irregu-
lar at first, the menses are repeated as a rule every 28 days,
but certain variations in this time are by no means uncommon. The
hemorrhagic discharge sets in slowly, reaches a maximum about the
second or third day, and then gradually subsides. Consequently, not
more than 4 or 5 days are usually consumed by it. In our
country, menstruation ceases at about the forty-fifth year, but it has
been noted to disappear as early as the twenty-eighth year and as late
as the sixty-third year. It is by no means a rare occurrence that
women of fifty and over bear children. The cessation of the menstrual
flow is the expression of a series of changes constituting the menopause.
Underlying these changes are a series of important metabolic altera-
tions, the completion of which often requires several years and renders
the woman particularly susceptible to pathological processes of all
kinds. During the period intervening between puberty and the meno-
pause, conception may take place at any time. In rare instances,
however, this result has also been known to have been attained long
before sexual maturity as exemplified by the changes just enumerated.
Menstruation ceases immediately upon conception and does not recur
until after the termination of the periods of pregnancy and lactation.^
The discharge of blood, however, does not actually constitute the
menstrual period. It really begins several days beforehand, and is
ushered in by a feeHng of fatigue, pains in the back, headache, an
increased irritability of the nervous system, an unusual tenseness and
sensitiveness of the mammae, a congestion of the vulva, and a more
1 Ploss, Das Weib in der Natur und Volkerkunde, Leipzig, 1894.
THE MALE AND FEMALE REPRODUCTIVE ORGANS 1133
copious secretion of vaginal fluid and mucus. These premonitory
symptoms are followed by a hemorrhagic oozing and later on by a
period of restitution which occupies almost two weeks. Consequently,
only a few days of absolute functional rest intervene between the
successive menstrual cycles.
The division of this process into the periods of premenstruation,
menstruation, restitution, and complete rest leads us to suspect that
the endometrium of the uterus retains a comparatively normal appear-
ance only during the last stage of restitution and the succeeding period
of rest.^ During the premenstrual state it presents distinct evidences
of proliferation, swelling and hypersecretion. The cells of the stroma
lose their elongated shape and become more rounded. The capillaries
are greatly distended with blood which in turn gives rise to a hyper-
plasia of the uterine glands. A few days later blood begins to escape
from the superficial vessels and forces its way into the lumen of the
uterine canal, and through the constricted orifice of the cervix into
the vagina. But this hemorrhagic extravasation is not associated with
any considerable destruction of tissue; in fact, the uterine lining re-
mains rather intact, although it may be perforated here and there and
even partially loosened from the under-lying layers by spaces which are
filled with blood. In most instances this congestion also involves
the tubes, ovaries and external genitals, but these organs do not con-
tribute to the hemorrhagic discharge and hence, menstruation is to
be regarded essentially as a phenomenon of the uterus. The quantity
of blood lost during this period may amount to as much as 100 to 300
grams. 2 Under ordinary conditions, however, it is mixed with consid-
erable quantities of mucus, which substance tends to preserve the
thrombocytes and, therefore, to prolong the coagulation-time. Men-
strual blood as such clots as readily as any other type of blood.
The phenomenon of heat exhibited by the lower mammals is the homologue
of menstruation. It is commonly divided into four periods, namely : (a) the pro-
estrum, during which the organs become congested and bleed, (6) the estrum, or stage
of sexual desire, (c) the metestrum, or period of restitution, and (d) the anestrum,
or stage of rest. Contrary to the human female, those of the other mammals take
the male only during the estrus. If sexual union or conception is prevented at
this time, the period for sexual intercourse gives way to the period of restitution,
but recurs again after a definite interval which in bitches is 12 to 16 weeks, in the
cow 3 to 4 weeks, in the sheep 2 to 4 weeks, in monkeys about 4 weeks, and in the
sow 9 to 18 days.
Relation Between Menstruation and Ovulation. — Among the
many theories proposed to explain the cause of menstruation is the
older view that the menstrual flow is the female fluid of fertilization.
Subsequent to the establishment of the fact that menstruation occurs
in periodic cycles, it was then believed that it is brought on by the ma-
1 Findley, Anat. of the menstr. uterus. Am. Jour. Obst., xlv, 1902, and Hitsch-
mann and Adler, Bau der Uterusschleimhaut, Manatsh. fiir Geb. und Gyn., xxvii,
1907.
2 Hoppe-Seyler, Zeitschr. fur physiol. Chemie, xlii, 1904, 545.
1134 THE REPRODUCTrV'E ORGANS
turing of the Graafian follicle and the discharge of the ovum. Pfltiger^
sought its cause in a reflex extravasation of blood evoked by the pres-
sure which the growing follicle exerts upon the nerves of the ovary.
This view, however, was put into question by the clinical experience
that ovulation and even pregnancy may result before the first menstrua-
tion as well as after the menopause. ^ It was also noted that conception
may take place during the period of lactation, whereas the menstrual
flow is then usually absent. Lastly, it has been observed by Rein^ that
pregnancy is possible in dogs even after all the nerves connecting the
uterus with the spinal cord have been divided. Certain experiments
are also at hand to show that menstruation does not cease after the
transplantation of the ovaries into some other part of the body, while
ovulation is then impossible. In 1871, Sigismund advocated the view
that menstruation succeeds ovulation and is the direct result of the
failure of the ovum to become fertilized. It has also been stated that
menstruation is a process of purification and, therefore, serves to clean
out the uterus and to establish a proper substratum for the fertilized
ovum to grow upon.^
Subsequent to the development of the hormone doctrine, FrankeP
proposed the theory that menstruation is dependent upon the forma-
tion of an internal secretion by the corpus luteum which controls the
blood supply of the ovary. ^ He believed ovulation to be related to
this process only in so far as the escape of the ovum initiates the forma-
tion of the corpus luteum which attains its full development about 7
days later, i.e., at a time when menstruation sets in. Consequently,
ovulation must take place 19 days after the last menstrual flow.
This explanation has many points in, its favor, and may be supported
by strong clinical evidence. In the first place, it is obvious that nien-
struation is dependent upon some activity of the ovaries, because the
removal of these organs gives rise to an artificial menopause which is
characterized by a cessation of the menses and an atrophy of the
uterus. Secondly, this cessation of the menstrual flow does not result
if the ovaries are transplanted into the uterus or elsewhere in the
abdominal cavity.^ Thirdly, menstruation may be made to recur by
grafting a piece of an ovary in the uterus or under the skin of the
abdomen,^ and a temporary condition of estrus may be incited in
mature animals by the injection of an extract of ovaries taken from
1 Bedeutung and Ursache der Menstruation, Berliij, 1865.
2 Berliner klin. Wochenschrift, 1871.
3 Pfluger's Archiv, xxiii, 1880, 68.
* Bryce and Teacher, Early development of the human ovum, 1908.
e Archiv fiir Gyn., 1910.
^ The dried extract of the corpora lutea of cows is made use of in the treatment
of suppressed menstruation and the grave symptoms sometimes following the
removal of the ovaries and premature production of the menopause.
^ Halban, Deutsche Gesellsch. fiir Gyn., ix, 1901; also: Glass, Medic. News,
1899, and Morris, Med. Rec, 1901.
8 Meredith, Brit. Med. Jour., 1904.
THE DEVELOPMENT OF THE EMBRYO 1135
an animal in heat.^ Having established this fact, it may then be
proved that ovulation is not synchronous with menstruation. Thus,
it is well known that the Mosaic Law regards Jewesses unclean during
the menstrual period and for 7 days thereafter. In these women,
therefore, conception must take place after this period and before the
onset of the next menstrual flow. Moreover, Pinard^ has shown that
about three-fifths of the women who marry during the interim between
two menstrual periods and miss the subsequent flow, give birth to full-
term children 280 days after the beginning of the last menses. In
these cases, the duration of pregnancy is less than 9 calendar
months. Consequently, if ovulation takes place some time before
the onset of the menstrual flow, the latter must be in the nature of a
process of purification which prepares the endometrium for the suc-
ceeding ovulation. This cyclic regeneration, therefore, tends to keep
the uterine membrane in a condition of irritability which enables it
to respond very promptly to the stimulus brought to bear upon it by
the fertilized ovum. It is thus in the best possible condition to de-
velop the decidual membranes.
CHAPTER XCV
THE DEVELOPMENT OF THE EMBRYO
The Migration of the Ovum. — In those animals in which the ovary
is enveloped by a peritoneal pouch into which the Fallopian tube
opens, no special difficulty confronts us in explaining the migration of
the newly formed ovum into the uterus. In those aninials, on the
other hand, in which the ovary and fimbriated extremity of the Fal-
lopian tube are not in direct contact with one another, we are forced to
assume that the ovum first escapes into the peritoneal spaces and then
enters the tube from without. This manner of migration is exemplified
by the human female. Attention was first called to this possibility by
Bischoff,^ who found that animals possessing bifurcated or bicornuated
uteri frequently present corpora lutea in the ovary opposite to that
horn of the uterus in which the embryos are developing. Two explana-
tions may be offered for this occurrence, namely: (a) that the ovum has
penetrated the tube on the same side and has later on been forced into
the cornu uteri of the opposite side, and (h) that it has migrated to the
opposite side to begin with and has then entered the tube and uterine
horn of the same side. The former process is called internal migra-
^ Marshall and Jolly, Phil. Transact., R. Soc, London, 1905.
2 Ann. de gyn. et d'obst., 1909.
3 Die Entwickelung des Kanincheneies, 1842; also Kussmaul, Von dem Mangel,
Verktimmerung und Uberwanderung des Eies, Wtirzburg, 1859.
1136 THE REPRODUCTIVE ORGANS
Hon and the latter, external migration. Leopold^ has proved that the
latter process is possible by excising one ovary and the tube of the op-
posite side. Many of these animals ' became pregnant. A similar
case has been reported by Kelly, ^ who removed the diseased left ovary
and right tube of a woman, leaving the right ovary and left tube in
situ. Fifteen months after the operation, this woman gave birth to a
normal child. Seventeen months later, the left tube had to be re-
moved for the relief of a ruptured extra-uterine pregnancy. Inas-
much as the ovum does not possess an inherent power of movement,
its progress must be determined by outside forces, such as gravity
and the action of the ciliated lining of the tube and uterus.
While much uncertainty prevails regarding the manner in which
the oyum gains entrance to the tube, it seems established that ex-
ternal migration occurs much more frequently than has been supposed.
In view of the preceding data, it would seem probable that the ovum
migrates through the narrow peritoneal spaces between the pelvic
viscera and may then be received by the tube of the same side as well
as by that of the opposite side.
The Migration of the Spermatozoa. — In the male, the climax of
the coitus is reached with the ejaculation of the semen which may
or may not occur synchronously with the orgasm of the female. The
latter betrays itself by an erection of the clitoris and vaginal folds, a
more copious secretion of vaginal fluid by the glands of the vestibulum
and the glands of Bartholini, a twitching of the external bands of vaginal
muscle tissue (sphincter vaginae), and an alternate depression and
elevation of the uterus. The spermatozoa deposited in the seminal
receptacle, the vagina, find their way into the uterus by their own
activity which consists in a lateral oscillatory progression of the head
in consequence of the whip-like action of the tail. The latter, how-
ever, does not contract as a whole from side to side^ but in the manner
of the tail of an eel (Fig. 535). Under favorable conditions the speed
attained by them may amount to 4 to 10 mm. in a minute. ^ They are
aided in their upward movement by the mucous secretion of the uterus
which attracts them. In other words, this secretion exerts a positive
chemotactic influence upon them, whereas the sour vaginal fluid
affects them negatively.^ Secondly, it is a well-known fact that the
cilia of the uterus and Fallopian tubes beat in a direction from above
downward and, therefore, might retard the progress of these elements.
This is not so actually, because the spermatozoa are stimulated by these
mechanical impacts to greater activity and are capable of advancing
even against the direction of the stream of the intra-uterine fluid.
They are, therefore, positively rheotactic and thigmotactic.
'^ Archiv fiir Gynec, xvi, 1880, 22.
2 Operative Gynec, ii, 1898, 187.
3 Lott, Anat. und Physiol, des Cervix uteri, Erlangen, 1871, and Henle, Lehrb.
der Anat., Leipzig, 1890.
^ Chrobak, Wiener klin. Wochenschr., 1901; and Low, Stizungsb. Wiener
Akad., 1902.
THE DEVELOPMENT OF THE EMBRYO 1137
The fact that the spermatozoa are capable of making their own way-
through the canal of the cervix into the uterus is proved by the cases
of pregnancy following incomplete coitus, and especially by the preg-
nancies which have occurred in women possessing perfect hymens.
Nevertheless, it has been thought by Litzmann, and others, that the
uterus contracts and relaxes at the height of the orgasm and actually
aspirates the semen into its cavity. Moreover, Kristeller^ has advo-
cated the view that a mucus plug is projected at this time from the
mouth of the cervix, which is then retracted, carrying with it large
numbers of spermatozoa.
The Place of Meeting of the Ovum and Spermatozoa. — The view
that the fertilization of the ovum is effected within the cavity of the
uterus, has now given way to the belief that the meeting between the
male and female sperm-cells takes place in the Fallopian tube and
chiefly in its funnel-shaped outer extremity. Since the distance
between this point of the generative tract and the mouth of the uterus
measures only about 16 cm., the spermatozoa may reach this receptacle
in less than 1 hour. In fact, the occurrence of ovarian pregnancy
in woman demonstrates that these elements may even advance as
far as this organ and that the fimbriated extremity of the tube is not
absolutely impermeable. This view, that impregnation takes place in
the Fallopian tube, also finds substantiation in the fact that living
spermatozoa have frequently been found here; in fact, they have been
noted to live within its lumen for an almost indefinite period of time.
In the tubes of the bat, for example, they have been known to retain
their activity for many months.
The Implantation of the Ovum. — After its fertilization the ovum
undergoes repeated segmentation and slowly progresses into the uterus
where it remains until the end of the period of gestation. It tra-
verses this distance in about 8 days after its impregnation, having
meanwhile attained a diameter of 0.2 mm. and completed the morula
stage. 2 The earliest specimen of developing ova has been described
by Bryce and Teacher. ^ It measured 0.77 mm. in length and 0.63
mm. in breadth, and was about 13 days old. This one, as well as all
the others representing a later stage of development, were found
deeply imbedded in the decidua and hence, well removed from the
cavity of the uterus. Spee, ^ therefore, assumes that the human ovum
attaches itself to the free surface of the endometrium and destroys
the underlying tissue by means of a tryptic ferment.^ In this way it
gradually sinks into the depth of the uterine decidua, its point of
1 Berliner klin. Wochenschr., 1871.
2 Grosser, Vergl. Anat. und Entwickelungsgesch. der Eihaute und Placenta,
Leipzig, 1909.
3 Early development and imbedding of the human ovum, Glasgow, 1908;
also Linzenmeier, Archiv fiir Gynec, cii, 1914, 1
^ Zeitschr. fiir Morph. und Anthropol., 1901, and Verh. deutsch. Ges. fiir
Gynec, 1906.
^ Grafenberg, Zeitschr. fiir Geburtshilfe und Gynec, 1910.
72
1138 THE REPRODUCTIVE ORGANS
entrance being obliterated very soon thereafter by the coalescence of
the edges of the opening.
Pregnancy. — With the descent of the ovum, the woman begins
to exhibit very characteristic local and general signs of pregnancy.
The virgin uterus is small, pear-shaped, almost solid, and only 6.5 cm.
in length. At the end of pregnancy, on the other hand, it has been
converted into a large thin-walled sac, measuring 32 cm. in length,
24 cm. in breadth, and 22 cm. in depth. Its volume, which now
amounts to 5000-7000 c.c, has been increased 519 times, and its weight
from 32 grams to 1000 grams. This hypertrophy really begins with
the moment of conception, and while all of its elements are involved
in this process, it affects more particularly its smooth muscle-cells.
The latter increase not only in their length and thickness, but also in
their number. A similar proliferation takes place in the elastic tissue
and mucous membrane, which attains a thickness of almost 0.5 cm.
by the time the ovum has entered the uterine cavity and of 0.75 cm.
at the end of the second month after conception. At the end of preg-
nancy, the uterine wall shows an average thickness of only 3-5 mm.
These changes account for the fact that the cervix uteri loses its firm
and almost cartilaginous consistency within a few weeks after con-
ception. A similar change is noted very shortly before the onset of
each menstrual flow.
The vascularity of the ovaries is increased, but ovulation ceases
as a rule during pregnancy. For this reason, it is not difficult to
detect the corpus luteum formed in the place of the impregnated
ovum. The vaginal wall also becomes more vascular and assumes a
peculiar violet color. Tts tissue is strengthened by new elements and
so is that of the vulva. Possibly the most striking change is exhibited
by the mammae which alter their consistency and size as well as color.
Already during the second month of pregnancy, these organs become
tense and nodular and are permeated by numerous large veins which
are sharply outlined against the lighter glandular tissue. The nipples
increase in size, become more erectile and assume a much deeper
color. The areola surrounding each becomes much broader, assumes
a darker color, and acquires numerous globular elevations which find
their origin in an enlargement of the sebaceous glands. Owing to the
increased distention of the integument, striae may be formed
which closely resemble those noted in the wall of the abdomen of
multipara. This enlargement of the mammae results in consequence
of the discharge of a specific hormone by the sexual organs. Quite
aside from the experiments of Claypon and Starling upon virgin rabbits,
which have been cited above but have more recently been criticized
by Frank and Unger,^ this conclusion is fully justified by the observa-
tions of Schants,^ upon the Blazek sisters, a pygopagous twin. One
1 Archiv of Int. Med., vii , 1911, 812.
2 Gynec. Rundschau, iv, 1910, 437.
THE DEVELOPMENT OF THE EMBRYO 1139
of these gave birth to a child which was subsequently suckled by either
with equally beneficial, results.
The enlarging uterus also inflicts certain spatial restrictions upon the neighbor-
ing pelvic and abdominal organs. Since these changes are effected chiefly by its
fundus, whereas the cervix tends to retain its previous size, a rather acute angle
is finally formed between these parts, which is augmented stillfurther as the fundus
progresses upward beyond the boundaries of the pelvis. At the fourth month the
upper border of the latter lies opposite a horizontal line drawn midway between the
umbilicus and the symphysis pubis, at the end of the sixth month opposite the
umbilicus, and at the end of 9 months almost opposite the ensiform cartilage. The
intestines are forced into the lateral extents of the abdominal cavity, so that the
anterior wall of the uterus comes to rest against the anterior wall of the abdomen.
The linea alba is broad and sharply outlined by its glistening white color. It need
scarcely be emphasized that these encroachments are responsible for a whole series
of far-reaching reflex actions.
Among the latter might be mentioned the vomiting of pregnancy, minor dis-
orders of digestion, constipation, and stagnation phenomena in the biliary passages. ^
The kidneys may be affected directly by pressure, as well as indirectly in conse-
quence of various disturbances of metabolism. The heart is displaced and its area
of dulness increased. The latter change has given rise to the statement that this
organ undergoes at this time a mild hypertrophy. ^ The pulse rate is not materially
increased, whereas, the pulse-pressure and total work of the heart are augmented
in a considerable measure. The respiratory movements are'somewhat hindered,
owing to the upward displacement of the diaphragm, but the total interchange of
the gases is rather increased. This is made possible by a broadening out of the
thorax. A moderate hypertrophy of the thyroid and parathyroid bodies is not
uncommon even during normal pregnancy,^ and a similar change may be displayed
by the hypophysis and the cortex of the adrenal glands.^ Peculiar yellowish
discolorations, the so-called chloasmas, appear in different regions of the skin.
The pregnant woman also displays mild mental disturbances which are associated
with an increased irritability, of the entire nervous system. Thus, she may
crave for the most unusual articles of food and suffer from mental depression
and all sorts of imaginary evils. For the neuropathic woman, this period is one of
danger, because these mild and functional psychoses may finaily develop into a
permanent or true psychosis.
In general, however, it cannot be doubted that pregnancy improves
the condition of the woman, and while this change may not be appar-
ent during the first few months, it certainly makes itself felt later on.^
The initial period of fatigue, lassitude and mental depression appears
to be associated with the rapid depletion of her energy by the rapidly
growing embryo. Later on, however, when a more stable equilibrium
has been established by the development of greater storative qualities,
her health improves perceptibly. This is especially true of her power
of retaining nitrogen and constructing proteid tissue, which in turn
leads to an increase in her weight and a decrease in the nitrogenous
content of her urine from its previous level of about 90 per cent, to
1 Opitz, Zeitschr, flir Geburtshilfe und Gynec, Ixxii, 1913, 351, and Hofbauer,
ibid., Ixi, 1908, 200.
2 Jaschke, Archiv fur Gynec, xciii, 1911, 809.
^ Seitz, Pnnere Sekretion und Schwangerschaft, Leipzig, 1913.
" Mayer, Archiv fiir Gynec, xc, 1910, 600.
^ Bar, Legons, de path, obstetricale, Paris, 1907.
1140 THE REPRODUCTIVE ORGANS
80 or 85 per cent. There may also be noted a slight increase in the
percentage of ammonia.
The Development of the Placenta. — The cytoplasm of the ovum
contains a certain amount of nutritive material which, however, does
not last for a longer time than its initial period of growth. Hence, a
new source of supply must be established as soon as the ovum has
become firmly attached to the maternal tissues. It will be remembered
that the defect through which the ovum has entered the uterine
decidua, closes soon afterward, the layer of tissue now investing the
ovum externally being known as the decidua reflexa, and that lining
the substance of the uterus as the decidua vera. Directly under-
neath the developing ovum lies the decidua basalis. The latter,
together with the enveloping membranes of the ovum, now enters into
the formation of a special organ, the placenta, the purpose of which
is to effect an interchange of materials between the fetus and the
mother. Evidently, this structure arises from a union of certain
fetal and maternal tissues, and consists essentially of vascular
outgrowths or villi of the chorion of the fetus which become approxi-
mated to large blood spaces formed in the decidua basalis of the uterus.
Consequently, the blood of the mother does not actually pass into the
channels of the fetus, but remains separated from that of the latter by
the lining of the blood-vessels and the epithelial layers of the villi of
the chorion.
To begin with, this separation is effected by a single layer of cells of the ectoderm
and constitutes the external envelope of the blastodermic vesicle. As soon as the
ovum has become firmly lodged upon the decidua, these cells proliferate and project
outward in the form of minute finger-like processes or villi, which impart a peculiar
fringed appearance to this layer. Each villus, therefore, is situated upon a substra-
tum of connective tissite with which it remains connected by a stalk, and consists
of an outer epithelial covering and an inner framework of connective tissue. The
cells of the former frequently proliferate, forming additional minute buds upon the
individual villi. It is also to be noted that the latter are very numerous in that
region of the ovum which lies most directly in contact with the basilar decidua.
Mention should also be made of the amnion which, when fully formed, com-
pletely invests the embryo, and eventually comes to lie in close contact with the
inner surface of the chorion. The amnion is developed as two layers, an external
one consisting of mesoderm and an internal one composed of cuboidal or flattened
ectoderm. A clear fluid then collects between these layers which gradually increases
in quantity as pregnancy progresses. Its average amount at term is 600 c.c. and its
specific gravity 1.002 to 1.028. It is derived chiefly from the mother's serum by
transudation through the amniotic epithelium, ^ but may also contain fetal urine
during the last months of pregnancy if the mother's kidneys become defective. ^
The function of this fluid is chiefly protective, because it serves to mitigate the force
of sudden shocks and to prevent the loss of heat from the fetus by investing its
surface with a medium of constant temperature. Secondly, it keeps the developing
fetus away from othertissuessothatitcannot become adherenttothem. Thirdly,
it may supply water as well as albumin to its tissues. Lastly, it serves as the
normal dilator of the cervix of the uterus during labor. In this case, it acts as a
1 Ahlfeld, Zeitschr. fiir Geb. und Gynec, Ixix, 1911, 91.
2 Wolff, in Oppenheimer's Handb. der Bioch., iii, 1910, 709.
f^~
r
'* '-
1142 THE REPRODUCTIVE ORGANS
a smooth and glistening appearance. The umbiUcal cord, containing
the blood-vessels which connect the fetus with the placenta, usually
enters near its center. It measures 1.0 to 2.5 cm. in diameter and
about 55 cm. in length. Its outer envelope consists of several layers
of epithelium which are directly continuous with the skin of the
fetus. Its connective tissue reticulum contains a mucoid substance,
known as the Whartonian jelly, which serves as a protection to its!
blood-vessels. The latter ramify extensively directly below the sur-
face of the amnion, so that they are already well subdivided before
they reach the chorion.
The Nutrition of the Embryo. — In the earliest stage of its develop-
ment the embryo possesses no circulatory system, but derives its
nutritive material from the media surrounding it. Shortly afterward
there is developed the yolk-circulation which, however, does not
continue for any length of time, because the supply in this material
is very limited. For this reason, its place is taken during the third
week by the circulatory mechanism pf the chorion which is eventually
changed into the complete circulatory system of the placenta. The
latter becomes functional at the end of the second month of intra-
uterine life, so that the fresh blood henceforth leaves the placenta by
way of the umbilical vein, while the impure blood is returned to it
by way of the umbilical arteries. The fetal heart beats as a rule at
the rate of 120 to 140 in -a minute. It may be heard at first directly
over the symphysis pubis, and during the later months at a point
about midway between the umbilicus and the superior iliac spine,
according to the position of the fetus. ^ Actual movements of the
fetus are perceived at about the eighteenth or twentieth week.
The oxygen requirement of the fetus is relatively small, because
the developing organism is protected against a loss of heat by the
mother. This implies that the heat produced in consequence of the
oxidations in its tissues is stored, giving rise to a temperature which
is usually somewhat higher than that of the mother. As far as the
actual transfer of oxygen is concerned, it has been proved that the
blood of the umbilical vein is lighter in color than that of the umbiUcal
arteries, and contains oxyhemoglobin. In this connection it might
also be mentioned that ether and chloroform, when administered to
the mother, are transferred to the fetal blood.
The occurrence of a transfer of nutritive material is proved con-
clusively by the constant growth of the fetus. In this process the
chorionic epithelium plays a part analogous to that of the intestinal
wall, i.e., it subjects the nutritive substances to radical changes in
order to render them assimilable by the cells of the fetal tissues.
This is true of the albuminous material as well as of fats. Both are
first reduced into simpler compounds and are then rebuilt into tissue-
protein and body fat. In the case of the fat, Hofbauer^ has shown that
1 First heard by Mayor of Geneva, in 1818..
2 Zeitschr. fur Geburtsh. und Gynec, Ixiv, 1909, 668.
THE DEVELOPMENT OF THE EMBRYO 1143
whereas fat stained with Sudan-red actually reaches the intervillous
spaces, it reappears as unstained globules within the syncytium of the
villi. But even the pigment so separated traverses these cells and
circulates in the fetal blood-. Glycogen is found in all the tissues of
the embryo during its period of most active growth, although later on,
when the liver becomes functional, it disappears almost completely
from the skin, lungs and other organs. In order to effect these reduc-
tions and syntheses, the chorionic epithelium must be in possession of
different enzj^mes, an assumption which has more recently found
experimental proof in the work of Bergell and Folk,^ and others.
Thus, the especially high requirement of the fetus in salts may bring it
about that the bones, and particularly the teeth, of the mother become
affected. Some women are more prone to suffer from this partial
decalcification than others, a difference which seems to be associated
with their varying power of assimilating calcium from their food.
It is also a well-known fact that drugs may be transmitted from
the mother to the fetus, as well as in the reverse direction. This is
true of potassium cyanid, alcohol, strychnin, and many inorganic
and organic salts. Bacteria as such are rarely transferred, so that
the placenta may be regarded as playing the part of a filter. This
power it loses if diseased. Neither does it seem to be able at any time
to exclude toxins. ^
Determination of Sex.: — In 1897 Schenk made the startling claim
that the nutrition of the embryo may be influenced in such a way as
to produce either a male or a female offspring. This speculation he
based upon the older view which contends that sex is dependent upon
the nutritive superiority of the father or mother. The work of Rauber,^
Morgan,^ Wilson^ and Doncaster,^ however, has proved that sex is
determined before the beginning of segmentation, i.e., either at the
time or immediately after the union of the sperm-cells. The actual
factor here concerned seems to be the spermatozoon which may or
may not embrace an accessory chromosome. Thus, it has been found
that the spermatocytes of many animals contain an odd number of
chromosomes, while in the oocytes they appear in pairs and are ar-
ranged in a similar manner. In fact, the spermatocytes are said to
appear in three forms, namely : (a) one in which a centrosome remains
without a mate, (h) one in which the chromosomes of one pair differ
in size, and (c) one in which they are all alike. The reduction, in the
number of these chromosomes during fertilization must then give rise
to three types of spermatozoa, namely : (a) one in which an odd chro-
mosome is present, (6) one in which the number of the chromosomes
is even but in which a small or aberrant chromosome is present, and
1 Miinchener med. Wochenschr., 1908.
^Lubarsch, Ergebn. der allg. Path, und path. Anat., 1896.
^ tJberschuss an Knabengeburten und seine biol. Bedeutung, Leipzig, 1900.
^ Heredity und Sex, New York, 1913.
^ Jour, of Exp. Zoology, iii, 1906, and Science, 1909.
^ The Determination of Sex, Cambridge, 1914.
1144 THE REPRODUCTIVE ORGANS
(c) one in which the chromosomes are evenly reduced and identical
in appearance. If either one of the first two varieties fertilizes the
egg, a male results, whereas that variety which possesses the identical
chromosomes gives rise to a female.
In man, the number of the chromosomes is given as 23 and 24
respectively. The first type of spermatozoon gives rise to males and
the second to females. Consequently, the segmentation nucleus
must contain 47 chromosomes in the first case and 48 in the second.
These facts, however, explain sex only and do not show why the
number of male children born at full term is greater than that of the
females. The ordinary relationship of 106 males to 100 females rises
to 130:100 in women whose first children were born after they had
reached their thirtieth year, and to 140 : 100 in women whose first
children were born after their fortieth year. The statistics gathered
more recently confirm the old view that a greater number of males are
born during times of war.
Parturition. — The fetus is fully developed and ready to be expelled
280 days after the first day of the last menstrual period, but this date
is only approximate, because normal children are also born as early as
240 and as late as 320 days after the day just specified. In fact, even
these extremes are exceeded sometimes. These discrepancies are due
in part to differences in the rate of development, and in part to our
inability of exactly determining the time of the fertilization of the
ovum. Evidently, this calculation cannot be based upon the day
of the coitus, because fertilization takes place at variable intervals
after insemination. Such differences have also been noted among the
domestic animals in which the duration of pregnancy is usually deter-
mined in accordance with a single coitus. In the cow, for example,
it is estimated at 280 days, with extremes of 240 and 310 days, and
in the mare at 366 days, with extremes of 307 and 412 days.
Labor consists essentially in the development of a driving force
which is capable of separating the fully formed fetus from the mother
without injury to either participant. Particularly at this time the
female genitals display their dynamic qualities most advantageously,
and this is true especially of the uterine musculature which plays the
principal part in this process. Already during pregnancy the woman
experiences intermittent contractions of this organ which, however,
do not give rise to unpleasant sensations. At the time of labor, these
contractions increase in intensity and are associated with a distinct
pain which possesses a peculiar bearing down character, i.e., they
begin in the sacral region and slowly pass to the abdomen and to-
ward the thighs. To begin with, they recur at intervals of from 15
to 30 minutes, but later on as frequently as every 2 minutes.
They may then last for 60 to 90 seconds. The dilatation of the cervix
having been accomplished, the climax of these 'labor pains" is reached
at the time when the head distends the vulva. In many cases, how-
THE DEVELOPMENT OF THE EMBRYO 1145
ever, the suffering is very slight and labor is completed almost
without pain.
These contractions possess a peristaltic character and may develop
a pressure of 30 pounds, the average being 17 pounds; in fact, in rare
instances pressures of from 50 to 100 pounds have been encountered.
It should not be forgotten, however, that the actual expulsion of the
fetus also brings into play the abdominal press which greatly
augments the force of the uterine musculature. In addition, the pa-
tient braces her body and contracts other muscles to steady herself.
The frequency of the heart and the arterial pressure increase during
the contractions, whereas the respiratory rate decreases. The process
of labor is usually divided into three stages, namely:
(a) From the begiiuiing of the first cramp-like pains to the completion of the
dilatation of the cervix; leading to the rupture of a few local blood-vessels and the
discharge of the amniotic fluid.
(6) From the rupture of the membranes to the complete delivery of the child.
(c) The placenta separates from the uterine wall and is expelled together with a
small quantity of blood (500 c.c). The uterus gradually recedes, forming a solid
tumor well below the umbilicus.
The average duration of labor in primiparse in 18 hours; 16 hours
of this period being consumed by the first, 1 hour and 45 minutes by
the second, and 15 minutes by the third stage. It is usually more pro-
longed in elderly women, but is much shorter in multipara. Labour
is essentially a reflex process in which the uterine musculature plays
the principal part. The correctness of this deduction is proved by
the fact that even a uterus the nerves of which have been divided, is
capable of successfully expelling its contents. Consequently, we may
omit many of the theories which have been formulated to explain the
onset of labor and confine ourselves to those which hold that this
process is not dependent upon a stimulation of certain nerve centers,
but is instigated by a local stimulus either in the form of mechanical
impacts or in the form of a hormone contained in the blood stream. In
the first instance, the presumption would be that the steadily growing
fetus eventually produces a maximal distention of the uterus and
thereby incites a contraction of its musculature. But this view does
not coincide with the observation that large fetuses are often retained
for a much longer time than those of smaller size. Among the chemical
theories might be mentioned the one advocated by Brown-Sequard
(1853), which states that the contractions of the uterus are incited by a
sudden increase in the carbon dioxid content of the mother's blood.
This explanation, however, does not clearly depict the cause of this
accumulation, nor is it quite certain that ordinary amounts of carbon
dioxid could actually produce this result. More plausible are those
theories which localize the stimulus in the fetus itself. Thus, Spiegel-
berg has stated that certain of its excretory substances eventually fail
to be eliminated and attack the uterus directly. This view finds
1146 THE REPRODUCTIVE ORGANS
substantiation in the experiments of Kruiger and Offergeld/ which
prove that even the denervated uterus may show a normal onset of
labor. In addition, Sauerbruck and Heide^ have demonstrated that
artificially united female rats (symbiosis) may influence one another.
Thus, it was noted that the onset of the uterine contractions in one
invariably produced these contractions in the other animal. If,
however, the other was not pregnant, it then showed certain symptoms
indicative of a serious illness. Eden^ and Williams^ have called atten-
tion to the fact that the placenta undergoes senile changes at term
which increasingly interfere with the nutrition of the fetus. The
accumulation of the waste products resulting in consequence of this
condition, undoubtedly evokes local stimuli which diminish the output
of nitrogen, and depress the general processes of oxidation. Conse-
quently, we are forced to conclude that labour is under the direct control
of a local mechanism which may be- activated either chemically or me-
chanically. The central nervous system, on the other hand, serves
merely as a regulating and correlating agent. It is a well-known fact
that emotions and other sensory impressions may influence the onset
and progress of labor as decidedly as the activated uterus may alter
the functional state of other organs.
1 Archiv fiir Gynec, Ixxxiii, 1907, 257.
2 Miinchener med., Wochenschr., 1910.
3 Jour, of Path, and Bact., 1897.
4 Jour, of Obst., xli, 1910.
INDEX
Abdominal press, 479, 531
in labor, 1145
in micturition, 1077
in vomiting, 1011
reflex, 598
type of respiration, 466
Abducens nerve, 650
Aberration, chromatic, 815
spherical, 815
Ablation of cerebellum, 711
of motor area, effects of, 679
Absorption bands of spectrum, 192
from cavities of body, 1033
from intestinal canal, 1027
of carbohydrates, 1029
of fats, 1030
mechanistic theory, 1031
chemical theory, 1031
of proteins, 1031
of water, 1027
through skin, 1034
Acapnia, 521, 523
Acceleration, heart, 309
Accelerator nerve fibers of heart, 311
Accessory nerve, 655
Accommodation in various animals,
820
of human eye, 822
normal, limit of, 828
proofs, 823
range, 828
reflex, 648, 812, 814
Acetone in urine, 1086
Achillis jerk, 599
Achlorhydria, 923
Achromatic lenses, DoUand's. 816
Achromatism, 816
Achromatopsia, 888
Achroo-dextrin, 993
Acid, cholalic, 947
cholic, 947
glycocholic, 947
hematin, spectrum of, 195
hippuric, in urine, 1087
hydrochloric, 952
sarcolactic, 1041
taurocholic, 947
Acidophiles, 199
Acidosis, 1043, 1086
Acini of glands, 892
Acromegaly, 979
Action, reflex, 109
Activator, 990
Active immunity, 246
Acuity, tactile, 736
visual, 838
Adaptation of sense organs, 732
Addison's disease, 969
Adenoid, 907
Adiadochokinesis from cerebellar dis-
ease, 713
Adrenal glands, 967
function, 970
innervation, 973
position, 967
removal, 969
structure, 967
Adrenalin, 952, 971
effect on circulation, 971
on eye, 975
on metabolism, 975
on muscle tissue, 975
on salivary secretion, 916
Adrenalin-glycosuria, 975
Adrenalin-hyperglycemia, 975
Adrenin, 971
effects on circulation, 971
Absorption, 1027
Aerobes, 445
Aerotonometer, 490
Bohr's, 491
Afferent nerve fibers of heart, 324
neuron, 109
After-birth, 1141
After-images, negative, 882
positive, 882
Age, effect of, on arterial blood pres-
sure, 370
on metabolism, 1054
on respiratory quotient, 516
Agglutinins, 248
Agnosia, auditory, 697
tactile, 684, 697
visual, 697
Agraphia, 690, 695, 696, 698
Air calorimeter, 1090
complemental, 480
composition of, effect on respiratory
quotient, 516
expired, character of, 486
inspired, character of, 486
minimal, 481
residual, 480
respired, quantitative determination,
479
stationary, 481
supplemental, 480
tidal, 480
and blood, interchange of gases
between, 488
chemical theory, 488, 494
physical theory, 489
1147
1148
INDEX
Air-bladder of fish, 450
Air-cells of lung, 451
Albuminuria, 1074
Alcohol, effect of, on speed of nerve con-
duction, 133
Alcoholic fermentation of milk, 901
stimulants, 1063
Alexia, 696
Alexin, 250
Alimentary canal, absorption of re-
duced foodstuffs from, 1022
length of, in various animals, 999
muscles of, 1000
of birds, 998
of mammals, 998
glycosuria, 966, 1043
Alteration theory of electrical current of
injury, 104
Alternating reflexes, 592
Altman's theory of structure of proto-
plasm, 24
Alveolar theory of structure of proto-
plasm, 24
Alveoli, 452
of lungs, 451
Amaurosis, 887
Amblyopia, 887
Amboceptor, 251
Ambrosial odors, 747
Ameboid movement, 38
Ametropia, 855
Amino-acids in urine, 1087
Amino-nitrogen, 1051
Amitosis, 1109, 1110
Ammonia, 1051
in urine, 1086
Amnion, 1140
Amniotic fluid, 1140
Amoeba, 20
Amphibian heart, 256
lung, 451
Ampulla, hair-cells of, activation of, 791
Amusia, 698
Amylase, 513, 935
Amylolytic action of pancreatic juice,
996
enzymes, 989
Amylopsin, 935, 996
Anabolism, 985
Anacrotic limb of arterial pulse, 383
Anaerobes, 445
Anaphase of mitosis of cell, 1111
Anaphylactin, 252
Anaphylaxis, 251
to apomorphin, 252
to cocain, 252
Anarthria, 695
Anelectrotonus, 143, 145
Anemia, pernicious, 905
theory of sleep, 723
Anencephalus, 671
Anesthesia, constriction of pupil in, 814
Anesthetics, effect of, on speed of nerve
conduction, 133
Anestrum, 1133
Angiometer, Hiirthle, 383
Animal electricity, 99
heat, 1089
reflex, 584
Animalculists, 1117
Animals, anosmatic, 690
arterial blood-pressure in, 364
circulatory system in, 254
homoiothermal, 1093
macrosmatic, 690
microsmatic, 690
osmatic, 690
poikilothermal, 1093
process of accommodation in, 820
Animate material, 19
Ankle-clonus, 75, 592
Annuli fibrosi, 264
Anode, 58
Anosmatic animals, 690
Anoxemia, 521
Antagonistic reflexes, 592
Anterolateral tract, superficial, 618
Antibodies, 247
Anti-enzyme, 992
Antigens, 247
Antiperistaltic wave, 1014
Antithrombin, 214
Antitoxic sera, 246
Antitoxin, diphtheria, 246
Antrum, mastoid, 764
pylori, 1006
Anvil bone of ear, 766
Aorta, 254
Aortic vestibule, 267
Apex beat, location, 282
Aphakia, 830
Aphasia, 693
motor, 694
sensory, 696
Aphemia, 695
Apnea, 522
fetalis, 523
spuria, 523
vagi, 523
vera, 523
Apomorphin, anaphylaxis to, 252
Apoplexy, 230
Appetite, 752
Appetizers, effect of, on gastric juice,
930
Apraxia, 695
Aqueous humor, 809
Arachnoid, 716
Arbor vitse, 707
Archipallium, 665
Area, body-sense, 681
frontal association, 699
motor, of cerebrum, 671
location, 673
Areas, touch, 739
Argyll-Robertson sign, 813
Aristotle's four mundane elements, 794
Aromatic odors, 747
Arterial blood pressure. See Blood pres-
sure, arterial.
INDEX
1149
Arterial pulse, 377
cause, 377
frequency, 379
percussion-wave, 384
registration of, 381
wave, anacrotic limb, 383
apex, 384
catacrotic limb, 384
character, 383
dicrotic, 384
notch, 384
postdicrotic, 384
predicrotic, 384
Arteries, 254
Arterioles, 254
Artery, umbilical, 260
Articulation, positions of, 55
Artificial respiration, 482. See Respira-
tion, artificial.
Aryepiglottic folds, 544
Arytenoid cartilages, 542
muscle, 547
Asphyxia, 525
color of blood in, 161
Assimilation leukocytosis, 201
phenomenon of, 31
Association area, frontal, 699
reflexes, 582, 592
system of cerebrum, 661
visual, 686
Astasia from cerebellar disease, 713
Astereognosis, 684
Asthenia from cerebellar disease, 713
Astigmatism, 855
against the rule, 856
irregular, 856
regular, 856
with the rule, 856
Asynergia from cerebellar disease, 712
Ataxia from cerebellar disease, 713
Atmosphere, 446
Atonia from cerebellar disease, 713
Atropin, effect of, on inhibitor reaction
of heart, 317
on salivary secretion, 916
Aubert and Forster's perimeter, 851
Auditory agnosia, 697
center, 689
fatigue, 780
meatus, 763
external, 764
nerve, 651
radiation, 661
Auricle, auditory, 763
Auricles of heart, 255
discharging period, 307
filling, in intra-auricular pressure,
299
function, 297
longitudinal layer, 265
musculature of, 265
structure, 263
transverse layer, 265
Auricular complex of electrocardio-
gram, 288
Auricular fibrillation, 279
systole, position of heart valves in,
307
Auriculoventricular bundle, 264
valves, 268
Auscultation method of recording arter-
ial blood pressure, 368
Autacoid substances, 952
Autonomic nervous system, 627. See
Nervous system, autonomic.
Avalanche conduction, 769
Axis-cylinder, 111, 113
function, 116
Axon, 108, 111
Axon-reflexes, 637
Babinski phenomenon, 599
Bacteria, intestinal, reaction of, on
carbohydrates, 997
on fats, 997
on proteins, 998
Bacteriolysins, 248
Bacteriolysis, 248
Bahnung, 573
Banting's cure for obesity, 1056
Barcroft's blood-gas apparatus, 501
modification of Topler's pump for
extraction of gases from blood, 499
Barometric pressure of gases, changes
in, 519
Bartholin's duct, 909
glands, 1136
Basal ganglia, 703
heat production, 1104
membrane, 775
Basedow's disease, 959
Basilar membrane, 772
Basket cells, 707
Basophiles, 199
Bathmotropic cardiomotor impulses,
315
Baths, effect of, on body temperature,
1098
Bell-Magendie law, 620
Bends, 522
Beri-beri, cause, 927
Bernstein's experiment on heart beat,
334
Bert's experiment proving centripetal
nerve conduction, 128
Betz, cells of, 613
Biconcave lens, 800
refraction by, 803
Biconvex lens, conjugate foci, 801
optical center, 800
principal axis, 800
focal distance, 801
refraction by, 800
secondary axis, 800
Bidder's ganglion, 318, 332
Bile, 938, 939
characteristics, 940
circulation, 947
formation, 943
function, 996
1150
INDEX
Bile, phospholipins, 948
pigments, 948
resorption, 944
special constituents, 947
storage, 941
Bilicyanin, blue, 948
Bilirubin, 948
Biliverdin, 948
Bimolecular reaction, 992
Binocular vision, 869, 872
Biot's respiration, 524
Biplegia, 679
Birds, alimentary canal of, 998
heart of, 258
lungs of, 451
Bismuth a;-ray study of stomach, 1008
Bladder, urinary, 1076
nervous control, 1077
Blastula, 1119
Blepharospasm, 592
Blind spot, 834
demonstration of, 835
form of, 836
Blindness, blue-, 888
color-, 887
green, 888
psychic, 688
red-, 888
word-, 688, 696
Block, heart-, 278
Blood, 157
absorption of gases by, 497
and tidal air, interchange of gases
between, 488
chemical theory, 494
physical theory, 489
and tissues, interchange of gases be-
tween, 496
as protective mechanism, 245
carbon dioxid in, condition of, 505
chemical composition, 168
cholesterin in, 169
circulating, total quantity, 357
circulation of, 253, 347. See also
Circulation.
coagulation of, 211. See also Coagri-
lation of blood.
color, 160
corpuscles, blood plasma and, relative
amount, 159
determining amount, direct
method, 159
indirect method, 160
red, 172
chemical properties, 181
color, 172
composition, 181
disintegration of, 198
duration of life, 197
hemoglobin and stroma of, sepa-
ration, 181
increase at high altitudes, 179
life history, 195
number, 176
physical characteristics, 172
Blood corpuscles, red, shadows, 181
shape, 172
size, 174
stroma of, constituents, 183
variations in number, 178
in shape, 175
. white, 199
allied functions, 207
chemical composition, 201
classifications, 199
color, 199
contractility, 202
dualistic origin, 202
fate, 202
formation of, in spleen, 904
monophyletic origin, 202
motion, 202
number, 200
origin, 202
physical properties, 199
shape, 199
size, 199
decalcification of, effect on coagula-
tion, 223
defibrination, 226
description, 159
distribution, 226, 228
dog's, composition, 168
dust, 159
electrical conductivity, 165
extraction of gases from, 497
flow, 394
friction of, 166
gaseous composition, 522
general characteristics, 157
greater circuit, 259
horse's, composition, 168
in asphyxia, 161
infusion of, 230
laked, 181
lecithin in, 169
loss of, 226, 230
menstrual, coagulability of, 226
methods of collecting, 221
of determining quantity of, 226
nitrogen in, condition of, 507
odor, 162
osmotic pressure, 164
oxygen in, condition of, 502
plasma, 159
and corpuscles, relative amount,
159
constituents, 170
salted, 223
plasma-poor, 180
platelets, 159, 207, 208, 214
fate, 208
methods of examination, 208
origin, 208
physical characteristics, 207
policemen, 204
pressure, 354
arterial, auscultation method of
recording, 368
cardiac variations, 377
INDEX
1151
Blood pressure, arterial, effect of age
on, 370
of change of position on, 372
of deep breathing on, 371
of eating on, 371
of labor on, 371
of menstruation on, 371
of muscular exercise on, 371
of pregnancy on, 371
of sleep on, 370
factors influencing, 370
graphic method of recording, 368
in animals, 364
in various arteries, 364, 366
methods of determining, 362
recording, Crampton's index of
conditions in, 372
direct method, 362
indirect method, 362, 366
palpation method, 366
variations in, 365
causes, 391
pulsatory, 377
respiratory, 390, 486
capillary, 376
venous, 373
indirect method of recording, 374
negative, area of, 374
variations in, cardiac, 388
respiratory, 390
causes, 391
reactions of, 164, 248
residual, 229
serum, 171, 212
sodium chlorid in, 169
specific gravity, 162
velocity, 402
determination of, 404
chemical method, 397
direct method, 394
indirect method, 397
stream, volume, 394
measuring of, calorimetric
method, 397
sugar content, 169
supply, cerebral, regulation of, 443
taste, 162
temperature, 162
total quantity, 226
transfusion of, 230
urea content, 170
viscosity of, 166
whole, composition, 167
Blood-vessels, elasticity of, 358
innervation of, 411
nervous regulation of, 411
Blue-bUndness, 888
Bodies, opaque, 795
purin, 1051
tigroid, 563, 564
translucent, 795
Body cavities, absorption from, 1033
ciliary, 819
different regions, temperature of,
1094
Body fat, source of, 1044
history of foodstuffs in, 1037
metabolic requirements, 1052
proteins, source of, 1048
sugar supply of, regulation, 1042
temperature, 1093
effect of baths on, 1098
of clothes on, 1101
of nervous depressants on, 1106
of varnishing skin on, 1105
factors varying, 1095
in various regions, 1094
regulation of, 1097
rise of, after death, 1105
voluntary factors controlling, 1101
Body-sense area, 681
localization, 681
Bohr's aerotonometer, 491
Bolometer, resistance, 1099
Bolus, food, 1001
Bone-marrow, myeloplaxes, 207
Bones, cranial, conduction of sound
waves by, 779
ear, 764, 766
movements, 767
Bornstein's chemical method of meas-
uring volume of blood stream, 401
Botulism, 1035
Boyle's law, 1025
Brain, growth, 717
human, convolutions of, 667
weight of, 666, 718
Brain-sand, 981
Breasts. See Mammary glands.
Breathing, deep, effect on arterial blood
pressure, 371
Brewster's stereoscope, 876
Brightness, 880
Brodie recorder, 399
Brodie and Russell's mel^hod of esti-
mating coagulation time of blood, 219
Bronchi, 451, 452
Bronchial capacity, 481
murmur, 477
Bronchiolar tubules, 451
Bronchioles, 451, 452
Brownian molecular motion, 37
Brown-S^quard's inhibition theory of
sleep, 723
Bruit de souffle, 368
Buds, lateral, 108
Buffy coat, 212
Bulb, olfactory, 644
Bulbocavernosus muscle, 1127
reflex, 599
Bulbospiral fibers of ventricles, 266
Bundle, anterior ground, 613
tectospinal, 616
Held's, 616
lateral ground, 613
Lissauer's, 616
Monakow's, 616
of Helweg, 616
of His, 264
septomarginal, 616
1152
INDEX
Burdach, column of, 613
Burning odors, 747
Burton- Opitz's apparatus for measuring
volume of blood stream, 395
Bush-tea, 1063
Biitschli's theory of structure of proto-
plasm, 24
Butter, 900
Butyrin of milk, 902
Cachexia thyreopriva, 957, 962
Caffeine, 1062
Caisson disease, 522
Calcium rigor, 337
Calliano's method of artificial respira-
tion, 483
Calorie, 1091
Calorimeter, 1090
air, 1090
micro-, of Hill, 1092
respiration, 1091
water, 1090
Calorimetric method of measuring
volume of blood stream, 397
Calorimetry, 1089
Canal, membranous, of cochlea, 775
of Schlemm, 805
osseous, of cochlea, 772
Canaliculus lacrymalis, 808
Canals, semicircular, 771, 785
Cannon and Mendenhall's graphic
coagulometer, 220
Capillaries, 254
contractility of, 416
endothelial lining cells of, 207
Capillary blood pressure, 376
electrometer, Lippmann's, 101
Caproic odors, 747
Caproin of milk, 902
Caprylin of rpilk, 902
Capsule of Tenon, 804, 869
Capsules, suprarenal, 967. See also
Adrenal glands.
Caput cornu posterioris, 605
Carbamid in urine, 1083
Carbohydrate-fat, 1041
Carbohydrates, 26
absorption of, 1029
metabolism of, 1038
of milk, 902
of muscle, 86
reaction of intestinal bacteria on,
997
Carbon dioxid, effect of, on speed of
nerve conduction, 133
in blood, condition of, 505
in starvation, 1053
production of, by muscle, 88
slight increase in partial pressure,
effect on respiratory quotient,
518
monoxid, affinity of hemoglobin for,
187
hemoglobin, spectrum of, 194
Carbonates in urine, 1082
Cardiac muscle, 42
tissue, 46
recess of stomach, 1006
Cardiogram, 284, 285
Cardiograph, 284
Cardiometer, 304
Johannson and Tigerstedt, 304
Roy's, 303
Cardiomotor fibers, 310
Cardio- pneumatic phenomenon, 1105
Cardiosensory fibers, 324
Carnitin, 87
Carnosin, 87
Cartilages of larynx, 541
Caruncula lacrymahs, 808
Caseinogen, 902
Castration, effect of, on animals, 982
on human beings, 983
Catabolism, 985
Catacrotic limb of arterial pulse wave,
384
Catalase, 513 ,
Catalysis, 987
Cataract, 830
Catelectrotonus, 143, 145
Cathode, 58
Caustics, 815
Celiac axis, 433
Cells, 21
basket, 707
carbohydrates of, 26
central or chief, of gastric glands, 920
cerebrosids of, 26
chemical energy, 32
chemistry, 25
cholesterin of, 26
constituents, 25
cytochrome, 564
cytoplasm of, 23
Daniell, 57
diagram, 57
deni-ilune, 909
devouring, 204
diagram, 25
endothelial lining of capillaries, 207
energetics, 32
fatty acids of, 26
fiber, of Retzius, 786
first, origin of, 20
form, 22
functional relation of cytoplasm and
nucleus, 27
germ, 1114
giant, 207
hair, of ear, 776, 777
inorganic substances in, 26
lipoids, 25
mast-, 200
mastoid, 764
metabohsm, 29, 30
movement by changes in turgor, 37
by swelling of walls, 37
neutral fat, 26
nuclein of, 26
nucleoproteids of, 26, 29
INDEX
1153
Cells, nucleus, 24
formation, 24
of Betz, 613
of Deiters, 776
of Golgi, 607
of Leydig, interstitial, function, 984
of Purkinje, 560, 708
olfactory, power of reaction, 744, 745
phosphatids of, 25
proteins of, 26
protoplasm of, 21
pseudonucleoli, 25
pyramidal, 560
size, 22
somachrome, 564
somatic, 1114
sperm-, 1117
stellate, of Kupffer, 939
structure, 22
water of, 26
Cell-division, direct, 1109
indirect, 1111
simple, 1110
Cell-globulin, 222
Center, 111
auditory, 689
coughing, 641
defecation, reflex, 1019
deglutition, 641
diabetic, 1042
for closure of eyelids, 641
for secretion of saliva, 641
geometrical, of spherical mirror, 796
glycogenic, 1042
hearing, 689
mastication, 641
micturition, reflex, 1077
of curvature of spherical mirror, 796
olfactory, 644, 690
sight, 684
smell, 690
sneezing, 641
speech, 691, 693
spinal, for ejaculations, 596
for erection, 596
sucking, 641
taste, 690, 691
visual, connection with other centers,
687
vomiting, 641, 1012
Centers, heat-accelerator, 1102
heat-inhibitory, 1102
spinal cord, 596
Centrum anospinale, 596
vesicospinale, 596
Cerebellar localization, 713
peduncle, superior, 661
Cerebellum, 706
ablation of, 711
arbor vitae, 707
asynergia from disease of, 712
connections, 709
convolutions, 707
function, 714
inferior vermis, 706
73
Cerebellum, lobuli complicati, 706
lobulus medianus posterior, 706
simplex^ 706
lobus quadratus anterior, 706
median lobe or vermis, 706
middle peduncle of, 709
monticulus, 706
moss fibers of, 708
roof ganglia of, 708
structure, 706
sulcus primarius, 706
superior peduncle, 709
vermis, 706
tendril fibers of, 708
Cerebral blood supply, regulation of,
443
circulation, 440
cortex, functional separation, 671
localization, 671, 681
reflex inhibition, 588
Cerebrosides, 26
Cerebrospinal fluid, 236, 718
function, 721
system, autonomic system and, con-
nections between, 631
Cerebrum, 657
anterior commissure of, 662
association system, 661
commissural system of, 661
comparative physiology, 664
general function, 657
gray matter of, general arrangement,
657
inherited absence of, 671
mode of development, 662
motor area of, 671, 673
projection system, 660
removal of, 668
tracts of, classification, 659
white matter, general arrangement,
658
Cerumen, 764, 895
Cervical sympathetic nerve, vasomotor
reaction of, 422
system, 631
Chalones, 952
Chauveau unipolar method of nerve
and muscle stimulation,
151
effects of, 154
Chauveau and Lortet's hemotachom-
eter, 405
Chemical energy, 729
imprint theory of Hght stimulation
of retina, 840
rays, 880
stimuli, 33
theories of sleep, 723
theory of fat absorption, 1031
of secretion, 892
Chemicals, effect of, on muscle contrac-
tion, 79
Chemistry of muscle fatigue, 89
Chest voice, 551
Chest-register, 553
1154
INDEX
Cheyne-Stokes respiration, 523
Chilarducci's reaction at a distance, 156
Chloasmse, 1139
Chlorheniatin, 188
Chlorids in urine, 1081
Chlorocruorin, 160
Cholagogues, 944
Cholalic acid, 947
Cholemia, 944
Cholesterin, 26
in blood, 169
of nerve, 114
Cholesterol, 947
Cholic acid, 947
Chorda tympani, 912
Chorda? tendinae, 267, 269
Chorion, 1140
Choroid, 806
Chromatic aberration, 815
Chronometric method of determining
hemoglobin, 190
Chronotropic cardiomotor impulses,
315
Churning, haustral, 1019
Chyle, 158, 234, 235
Chyme, 1009
Chymosin, 925
Ciha, 39
Ciliary body, 806, 819
ligaments, 806
movement, 39
muscle, 806
innervation of, 830
Cingulum, 661
Circuit, primary, 62
secondary, 62
Circular fibers of ventricles, 267
Circulating blood, total quantity, 357
protein, 1048
Circulation, 253, 347
action of epinephrin on, 971
analogous features, 352
cerebral, 440
coronary, 427, 430
effects of adrenalin on, 971
of adrenin on, 972
Harvey's discovery of, 18
mechanics, 347
of bile, 947
peripheral resistance to, 361
physical consideration, 347
portal, 433
pulmonary, 430
renal, 433
time required for, 409
under microscope, 408
Circulatory system, comparative study,
253
coronary circuit of, 259
development, 158
during fetal life, 260, 261
greater circuit of, 259
lesser circuit of, 260
of fish, 256
of lower animals, 254
Circulatory system of mammals, 258
of sponges, 254
of vermes, 255
of vertebrates, 255
portal circuit of, 259
pulmonary circuit of, 260
systemic circuit of, 259
Circumvallate papillae of tongue, 748
Clarke's vesicular column of cells, 607
Clausius' and Schonbein's ozone-auto-
zone theory of activation of oxygen,
511
Cleavage nucleus, 1119
Clonic contracture of muscle, 75
reflexes, 592
Clonus, ankle, 592
Clothes, effect of, on body temperature,
1101
Clotting of blood, 211. See also Coagu-
lation of blood.
Coagulability of menstrual blood, 226
Coagulating enzymes, 989
Coagulation of blood, 211
chemical changes in, 212
conditions influencing time, 221
effect of admixture of neutral salts
on, 223
of decalcification on, 223
of hirudin on, 225
of peptonization on, 224
of snake poisons on, 225
of substances derived from tis-
sues on, 222
of temperature on, 221
extra vascular, 21.1
intravascular, 217
physical changes in, 211
time required for, 219
of milk, 901
Coagulation-rigor of muscle, 93
Coagulins, 222, 248
Coagulometer of Cannon and Menden-
hall, 220
Coagulum of blood, 211
Coat, buffy, 212
Cocain, anaphylaxis to, 252
Cochlea, 771
membranous canal of, 775
osseous canal of, 772
Coelenterates, circulatory system of, 254
Coffee, 1063
Coil, induction, 62 .
Cola, 1063
Cold spots of skin, 742
Collapse of lung, 457
Colloid goiter, 961
Color contrast, 882
fusion, 880
saturation of, 880
sensibility of retina, 884
vision, 879
Hering theory of, 886
Ladd- Franklin theory, 887
theories of, 885
Young- Helmholtz theory, 886
INDEX
1155
Color-blindness, 887
Holmgren's tests for, 888
Color-wheel of Maxwell, 880
Colors, complementary, 880
Colostrum, 900
corpuscles, 898
Column, Turck's, 612
of Burdach, 613
of Flechsig, 613
of Goll, 613
Columnae carnese, 267
Comma tract of Schultze, 616
Commissural system of cerebrum, 661
Commissure, anterior, of cerebrum, 662
hippocampal, 662
Commutator, Pohl's, 61
Compensation method of detecting
electric variations of muscle, 102
Compensatory pause in heart beat, 343
Complement, 251
Complemental air, 480
Complementary colors, 880
Complementophile, 251
Complex lung, 451
reflexes, 592
Compression-paralysis of nerve, 131
Concavo-convex lens, 800
Conception, 1132
Concha, 763
Condiments in diet, 1062
Conduction, avalanche, 769
nerve. See Nerve conduction.
Conductivity, electrical, of blood, 165
of nerve, 124
irritability and, differentiation, 124
of protoplasm, 35
Cone-granules of retina, 832
Conjugation, 1111
Conjunctiva, 807 .
Conjunctival sac, 807
Consonants, sound production of, 554
Constant current, 62
Consumption, luxus, 1057
Contractility of protoplasm, 35
Contraction of muscle, 48. See also
Muscle contraction.
of degenerated human muscle and
nerve, law of, 155
of normal human nerve and muscle,
law of, 150
period of muscular movement, 43
Pflliger's law of, 146, 148, 149
wave of muscle, 68
Contracture of muscle, 74
clonic, 75
tonic, 75
Contralateral effects of hemisection of
spinal cord, 626
Conus arteriosus, 256, 267
Convolutions of cerebellum, 707
Cooking, proper, value of, 1061
Coppie's anemia theory of sleep, 723
Copulation, 1127
Cord, umbilical, 1142
Cords, vocal, 550
Core-conductor, Hermann's, 133
Cornea, 805, 809
anterior homogeneous lamella of, 805
posterior homogeneous lamella of, 805
refractive power, 809
Corniculse laryngis, 542
Coronary circuit of circulatory system,
259
circulation, 427
Corpora Arantii, 272
fibrosa or albicantia, 1131
quadrigemina, 704
Corpus callosum, 661, 701
luteum, 1131
false, 1131
true, 1131
striatum, 703
Corpuscles, colostrum, 898
Golgi-Mazzoni, 734
Krause's, 735, 736
Malpighian, 904
of Grandry and Merkel, 735
of Herbst, 735
of Meissner, 734
pus-, 201
red, 172. See also Blood corpuscles ,
red.
salivary, 910
white, 199t See also Blood corpuscles,
white.
Corpuscular theory of light, 794
Cortex, cerebral, functional separation,
671
Cortical function, dynamic theory, 701
Corti's organ, activation, 777
function, 777
structure, 775
rods, 776
tunnel, 776
Costal type of respiration, 466
Coughing, 482
center for, 641
Cowper's glands, 1126
Crampton's index of condition in re-
cording blood pressure, 372
muscle, 822
Cranial bones, conduction of sound
waves by, 779
nerves, 640, 642
functional system of, 642
system, 631
Cranioscopy, Gall's system of, 672
Cream, 900
Creatin, 87, 1051
in urine, 1087
Creatinin, 87, 1051
in urine, 1087
Cremaster muscle, 1123
Cremasteric reflex, 592, 598
Crescents of Gianuzzi, 909
Cretinism, 957
Crico-arytenoid muscle, lateral, 547
posterior, 547
Cricoid cartilage, 542
Crista acustica, 785
1156
INDEX
Croaking reflex of frog, 588
Crusta inflammatoria, 212
Crying, 482
Crypts of faucial tonsils, 906
of Lieberkuhn, 908, 949
Crystalline lens, 820
changes in shape and refractive
power, 827
wabbling of, 826
Crystals, hemoglobin, 184
Cuneiform cartilages, 543
Cuorin, 86
Curd, 901
Curvature of spherical mirror, center
of, 796
Cushny's modern theory of urinary
secretion, 1072
Cutaneous receptors, structure, 734
secretions, 889
Cuticle, 893
Cutis vera, 893
Cybulski's photo-hemotachometer, 405
Cycle, cardiac, 272
Cytochrome cells, 564
Cytocym, 215
Cytolysins, 248
Cytolysis, 248
Cytophile, 251
Cytoplasm, 23
formed elements, 23
of cell, nucleus and functional rela-
tion, 27
Dalton's law of pressures, 497
Daniell cell, 57
Dartos, 1123
Darwin's theory of evolution, 1121
Deafness, mind-, 688
word-, 688, 689
Deamination of ferments, 990
Death, reflex cardiac, 326
rise of body temperature after, 1105
Decalcification of blood, effect of, on
coagulation, 223
Decarboxylation of ferments, 990
Decidua basalis, 1140
reflexa, 1140
vera, 1140
Defecation, 1019
reflex center for, 1019
spinal center for, 596 '
Defibrination of blood, 226
Deficiency diseases, 927
Degeneration, fatty, 1047
of nerve, 117 See Nerve degenera-
tion.
Wallerian law of, 621
Deglutition, 998, 1001
center for, 641
function of esophagus in, 1002
mechanism of, 1002
nervous control, 1004
Deiters' cells, 776
Delirium cordis, 279
Demilune cells, 909
Dendrites, 108, 560
Dental germ, 1001
special, 1001
sac, 1001
sounds, 554
Depression, fatigue of, 571
Depressor nerve, 325, 329
vasomotor reaction, 427
Deprez-d' Arson val galvanometer, 99
Dermis, 893
Detention theory of accommodation of
eye, 822
Deuterocerebron of crayfish, 580
Deuteroplasm, 1130
Diabetes mellitus, 965
Diabetic center, 1042
Dialyser, 1024
Dialysis, 1024
Diaminizing enzymes, 989
Diapedesis of leukocytes, 206
Diaphragm, 454
function of, in respiratory cycle, 462
Diaphragmatic type of respiration, 466
Diaschisis effect of Monakow, 701
Diastase, 513
Diastole as period of assimilation, 341
Diastolic pressure, intracardiac, 296
Diathesis, exudative, 1051
Diencephalon, 664
Diet, flavors and condiments in, 1062
inorganic salts in, 1061
of man, normal, 1058
stimulants in, 1062
value of proper cooking, 1062
Diffusion, 1023
of gases, 446
of proteins, 1026
pressure, 446
Digestion, 985
chemistry of, 985
leukocytosis, 201
mechanics of, 998
Digestive secretions, 908, 918, 938
Dilatation of heart, 345
Dimethyl xanthin, 1062
Diphtheria antitoxin, 246
Diplopia, 873
heteronymous, 872
homonymous, 872
Direct blood transfusion, 231
vision, 837
Disaccharides, 987
Discrimination, tactile, 625, 736
Discus proligerus, 1129
Dismetry from cerebellar disease, 713
Dissimilation, phenomena of, 31
Diuresis, 1073
Diuretics, 1071
Diver's palsy, 522
Dog blood, composition, 168
talking, 692
Dolland's achromatic lenses, 816
Dromotropic cardiomotor impulses, 315
Drugs, action of, on salivary secretion,
916
INDEX
1157
Drugs constricting pupil, 814
dilating pupil, 814
effect of, on muscle contraction, 79
DuBois-Reymond's experiment in
double nerve conduction, 126.
induction coil, 62
inductorium, 63
key for making and breaking current,
60
molecular theory of electrical current
of injury, 104
Duct, Bartholin's, 909
pancreatic, 932
of Santorini, 932
of Wirsung, 932
Ductless glands, 889
Ducts, ejaculatory, 1126
Ductus arteriosus, 262
choledochus, 941
endolymphaticus, 783
pneumaticus, 450
venosus, 261
Dudgeon's sphygmograph, 382
Duke and Howell's theory of cardiac
inhibition, 319
Duodenal juice, 931
Dura mater, 716
Dust, blood, 159
Dynamic phase of respiratory cycle,
461
sense, 730, 785
theories of reproduction, 1117
theory of cortical function, 701
Dynamograph, 81, 82
Dyschromatopsia, 888
Dysoxidizable substances, 510
Dyspnea, 471, 525
heat, 475
Ear, anvil bone of, 766
bones, 764, 766
movements, 767
external, 763
hair cells, 776, 777
hammer-bone, 765
inherent muscles of, 770
internj^l, 771
middlfe, 763, 764 X
saccule, 771, 782 \
stirrun bone, 767
utriclef 771, 782
Eardrum, 764, 765
Ear-wax, 895
Echinochrome, 160
Eck fistula, 946
Effectors, different types, 583
Efferent nerve fibers of heart, 310
neuron, 109
Ehrlich's side-chain theory of im-
munity, 249
Einthoven's string galvanometer, 99, 286
Ejaculation of semen, 1127
spinal center for, 596
Ejaculatory ducts, 1126
Elasticity of muscle, 65
Electric conductiyity of blood, 165
current, axial, in nerve, 136
constant ascending, reaction of
nerve to, 142
descending, reaction of nerve to,
142
reaction of normal and abnormal
nerve and muscle to, 142
demarcation, 103
external resistance, 58
in muscles, phases, 106
internal resistance, 58
interrupted, reaction of normal and
abnormal nerve and muscle to,
142
making and breaking, 60
measurement, 58
of action, 103
in nerve, 137
wave of neg^vity and, relation
of nerve^im pulse to, 138
of injury ,^3
alteration theory of, 104
in nerve, 135
molecular theory of, 104
of rest, 103
types, 62
stimulation of muscle, 57
stimuH, 35
theory of light stimulation of retina»
840
of nerve conduction, 133
variations of heart, 286
Electricity, animal, 99
Electrocardiogram, 287
auricular complex, 288
ventricular complex, 288
Electrocardiograph, 287
Electrocardiography, 286
Electrodes, non-polarizable, 59
Electrolytes, 1025
Electrometer, capillary, Lippmann's,
101
Electromotive force, 58
Electronegative oxygen, 510
Electrotonic condition of nerve, method
of testing, 146
differences on making and breaking
galvanic current, 144
Electrotonus, 142, 143
extrapolar, 143
intrapolar, 143
physical, 143
physiological, 143
Embolus, 218
Embryo, development 1135
nutrition of, 1142
Emission of semen, spontaneous, 1128
theory of light, 794
Emmetropia, 855
Emphysema, 457
Encephalon, 716
Endocardium, 263
Endocrine organs, 953
Endo-enzyme, 988
1158
INDEX
Endogenous protein, 1049
Endolymph, 771
Endoneuriumj 111
End-organs of nerve-fiber, 113
End-products of protein metabolism,
1050
Energy, chemical, 729
different manifestations of, 727
vibratory, 728
Engelmann's artificial muscle, 49
method of testing electrotonic condi-
tion of nerve, 145
theory of muscle contraction, 49
Enterograph, 1013
Enterokinase, 932, 935, 950, 997
Entoptic phenomena, 854
Enzymes, 981
muscle, 87 ^ ^
of pancreatic juice, 935
Eosinophilic leukocytes, 200
Ependyma, 663
Epicardium, 263
Epidermis, 893, 1123
Epiglottis, function, 543
Epilepsy, Jacksonian, 677
trauniatic, 677
Epimysium, 43
Epinephrin, action on autonomic nerv-
ous system, 974
action on circulation, 971
Epineurium, 111, 970, 971
Epiphysis cerebri, 980
Equilibrium, nerve of, 651
nitrogen-, 1049
sense of, 781
Erb's reaction, 156
Erectile tissues, male, 1126
Erection of penis, 1127
spinal center for, 596
Erepsin, 932, 935, 950, 997
Ergograph, 81, 82
Ergotoxin, effect of, on salivary secre-
tion, 916
Erythroblasts, 196
Erythrocytes, 172. See also Blood cor-
puscles, red.
Erythro-dextrin, 993
Esophagus, function of, in deglutition,
1002
Esthesiometer, 735
Estrus, 1133
Ether, 794
luminiferous, 794
Ethereal odors, 747
Ethylene, 187
Euglobulin, 172
Euler and Huyghens' undulatory theory
of Hght, 794
Eustachian tube, 764, 769
valve, 262
Evolution, Darwin's theory of, 1121
Excised heart, 331
Excitation, fatigue of, 571
of muscle, 51
Excretion, 1064
Exercise, muscular, effect of, on metab-
olism, 1054
Exo-enzyme, 988
Exogenous protein, 1049
Expiration, 448, 461
Expiratory movement, 470
Expired air, character of, 486
Explosive sounds, 554
Extensibility of muscle, 65
External ear, 763
Exteroceptors, 730
Extractives of muscle, 87
Extramural circulatory system, 428
Extrasystole, 338
cause, 341
Extravascular coagulation of blood,
211
Extrinsic muscles of inspiration, 466
Eye, 803
anterior chamber, 806
constant optical defects, 853
effect of adrenalin on, 975
electrical variations in, on vision,
844
functions, 804
human, accommodation of, 822
limit, 828
proofs, 823, 824
range, 828
humors of, 237
optical defects of, acquired, 855
inconstant, 855
posterior chamber, 806
protective appendages, 803
reduced, 846
refraction of, abnormalities in, 853
refractive power of, ophthalmoscopic
test, 863
shadow test, 867
schematic, 846
suspensory ligament, 821
teeth, 1001
visual axes of, secondary, 837
axis of, 837
white of, 805
Eyeball, 803
anterior cavity, 805
general structure, 803, 804
measurements, 804
minute structure, 805
movements of, 869, 870
posterior cavity, 805
sclera, 805
Eyelids, 806
closure of, center for, 641
Facial muscles, reflexes from, 599 ,
nerve, 650
Facilitation, 573
Falsetto voice, 551
Falx cerebri, 716
cerebelH, 716
Faradaic current, 62
Far-point of vision, 828
Far-sightedness, 860
INDEX
1159
Fasciculus anterior proprius, 613
anterolateralis superficialis, 613
cerebrospinalis anterior, 612
lateralis, 613
cuneatus, 613
gracilis, 613 ^
lateralis proprius, 613
longitudinal, inferior, 661
longitudinal, superior, 661
occipitofrontal, 661
spinocerebellaris, 613
uncinate, 661
Fatigue, auditory, 780
effect of, on muscle contraction, 80
muscle, chemistry of, 89
Treppe phenomenon, 90
nerve, 139, 140
of depression^ 571
of excitation, 571
of nerve cells, 568
cause, 570
of sense-organs, 732
reflex, 585
substances, 90
Fat, body, source of, 1044
carbohydrate-, 1041
Fats, absorption of, 1030
chemical theory, 1031
mechanistic theory, 1031
metabolism of, 1044
of milk, 902
reaction of intestinal bacteria on, 997
utilization, 1046
Fat-splitting enzyme of saliva, 994
Fatty degeneration, 1047
Faucial tonsils, crypts of, 906
function, 906
removal of, effects, 907
Feces, character, 1035
contents, 1035
formation, 1035, 1036
Fechner's psychophysical law, 733
Fecundation, 1117
Female reproductive organs, 1122
Fenestra ovalis, 764
rotunda, 764
Fermentation, 987
of milk, alcoholic, 901
Ferments, 987
classification, 988
deamination of, 990
decarboxylation of, 990
hydrolysis by, 990
intermediate products of, 991
manner of action, 990
nature of, 988
number of molecules in action of, 991
optimum temperature for, 991
oxidation of, 991
reduction of, 991
respiratory, 513
reversibility of , 991
self-inhibition of, 962
Fertilization, 1117
of ovum, 1118
Fetal life, circulatory system in, 260,
261
Fetid odors, 747
Fetus, oxygen requirement of, 1142
Fever, high, 1106
Liebermeister's neurogenic theory,
1107
low, 1106
toxogenic theory, 1107
Fiber cells of Retzius, 786
Fibers, fillet system of, 661
frontopontine, 661
moss, of cerebellum, 708
muscle, 43, 44
intermediate discs, 44
transverse discs, 441
temporopontine, 661
tendril, of cerebellum, 708
Fibrillse, 44
Fibrillar hypothesis of nervous system,
565
theory of structure of protoplasm,
24
Fibrillation, auricular, 279
of heart muscle, 279
ventricular, 279
Fibrin, 212, 217
Fibrin-ferment, 171, 215
Fibrinogen, 170, 171, 213, 216
tissue-, 222
Field, visual, 851
Figures, Miiller-Lyer, 878
Purkinje's, 839
Filiform papillae of tongue, 748
Fillet, median, 684
system of fibers, 661
Filtration theory of formation of lymph,
238
of salivary secretion, facts dis-
proving, 917
of secretions, 892
of urinary secretion, 1067
Filum terminale, 604
Fish, circulatory system of, 256
swim-bladder of, 450
Fistula, Eck, 946
Flavors in diet, 1062
Flechsig's column, 613
tract, 617
Fleischl's hemoglobinometer, 191
Flesh, goose, 894
Fluoroscopic examination of intestinal
movements, 1013
Focus, virtual, 798
FolUcles, Graafian, 1129
hair, 893
primordial, 1129
Fontana, spaces of, 805
Food, 986
bolus, 1001
effect of, on arterial blood pressure,
371^
nutritive value, 1058
Foodstuffs, 986
history of, in body, 1037
1160
INDEX
I'oodstuffs, reduced, absorption of, from
alimentary canal, 1022
Foramen ovale, 262
Foramina Thebesii, 264, 428
Forebrain, 663, 664
Fovea centralis, 836
Fragrant odors, 747
Frank's instrument for registering
heart-sounds, 290
membrane manometer, 297
Fraunhof er lines of spectrum, 193
Friction of blood, 166
Frog preparation, rheoscopic, 104, 105
Frontal association area, 699
Frankel's theory of menstruation, 1134
Friction sounds, 554
Frog, compound, 1116
Frontopontine fibers, 661
Fundus of stomach, movements of,
1005
Fungiform papillae of tongue, 748
Funiculus, anterior, 612
lateral, 613
posterior, 613
Fusion of colors, 880
Gad's pneumatograph, 480
Galactosids of nerve, 114
Gall's system of cranioscopy, 672
Gall-bladder, 939
innervation, 942
Galvanic current, 62. See also Electric
current, constant.
Galvanism, 99
Galvanometer, 99
string, Einthoven's, 286
for measuring speed of nerve con-
duction, 130
Galvanotonus, 152
Galvanotropic reaction, 789
Ganglia, basal, 703
roof, of cerebellum, 708
Ganglion, Bidder's, 318, 332
in peripheral nervous system, 111
intervertebral, 619
Remak's, 318, 332
spirale, 777
Garlic odors, 747
Gartner's method of estimating hemo-
globin, 191
Gases, absorption of, by blood, 497
by liquids, 496
diffusion, 446
extraction of, from blood, 497
interchange of, between blood and
tissues, 496
between tidal air and blood, 488
chemical theory, 494
physical theory, 489
in placenta, 451
Gaskell s trophic theory of cardiac
inhibition, 319
Gastric artery, 433
cells, central or chief cell of, 920
'glands, 918
Gastric glands, histological changes in
secretion, 920
of cardiac end, 919
of fundus, 919
oxyntic cells of, 920
parietal cells, 920
hunger, 754
juice, 920
acidity, 923
antiseptic action, 994
artificial, 922
effect of appetizers on, 930
function, 993
hydrochloric acid of, 923
inverting action of, 994
methods of obtaining, 921
origin of active principles, 920
psychic element in formation,
930
secretion, nervous control, 928
regulation of, 926
study of, by psychic feeding, 930
by sham feeding, 930
mucosa, internal secretion of, 967
secretin, 927
secretions, 918
Gastrin, 927, 931
Gastro-enterostomy, 1010
Gemmules, lateral, 108
Grenital organs, female, 1122
internal secretions of, 981
male, 1122
Geometrical center of spherical mirror,
796
Germ cells, 1114
dental, 1001
special, 1001
Germinal spot, 1130
Giant cells, 207
Gianuzzi, crescents of, 909
Gills, 448
structure, 449
Glan and Vierordt's method of deter-
mining hemoglobin, 190
Gland, pineal, 980
pituitary, 977. See also Pituitary
gland.
prostate, 1126
thymus, 951, 963. See also Thymus
gland.
thyroid, 951, 954. See also Thyroid
gland.
Glande interstitielle I'ovaire, 982
Glands, acini of, 892
adrenal, 967. See also Adrenal
glands.
Bartholin's, 1136
Cowper's, 1126
ductless, 889
endocrine, 953
gastric, 918. See also Gastric glands.
intestinal, 948
lacrimal, 807
secretion, 807
lobes and lobules, 892
INDEX
1161
Glands, mammary, 897. See Mam-
mary glands.
meibomian, 809
mucous, secretory product, 907
parathyroid, 951, 954. See also
Parathyroid glands.
racemose, 892
salivary, 908. See also Salivary
glands.
sebaceous, 894
sexual, 982
sweat-, 895
tubular, 892
tubulo-racemose, 892
urethral^ 1126
Glans pems, 1126
Globin, 183
Globulin, cell-, 222
Glossopharyngeal nerves, 534, 653
function, 749
Glottis, 540, 543
Gluteal reflex, 598 .
Glycocholic acid, 947
Glycogen, 965, 1039
disappearance of, in muscle, 89
formation of, 1038
Glycogenase, 513, 1039
Glycogenesis, 1042
Glycogenic center, 1042
Glycogenolysis, 1039, 1042
Glycolysis, 1042
Glycosuria, adrenalin-, 975
alimentary, 1043
conditions causing, 966
hepatic, 1043
pancreatic, 1043
phloridzin, 1043
renal, 1043
Goiter, colloid, 961
springs, 958
Golgi's cell, 607
Golgi-Mazzoni corpuscles, 734
Goll, column of, 613
Goose flesh, 634, 894
Gouty diathesis, 1051
Gower's fluid, 177
hemoglobinometer, 191
tract, 613, 618
Graafian follicles, 1129
mature, 1130
Grandry and Merkel, corpuscles of,
735
Granula theory of structure of proto-
plasm, 24
Granules, Nissl's, 108, 563, 564
zymogen, 909
Graphic method of recording arterial
, blood pressure, 368
j Graves' disease, 959
Gray matter, cerebral, general arrange-
ment, 657
of spinal cord, functional basis, 606
' Green-blindness, 888
Gr6hant and Quinquaud's method of
determining quantity of blood, 227
Ground bundle, anterior, 613
lateral, 613
Growth, 29, 1109
factor of, in metabolism, 1059
movement by, 38
Guanidin metabolism m thyroid gland,
963
Guanine, 1051
Guarana, 1063
Gustometry, 751
Guttural sounds, 554
Hair, 893
cells of ampulla, activation of, 791
of ear, 776, 777
follicles, 893
roots, 893
Haldane and Smith's method of esti-
mating oxygen tension in
arterial blood, 492
quantity of blood, 227
Hammer-bone of ear, 765, 766
Haptophore, 249
Harmonies, 760
Harmozones, 953
Harvey's discovery of circulation of
blood, 18
Haustral churning, 1019
Hayem's fluid, 177
Head-pressure, 350
Hearing, center, 689
, limits of, 780
nerve of, 651
sense of, 756
Heart, 158, 255
acceleration, 309
character, 323
accelerator nerve fibers, 311
action current of, 286
afferent nerve fibers of, 324
beat, compensatory pause, 341
effect of Ringer's solution on,
336
internal stimulus, nature of, 336
myogenic theory, 334
neurogenic theory, 332
origin, 331
premature, 343
refractory period, 338, 341
center, 309
compensatory hypertrophy, 343
contraction, character, 274
wave, path of, 275
speed of, 275
cycle of, 272
number, 272
phenomena in, 280
time relation of, 305
dilatation, 345
effect of pressure on vagus on, 327
efferent nerve fibers, 310
electrical variations, 286
excised, 331
filling of, 292
first sound, 290
1162
INDEX
Heart, form, of, changes, 281
methods of registering, 281
hypertrophy, 345
impulse, 282
inhibition, 309
cause, 318
character, 312
escape of, 323
Howell and Duke's theory, 319
nature of, 315
result, 320
trophic theory of, 319
inhibitor nerve fibers. 310
measurements, 263
mechanics of, 253
muscle, fibrillation of, 279
physiological properties, 338
tissue, functional pecuHarities, 331
tonus of, 344
musculature of, arrangement, 263
nervous regulation, 309
of amphibians, 256
of birds, 258 .
of reptiles, 257
output, 302
reflex death, 326
second sound, 289, 291
secondary augmentation, 314
sounds, 289
relationship between, 291
third sound, 289, 292
trigeminus reflex, 327
valves, 263
arrangement, 267
plan of, 306
position of, in auricular systole, 307
in ventricular systole, 307
variations in arterial blood pressure,
377
Heart-block, 278
Heat, dissipation of, 1089, 1097
dyspnea, 475
in animals, 1133
of body, 1093. See also Body tern-
fierature.
^ ypnea, 1095
production, 1089, 1092, 1097
basal, 1104
ordinary, 1105
sources, 1092
spots of skin, 742
total quantity, 1103
unit of measurement, 1090
Heat-accelerator centers, 1102
Heat-inhibitory centers, 1102
Heat-rays, 880
Heidenhain's chemical or vitaHstic
theory of secretion, 892
classification of salivary glands, 908
theory of formation of lymph, 238
of urinary secretion, 1068
Held's bundle, 616
Helicotrema, 773
Helmholtz's detention theory of accom-
modation of eye, 822
Helmholtz's method of determining
speed of nerve conduction, 129
ophthalmometer, 858
ophthalmoscope, 863
phacoscope, 826
resonator, 762
resonance theory of hearing, 777
Helweg's bundle, 616
Hematin, 183, 188
acid, spectrum of, 195
Hematoblasts, 208
Hematocrit, 159
Hematoidin, 189
Hematopoiesis, 197
Hematopoietic function of faucial ton-
sils, 906
of spleen, 905
tissues, 196
Hematoporphyrin, 189, 1080
spectrum of, 195
Hemerythrin, 160
Hemianopia, bilateral, 685
Hemianopsia, 685, 696
Hemic murmurs, 780
Hemin, 188
crystals, 188
Hemiplegia, 679, 695
Hemochromogen, 183, 188
spectrum of, 195
Hemoconise, 159
Hemocyamin, 160
Hemocytometer, Thoma-Zeiss, 176
Hemodromograph, Chauveau and Lor-
tet's, 405
Hemodromometer, Volkmann's, 404
Hemodynamics, 347
Hemoglobin, affinity of, for carbon
monoxid, 187
and oxygen, compoimds of, proper-
ties, 185
and stroma of red corpuscles, separa-
tion, 181
carbon monoxid, spectrum of, 194
compounds, 186
constituents, 183
crystals, 184
derivative compounds, 187
spectroscopic analysis, 192
determination, chronometric method,
190
cHnical methods, 189
estimation, Tallquist's method, 191
nitric oxid, spectrum of, 194
reduced, 183
spectrum of, 193
spectroscopic analysis,' 192
Hemoglobinometer, Fleischl's, 191
Gower's, 191
Hoppe-Seyler's,'^191
Hemolysins, 181
Hemolysis, 181, 248
Hemometer, 191
Hemophilia, 221
Hemophotographic method of estimate
ing hemoglobin, 191
INDEX
1163
Hemopyrrol, 189
Hemorrhage, 230
Hemotachometer, Chauveau and Lor-
tet's, 405
Henderson's cardiometer, 304
Henle's sphincter, 1128
U-shaped loop, 1065
Hepatic artery, 433
glycosuria, 966, 1043
plexus, 939
Herbst, corpuscles of, 735
Hering's method of estimating circula-
,tion time, 409
theory of color vision, 886
Hermann's core-conductor, 133
demarcation current, 103
Herpes zoster, 622
Heteronymous diplopia, 872
Heterophoria, 873
Hibernating animals, respiratory quo-
tients in, 515
Hiccough, 482
High fever, 1106
Hill's micro-calorimeter, 1092
Hindbrain, 663, 664^
Hippocampal commissure, 662
Hippuric acid in urine, 1087
Hirudin, effect of, on coagulation of
blood, 225
His's bundle, 264
theory of neuroblasts, 559
Holmgren's tests for color-blindness, 888
Homoiothermal animals, 1093
Homolateral effects of hemisection of
spinal cord, 626
Homonymous diplopia, 872
Hoppe-Seyler's hemoglobinometer, 191
indirect method of determining
amount of blood corpuscles, 160
theory of activation of oxygen, 512
Hoppe-Seyler and Welker's chrono-
metric method of determining hemo-
globin, 190
Hormones, 926, 952, 953
Horopter, 874
Horse blood, composition, 168
talking, 692
Howell and Duke's theory of cardiac
inhibition, 319
Humor, aqueous, 809
vitreous, 810
Humors of eye, 237
Hiirthle's angiometer, 383
apparatus for estimating volume of
blood stream, 395
membrane manometer, 296
Hunger, 753
gastric, 754
sense^ 743
somatic, 754
Hutchinson's spirometer, 479
Wintrich's modification, 479
Huyghens and Euler's undulatory
theory of hght, 794
Hyaloplasm, 24
Hydraulic pressure, 347
Hydremic plethora, 1074
HydrobiUrubin, 948
Hydrochloric acid, 952
of gastric juice, 923
Hydrodynamic pressure, 347
Hydrolysis of ferments, 990
Hydrolytic oxidations, 511
Hydrostatic pressure, 347
Hydrothorax, 457
Hyperchlorhydria, 923
Hypermetropia, 855, 860
Hypermetry in cerebellar disease, 713
Hyperosmotic solution, 1025
Hyperpnea, 524
Hyperpyrexia, 1106
Hyperthermy, 1106
Hyperthymusism, 964
Hyperthyroidism, 957, 959
Hypertonic solution, 1025
Hypertrophy of heart, 345
Hypnotic sleep, 724
Hypogastric arteries, 262
Hypoglossal nerve, 656
Hypoleukocytosis, 201
Hypophysin, 978
Hypophysis cerebri, 977. See also
Pituitary gland. ^
Hyposmotic solution, 1025
Hypothermy, 1106
Hypotonic solution, 1025
Hypoxanthine, 1051
Icterus, 944
Ileocecal valve, 1017
Illusions, optical, 876
touch, 739
Image, real, 797
retinal, formation, 846, 848
virtual, 798
Images, Purkinje's, 839
Immune body, 251
Immunity, 245
acquirea, 246
active, 246
antibodies in, 247
causes, 247
complete, 245
Ehrlich's side-chain theory, 249
general, 246
local, 246
natural, 246
nature of reactions in, 248
partial, 245
passive, 246
permanent, 246
phagocytosis in, 247
temporary, 246
Implantation of ovum, 1137
Impulsus cordis, 282
Inanimate material, 19
Incus, 766
Index of refraction, 798
opsonic, 206
Indican in urine, 1082
1164
INDEX
Indirect blood transfusion, 231
vision, 837
Indol in urine, 1082
Induced current, 62
Induction coil, 62
Inductorium, DuBois-Reymond, 63
Infantilism, 957
Infundibula, 452
Infundibulum of pituitary gland, 977
Infusion of blood, 230
Inhibition, heart, 309
of nerve cell, 574
of reflexes, 588
theory of sleep, 723
Inhibitor nerve fibers of heart, 310
Innervation of adrenal glands, 973
of ciliary muscle, 830
of gall-bladder, 942
. of iris, 817
of larynx, 535, 547
of mammary glands, 899
of salivary glands, 911
of stomach musculature, 1012
of sweat-glands, 897
Inorganic salts in diet, 1061
Inotropic cardiomotor impulses, 315
Insects, respiration in, 448
Inspiration, 448, 461
muscles of, 466
Inspiratory movement, 466
Inspired air, character of, 486
Insufflation, constant, 486
Intensity of sounds, 758
Intercostal muscles, action of, in res-
piration, 468
Intermediary substance of nerve, 116
Internal ear, 771
secretions, 951
classification, 952
of gastric mucosa, 967
of genital organs, 981
of intestinal mucosa, 967
Interoceptors, general, 730, 752
special, 730, 743
Interpolated systole, 343
Interrupter, Neff's, 64
Intervertebral ganglion, 619
Intestinal bacteria, reaction of, ou
carbohydrates, 997
on fats, 997
on proteins, 998
canal, absorption from, 1027
glands, 948
juice, 938
function, 997
secretion of, 949
mucosa, internal secretion of, 967
Intestine, large, divisions of, 1010
movements of, 1017
small, movements, 1013
pendular motion, 1014
Intestines, movements, 1013
fluoroscopic examination, 1013
nervous control, 1015
vasomotor nerves of, 437
Intra-abdominal pressure, changes in.
478 ^ ' 6 ,
Intra-auricular pressure, 297
filling of auricles in, 299
Intracardiac pressure, changes in, 292
diastolic, 296
mean, 296
methods of registration, 292
systolic pressure, 296
Intracranial pressure, 441
Intramural circulatory system, 428
Intraocular pressure, 805, 810
Intrapleural pressure, 457
Intrapulmonic pressure, 457
changes in, 478
Intrathoracic pressure, 457
cause of negativity of, 460
changes in, 477
Intravascular clotting of blood, 217
lymph, 233
Intraventricular pressure, 300
Intrinsic muscles of inspiration, 466
Inversion of retinal image, 848
Invertase, 950
Invertin, 931
Inverting enzymes, 989
lodothyrin, 952, 960
Ionization theory of activation of oxy-
gen, 511
Iris, 811
function, 812
innervation of, 817
Irritability of muscle, independent, 52
of nerve, 124
conductivity and, differentiation,
124
of protoplasm, 35
Ischiocavernosus muscle, 1127
Islands of Langerhans, 932, 965
Isometric myograms, 56
Isosmotic solution, 1025
Isotonic myograms, 56
solution, 1025
Jacksonian epilepsy, 677
Jacobson's nerve, 912
Janeway's sphygmomanometer, 369
Jaw jerk, 599
Jejunum, 1036
Jenson's theory of muscle contraction,
50
Johannson and Tigerstedt's cardiom-
eter, 304
Karyokinesis, 1111
KephaHn, 222
of nerve, 114
Kephir, 901
Ketosis, 1043
Kidney oncometer, 398
structure, 1064
vasomotors of, 435
ICinase, 170, 990
Knee-jerk, 599
Konig's resonator, 762
INDEX
1165
Koumiss, 901
Krause's corpuscle, 735, 736
Kj-ies' apparatus for recording capillary
pressure, 376
Krogh's microtonometer, 491
Kuhne's method of proving double
nerve conduction, 127
Kupf er's stellate cells, 207, 939
Labial sounds, 554
Labor, 1444
abdominal press in, 1145
average duration, 1145
effect of, on arterial blood pressure,
371
pains, 1144
stages, 1145
Labyrinth, 763
of ear, 771
osseous, 771
Labyrinthine reflexes, 789
tonus, 789
Lacrimal glands, 807
secretion, 807
lake, 808
Lactalbumin, 902
Lactase, 990, 997
Lactation, mammary glands during, 899
Lacteals, 235
Lactic acid of muscle, 87
formation, 88
Lactoglobulin, 902
Lactose, 902
Ladd-Franklin theory of color vision,
887
Laennec's stethoscope, 757
Lake, lacrimal, 808
Laked blood, 181
Lamella, anterior homogeneous, of
cornea, 805
posterior homogeneous, of cornea, 805
Lamina basilaris, 775
dental, 1001
spiralis, 772
Langenbeck's proof of accommodation
of eye, 824
Langerhans, islands of, 932, 965
Laryngeal branch of vagus, superior,
534
branches of vagus, inferior, 535
chamber, 540
Larynx, 540
artificial, 551
cartilages of, 541
examination of, in reflected light, 550
general structure, 541
innervation of, 535, 547
ligaments of, 541
Laughing, 482
Law, Bell-Magendie, 620
of degeneration, Wallerian, 621
Weber's, 733
Lecithin, 948
in blood, 169
of nerve, 114
Lecithoprotein, 217
L6clanche cell, 57
Leech extract, effect of, on coagulation
of blood, 225
Lens, biconcave, 800
^ refraction by, 803
biconvex. See Biconvex lens.
crystalline, 820
changes in shape and refractive
power, 827
wabbling of, 826
Lenses, achromatic, of Dollard, 816
refraction by, 799
varieties, 799
Leukocytes, 200'
basophilic, 200
diapedesis, 206
eosinophilic, 200
mononuclear, 200
polymorphonuclear, 200
polynuclear, 200
transitional type, 200
Leukocytosis, 201
assimilation, 201
pathological, 201
Leukocythemia, 904
Leukopenia, 201
Levers, different systems, 47, 48
Leydig, cells of, interstitial, function,
984
Lieberkiihn, crypts of, 908, 949
Life, general conditions, 33
phenomena, 29
spontaneity of, 33
structural basis of, 21
Ligaments of larynx, 541
Light, cause of, 794
corpuscular theory, 794
emission theory, 794 >
nature of, 794
qualities of, 879
reflection of, 795
reflex, 648, 812
sources of, 794
stimulation by, chemical and physical
changes in retina from, 840
undulatory theory, 794
velocity of, 794
white, 879
Lindemann's method of determining
_ quantity of blood, 228
Linea diaphragmatica, 464
Lines, Zollner's, 878, 879
Lingual tonsils, 907
Linguopalatal sounds, 554
Lipase, 513, 935
of saliva, 994
Lipins of muscle, 86
Lipochrome, 171
Lipoids, 25
of nerve, 114
Lipolytic action of pancreatic juice,
996
enzymes, 989
Lippmann's capillary electrometer, 101
1166
INDEX
Liquid, flovz of, through elastic tubes,
351
through rigid tubes, 349
Liquor amnii, 1140
folHculi, 1129
spinaHs, 605
Lissauer's bundle, 616
Liver, 938, 951, 964
blood supply, 938
disintegration of red corpuscles by,
198
extirpation, 945
function, 940
internal secretory power, 964
' origin of urea in, 1084
vasomotor nerves of, 438
Living substance, 17
metabolic function, 20
reproduction of, 32
Lobes of glands, 892
Lobules of glands, 892
Tiobuli complicati of cerebellum, 706
Lobulus medianus posterior of cere-
bellum, 706
simplex of cerebellum, 706
Lobus quadratus anterior of cerebellum,
706
Localization, cerebellar, 713
cerebral, 671, 681
tactile, 736
Locomotion, action of striated muscle
in, 46
lever movements in, 47
Loring's ophthalmoscope, 864
Low fever, 1106
Lower extremity, motor points in, 153
Ludwig's filtration theory of urinary
secretion, 1067
mechanistic theory of secretion, 892
stromuhr, 395
theory of formation of lymph, 237
Lumbar puncture, 720
Luminiferous ether, 794
Luminosity, 880
Lung, air-cells or alveoli of, 451
amphibian, 451
birds', 451
capacity, estimation of, 481
changes in position, in respiration,
475
collapse, 457
complex, 451
elementary, 447, 448
structure and function, 445
general topography, 454
mammalian, 452
Lungmotor, 484
Lutein, 171
Luxus consumption, 1057
Lymph, 158, 233
as protective mechanism, 245
augmentation of flow, 240
constituents, 235
factors controlling flow, 243
formation, 233, 237
Lymph, intravascular, 233
properties, 233, 234
sources, 237
Lymphagogues, 240
Lymphatic secretions, 903
Lymphatics, distribution of, 234
Lymphocytes, types, 200
Lymph-hearts of amphibia and birds,
244
Macrocytes, 175
Macrophages, 198
Macrosmatic animals, 690
Macula acustica, 783
sacculi, function, 783
utriculi, function, 783
Magnesium sulphate, effect on speed of
nerve conduction, 133
Malapterurus, electrical organ of,
double nerve conduction in, 128
Male erectile tissues, 1126
reproductive organs, 1122
Malleus, 765, 766
Malpighian corpuscles, 904
Maltase, 950, 990, 997
Mammalian lung, 452
Mammals, alimentary canal of, 998
circulatory system in, 258
spinal reflexes in, 595
Mammary glands, 897
during lactation, 899
effect of pituitrin on, 979
histological character, 898
in pregnancy, 898, 1138
innervation of, 899
relation to female sexual organs,
899
Mammillary reflex, 598
Man, normal diet of, 1058
Manometer, membrane, 296
mercury, 293,
Marey's pneumograph, 473
sphygmograph, 382
tambour, 285
Mast-cells, 200
Mastication, 998, 1000
center for, 641
Mastoid antrum, 764
cells, 764
Mate, 1063
•Material, animate, 19
inanimate, 19
Matteucci's current of rest, 103
Mayer curves, 393
theory of muscle contraction, 49
Maximal stimuli, 34
Maxwell's color wheel, 880
McDougall's theory of muscle contrac-
tion, 50
Meatus, auditory, 763
external, 764
Mechanical block theory of sleep, 723
imprint theory of light stimulation
of retina, 840
stimuli, 33
INDEX
1167
Mechanical theory of urinary secre-
tion, facts contradicting, 1068
Mechanistic theory of fat absorption,
1031 .
of secretions, 892
Media, transparent, 795
Mediastinum, 455
Medulla oblongata, 640
as automatic center, 641
as reflex center, 640
function, 640
Medullary sheath of nerve, 111
substance of nerve-fiber, 113
Megakaryocytes, 210
Megalocytes, 175
Meibomian glands, 809
Meigg's theory of muscle contraction,
50
Meissner, corpuscles of, 734
Membrana granulosa, 1130
vestibularis, 775
Membrane, basal, 775
basilar, 772
manometer, 296
nictitating, 807
of Reissner, 775
tectorial, 777
tympanic, 765
Membranous canal of cochlea, 775
Mendel's law, 1120
Mendenhall and Cannon's coagulom-
eter, 220
Meniere's disease, 790
Menopause, 1132
Menstrual blood, coagulability of, 226
Menstruation, 1132
effect of, on arterial blood pressure,
371
ovulation and, relation, 1133
symptoms during, 1132
theories of cause, 1133
Mercury manometer, 293
Mesencephalon, 664
Mesenteric artery, inferior, 433
superior, 433
Mesoporphyiin, 189
Metabolic function of living matter,
20
requirements of body, 1052
Metabolism, 29, 30, 985
effect of adrenalin on, 975
of age and sex on, 1054
of muscular exercise on, 1054
of sleep on, 1054
of temperature on, 1054
excessive, 1057
factor of growth in, 1059
normal, 1055
of carbohydrates, 1038
of fats, 1044
of proteins, 1048
end products of, 1050
specific dynamic action of proteins
in, 1059
Metaphase of mitosis of cell, 1111
Metchnikoff 's phagocytosis, 39
Metestrum, 1133
Methemoglobin, 186
spectrum of, 194
Methylpropylpyrrol, 189
Micro-calorimeter of Hill, 1092
Microcytes, 175
Microscope, examination of circulation
by, 408
Microsmatic animals, 690
Microtonometer, Krogh's, 491
Micturition, abdominal press in, 1077
mechanism of, 1077
reflex center for, 596, 1077
spinal center for, 596
Midbrain, 663, 664
reflex inhibition by, 589
Middle ear, 763, 764
Migration of ovum, 1135
of spermatozoa, 1136
Milk, alcoholic fermentation, 901
amount required by infant, 901
secreted by mother, 901
carbohydrate, 902
coagulation, 901
composition, 901
cow's, humanized, 903
human and cows' comparison, 902,
903
properties, 900
protein, 902
salts of, 902
skin formation from boiling, 901
teeth, 1001
Milk-curdling action of pancreatic
juice, 996
of saliva, 994
Milk-sugar, 902
Mind-blindness, 688
Mind-deafness, 688
Minimalair, 481
stimuli, 34
Miosis, 817
Mirror, plane, reflection from, 796
spherical, 796. See also Spherical
mirror.
Mitosis, nil
Mitral valve, 268
Moderator bands, 267
Modiolus, 772
Molecular motion, Brownian, 37
theory of current of injury, 104
Monakow's bundle, 616
diaschisis effect of, 701
Mononuclear leukocytes, 200
Monosaccharides, 987
Monticulus of cerebellum, 706
Morgagni, ventricles of, 545
Morse's key for making and breaking
electrical current, 61
Morula, 1119
Moss fibers of cerebellum, 708
Mosso's ergograph, 81, 82
plethysmograph for arm, 399
Motion, 36. See also Movement.
1168
INDEX
Motor aphasia, 694
area a true center, 676
ablation of, effects, 679
of cerebrum, 671
location, 673
Motor end-organ or effector, location of,
415
neuron, 109
paralysis from hemisection of spinal
cord, 626
points in lower extremity, 153
in upper extremity, 152
Motor-plate of muscle, 51
Mountain sickness, 519
Mouth-to-mouth method of artificial
respiration, 484
Movement, 36
ameboid, 38
by changes in cell turgor, 37
in specific gravity, 38
by growth, 38
by secretion, 38
by swelling of cell-walls, 37
ciliary, 39
molecular, Brownian, 37
muscular, 42
period of contraction, 43
of relaxation, 43
passive, 36
sense of, 785
types, 36
Mucin, 907
action of, 993
Mucous glands, secretory product, 907
secretions, 903
Mucus, 907
Miiller's theory of muscle contraction,
50
Miiller-Lyer figures, 878
Murmur, bronchial, 477
hemic, 780
Muscse volitantes, 854
Muscarin, effect on inhibitor reaction of
heart, 316, 317
Muscle, abnormal, reaction to constant
and interrupted electrical currents,
142
absolute power of, 95
artificial, of Engelmann, 49
as electrogenic organ, 98
as thermogenic organ, 97
bulbocavernosus, 1127
carbohydrates, 86
cardiac, 42
chemistry of, 85
ciliary, innervation of, 830
coagulation-rigor, 93
contracting, chemical changes in, 87
contraction, 48
character of, 70
factors varying, 76
effect of drugs and chemicals on,
79
of duration of stimulus on, 77
of fatigue on, 80
Muscle,' contraction, effect of load on»
77
of muscle substance on, 77
of strength of stimulus on, 76
of veratrin on, 79
Engelmann's theory, 49
fusion, 71
graphic registration, 53
induced, 104
influence of temperature on, 78
Jenson's theory, 50
McDougall's theory, 50
maximal, 77
Mayer's theory, 49
Meigg's theory, 50
minimal, 77
Miiller's theory, 50
Ranvier's theory, 50
refractory period, 72
registration, muscle-nerve prepara-
tion for, 53
methods, 54
Schafer's theory, 50
summation, 71
supramaximal, 77
tetanic, 72
thermodynamic theory, 49
threshold, 76
Verworn's theory, 50
voluntary, 73
wave, 68
Weber's theory, 49
contracture, 74
clonic, 75
tonic, 75
Crampton's, 822
cremaster, 1123
crico-arytenoid, lateral, 547
posterior, 547
different phases of electric currents
in, 106
direct stimulation, 52
disappearance of glycogen in, 89
effect of sodium chlorid on, 80
elasticity, 65
electric currents in, phases, 106
stimulation, 57
variations in, character, 103
compensation method of detect-
ing, 102
energy, production of, 93
enzymes, 87
excitation, 51
extensibility, 65
extractives, 87
fatigue, Treppe phenomenon, 90
fiber, 43, 44
intermediate discs, 44
transverse discs, 44
fibrnise, 44
forms of energy liberated by, 93
general composition, 85
heat rigor, 79
thermoelectric method of measur-
ing, 97
INDEX
1169
Muscle human, degenerated, law of
contraction, 155
indirect stimulation, 52
inorganic constituents, 86
irritability of, independent, 52
ischiocavernosus, 1127
lactic acid in, 87
formation, 88
lipins, 86
methods of stimulation, 53
motor plate, 51
negative variation of primary demar-
cation current in, 107
non-striated, 42
normal human, law of contraction,
150
reaction to constant and inter-
_ rupted electrical currents, 142
. orbicularis palpebrarum, 807
pale, 44
physiology of, 17
pigments, 87
production of carbon dioxid by, 88
proteins, 85
purins, 87
red, 44
retractor bulbi, 870
lentis, 821
simple twitch, 70
smooth, character of contraction, 83,
84
tonicity of, 83
sound, 69
spindles, function, 784
stapedius, 765
stimulation, unipolar method, 151
effects of, 154
striated, 42
action in locomotion, 46
stroma, 85
proteins of, 86
subminimal stimuli, summation,
76
substance, effect of, on contraction,
77
summation of contractions, 340
of stimuli, 340
tensor tympani, 765
thyro-arytenoid, 547
tissue, cardiac, 46
effect of adrenalin on, 975
peculiarities, 65
smooth, 45
structure, 43
tonicity of, 66
trophic, state, 67
water-rigor, 93
work performed by, 94
Muscle-curve, latent period, 71
period of contraction, 70
of relaxation, 70
Muscle-nerve preparation for register-
ing muscle contraction, 53
Muscle-plasma, proteins of, 86
Muscle-spindle, 51
74
Muscles, of ear, inherent, 770
of inspiration, 466
accessory, 466
extrinsic, 466
intrinsic, 466
normal, 466
papillary, 267
Muscular exercise, effect of, on arterial
blood pressures, 371
respiratory quotient in, 515
movement, 42
period of contraction, 43
of relaxation, 43
Musculature, skeletal, 42
visceral, 42
Musculi pectinati, 264
Musical sounds, 758
Mydriasis, 817
Myelin sheath of nerve. 111
function, 116
Myeloplaxes of bone-marrow, 207
Myocardium, 263
Myogen, 86
Myogenfibrin, 86
Myogenic theory of heart beat, 334
of peristalsis, 1016
Myograms, isometric, 56
isotonic, 56
Myography, 54
Myoids, 42
Myopia, 855, 859
Myosin, 86
Myosinfibrin, 86
Myxedema, 957, 958
Narcosis, 716, 725
Narcotics, effect of, on speed of nerve
conduction, 133
Nasal sounds, 554
Nauseating odors, 747
Near-point of vision, 828
Near-sightedness, 859 '
Neff's interrupter, 64
Negative variation of primary demar-
cation current in muscle, 107
Neopalhum, 665
Nerve, abducens, 650
abnormal, reaction to constant and
interrupted electrical currents, 142
accessory, 655
auditory, 651
axial current in, 136
axis-cylinder, function, 116
band fiber, 121
cells, fatigue of, 568
cause, 570
inhibition of, 574
refractory period, 571
summation of stimuli in, 572
center, 111
chemistry, 114
cholesterin, 114
compression-paralysis, 131
conduction, centrifugal, 126
centripetal, 126
1170
INDEX
Nerve, conduction, chemical theory,
134
direction, 125
double, in electrical organ of Ma-
lapterurus, 128
Kuhne's method of proving, 127
law of, 126
electrical theory of, 133
forward, law of, 126
nature of, 133
speed, 128
effect of alcohol on, 133
of anesthetics on, 133
of carbon dioxid on, 133
of immersion in water on, 132
of magnesium sulphate on, 133
of narcotics on, 133
of temperature on, 132
factors altering, 131
Helmholtz's method of deter-
mining, 129
string galvanometer for meas-
uring, 130
wave of negativity in, 134
theory of, 133
conductivity, 124
current of action in, 137
of injury in, 135
degeneration, 117
ascending, 120
descending, 120
morphological changes, 120
primary, 118
retrogressive, 119, 122
secondary, 118, 621
tertiary, 119
Wallerian law of, 119
depressor, 325, 329
dorsalis penis, 1129
electrotonic condition, method of
testing, 146
energies, specific, doctrine of, 730
erigens, 1129
facial, 650
fatigue, 139, 140
function, 115
of different parts, 116
galactosids, 114
glossopharyngeus, 534, 653
function, 749
going to sleep, 131
human, degenerated law of contrac-
tion, 155
hypoglossal, 656
ileo-inguinalis, 1129
impulse, relation to wave of negativ-
ity and action current, 138
inorganic salts in, 115
intermediary substance, 116
irreciprocal conduction, 115
irritability, 124
conductivity and, differentiation,
124
kephalin, 114
lecithin, 114
! Nerve, liberation of energy by, 134
lipoids, 114
medullary sheath. 111
metabolism during activity, 138
methods of stimulation, 53
myelin sheath. 111
function, 116
neurilemma, function, 117
normal human, law of contraction,
150
reaction to constant and inter-
rupted electrical currents, 142
oculomotor, 647
of equilibrium, 651
of hearing, 651
of Jacobson, 912
olfactory, 644
optic, 645
phenomena of conduction, 124
physiology, 17, 108
plexus, 112
pneumogastric, 654. See also Vagtis
nerve.
potassium in, 115
primitive sheath. 111
proteins, 114
pudendus, 1129
reaction of, to ascending constant
electric current, 142
to descending constant electric cur-
rent, 142
to polarization current, 142
receptor substance, 116
refractory period, lengthening of, 141
regeneration, 122
embryonic fibers in, 123
morphologic changes, 122
stimulation, unipolar method, 151
effects, 154
structure, 111
tetanus of^ secondary, 148
tissue, assimilative changes, 139
dissimilative changes, 139
refractory period, 139
trigeminus, 534, 649
trochlear, 649
vagus, 654. See Vagus nerve.
Nerve-fiber, 111
axis cylinder, 113
band, 121
degenerating, histology, 123
end-organs, 113
medullary substance, 113
neurilemma, 113
retrogressive degeneration, 611
thickness, 112
Nerve-fibrils, 112
Nerves, cranial, 642
functional system of, 642
glossopharyngeal, 534
in lower extremity, 153
Nervous depressants, effect on body
temperature, 1106
regulation of respiration, 528
system, anatomia division, 557
INDEX
1171
Nervous system, autonomic, 627
action of epinephrin on, 974
afferent conduction in, 635
cerebrospinal system and, con-
nections between, 631
characteristics, 629
function, 630
central, 557
mass, 557
cerebrospinal, autonomic system
and, connections between, 631
cervical sympathetics, 631
chemical grounds, 557
cranial, 631
fibrillar hypothesis, 565
functional arrangement, 565
grounds, 557
significance, 557
unit, 574
histological grounds, 557
joining of reflex circuits, 580
lessening irritability of, reflex in-
hibition from, 590
neuron concept of, 558
parasympathetic, 627, 631
peripheral complex, 557
protective mechanisrns, 706, 716
reflex circuit, 575
concept, 574
evolution into reaction system,
578
rudimentary, a reflex system, 376
sacral sympathetic, 631
structural arrangement, 557
unit, 558
subdivisions, 557
sympathetic, 627
thoracic sympathetic, 631
visceral, 621
Waldeyer's neuron doctrine of, 565
arguments in favor, 567
Nervus accelerans, 310
perinei, 1129
Neurilemma, 111
of nerve, function, 117
of nerve-fiber, 113
Neurit, 108
Neuroblast, 108, 559
Neurogenic theory of fever, 1107
of heart beat, 332
of peristalsis, 1016
Neuroglia, 108
Neurokeratin, 113
Neuron, 108, 558
afferent, 109
concept of nervous system, 558
conducting paths, 108
doctrine of nervous system, Wal-
deyer's, 565
arguments in 'favor, 567
efferent, 109
external characteristics, 558
form and size, 108
function, 109
internal characteristics, 563
Neuron, motor, 109
sensory, 109
types of, 560, 561, 562
Neutral salts, effect of, on coagulation
of blood, 223|
Neutrophile granules, 200
Neutrophiles, 199
New-born infant, respiration in, 460
Newton's emission or corpuscular
theory of light, 794
Nicotin, effect on inhibitor reaction of
heart, 316
on salivary secretion, 916
Nictitating membrane, 807
Nissl's granules, 108, 563, 564
Nitric oxid hemoglobin, spectrum of,
194
Nitrogen, amino-, 1051
elimination of, in starvation, 1053
excretion of, premortal rise, in
starvation, 1053
function, 447
'in blood, condition of, 507
relation to sulphur, in starvation,
1053
Nitrogen-equilibrium, 1049
Nobili's galvanometer, 99
Node, sino-auricular, 277
Nodes of Ranvier, 113
Noises, 757
perception of, 780
Non-polarizable electrodes, 59
Non-striated muscle, 42
Non-threshold substances, 1073
Normoblasts, 197
No vain, 87
Nuclein, 26, 29
Nucleoproteids, 26
tissue, 222
Nucleoprotein, 171
Nucleus in central nervous system, 111
of cell, 24
cytoplasm and functional relation,
27
cleavage, 1119
segmentation, 1119
Obesity, 1047
Banting's cure, 1056
Occipitofrontal fasciculus, 661
Oculomotor nerve, 647
Odors, classification, 747
Odores factores, 747
intermediae, 747
suaveolentes, 747
Ohm, 58
Old-sightedness, 830
Olein of milk, 902
Olfactometer of Zwaardemaker, 746
Olfactometry, 745
Olfactory bulb, 644
cells, power of reaction, 745
specific action, 744
center, 644, 690
nerve, 644
1172
INDEX
Olfactory nucleus, secondary, 644
organ, structure, 743
sensations, qualitative differences in,
747
tract, 644
Oligocythemia, 180
Olivospinal tract, 616
Oncometer, kidney, 398
splenic, 398
Oocyte, 1129
Opaque bodies, 795
Ophthalmodiaphanoscopy, 864
Ophthalmometer, Helmholtz's, 858
Ophthalmoscope for testing refractive
power of eye, 863
Helmholtz's, 863
Loring's, 864
Ophthalmoscopy, direct, 864
indirect, 867
Opsonic index, 206
Opsonins, 205
Optic defects of eye, acquired, 855
inconstant, 855
disc, 834
illusions, 876
nerve, 645
thalamus, 703
Optics, 794
physiological, 794
Optimum stimuli, 34
Optogram, 842
Ora serrata, 806, 831
Orbicularis palpebrarum muscle, 807
Organ of Corti, activation, 777
function, 777
structure, 775
Orgasm, 1136
Ornithin, 1084
Osmatic animals, 690
Osmometer, 1023
Osmosis, 1023
Osmotic pressure, 1024
stimuli, 33
Osseous canal of cochlea, 772
labyrinth of ear, 771
Ossicles, 764, 766
movements, 767
Otocyst, 781
Otolithic cavity, 781
Otoliths, 781
Ovaries, 1129
function, 981
Overtones, fundamental, 759
Ovists, 1117
Ovulation, menstruation and, relation,
1133
Ovum, 1117
fertilization of, 1118
implantation of, 1137
migration of, 1135
polar bodies of, 1118
spermatozoa and, place of meeting,
1137
Oxidase, 513
Oxidations, hydrolytic, 511
Oxidations of ferments, 991
seat and nature, 508
Oxidative glycosuria, 966
power of tissues, 508
Oxidizing enzymes, 989
Oxygen, activation of, theories, 511
and hemoglobin, compounds of, prop-
erties, 185
deficiency, effects of, 519
diminution in partial pressure, effect
on respiratory quotient, 517
electronegative, 510
in blood, condition of, 502
increase in partial pressure, effect
on respiratory quotient, 517
ingo in starvation, 1053
requirement of fetus, 1142
respiratory, 445
Oxyhemoglobin, 183
preparation and quantity, 184
spectrum of, 193
Oxyntic cells of gastric glands, 920
Ozone-autozone theory of activation of
oxygen, 511
Pacinian corpuscles, 734
Pace-maker, 315
of peristalsis, 1015
Pain, sense, 734, 740
Pains, labor, 1144
Pale muscle, 44
Pallium, 665
Palmitin of milk, 902
Palpation method of recording arterial
blood pressure, 366
Palsy, diver's, 522
Pancreas, 932, 951, 965
histological changes in cells of, during
secretion, 933 ^
internal secretion of, function, 966
removal of, 965
vasomotor nerves of, 438
Pancreatic duct, 932
glycosuria, 966, 1043
juice, amylolytic action, 996
character of, 935
enzymes of, 935
function, 995
lipolytic action, 996
methods of procuring, 933
milk-curdling power, 996
proteolytic power, 995
secretion, regulation of, 935
secretions, 918
Papillary muscles, 267
Parabiosis, 1116
Paraglobulin, 170, 171
Paragraphia, 698
Paralytic secretion of saliva, 911
Paraphasia, 694
Parasympathetic system, 631
Parathyroid glands, 951, 954
extirpation, 955
symptoms from, 956
function, 961
INDEX
1173
Parathyroid glands, position, 955
structure, 955
Parhormones, 953
Parietal cells of gastric glands, 920
pleura, 455
Parotid salivary glands, 908
Pars intermedia, 977
Parthenogenesis, 1117, 1119
artificial, 1119
Parturition, 1144
Passive immunity, 246
motion, 36
Patellar reflex, 599
nature, 599
Peduncle, inferior, of cerebellum, 710
middle, of cerebellum, 709
superior, of cerebellum, 709
Pendular motion of small intestine, 1014
Penis, 1127
erection of, 1127
Pepsin, 924
Peptonization, effect of, on coagulation
of blood, 224
Perception reflexes, 592
Percussion, 476
Perhydridase, 513
Pericardial fluid, 237, 263
sac, 255
Pericardium, function, 264
Perilymph, 771
Perimeter, 851
Perimetry, 851
Perimysium, 43
Perineurium, 111
Periodic reflexes, 592
Periosteal reflexes, 599
Peristalsis, myogenic theory, 1016
neurogenic theory, 1016
pacemaker of, 1015
Peristaltic wave, 1014
regular, 1014
Peritoneal cavity, absorption from,
1033
Pernicious anemia, 905
Peroxidase, 513
Pfeffer's experiment in phagocytosis,
204
Pfliiger's aerotonometer, 490, 491
law of contraction, 146, 148, 149
theory of sleep, 724
Phagocytes, 204
Phagocytosis, 203
Pfeffer's experiment, 204
in immunity, 247
Pharyngeal reflex, 598
thirst, 755
tonsils, 907
Phenomenon of Purkinje, 880
Phlebogram, 388
Phloridzin glycosuria, 1043
Phonating organs, general arrangement,
540
Phonation, 549
Phosphates in urine, 1082
Phosphatides, 25
Phosphenes, 844
Phospholipin, 217
Phospholipins of bile, 948
Photic stimuli, 33
Photo-hemotachometer, Cybulski's, 405
Phylloporphyrin, 189
Physiology, definition, 17
history of science, 18
scope, 17
Pia mater, 716
Pieron's theory of sleep, 724
Pigments, muscle, 87
Pilocarpin, effect of, on salivary secre-
tion, 916
Pineal gland, 980
position and function, 980
Pinna, 763
Pitch of sounds, 758
Pithing, 530
Pitot's tubes, 405
Pituitary gland, 977
anterior lobe, function of, 979
position, 977
posterior lobe, function of, 978
removal of, effects, 977
structure, 977
Pituitrin, 978
effect on mammary gland, 979
on uterus, 978
Placenta, 1140
development, 1140
function, 1141
interchange of gases in, 451
Plane mirror, reflection from, 796
Plano-concave lens, 800
Plano-convex lens, 800
Plantar reflex, 599
Plasma of blood, 159
corpuscles and, relative amount, 159
salted, 223
Plasmozym, 215
Plate, refraction by, 799
Platelets, blood, 159, 207, 208, 214.
See also Blood platelets.
Plethora, hydremic, 1074
Plethysmograph, air, Schafer's, 398
detection of vasomotor action by, 420
glass, 400
Mosso's, for arm, 399
Plethysmographic method of estimating
blood supply, 398
Pleura, 455
parietal, 455
visceral, 455
Pleural cavity, complementary, 462
Pleurisy, 457
Plexus cardiacus, 310
gastricus anterior, 434
posterior, 434
ventralis, 434
hepatic, 939
nerve, 112
renalis, 435
Solaris, 434
suprarenalis, 434, 968
1174
INDEX
Plica semilunaris, 808
Pneumatogram, 473
Pneumatograph, Gad's, 480
Pneumogastric nerve, 654. See also
Vagus nerve.
Pneumograph, Marey's, 473
Pneumonia, 477
Pneumothorax, 457
Pohl's commutator, 61
pole changer, 61
Poikilocytes, 175, 176
Poikilothermal animals, 1093
Poiseuille's manometer, 293
Poisons, snake, effect of, on coagulation
of blood, 225
Polar bodies of ovum, 1118
Polarization current, reaction of nerve
to, 142
external, 143
in voltaic cell, 58
internal, 143
Polarizing current, 144
Pole-changer, Pohl's, 61
Policemen of blood, 204
Pollutions, seminal, 1129
Polycythemia, 163, 180
Polymorphonuclear leukocytes, 200
Polynuclear leukocytes, 200
Polypnea, 525
heat, 1095
Pomum Adami, 542
Portal circuit of circulatory system, 259
circulation, 433
vein, 259
Porous opticus, 834
Position, change of, effect on arterial
blood pressure, 372
sense of, 781
Post-anelectrotonus, 144
Post-catelectrotonus, 144
Posterolateral tract, 613 J
Posteromedian tract, 613
Potassium in nerve, 115
theory of cardiac inhibition, 320
Precipitins, 248
Preformation theory of reproduction,
1117
Pregnancy, 1138
effect of, on arterial blood pressure,
371
on general health, 1139
mammary glands in, 898, 1138
signs of, 1138
uterus at end of, 1138
uterus during, 1138, 1139
vomiting of, 1139
Premenstruation, 1133
Prepuce, 1127
Prepyramidal tract, 616
Presbyopia, 830, 855
Press, abdominal, 479, 531, 1011
in labor, 1145
in micturition, 1077
Pressure, diffusion, 446
head-, 350
Pressure, intra-abdominal, changes in,
\ 478
intrkcranial, 441
intra-ocular, 805, 810
intrapleural, 457
intrapulmonic, 457
changes in, 478
intrathoracic, 457
cause of negativity, 460
changes in, 477
lateral or side, 349
osmotic, 1024
resistance-, 350
sense, 734
sources, 347
velocity-, 350
Preyer's chemical theory of sleep, 724
Priapismus, 1128
Primitive sheath of nerve. 111
Primordial follicles, 1129
Prism, refraction by, 799
Prismatic spectrum, 879
Prochymosin, 925
Pro-estrum, 1133
Proferment, 215, 990
Projection system of cerebrum, 660
Prophase of mitosis of cell, 1111
Proprioceptors, 730
Prorennin, 925
Prosecretin, 936
Prosencephalon, 664
Prostate gland, 1126
Protease, 513
Proteins, 26
absorption of, 1031
circulating, 1048
diffusion of, 1026
endogenous, 1049
exogenous, 1049
metabolism of, 1048
end-products of, 1050
of body, source, 1048
of milk, 903
of muscle, 85
of muscle-plasma, 86
of muscle-stroma, 86
of nerve, 1 14
reaction of intestinal bacteria on, 998
specific dynamic action, 1059
in metabolism, 1059
tissue-, 1048
utilization, 1049
Proteolytic-enzyme of saliva, 994
enzymes, 989
property of pancreatic juice, 995
Prothrombin, 213, 215
Protocerebron of crayfish, 580
Protoplasm, 22
alternate contraction and expansion,
38
conductivity, 35
contractility, 35
irritability of, 35
of cell, 21
theories of structure, 24
INDEX
1175
Pseudoglobulin, 172
Pseudonucleoli of cell, 25
Pseudopodia, 203
Pseudo-reflexes, 637
Psychic blindness, 688
feeding for study of gastric juice,
930
Psycho-auditory region, 689 •
Psychophysical law of Fechner, 733
Psycho visual region, 684
Ptyalin, 909,988
action of, 993
Ptyalinogen, 909
Puberty, 1125
Pulmonary circuit of circulatory sys-
tem, 260
circulation, 430
Pulmotor, 484
Pulse^ arterial, 377. See also Arterial
'pulse.
pressure, 386
venous, 388. See also Venous -pulse.
Pulsus alternans, 388
bigeminus, 388
celer, 387
deficiens, 387
durus, 387
frequens, 387
inequalis, 387
intercurrens, 388
intermittens, 387
magnus, 387
mollis, 387
parvus, 387
rarus, 387
tardus, 387
Punctiim proximum of vision, 828
remotum of vision, 828
Puncture, lumbar, 720
Pupil, constriction of, in anesthesia,
814
dilation of, spinal center for, 596
drugs constricting, 814
dilating, 814
Purin bodies, 1051
bases in urine, 1087
excretion in starvation, 1053
of muscle, 87
Purkinje, cells of, 560, 708
figures or images, 839
phenomenon, 880
Purple, visual, 840. See also Visual
purple.
Pus-corpuscles, 201
Pycnometer, 162
Pylorus, movements of, 1005
Pyramidal cells, 560
spinal tracts, 615
tract, 661
Pyrexia, 1106
Quincke's method of determining
quantity of bldod, 2281
Quinquaud and Grehant's method of
determining quantity of blood, 227
Racemose glands, 892
Radiating stimuli, 33
Radiation, auditory, 661
Radiolaria, 20
Radiometer, resistance, 1099
Rami viscerales, gray, 414
white, 414
Ramus albus communicans, 633
griseus communicans, 633
sacculo-ampullaris, 787
utriculo-ampullaris, 787
Ranvier's nodes, 113
theory of muscular contraction, 50
Rays, chemical, 880
heat, 880
Reaction, 575
bimolecular, 992
Erb's, 156
galvanotropic, 789
of blood, 164
imimolecular, 992
Reactions, paradoxical temperature,
743
voluntary, 110
Receptor substance of nerve, 116
Receptors, 249
cutaneous, structure, 734
different types, 583
somatic, 730
visceral, 730
Recessus utriculi, 483, 783
Recording stromuhr, 396
Red blood corpuscles, 172. See also
Blood corpuscles^ red.
muscle, 44
Red-blindness, 888
Reflection from convex spherical mirror,
797
from plane mirror, 796
of light, 795 '
Reflex action, 109, 583
animal, 584
cardiac death, 326
center for defecation, 1019
for micturition, 1077
spinal cord as, 594
circuits, 110
joining of, 580
of nervous system, 575
concept of nervous system, 574
croaking of frog, 588
fatigue, 585
regulation of respiration, 533
scratching, 592
spinal. See Spinal reflex.
stimulus, subminimal, 585
time, 585
Reflexes, 110, 575
accelerating and conditioning of, 591
accommodation, 648, 812, 814
alternating, 592
antagonistic, 592
association, 582, 592
axon-, 637
classification, 591
1176
INDEX
Reflexes, clonic, 592
complex, 592
cremasteric, 592
crossing, 586
inhibition of, 588
by afferent impulses, 589
by midbrain, 589
cerebral, 588
from lessening irritability of nerv-
ous system, 590
labyrinthine, 789
light, 648, 812
perception, 592
periodic, 592
pseudo-, 637
simple, 591
spastic, 592
spreading, 586, 592
threshold, 585
tonic, 592
trigeminus cardiac, 827
yawning, 593
Refraction, 798
by biconcave lens, 803
by biconvex lens, 800
by plate, 799
by prism, 799
index of, 798
of eye, abnormalities in, 853
Refractive media, 799
power of cornea, 809
of crystalline lens, changes in, 827
of eye, shadow test, 867
tests for, 861
Refractory period of heart beat, 341
Regeneration, 1109, 1113
of nerve, 122. See also Nerve regen-
eration.
Regio olf actoria, 744
respiratoria, 744
Registers, vocal, 553
Reissner's membrane, 775
tlelaxation period of muscular move-
ment, 43
Remak's ganglion, 318, 332
Renal circulation, 433
glycosuria, 966, 1043
Rennet, 925
Rennin, 901, 924
Reproduction, 1109, 1116
dynamic theories of, 1117
of living substance, 32
preformation theory, 1117
sexual, 1117
Reproductive organs, 1109, 1117
female, 1122
male, 1122
Reptile heart, 257
Repulsive odors, 747
Residual air, 480
blood, 229
Resistance, 245
Resonance of sounds, sympathetic,
761
Resonant sounds, 554
Resonator, Helmholtz's, 762
Kqnig's, 762
Respiration, 445
abdominal type, 466
accessory movements, 471
action of intercostal muscles in, 468
artificial, 482
Galliano's method, 483
for animals, 484
mouth-to-mouth method, 484
Sylvester's method, 483
Biot, 524
calorimeter, 1091
changes in position of lungs in, 475
chemical regulation of, 532
chemistry of, 486
Cheyne-Stokes, 523
costal type, 466
diaphragmatic, type, 466
external, 447, 487
in insects, 448
in new-born infant, 460
internal, 447, 487, 507
nervous regulation of, 528
number, 474
of swallowing, 1002
reflex regulation, 533
self-regulation of, 538
tissue, 507
Respiratory capacity, 481
center, cause of activity, 530
location, 528
nervous connections, 528
regulation of activity, 531
cycle, 455
dynamic phase, 461
function of diaphragm in, 462
of ribs in, 465
static phase, 456
ferments, 513
interchange, 514
through skin, 450
movements, 461
character, 472
frequency, 472
mechanics of, 454
methods of recording, 472
modified, 481
muscles, classification of, 471
organs, special, 448
oxygen, 445
passage, upper, innervation of, 534
pause, 456
quotient, 514
effect of composition of air on, 516
of diminution in partial pressure
of oxygen on, 517
of external temperature on, 516
of increase in partial pressure of
oxgyen on, 517
of rat& and depth of respiratory
movements on, 516
slight increase ih partial pressure
of carbon dioxid on, 518
in hibernating animals, 515
INDEX
1177
Respiratory quotient in sleep, 515
influence of sex on, 516
variations in, from character of
food, 515
sounds, 476
variations in blood pressure, 486
Resistance-pressure, 350
Respired air, quantitative determina-
tion, 479
Resurrection plant, 37
Rete Malpighii, 893
testis, 1123
Retina, 806, 831
blind spot, 834
demonstration, 835
form of, 836
chemical and physical changes in, on
stimulation by light, 840
corresponding points on, 873
general structure, 831
layers of, 831
rods and cones, 833
sensibility of, to colors, 884
yellow spot, 836
Retinal image, formation, 846, 848
inversion, 848
size, 850
Retinoscopy, 867
point of reversal in, 868
Retractor bulbi muscle, 870
lentis muscle, 821
Retzius, fiber cells of, 786
Reversibility of ferments, 991
Revolutio cordis, 272
Rheocord, 102
Rheoscopic frog preparation, 104,
105
Rhodopsin, 840. See also Visual pur-
ple.
Rhombencephalon, 664
Ribs, function of, in respiratory cycle,
465
Rigor, calcium, 337
caloris, 79
chemistry of, 93
mortis, chemistry of, 91
Rima glottidis, 543
palpebraris, 807
vocalis, 552
Ringer's solution, 182
effect on heart beat, 336
Ritter's tetanus, 146
Riva-Rocci's sphygmomanometer, 367
Rod-granules of retina, 832
Rods and cones of retina, 833
of Corti, 776
Rolando's substantia gelatinosa, 606
Roof ganglia of cerebellum, 708
Roots, hair-, 893
Rothe's rotatory apparatus for color
discs, 881
Rubrospinal tract, 616
Russell and Brodie's niethod of esti-
mating coagulation time of blood,
219
Sac, conjunctival, 807
dental, 1001
Saccule of ear, 771, 782
Sacral sympathetic system, 631
Saliva, 908
derivation of, 909
fat-splitting enzyme of, 994
function, 993
general character, 918
milk-curdling power of, 994
paralytic secretion, 911
proteolytic enzyme of, 994
Salivary corpuscles, 918
glands, 908
histological changes during activity,
910
character, 909
innervation of, 911
parotid, 908
sublingual, 908
submaxillary, 908
secretion, center for, 641
of adrenalin on, 916
of atropin on, 916
of ergotoxin on, 916
of nicotin on, 916
of pilocarpin on, 916
filtration theory of, facts dis-
proving, 917
mechanism, 913
Salivation, 911
Salted blood plasma, 223
Salts of milk, 902
Sand, brain-, 981
Santorini, duct of, 932
Sarcolactic acid, 1041
Sarcolemma, 44
Sarcoplasm, 44
Sarcostyles, 44
Scala tympani, 772
vestibuli, 772
Scapular reflex, 598
Schafer's air plethysmograph, 398
theory of muscle contraction, 50
of structure of protoplasm, 24
Scheiner's accommodation experiment,
827
Schlemm, canal of, 805
Schonbein and Clausius' ozone-autozone
theory of activation of oxygen, 511
Schultze, comma tract of, 616
Sciatic center, 595
nerve, vasomotor reaction, 421
Sclera, 805
Scrotal reflex, 598
Scrotum, 1122
Scurvy, cause, 927
Sea-sickness, 790
Sebaceous glands, 894
Sebum, 895
Second sight, 861
Secretion, 936
gastric, 927
Secretion externe, 951
interne, 951
1178
INDEX
Secretion, histological changes in cells of
pancreas during, 933
movement by, 38
of urine, 1064. See Urine secretion.
skin as organ of, 894
Secretions, 891
chemical theory, 892
classification, 889
cutaneous, 889
digestive, 908, 918, 938
external, 889
factors in formation of, 892
filtration theory of, 892
gastric, 918
internal, 951. See also Internal
secretions.
lymphatic, 903
mechanistic theory, 892
mucous, 903
pancreatic, 918
vitalistic theory, 892
Segmentation nucleus, 1119
Semen, 1126
ejaculation of, 1127
pollutions, 1129
spontaneous emissions, 1128
Semicircular canals, 771, 785
anterior or superior, 786
effects of lesions of, 787
of stimulation of, 788
external or horizontal, 786
posterior or inferior, 787
relative position, 786
Semilunar valves, 271
Seminal vesicles, 1126
Seminiferous tubules, 1123
Semivowels, sound production of, 554
Sensations, olfactory, qualitative dif-
ferences in, 747 ,
• tactile, methods of evoking, 735
Sense, dynamic, 730, 785
of equilibrium, 781
of hearing, 756
of hunger, 743
of movement, 785
of pain, 734, 740
of position, 781
of pressure, 734
of sight, 794
of smell, 743
of taste, 743
topography of, 751
of temperature, 734, 741
of thirst,* 743
of touch ,734
static, 578, 730, 781
Sense-organs, 727
adaptation of, 732
classification, 727, 729
fatigue of, 732
Sensibilin, 252
Sensitive plant, 37
Sensitizing substance, 250
Sensory aphasia, 696
neuron, 109
Sensory paralysis from hemisection of
spinal cord, 626
Septomarginal bundle, 616
Sera, antitoxic, 246
Serum, blood, 171, 212
sickness, 251
Serum-albumin, 170, 171, 172
Serum-casein, 171
Serum-globulin, 170, 171
Sex, determination of, 1143
effect of, on metabolism, 1054
influence of, on respiratory quotient,
516
Sexual glands, 982
maturity, 1125
organs, female, relation to mammarv
glands, 899
reproduction, 1117
Shadow test of refractive power of eye,
867 ^
Sham feeding for study of gastric juice,
930
Shingles, 622
Shivering, 1098
Shock, 589
theories of, 590
Sickness, mountain, 519
serum, 251
Side-chain theory of immunity, 249
Sighing, 482
Sight center, 684
nerve of, 645
second, 861
sense of, 794
Sigismund's theory of menstruation,
1134
Sign, Argyll-Robertson, 813
Singing, 553
voice, range, 553
Sino-auricular node, 277
Sinospiral fibers of ventricles, 266
Sinus of Valsalva, 272
venosus, 255
Skeletal muscle tissue, vasomotors of,
421
musculature, 42
Skiascopy, 867
Skin, absorption through, 1034
as organ of protection, 893
of secretion, 894
cold spots, 742
respiratory interchange through, 450
varnishing, effect on body tempera-
ture, 1105
warm spots, 742
Sleep, 716, 721
adult requirement, 721
anemia theory, 723
changes in depth, 722
chemical theories, 723
effect of, on arterial blood pressure,
370
on metabolism, 1054
hypnotic, 724
inhibition theory, 723
INDEX
1179
Sleep, mechanical block theory, 723
phenomena of, 722
respiratory quotient in, 515
theories of, 723
Smegma preputii, 895
Smell, center for, 690
nerve of, 644
sense of, 743
Smith and Haldane's method of deter-
mining quantity of blood, 227
Snake poisons, effect of, on coagulation
of blood, 225
Sneezing, 482
center for, 641 •
Snellen's test types, 861
Sniffing, 482
Snoring, 482
Sobbing, 482
Sodium chlorid, effect of, on muscle, 80
in blood, 169
citrate method of blood transfusion,
231
Solar spectrum, 879
Solution, hyperosmotic, 1025
hypertonic, 1025
hyposmotic, 1025
hypotonic, 1025
isosmotic, 1025
isotonic, 1025
Ringer's, 182
Stokes's, 186
Somachrome cells, 564
Somatic cells, 1114
hunger, 754
receptors, 727, 730
Sound, muscle, 69
waves, cause, 756
character, 756
conduction by cranial bones, 779
rate of speed, 757
reinforcement and interference,
760
Sounds, 757
color, 759
intensity, 758
loudness, 758
musical, 758
pitch, 758
quality, 759
stamp, 759
sympathetic vibration or resonance,
761
timbre, 759
tone, 758
vocal. See Vocal sounds.
Spaces of Fontana, 805
Spastic reflexes, 592
Spaying, effects of, 982
Specific gravity, movement by changes
in, 38
Spectrophotometric method of deter-
mining hemoglobin, 190
Spectroscope, 192, 193
Spectroscopic analysis of hemoglobin
and derivative compounds, 192
Spectrum, absorption bands, 192
Fraunhofer lines, 193
of acid hematin, 195
of carbon monoxid hemoglobin, 194
of hematoporphyrin, 195'
of hemochromogen, 195
of methemoglobin, 194
of nitric oxid hemoglobin, 194
of oxyhemoglobin, 193
of reduced hemoglobin, 193
solar, 879
Speech, 540, 553
center, 691
location, 693
circuit, 691
Spermatids, 1124
Spermatocytes, 1124
Spermatogonia, 1124
Spermatozoa, 1124, 1125
development and character, 1124
migration of, 1136
ovum and, place of meeting, 1137
rheotactic quality, 1136
thigmotactic quality, 1136
Spermatozoon, 1117
Sperm-cell, 1117
Spermin, 1126
action of, 982
Spherical aberration, 815
mirror, 796
center of curvature, 796
concave, 796
convex, 796
reflection from, 797 -
geometrical center, 796
principal axis, 797
focus, 797
secondary axis, 797
Sphincter antri pylori, 1005
of Henle, 1128
urethrse membranacese, 1128
Sphygmogram, 383
clinical significance, 387
Sphygmograph, Dudgeon's, 382
Marey's, 382
Sphygmography, 381
Sphygmomanometer, Janeway's, 369
Riva-Rocci's, 367
von Basch, 366
Spinal conduction, localization of,
methods used for, 609
Spinal cord as conducting path, 603
as reflex center, 594
automatic activity, 597
centers, 596
fasciculi, classification, 612
function, 594, 622
general structure, 603
gray matter, functional basis, 606
hemisection, effects of, 626
posterior roots, distribution of im-
pulses from, 623
roots, function of, 519
tracts, 610
ascending, 616
1180
INDEX
Spinal cord tracts, classification, 614
descending, 615
posterior, 616
pyramidal, 615
trophic function, 603, 621
vasomotor reaction of, 421
white matter, functional basis, 608
reflex, abdominal, 598
achillis jerk, 599
bulbocavernosus, 599
centers, localization, 594
cremasteric, 598
gluteal, 598
jaw jerk, 599
mammillary, 598
patellar, 599
plantar, 599
pharyngeal, 598
scapular, 598
scrotal, 598
sternal, 598
tensor tympani, 599
winking, 599
wrist jerk, 599
reflexes, abolition, 601
deep, 598
exaggeration, 601
from facial muscles, 599
in mammals, 595
organic, 598
periosteal, 599
reinforcement, 600
superficial, 598
Spinocerebellar tract, 617
Spinotectal tract, 681
Spinothalamic tract, 618
Spindles, muscle, function, 784
Spiral ganglion, 777
Spirometer, Hutchinson's, 479
Wintrich's modification, 479
Splanchnic nerve, greater, vasomotor
reaction of, 425
nerves, function, 434
system, 435
Splanchnici minores, 435
Spleen, 903
disintegration of red corpuscles by,
198
formation of white blood corpuscles
by, 904
function, 904
hematopoietic function, 905
pulp of, 905
removal of, effects, 904
transplantation, 904
vasomotor nerves of, 438
Splenic artery, 433
oncometer, 398
Sponges, circulatory system in, 254
Spongioplasm, 24
Spontaneity of life, 33
Spontaneous emission of semen, 1128
Spot, bHnd, 834
demonstration of, 835
form of, 836
Spot, germinal, 1130
yellow, 836
Squint, 873
Stannius' experiment on heart beat, 333
Stapedius muscle, 765
Stapes, 767
Starling's theory of formation of lymph,
238
Starvation, carbon dioxid in, 1053
effect of, 1052
elimination of nitrogen in, 1053
oxygen ingo in, 1053
premortal rise in excretion of nitrogen
in, 1053
purin excretion in, 1053
relation of sulphur to nitrogen in,
1053
urea nitrogen in, 1053
Static phase of respiratory cycle, 456
sense, 578, 730, 781
Stationary air, 481
Statocyst, 781
StatoUth, 781
Steapsin, 935, 996
Stearin of milk, 902
Stellate cells of Kupffer, 939
StercobiUn, 196, 1080
Stercorubin, 948
Stereoscope, 876
Sternal reflex, 598
Sternzellen of Kupfer, 198, 207
Stethograph, 473
Stethoscope, Laennec, 757
Stewart[s method of estimating circula-
tion time, 410
of measuring volume of blood
stream, 397
Stigma, 1130
Stigmse, 448
Stimulants, alcoholic, 1063
in diet, 1062
Stimulation, futurity, 34
phenomena of, 33
threshold of, 34
Stimuli, adaptation state, 35
chemical, 33
electric, 35
maximal, 34
mechanical, 33
minimal, 34
optimum, 34
osmotic, 33
photic, 33
radiating, 33
refractory state, 35
strength of, 34
subminimal, 34
thermal, 33
Stirrup bone of ear, 767
Stokes' solution, 186
Stomach, antrum pylori, 1006
bismuth x-ray study of, 1008
contents, evacuation of, 1009
time of, 1009
fundus, 1006
INDEX
1181
Stomach fundus, movements of, 1005
layer of circular muscle strands, 1005
movements of, 1005
musculature, innervation of, 1012
outer longitudinal muscular layer,
1006
pyloric portion, 1006
resistance of, to gastric ferments, 925
teeth, 1001
vasomotor nerves of, 438
Strabismus, 873
Striated muscle, 42 I
action in locomotion, 46
String galvanometer, Einthoven's, 286
for measuring speed of nerve con-
duction, 130
Stroma and hemoglobin of red corpus-
cles, separation, 181
muscle, 85
Stromuhr, detection of vasomotor ac-
tion by, 420
Ludwig's, 395
recording, 396
Subarachnoid system, 717
Subarachnoidal space, 716
Sublingual salivary glands, 908
Submaxillary salivary glands, 908
Subminimal stimuli, 34'
Substance, living, 17
Substantia gelatinosa, 605
of Rolando, 606 1
Substrate, 987
Succus entericus, 949
Sucking, center for, 641
Sugar content of blood, 169
of milk, 902
supply of body, regulation of, 1042
utiUzation of, 1040
, Sulcus primarius of cerebellum, 706
( Sulphates in urine, 1082
Sulphur, relation to nitrogen, in starva-
tion, 1053
Sunhght, speed of, 795
Supplemental air, 480
Supraglottic cavity, 544
Suprarenal bodies, vasomotors of, 435
capsules, 967. See also Adrenal
glands.
plexus, 968
Suspensory ligament of eye, 821
Swallowing, 998, 1001. See also Deg-
lutition.
respiration of, 1002
Sweat, 896
quantity secreted, 896
Sweat-glands, 895
innervation of, 897
Swim-bladder of fish, 450
Sylvester's method of artificial respira-
tion, 483
Sympathetic system, 627
Synapse, 110
Synovial fluid, 237
Systemic circuit of circulatory system,
259
Systole as period of decomposition, 341
auricular, position of heart valves in,
307
interpolated, 343
ventricular, position of heart valves
in, 307
Systohc pressure, intracardiac, 296
Tactile acuity, 736
agnosia, 684, 697
discrimination, 625, 736^
localization, 625, 736
sensations, methods of evoking, 735
Talking dog, 692
Tallquist's method of estimating hemo-
globin, 191
Tambour, Marey's, 285
Taste buds, activation of, 750
innervation of, 749
power of reaction, 751
structure, 748
center, 691
sense of, 743
topography of, 751
Taste-pore, 748
Taurin, 87
Taurocholic acid, 947
Tea, 1063
Tectorial membrane, 777
Tectospinal bundle, anterior, 616
Teeth, eye, 1001
milk, 1001
permanent, 1001
stomach, 1001
wisdom, 1001
Teichmann's hemin crystals, 188
Telophase of mitosis of cell, 1112
Temperature, effect of, on metabolism,
1054
on muscle contraction, 78
on speed of nerve conduction, 132
external, effect of, on respiratory
quotient, 516
of blood, 162
of body, 1093. See also Body tem-
perature.
reactions, paradoxical, 743
sense of, 734, 741
Temporopontine fibers, 661
Tendril fibers of cerebellum, 708
Tenon's capsule, 804, 869
Tensor tympani muscle, 765
reflex, 599
Tentorium cerebelli, 716
Test breakfast, 923
tube, Uving, 222
types, Snellen's, 861
Testes, function, 982
Testicles, 1122
Tetania parathyreopriva, 962
Tetanic current, 62
Tetanus, 71, 72
incomplete, 71
of nerve, secondary, 148
Ritter's, 146
1182
INDEX
Tetanus, secondary, 104
Wendt's, 146
Tethelin, 980
Thalamocortical tract, 660
Thalamus opticus, 703
Thebesius foramina of, 428
Theca foUiculi, 1130
Theine, 1063
Theobromine, 1062
Theorem of Toricelli, 348
Thermal stimuli, 33
theory of light stimulation of retina,
840
Thermodynamic theory of muscle con-
traction, 49
Thermogenesis, 1092, 1097
Thermolysis, 1099
Thermometry, 1089
Thermotaxis, 1097
nervous mechanism regulating, 1102
Thiery's method of obtaining intestinal
juice, 949
Thirst, 754
general, 755
pharyngeal, 755
sense, 743
Thoma-Zeiss hemocytometer, 176
Thoracic duct, 234
sympathetic nerve, 434
system, 631
Thorax, aspiratory power of, 464
Threshold contraction of muscle, 76
substances, 1073
Thrombin, 213, 215
Thrombocytes, 159, 207, 208, 214
Thrombogen, 170, 172, 213, 215
Thrombokinase, 210, 213, 214
Thromboplastic substance, 222
Thymus gland, 951, 963
extirpation of, effects, 964
function, 964
position, 963
structure, 963
Thyro-arytcnoid muscle, 547
Thyroid cartilage, 542
gland, 951, 954
active principle, nature of, 960
extirpation, 955
symptoms from, 956
function, 961
guanidin metabolism in, 963
position, 954
structure, 954
Thyroidin, 960
Thyro-oxy-indol, 960
Thyroxin, 960
Tidal air, 480
blood and, interchange of gases
between, 488
Tigroid bodies, 563, 564
Timbre of sounds, 759
Time, reflex, 585
Tissue nucleoproteid, 222
oxidative power, 508
respiration, 507
Tissue, thirst, 755
Tissue-fibrinogen, 222
Tissue-fluid, 233
reactions of, 248
Tissue-protein, 1048
Toisson's fluid, 177
Tones, fundamental, 759
Tonic contracture of muscle, 75
reflexes, 592
Tonicity of muscle, 66
of smooth muscle, 83
Tonsils, 906
faucial, crypts of, 906
function, 906
removal of, effects, 907
pharyngeal, 907
Tonus, labyrinthine, 789
Topler's pump for extraction of gases
from blood, Barcroft modification,
499
Toricelli's theorem, 348
Tormina intestinorum, 1019
Touch areas, 739
illusions, 739
sense, 734
Toxogenic theory of fever, 1107
Toxogenin, 252
Toxophore, 249
Trachea, 452, 455
Tract, anterolateral superficial, 618
comma, of Schultze, 616
direct, 617
Flechsig's, 617
Gower's, 613, 618
olfactory, 644
olivospinal, 616
posterolateral, 613
posteromedian, 613
prepyramidal, 616
pyramidal, 661
rubrospinal, 616
spinocerebellar, 617
spinotectal, 618
spinothalamic, 618
thalamocortical, 660
vestibulospinal, 616
Tracts of cerebrum, classification, 659
of spinal cord, 610
classification, 614
Transfusion of blood, 230
Translucent bodies, 795
Transparent media, 795
Traube-Hering curves, 364, 393
Traube's theory of activation of oxygen,
512
Traumatic epilepsy, 677
Tremors from cerebellar disease, 713
Treppe phenomenon of muscle fatigue,
90
Tricuspid valve, 268
Trigeminus cardiac reflex, 327
nerve, 534, 649
vasomotor reaction of, 422
Tritocerebron of crayfish, 580
Trochlear nerve, 649
INDEX
1183
Trophic state of muscle, 67
theory of cardiac inhibition, 319
Trypsin, 935
Tubular glands, 892
Tubulo-racemose glands, 892
Tunica albuginea, 1123, 1127
externa, 415
media, 415
Tunnel of Corti, 776
Ttirck's column, 612
Turk's mixture for counting white blood
corpuscles, 201
Tweenbrain, 664
Tympanic membrane, 764, 765
Tympanum, 763, 764
Tyrosinase, 513, 514
Umbilical artery, 260
cord, 1142
vein, 260
Uncinate fasciculus, 661
Undulatory theory of light, 794
Unimolecular reaction, 992
Unipolar stimulation of muscle and
nerve, 151
effects of, 154
Upper extremity, motor points in, 152
Urea, 1051
content of blood, 170
daily excretion of, 1085
in urine, 1083
nitrogen in starvation, 1053
origin of, in liver, 1084
Uremia, 1084
Ureters, 1076
Urethra, 1123
Urethral glands, 1126
Uric acid in urine, 1087
Urinary bladder, 1076
nervous control, 1077
tubules, absorption of water from, in
urine secretion, 1071
Urine, 1080
acetone in, 1086
amino-acids in, 1087
ammonia in, 1086
carbamide in, 1083
carbonates in, 1082
chlorids in, 1081
color, 1080
composition, 1080, 1081
creatin in, 1087
creatinin in, 1087
freezing point, 1081
general characteristics, 1080
hippuric acid in, 1087
indican in, 1082
indole in, 1082
inorganic constituents, 1081
odor, 1080
organic constituents, 1083
phosphates in, 1082
purine bases in, 1087
quantity, 1080
reaction, 1081
Urine, regurgitation of, prevention,
1076
secretion of, 1064
absorption of water from urinary
tubules in, 1071
Ludwig's filtration theory, 1067
modem theory, 1072
pure mechanical theory, facts con-
tradicting, 1068
stimulation of, 107
theories of, 1067
specific gravity, 1080
sulphates in, 1082
taste, 1080
urea in, 1083
uric acid in, 1087
viscosity, 1081
UrobiUgen, 948
Urobilin, 196, 948, 1080
Urobilinogen, 1080
Urochrome, 196, 1080
Uroerythrin, 1080
Uterus at end of pregnancy, 1138
contraction of, spinal center for, 596
effect of pituitrin on, 978
in pregnancy, 1138, 1139
virgin, 1138
Utricle of ear, 771, 782
Vagi nerves, function, 434
Vagus nerve, 654
divided, excitation of central end,
537
stimulation of distal end, 537
function of, 536
inferior laryngeal branches, 535
pressure on, effect on heart, 327
specificity of, 316
superior laryngeal branch of, 534
Valsalva, sinus of, 272
Valve, Eustachian, 262
ileocecal, 1017
Valves, auriculoventricular, 268
of heart, 263
arrangement, 267
play of, 306
semilunar, 271
van't Hoff's theory of activation of
oxygen, 511
Vas deferens, 1123 ,
Vasa efferentia, 1123
recta, 1123
Vascular system, general arrangement,
253
Vasoconstriction, 412
theories of, 417
Vasoconstrictors, 412
Vasodilatation, 412
theories of, 417
Vasodilators, 412
Vasomotor action, methods of detect-
ing, 420
center, 412
activity of, 413
location of, 412
1184
INDEX
Vasomotor fibers, distribution of, 414
nerves of intestines, 437
of kidneys, 435
of liver, 438
of pancreas, 438
of spleen, 438
of stomach, 438
of suprarenal bodies, 435
reaction, nature of, 417
of cervical sympathetic nerve, 422
of depressor nerve, 427
of greater splanchnic nerve, 425
of sciatic nerve, 421
of spinal cord, 421
of trigeminus nerve, 422
results, 418
Vein, umbilical, 260
Veins, 254
Velocity pressure, 350
Vena cava, 254
gastrolienalis, 433
pancreatica, 433, 933
Venae mesentericse, 433
Venous blood pressure, 373. See also
Blood pressure, venous.
pulse, 388
pathological, 390
physiological, 388
speed and character, 389
Ventilation, 526
negative, 539
positive, 539
Ventricle, fourth, 663
Ventricles, bulbospiral fibers, 266
circular fibers of, 267
discharging period, 307
function, 300, 302
musculature of, 265
of heart, 255
of Morgagni^ 545
period of filhng, 308
setting period, 308
sinospiral fibers, 266
structure, 263
Ventricular complex of electrocardio-
gram, 288
fibrillation, 279
systole, position of heart valves in, 307
Venules, 254
Veratrin, effect of, on muscle, 79
Vermes, circulatory system of, 255
Vermis, inferior, of cerebellum, 706
median, of cerebellum, 706
superior, of cerebellum, 706
Vernix caseosa, function, 895
Vertebrates, circulatory system in, 256
Verworn's theory of muscle contraction,
50
Vesicles, seminal, 1126
Vestibular membrane, 775
Vestibule, aortic, 267
Vestibulospinal tract, 616
V. Helmholtz's method of determining
speed of nerve conduction, 129
Vibration sympathetic, * of sounds, 761
Vibratory energy, 728
Vierordt method of estimating coagula-
tion time of blood, 219
Vierordt and Glan's method of deter-
mining hemoglobin, 190
Virgin uterus, 1138
Virtual focus, 798
image, 798
Visceral musculature, 42
nervous system, 627 " >
pleura, 455
receptors, 727, 730
Viscosimeter, 167
Viscosity of blood, 166
variation, 167
of urine, 1081
Vision. See Sight.
binocular, 869, 872
color, 879. See also Color vision.
direct, 837
electrical variations in eye on, 844
far-point of, 828
indirect, 837 -
near-point of, 828
Visual acuity, 838
after-effects, 882
agnosia, 697
association, 686
axis of eye, 837
axes of eye, secondary, 837
center, connection with other centers,
687
field, 851
judgment, 874
purple, 840
bleaching property, 842
extraction of, 842
function, 843
white, 843
yellow, 843
Vital capacity, 481
Vitalism, 238, 893
Vitalistic theory of secretion, 892
Vitamines, 926
Vitreous humor, 810
Vividiffusion, 1049
V. Kries apparatus for recording capil-
lary blood pressure, 376
Vocal aperture, 552
cords, 540, 543, 550
approximation of, 546
false, 543
true, 543
tension, 545
registers, 553
sounds, characteristics, 551
dental, 554
explosive, 554
friction, 554
guttural, 554
labial, 554
linguopalatal, 554
loudness, 552
nasal, 554
peculiarities, 553
INDEX
1185
Vocal sounds, pitch, 552
production of, 551
quality, 552
resonant, 554
Voice, 540
breaking of, 552
chest, 551
falsetto, 551
singing, range, 553
Volkmann's hemodromometer, 404
Voltaic cell, polarization in, 58
Voluntary muscle contraction, 73
reactions, 110
Vomiting, 1011
center for, 641, 1012
of pregnancy, 1139
von Basch sphygmomanometer, 366
Vowels, sound production of, 554
Waldeyer's neuron doctrine of nervous
system, 565
arguments in favor, 567
"Waller's ergograph or dynamograph,
81, 82
law of nerve degeneration, 119, 621
Warm spots of skin, 742
Water, absorption of, 1027
from urinary tubules in urine
secretion, 1071
calorimeter, 1090
Water-rigor of muscle, 93
Wave, antiperistaltic, 1014
peristaltic, 1014
regular, 1014
theory of nerve conduction, 133
Weber's law, 733
theory of muscle contraction, 49
Welker's method of determining quan-
tity of blood, 226
Welker and Hoppe-Seyler's chrono-
metric method of determining hemo-
globin, 190
Wendt's tetanus, 146
76
Wernicke's sensory aphasia, 696
Whartonian jelly, 1142
Whey, 901
Whispering, 553
White blood corpuscles, 199. See also
Blood corpuscles, white.
light, 879
matter, cerebral, general arrangement,
658
of spinal cord, functional basis,
608
of eye, 805
visual, 843
Winking reflex, 599
Wintrich's modification of Hutchinson's
spirometer, 479
Wirsung, duct of, 932
Wisdom teeth, 1001
Word-blindness, 688, 696
Word-deafness, 688, 689
Work-adder, diagram of, 96
Wrist jerk, 599
Xanthin, 1051
Xanthinoxidase, 513
X-ray bismuth study of stomach, 1008
Yawning, 482
reflex, 593
Yellow spot, 836
visual, 843
Young-Helmholtz theory of color vision,
886
Zollner's lines, 878, 879
Zona pellucida, 1130
Zuntz's indirect method of determining
cardiac output, 302
Zwaardemaker's olfactometer, 745
Zymase, 988
Zymogen, 990
granules, 909
Zymoplastic substance, 222
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